Correction: Hydrogel microfibers with perfusable folded channels for tissue constructs with folded morphology

Correction for ‘Hydrogel microfibers with perfusable folded channels for tissue constructs with folded morphology’ by Yupeng Liu et al., RSC Adv., 2018, 8, 23475–23480.

The authors regret that incorrect details were given for ref. 49 in the original article. The correct version of ref. 49 is given below.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR,HPLC and LC-MS methods

Correction for ‘Chemical stability and interactions in a new antihypertensive mixture containing indapamide and dihydralazine using FT-IR, HPLC and LC-MS methods’ by Anna Gumieniczek et al., RSC Adv., 2018, 8, 36076–36089.

The authors regret that incorrect details were given for ref. 19 in the original article. The correct version of ref. 19 is shown in the references section below.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: Oxidative carboxylation of olefins with CO2: environmentally benign access to five-membered cyclic carbonates

Correction for ‘Oxidative carboxylation of olefins with CO₂: environmentally benign access to five-membered cyclic carbonates’ by Liang Wang et al., RSC Adv., 2020, 10, 9103–9115.

The Royal Society of Chemistry regrets that incorrect details were given for Ref. 10b, 11b and 11c in the original article. The correct versions of Ref. 10b, 11b and 11c are given below as Ref. 1, 2a and 2b, respectively.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: Homo-condensation of acetophenones toward imidazothiones

Correction for ‘Homo-condensation of acetophenones toward imidazothiones’ by Phuc Hoang Pham et al., RSC Adv., 2020, 10, 40225–40228, DOI: 10.1039/D0RA03047C.

The authors regret the omission of two references, shown below as ref. 1(a) and (b), which should have appeared as ref. 7(a) and (b).On page 40227, at the end of the paragraph which starts “With the results in hand, we proposed a possible mechanism for the annulation (Scheme 5)…” the following sentence should have been added:“It should be noted that Asinger and co-workers reported a similar transformation using ammonia, instead of ammonium acetate, that occurred in methanol solvent.¹ For that reason, an alternative mechanism should not be excluded.”The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: Nano N-TiO2 mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes

Correction for ‘Nano N-TiO₂ mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes’ by Kaliyamoorthy Selvam et al., RSC Adv., 2012, 2, 2848–2855, DOI: 10.1039/C2RA01178F.

The authors regret omitting citations of their related papers in Journal of Molecular Catalysis A: Chemical and Applied Catalysis A: General: ‘Cost effective one-pot photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂’ (DOI: 10.1016/j.molcata.2011.09.014)¹ and ‘Mesoporous nitrogen doped nano titania—A green photocatalyst for the effective reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol’ (DOI: 10.1016/j.apcata.2011.11.011).² The citations should have appeared in the following places as ref. 36 (ref. 1, in the reference list here) and ref. 37 (ref. 2, in the reference list here):In the sentence starting on line 5 of paragraph 5 in the introduction:‘Photocatalytic synthesis of quinolone derivatives from nitrobenzene using TiO₂, metal doped TiO₂ and others had been reported earlier.^1,23–25’At the end of Section 3.12 with the addition of the following sentence:‘This catalyst was also found to be effective for the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol.²’The authors regret that it was not clear in the original article that the bare TiO₂ and N-TiO₂ characterisation data had been reproduced from their related Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 Although the Catalysis Communications article was cited as ref. 25 (ref. 3, in the reference list here) in the original article, it was not made clear that some of the data was reproduced from this article. The appropriate figure captions have been updated to reflect this.Fig. 2: Diffuse reflectance spectra of (a) bare TiO₂, (b) N-TiO₂ and (c) TiO₂-P25. The bare TiO₂ data in Fig. 2a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 2b have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 3: Photoluminescence spectra of (a) bare TiO₂, (b) TiO₂-P25 and (c) N-TiO₂. The bare TiO₂ data in Fig. 3a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 3c have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 4: HR-TEM analysis: (a and b) images at two different regions of N-TiO₂, (c) SAED pattern of N-TiO₂, (d) lattice fringes of N-TiO₂ and (e) particle size distribution of N-TiO₂. Fig. 4 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 5: X-ray photoelectron spectra of N-TiO₂: (a) survey spectrum, (b) Ti 2p peak, (c) O 1s peak, (d) N 1s peak and (e) C peak. Fig. 5 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 6: (a) N₂ adsorption–desorption isotherms of N-TiO₂ and (b) its pore size distribution. Fig. 6 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 8: GC-MS chromatograms at different reaction times for the photocatalytic conversion of nitrobenzene with N-TiO₂. Fig. 8 has been entirely reproduced with permission from ref. 3. Copyright 2011 Elsevier.The authors also wish to remove Fig. 1 from the original article due to similarities between two of the spectra and the raw data no longer being available. This does not affect the conclusions as the presence of nitrogen was confirmed by other techniques.The authors also wish to clarify the differences between this RSC Advances paper and the Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 The Journal of Molecular Catalysis A: Chemical paper discusses the photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂.¹ The Applied Catalysis A: General paper reports the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles using mesoporous nitrogen doped nano titania.² The Catalysis Communications paper, ref. 25 in the original article, discusses the synthesis of quinaldines from nitroarenes with gold loaded TiO₂ nanoparticles.³ The original RSC Advances paper discusses the catalytic ability of N-TiO₂ in the synthesis of quinaldines from nitrobenzenes. In each paper, either a different catalyst was used or a different synthetic reaction was investigated.     

TEMPORAL EVOLUTION AND PREDICTORS OF SUBJECTIVE COGNITIVE COMPLAINTS UP TO 4 YEARS AFTER STROKE

ObjectiveTo examine the temporal evolution of subjective cognitive complaints in the long-term after stroke, and to identify predictors of long-term subjective cognitive complaints.MethodsProspective cohort study including 395 stroke patients. Subjective cognitive complaints were assessed at 2 months, 6 months and 4 years post-stroke, using the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24). The temporal evolution of subjective cognitive complaints was described using multilevel growth modelling. Associations between CLCE-24 cognition score at 4 years post-stroke and baseline characteristics, depression, anxiety, cognitive test performance, and adaptive and maladaptive psychological factors were examined. Significant predictors were entered in a multivariate multilevel model.ResultsA significant increase in subjective cognitive complaints from 2 months up to 4 years (mean 3.7 years, standard deviation (SD) 0.6 years) post-stroke was observed (p≤0.001). Two months post-stroke, 76% of patients reported at least one cognitive complaint, 72% at 6 months, and 89% at 4 years post-stroke. A higher level of subjective cognitive complaints at 2 months and lower scores on adaptive and maladaptive psychological factors were significant independent predictors of a higher level of subjective cognitive complaints at 4 years post-stroke.ConclusionPost-stroke subjective cognitive complaints increase over time and can be predicted by the extent of subjective cognitive complaints and the presence of adaptive and maladaptive psychological factors in the early phases after stroke.LAY ABSTRACTMany people suffer a stroke in the brain leading to consequences in different areas of functioning. Complaints in the domain of thinking (memory, attention, planning and organization) are frequent post-stroke. This study investigated the occurrence and type of complaints experienced in the first years after a stroke. The study found that these complaints increase over time. Longterm complaints are found in those people who already have problems early after stroke.Key words: stroke, rehabilitation, cognition, cognitive complaints

Subjective cognitive complaints (SCC) are common after stroke, with prevalence rates varying between 28.6% (1) and 90.2%, (2), depending on stroke characteristics, time since stroke, SCC definitions and the instruments used. The most commonly reported complaints are mental slowness (in 46–80% of patients) and difficulties in concentration and memory (in 38–68% and 38–94% of patients, respectively) (3). Previous cross-sectional studies showed that SCC are present in both the early stages after stroke (1–6 months after stroke) (4–6), and in the long-term (> 1 year after stroke) (1, 7, 8). To date only a few studies have examined the temporal evolution of SCC. Tinson & Lincoln observed an increase in SCC between 1 and 7 months post-stroke (n = 95) (9). The authors used the Everyday Memory Questionnaire (10), focusing on memory-related complaints. Wilz & Barskova also found an increase in SCC over time after stroke (3 vs 15 months post-stroke, n = 81) (11). SCC were measured with the Patient Competency Rating Scale cognition subscale (12). Van Rijsbergen et al., who used the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24) (13), recently found that SCC remained stable between 3 and 12 months after stroke (n = 155) (14). Long-term results on the course of post-stroke SCC are lacking. Since SCC were found to be independently related to lower quality of life in patients with mild cognitive impairment (15), and patients with subarachnoid haemorrhage (16), it is important to assess SCC after stroke. Furthermore, earlier research showed that SCC were most strongly associated with participation after stroke, compared with cognitive tests in a neuropsychological test battery, and the Montreal Cognitive Assessment (MoCA) (17, 18). Hence, in order to improve participation and integration in society after stroke, it is important to take the patients’ perspective into account, rather than only determining objective cognitive measures.The presence and severity of SCC is expected to be a direct reflection of the presence and severity of cognitive deficits. However, previous studies investigating the relationship between SCC and cognitive performance in stroke patients have shown conflicting results (1–4, 7, 8, 13, 19, 20). Other factors have shown to be related to SCC, in particular psychological factors, such as depressive symptoms (2, 4, 6, 7, 21), anxiety (21, 22), perceived stress (14), personality traits (7, 22), and coping style (23). To date, only one study on SCC used a longitudinal design (14), which prevents conclusions on the temporal evolution of SCC in stroke patients in the long term. Since more stroke patients survive, recover well and are discharged home nowadays, it is important to address predictors of SCC in the early phases after stroke, in order to identify patients who need more intensive monitoring at follow-up. Once identified, it is possible to investigate whether the patients will benefit from more focused rehabilitation programmes.The aim of this longitudinal study was to examine the temporal evolution of SCC, from 2 months until 4 years post-stroke. Furthermore, the study assessed which factors are predictive of SCC at 4 years post-stroke, taking into account demographic and stroke-related characteristics at baseline, and cognitive deficits and psychological factors measured at 2 months post-stroke.     

Correction: Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance

Correction for ‘Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance’ by Qunpeng Duan et al., RSC Adv., 2020, 10, 21954–21962, DOI: 10.1039/D0RA03138K.

The authors regret omitting a citation of their related paper published in Frontiers in Chemistry: ‘Facile one-step electrodeposition preparation of cationic pillar[6]arene-modified graphene films on glassy carbon electrodes for enhanced electrochemical performance’ (DOI: 10.3389/fchem.2020.00430) shown as ref. 1 here. The citation should appear as ref. 58 in the original article.¹The authors regret that it was not clear in the original article that the ErGO-CP6/GCE film had been previously reported by them in their related Frontiers in Chemistry paper¹ and therefore the sentence at the start of paragraph 3 on page 2 ‘In this work, we report for the first time preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1).’ should be ‘In this work, we report the preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1), which was previously reported by us.⁵⁸’.The authors also wish to clarify the differences between this RSC Advances paper and the Frontiers in Chemistry paper.¹ The papers use different guests molecules and different optimum pulse electrodeposition parameters and the RSC Advances paper reports an improvement in electrochemical performance with additional characterisation, stability studies and the analysis of real samples which are not reported in the Frontiers in Chemistry paper.¹The appropriate figure captions have been updated to reflect the data reproduced from the Frontiers in Chemistry paper.¹Scheme 1 Schematic illustration for the pulsed electrodeposition preparation of ErGO and ErGO-CP6 films on the surface of GCE and sensing the guest molecules by an electrochemical strategy. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 1 Characterization of materials. FTIR spectra (A), UV-vis absorption spectra (B), TGA curves of CP6, GO-CP6, and GO (C), and XPS survey spectra of GO and GO-CP6 (D). The data in (a, c and d) have been reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 4 (A) Raman spectra of GO and ErGO. (B) Raman spectra of GOCP6 and ErGO-CP6. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.     

Correction: Porous conducting polymer and reduced graphene oxide nanocomposites for room temperature gas detection

Correction for ‘Porous conducting polymer and reduced graphene oxide nanocomposites for room temperature gas detection’ by Yajie Yang et al., RSC Adv., 2014, 4, 42546–42553.

The authors wish to draw the reader’s attention to their previous related study, published in ACS Applied Materials & Interfaces,¹ which was not cited in this RSC Advances paper. The RSC Advances paper is a valuable and necessary supplement to the publication in ACS Applied Materials & Interfaces and focused on the reduced gas sensing performance of the devices instead of film characterization and film conductive performance.The authors regret not giving correct attribution to Fig. 1–6 which duplicate data from ref. 1 and therefore should be attributed to that paper. Additionally, there are portions of overlapping text in the discussion of these figures and the Introduction and Conclusion sections of the RSC Advances paper, which should be attributed to ref. 1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

PREDICTORS FOR SELF-REPORTED FEELING OF DEPRESSION THREE MONTHS AFTER STROKE: A LONGITUDINAL COHORT STUDY

ObjectiveDepression and impaired cognition are common consequences of stroke. The aim of this study was to determine whether cognitive impairment 36–48 h post-stroke could predict self-reported feeling of depression 3 months post-stroke.DesignA longitudinal, cohort study.PatientsPatients aged ≥ 18 years at stroke onset.MethodsCognition was screened using the Montreal Cognitive Assessment, 36–48 h after admission to the stroke unit at Sahlgrenska University Hospital. Information about self-reported feeling of depression 3 months post-stroke was retrieved from Riksstroke (the national quality register for stroke in Sweden). Bootstrapped binary logistic regression analyses were performed.ResultsOf 305 patients, 42% were female, median age was 70 years, and 65% had mild stroke. Three months post-stroke, 56% of patients had self-reported feeling of depression; of these, 65% were female. Impaired cognition at baseline could not predict self-reported feeling of depression 3 months later. The odds for self-reported feeling of depression were twice as high in female patients (odds ratio 2.01; 95% confidence interval, 0.20–1.22; p < 0.01).ConclusionImpaired cognition early after stroke could not predict self-reported feeling of depression 3 months post-stroke. Compared with male patients, female patients had twice the odds of self-reported feeling of depressionLAY ABSTRACTDepression and impaired cognition are common consequences of stroke. This study investigated whether screening for cognitive function 36–48 h after stroke could predict self-reported feeling of depression 3 months later. Of the 305 patients with mild stroke, 56% had self-reported feeling of depression. Cognitive impairment could not predict self-reported feeling of depression. Therefore, cognitive screening within the first 2 days after stroke might be too early to predict self-reported feeling of depression 3 months after stroke. However, the high proportion of patients with self-reported feeling of depression indicates the severity of the problem that needs to be addressed.Key words: stroke, cognition, assessment, depression, selfperceived, prediction, bootstrapping

Post-stroke depression (PSD) is a common condition identified in up to 40% of patients, 3 months after stroke (1–3). Since approximately only 17% of patients with PSD have a previous history of depression, PSD can primarily be considered a consequence of stroke (4). A previous study showed a high number of patients developing PSD in the first month after stroke (5). The prevalence of depression in the acute phase after stroke was 25%, with a slight increase of to 31% after 3 months (5). PSD is associated with increased mortality, decreased quality of life, physical disability, and poor functional outcomes after stroke (6). Therefore, timely detection of depression is important (1), but can be hindered by various factors, such as short duration of hospitalization, insufficient healthcare resources, and poor communication between healthcare facilities (7). Thus, the availability of other information gathered early after stroke that can help predict PSD will be of clinical value.The mechanisms underlying PSD are complex and associated with multiple factors; including patients’ pre-stroke characteristics, stroke-related risk factors, and post-stroke conditions (8). Impaired cognition has been linked to PSD (9, 10). Executive dysfunction, language impairment, and orientation deficits were also related to PSD (11). However, the cause–effect relationship between cognition and depression is unclear. Neurobiological pathways, such as vascular depression and neuroinflammation can cause PSD (12, 13). Nevertheless, none of these can be considered more dominant or the leading cause of PSD. However, these pathways could still be possible causes of PSD, together with cognitive impairment.Unlike cognitive function, female sex is a well-known predictor of PSD (14, 15). Female patients are also more likely to be widowed before stroke, have a high mean age, more severe stroke, and a higher level of post-stroke disability (14). However, the results regarding patients’ age and risk of PSD are conflicting, indicating that both young and old patients have a high risk of PSD 3–12 months after stroke (14, 16, 17). Furthermore, patients younger than 70 years have a high risk of PSD (16, 18). Other well-known predictors of PSD are severe stroke, stroke localization, high dependency level, and social isolation post-stroke (15, 16).The predictive value of cognitive function for PSD remains unclear. Moreover, no studies were found that assessed the association between screening of cognition very early post-stroke and self-reported feeling of depression (SRFD) 3 months after stroke, when the first post-stroke follow-up is commonly done. Thus, the primary aim of this study was to explore the association between cognitive function screened very early after stroke and SRFD 3 months later. The secondary aims were to study the influences of sex and age on cognition and SRFD 3 months post-stroke.     

EFFECTS OF VIRTUAL REALITY-BASED NECK-SPECIFIC SENSORIMOTORTRAINING IN PATIENTS WITH CHRONIC NECK PAIN: A RANDOMIZED CONTROLLED PILOT TRIAL

ObjectiveTo evaluate the effects of neck-specific sensorimotor training using a virtual reality device compared with 2 standard rehabilitation programmes: with, and without general sensorimotor training, in patients with non-traumatic chronic neck pain.DesignPilot randomized control study.Patients and methodsA total of 51 participants were randomly assigned to 1 of 3 groups: 1: control group; 2: sensorimotor group; 3: virtual reality group. All 3 groups received the clinic’s standard rehabilitation programme. Group 2 also received “general sensorimotor training” in the form of group therapy, for a total of 120 min. Group 3 received additional virtual reality-based “neck-specific sensorimotor training” for a total of 120 min. Participants’ neck pain, headaches, active cervical range of motion, and Neck Disability Index were determined before and after 3 weeks of intervention.ResultsCompared with the control group, the virtual reality group showed significant (p < 0.05) advantages in relief of headaches, and active cervical range of motion in flexion and extension. Compared with the sensorimotor group, the virtual reality group showed significant improvements in cervical extension.ConclusionVirtual reality-based sensorimotor training may increase the effects of a standard rehabilitation programme for patients with non-traumatic chronic neck pain, especially active cervical range of motion in extension.LAY ABSTRACTThe aim of this study was to evaluate the effectiveness of neck-specific coordination training using a virtual reality device, in comparison with general coordination training and a standard exercise programme as part of inpatient rehabilitation for patients with chronic neck pain. Pain, disability and mobility of the neck were determined before and after 3 weeks of training intervention in 51 patients. The virtual reality training group exhibited greater effects in relief of headaches, and bending the neck forwards and backwards compared with the standard exercise group, and an increased ability to bend the neck backwards compared with the coordination training group. The results suggest that neck-specific coordination training using a virtual reality device increases the benefits of standard inpatient rehabilitation in patients with chronic neck pain, particularly in bending the neck backwards.Key words: neck pain, rehabilitation, virtual reality, kinematics

Neck pain is a widespread problem; 60–80% of individuals develop neck pain during their life-time, with 30–50% of the general population reporting neck pain annually (1–3). Many patients experience neck pain as a complex biopsychosocial disorder, with problematic physical and psychological symptoms (3), such as reduced cervical range of motion, headaches, lack of concentration, emotional and cognitive disorders (4, 5). Aside from the decreased quality of life, these complaints are a major cause of inability to work (6, 7) and lead to considerable economic damage (8). Hence, the demand for an effective treatment is indisputable.According to a recently published review (9), the strongest treatment effects for neck pain are those associated with exercise. However, the evidence for this claim is only of moderate quality. Since there is no data available at present to show that any one form of exercise is evidentially more effective than another, multimodal care is concordantly recommended by leading experts (3, 9).Sensorimotor training methods are a current trend in exercise therapy, and for the first time they take into account the special function of the neck, by including connections between the perceptions of sensory organs located in the head and neck muscles (10–14). Alterations of sensorimotor control have been identified in many patients with neck pain, and are thought to play an important role in the aetiology and maintenance of associated disorders (14, 15).To date, there are only a few sensorimotor training concepts that have been specially developed for the neck region. Initial studies found that patients undergoing these training methods experienced reduced neck pain, as well as improvements in cervical range of motion, self-reported disability, and general health (11, 13, 14, 16). However, a systematic review from 2014 (17) revealed very little evidence for eye-neck coordination and proprioceptive exercises. Furthermore, a randomized controlled trial (RCT) found that neck coordination exercises did not produce a larger effect than strength training and massages (18).Application of a virtual reality (VR) device is a novel and promising option for training cervical kinematics (10, 12, 19). In theory, this technique provides several advantages: distracting attention and therefore reducing pain and kinesiophobia (20, 21), engaging and motivating physical activities, and improving the effectiveness of exercise (22, 23).To date, only one RCT has compared the effects of VR-based training with conventional kinematic training using laser beams in patients with chronic neck pain (12). The VR group exhibited significant improvements in motion velocity, pain intensity, health status, and accuracy of neck motion.Due to the conflicting evidence and lack of research, there is a need for more studies that consider the effectiveness of VR-based sensorimotor training concepts, especially in combination with other effective therapeutic exercises or as part of individually tailored programmes (12).The aim of this study was therefore to evaluate the effects of neck-specific sensorimotor training using a VR device, in comparison with standard rehabilitation programmes, both with and without general sensorimotor training, in patients with non-traumatic chronic neck pain.     

ASSOCIATION BETWEEN PRE-STROKE PHYSICAL ACTIVITY AND MOBILITY AND WALKING ABILITY IN THE EARLY SUBACUTE PHASE: A REGISTRY-BASED STUDY

ObjectiveTo investigate associations between prestroke physical activity and mobility, walking ability, and self-perceived upper extremity function during stroke unit care.DesignA longitudinal, registry-based study with a consecutively collected cohort.Subjects/patientsA total of 1,092 adults with stroke admitted to 3 Swedish stroke units between 2017 and 2018.MethodsLogistic mixed effects regression models were performed to investigate associations (adjusted for age and sex). Pre-stroke physical activity was assessed with Saltin-Grimby Physical Activity Level Scale on admission. Mobility, walking ability, and self-perceived upper extremity function were assessed at admission and discharge from the stroke units and compared between pre-stroke physically active (45%) and inactive (55%) groups.ResultsAll groups of patients showed improvements in mobility (p < 0.001), walking ability (p < 0.001), and upper extremity function (p < 0.001). The changes over time tended to differ between the physically inactive and active groups for mobility (p < 0.062) and walking ability (p < 0.056), but the differences were not significant.ConclusionPre-stroke physically active people showed a tendency to be more independent in physical functioning early after stroke. Regardless of prestroke physical activity, all patients showed improvements in mobility, walking ability, and self-perceived upper extremity function during inpatient care.LAY ABSTRACTTo be physically active prior to a stroke may improve the post-stroke recovery process. Therefore, we hypothesized that pre-stroke physical activity might reduce the consequences of a stroke. This study investigated associations between pre-stroke physical activity and post-stroke recovery of mobility, walking ability, and arm and hand function. A total of 1,092 patients were examined; 44% were women, 89% had ischaemic stroke, and 55% were physically inactive before the stroke. All patients showed improvements during care at the stroke units, regardless of their previous physical activity level. At hospital discharge, 71% of patients showed independent mobility, 68% could walk independently, and 55% reported self-perceived arm and hand impairments. Patients with higher pre-stroke physical activity levels had a tendency of being more independent in mobility and walking compared with inactive patients. However, the frequencies of self-perceived arm and hand impairments were similar between the physically active and physically inactive groups. To be physically active prior to a stroke may improve the post-stroke recovery process.Key words: prestroke, stroke, exercise, physical activity, mobility, transfers, walking, upper extremity

The number of people living with the consequences of a stroke has increased over time (1), which has substantially increased the global burden of adult disability (2). The overall goal of stroke rehabilitation is to regain independence (2), but it has been shown that 43% have remaining disability one month after stroke, and 39% after 5 years (3). Recovery can be defined as an improvement over time, evaluated as the return to pre-stroke functions and activities, or alternatively, evaluated in terms of the underlying mechanisms (4). Agreed definitions of phases in stroke recovery are acute (1–7 days), early (7 days to 3 months), and late (3–6 months) subacute, and chronic (more than 6 months) (4). Improvements mainly occur in the early subacute phase after a stroke (4), and care at a stroke unit is important for positive outcomes (5). Stroke-unit care and rehabilitation increases the probability that patients will survive, return to their own homes, and regain independence (5) at one year post-stroke (6). In stroke rehabilitation research, stroke-related impairments (sensorimotor deficiencies, quality of life, and global disability) should be evaluated with measures capturing mobility, walking, and motor function (7). According to the International Classification of Functioning, Disability, and Health (ICF) (8), mobility and walking ability are categorized as “activities and participation”, and upper extremity (UE) function is included in the category of “body structures”.Pre-stroke physical activity may promote neuroprotective mechanisms, such as angiogenesis, and neuroplasticity, in both human and animal subjects (9). This could contribute to better motor function, and motor recovery (9). Previous studies have shown that physical activity could reduce the risk of stroke by 25–30% (10). Physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure (11). Different types of physical activity can be categorized as occupational, sports, conditioning, household, or other activities (11). Exercise, which is a subcategory of physical activity, is planned, structured, and repetitive, and its purpose is to improve or maintain physical fitness (11). Pre-stroke physical activity was previously related to a reduction in the size of a cerebral infarction (12), less severe acute stroke symptoms (12–15), less post-stroke disability (12, 15, 16), and improved performance in activities of daily living (ADL) (15, 17, 18). Previous studies on disability after stroke often included a mobility assessment, but, typically, mobility was not measured separately from other abilities. Moreover, few studies have focused on associations between pre-stroke physical activity and post-stroke physical functioning (19) (i.e. mobility, walking ability, and UE function). However, 3 small studies showed that pre-stroke physical activity was positively related to post-stroke improvements in balance, walking speed (17), independent gait (20), and walking frequency (21). No studies have investigated the association between pre-stroke physical activity and UE function. Overall, little evidence is available on associations between pre-stroke physical activity and different post-stroke consequences, and the published results are conflicting (19, 22). The current study aimed to investigate associations between pre-stroke physical activity and post-stroke mobility, walking ability, and self-perceived UE function during inpatient stroke unit care.     

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond.

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors.

The 1,2,4-thiadiazinane 1,1-dioxide motif can be found in many biologically active compounds for vastly different medical conditions. For example, verubecestat (1) has been in phase III clinical trials as a β-amyloid precursor protein cleaving enzyme (BACE 1) inhibitor to treat moderate and prodromal Alzheimer''s disease.¹ Ribizzi et al. have shown that taurolidine (2) displays cytotoxic activity against certain human tumour cells,² but primarily it is used as an antibacterial agent.³ In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders.⁴ 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods;^5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition.^14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.^16–18 The literature on this reagent describe it as a connector molecule,¹⁹ and a warhead in chemical biology.^20–22 There are only four publications that, so far, have reported the use of α,β-unsaturated sulfonyl fluoride based compounds as starting materials in organic synthesis.^23–26 Based on our earlier experience with the reactivity of aryl α,β-unsaturated sulfonyl fluoride towards various amine nucleophiles¹⁷ (Scheme 1), we hypothesized that an α,β-unsaturated sulfonyl fluoride of type 4 can possibly be explored for the synthesis of thiadiazinanes. This hypothesis was based on observation of low amounts of the six-membered product was formed along with the major β-sultam product 5 when p-nitrophenylethenesulfonyl fluoride was subjected to excess methyl amine in methylene chloride as a solvent and triethylamine as additional base at room temperature (Scheme 1).Open in a separate windowScheme 1Formation of 1,2,4-thiadiazinane 1,1-dioxides, along with β-sultams, when aryl ethenesulfonyl fluorides are subjected to large excess of primary amines in DCM as solvent and DBU as catalyst.The reactivity of dichloromethane (DCM) as a methylene donor was unfamiliar to us at the time, but a literature survey quickly revealed that organic solvents (DMF,²⁷ DMSO,^28–30 CHCl₃ (ref. 31 and 32) and CH₂Cl₂ (ref. 33 and 34)) have proved to be more than solvents. DCM has indeed been reported to act as a bis-electrophilic methylene donor in the presence of strong bases and nucleophiles³³ (e.g. carboxylic acids,³⁵ thiols,³⁶ amines, etc.). DCM may also form hydrochloride salts,³⁷ aminals,³⁸ and quaternary salts³⁹ when reacted with tertiary and secondary amines. These reactions were reviewed by Mills et al.⁴⁰ and the kinetics of the reaction of DCM with pyridine was documented by Rudine et al.⁴¹ Liu and co-workers reported formation of methylene-bridged 3,3′-bis-(oxazolidin-2-one) through reaction of oxazolidin-2-ones with DCM and sodium hydride.⁴² Cui et al. reported the synthesis of bispidine with the utilisation of DCM as a C1 unit.⁴³ Dipyrrolidylmethane CH₂(pyr)₂ and dipiperidylmethane, CH₂(pip)₂ were synthesized via the condensation of the secondary amine precursors and DCM at room temperature in the absence of light.⁴⁴ Another reaction of amines with methylene chloride yielded aminals rapidly.⁴⁵ Matsumoto et al. reported the reaction of DCM with ketones or esters in the presence of secondary amines at high pressure whereby DCM was used as methylene bridge in forming both C–C and C–N bonds.⁴⁶ Zhang and co-workers also published the formation of simultaneous carbon–carbon bond and carbon-nitrogen bonds whereby DCM acted as a synthon in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and a copper catalyst.⁴⁷     

Correction: Directed evolution of mevalonate kinase in Escherichia coli by random mutagenesis for improved lycopene

Correction for ‘Directed evolution of mevalonate kinase in Escherichia coli by random mutagenesis for improved lycopene’ by Hailin Chen et al., RSC Adv., 2018, 8, 15021–15028.

The authors wish to draw the readers’ attention to their closely related paper, published in Microbial Cell Factories,¹ which should have been cited in this RSC Advances paper.The authors regret that there is unattributed overlap in text between this RSC Advances paper and ref. 1. The authors confirm that new data has been reported in this RSC Advances article.Two different rate-limiting enzymes in the lycopene synthetic pathway were studied using the same methods, mevalonate kinase (MK) in this paper and isopentenyl diphosphate isomerase (IDI) in ref. 1. In the RSC Advances paper, a directed evolution strategy was used to optimize the activity of MK to enhance the tolerance for farnesyldiphosphate (FPP) and geranylgeranyldiphosphate (GGPP), to enhance the affinity of mevalonate and MK, and to improve lycopene production. The catalytic mechanisms of both enzymes are very different; however improving their activities can improve lycopene production.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

PARTICIPATION AND QUALITY OF LIFE IN PERSONS LIVING WITH SPINAL CORD INJURY IN NORWAY

ObjectivesTo describe the association between sociodemographic and spinal cord injury characteristics, of people living with spinal cord injury, and participation and quality of life, and to study the association between participation and quality of life in this group of people.DesignPersons registered in the Norwegian Spinal Cord Injury Registry after post-acute rehabilitation between 2011 and 2017 were invited to participate in a survey in 2019 when they were in a community setting.SubjectsA total of 339 people living with spinal cord injury.MethodsThe Frequency scale and Restrictions scale of the Utrecht Scale for Evaluation of Rehabilitation-Participation were used to measure participation. Quality of life was measured as life satisfaction with the World Health Organization Quality of life assessment (WHOQoL-5) and mental health was measured using the Mental Health subscale (MHI-5).ResultsOverall, sociodemographic characteristics were more prominently associated with quality of life and participation than were spinal cord injury characteristics. Currently working as main activity and having a family income in the highest quartile were associated with higher scores on all 4 measures of participation and quality of life. There was a strong gradient between higher level of participation (frequency and restrictions) and better quality of life.ConclusionParticipation was strongly associated with life satisfaction and mental health in people living with spinal cord injury. This indicates that participation issues should be given greater priority during post-acute rehabilitation, follow-up and subsequent care efforts provided in the community.LAY ABSTRACTHaving paid work, leisure-time activities and good relationships with other people is important for one’s quality of life. For people living with spinal cord injury, it may be more difficult to participate in such activities than it is for people without health problems. A survey on participation problems was carried out among Norwegians living with spinal cord injury. Sociodemographic factors, such as family income and education, were found to have a greater impact on quality of life and participation, than the severity of the injury itself. Participation was strongly associated with life satisfaction and mental health. This indicates that participation issues should be given greater priority.Key words: spinal cord injuries, participation, quality of life, Norway

Participation provides opportunities for the fulfilment of basic human needs and can be an important determinant of quality of life (QoL) (1). Persons living with spinal cord injury (SCI) may, however, experience restrictions or barriers to participation in different domains, including employment or social-recreational activities (2). Research on issues related to participation problems among persons with SCI is, however, limited. In a critical systematic review on social and community participation following SCI (3), the authors emphasized that the samples in the reviewed studies were relatively small, that the instruments used were often developed before the introduction of the International Classification of Functioning, Disability and Health (ICF), and that the use of the term ”participation” varied. In addition, knowledge about the impact of injury characteristics on participation is underdeveloped (2). Furthermore, limited attention has been given in the literature to how clinical practice can be adapted to improve participation in persons with SCI. To do so, more knowledge of factors influencing participation is needed.In the ICF, ”participation” refers to the involvement of an individual in a life situation and represents the social perspective on functioning (4). To measure participation, it has been recommended to measure participation both as the so-called objective state and subjective experience (5). Objective participation can be measured as self-reported frequencies of behaviour, while subjective participation concerns self-reported experienced restrictions in participation in society. It has been commented that the ICF definition of participation does not adequately capture this (6).QoL is a broad concept, and has been defined by the World Health Organization (WHO) as the individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It can be operationalized to distinguish between the cognitive component that refers to life satisfaction and the emotional component that refers to a person’s affect or mental health (8).People with SCI experience lower QoL, as shown by higher levels of distress, worse mental health and lower levels of life satisfaction compared with the general population (9, 10). Studies have indicated that decreased mobility (11, 12), having secondary impairments (11, 12), pain (11, 13) and unemployment (14) are associated with lower QoL. Increased QoL has been associated with psychosocial characteristics, such as higher self-efficacy (15), good social skills (15), more social support (9) and a feeling of acceptance (16). The associations between QoL and age, sex, education, injury level and injury duration are inconsistent (9, 12, 17). However, there is variation in study design, inclusion criteria, and measure instruments, and cohort studies with a representative sample and sufficient sample size have been requested (9).Studies exploring the association between participation and QoL indicate that participation is related to higher life satisfaction (1, 18). However, little is known about risk groups for poor participation and poor QoL and knowledge about risk profiles can help in intervention planning.The objectives of this study were therefore to assess participation and QoL with validated generic measurement instruments in a representative sample. Specific aims were: (i) to describe the association between sociodemographic and SCI characteristics with participation and QoL; (ii) to detect groups at risk for low participation/poor QoL; and (iii) to study the association between participation and QoL.     

Correction: Consequences of gamma-ray irradiation on structural and electronic properties of PEDOT:PSS polymer in air and vacuum environments

Correction for ‘Consequences of gamma-ray irradiation on structural and electronic properties of PEDOT:PSS polymer in air and vacuum environments’ by Aswin kumar Anbalagan et al., RSC Adv., 2021, 11, 20752–20759, DOI: 10.1039/D1RA03463D.

The authors regret that incorrect details were given for ref. 18. The correct version of ref. 18 is given here as ref. 1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: A simple and straightforward synthesis of phenyl isothiocyanates,symmetrical and unsymmetrical thioureas under ball milling

Correction for ‘A simple and straightforward synthesis of phenyl isothiocyanates, symmetrical and unsymmetrical thioureas under ball milling’ by Ze Zhang et al., RSC Adv., 2013, 3, 16940–16944, DOI: 10.1039/C3RA43252A.

The authors regret that it was not clear in the original article that part of the graphical abstract image had been reproduced from the graphical abstract of an earlier ChemComm paper.¹ Although the ChemComm article was cited as ref. 15b, and here as ref. 1, it was not made clear that some of the image was reproduced from this article.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent

Correction for ‘An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent’ by Thanh Thi Nguyen et al., RSC Adv., 2019, 9, 38148–38153, DOI: 10.1039/C9RA08074K.

The authors apologise that a related reference, given here as ref. 1–5, was not cited in the original article. On page 38148, in the first paragraph of the Introduction, a citation to the reference should be added at the end of the sentence beginning “Among them, Lewis acidic…”. The paragraph should be changed as follows “In past decade, deep eutectic solvents (DESs) have attracted much attention in both reaction media and catalysts due to their unique properties such as wide liquid range, biodegradability, excellent thermal stability, and negligible vapor pressure.^1,2 Among them, Lewis acidic deep eutectic solvents (LADESs) have been intensively studied as efficient media for organic syntheses.^3–5”.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

SUSTAINED EFFICACY OF INCOBOTULINUMTOXINA FOLLOWING REPEATED INJECTIONS FOR UPPER-LIMB POST-STROKE SPASTICITY: A POST HOC ANALYSIS

ObjectiveThis post hoc analysis assessed the impact of repeated incobotulinumtoxinA injections on muscle tone, disability, and caregiver burden in adults with upper-limb post-stroke spasticity.DesignData from the double-blind, placebo-controlled main period and three open-label extension cycles of two Phase 3, randomized, multicentre trials were pooled.MethodsSubjects received incobotulinumtoxinA 400 Units at 12-week intervals (±3 days) (study 3001, {"type":"clinical-trial","attrs":{"text":"NCT01392300","term_id":"NCT01392300"}}NCT01392300) or ≤ 400 Units at ≥12-week intervals based on clinical need (study 0410, {"type":"clinical-trial","attrs":{"text":"NCT00432666","term_id":"NCT00432666"}}NCT00432666). Ashworth Scale (AS) arm sumscore (sum of elbow, wrist, finger and thumb flexor, and forearm pronator AS scores), Disability Assessment Scale (DAS), and Carer Burden Scale (CBS) scores were assessed.ResultsAmong 465 subjects, from study baseline to 4 weeks post-injection, mean (standard deviation) AS arm sumscore improved continuously: main period, –3.23 (2.55) (placebo, –1.49 (2.09)); extension cycles 1, 2, and 3, –4.38 (2.85), –4.87 (3.05), and –5.03 (3.02), respectively. DAS principal target domain responder rate increased from 47.4% in the main period (placebo 27.2%) to 66.6% in extension cycle 3. Significant improvements in CBS scores 4 weeks post-injection accompanied improved functional disability in all cycles.ConclusionIncobotulinumtoxinA conferred sustained improvements in muscle tone, disability, and caregiver burden in subjects with upper-limb poststroke spasticity.LAY ABSTRACTSpasticity (muscle overactivity) often occurs in patients after stroke and may lead to further disability. The results of 2 clinical trials were used to assess the effect of incobotulinumtoxinA injections (maximum dose used per injection session 400 Units) on arm and hand spasticity in patients after stroke. This study looked at the impact of treatment on disability and the burden on carers. The results from 4 treatment cycles were assessed. There was a continuous decrease in spasticity, together with improvements in disability in all treatment cycles. The burden on those who cared for patients also decreased. We showed that repeated incobotulinumtoxinA treatment across 4 cycles led to a decrease in spasticity, patient disability and burden on carers.Key words: botulinum neurotoxin, duration of effect, incobotulinumtoxinA, upper limb, spasticity, caregiver burden, rehabilitation

Stroke is an increasing cause of disability globally (1), and the development of spasticity in stroke survivors may contribute to further disability (2, 3). The prevalence of post-stroke spasticity ranges from 4.0% to 42.6% (2, 4, 5) and may be associated with reduced ability to perform the basic activities of daily living, and detrimental effects on quality of life (4, 6, 7). In addition to the loss of independence experienced by those affected, post-stroke spasticity can also result in a considerable burden on caregivers (6).The safety and efficacy of botulinum neurotoxin type A (BoNT-A) injections have been well established for the treatment of upper-limb post-stroke spasticity (8–13). Notably, the 24-week BEST study evaluated the efficacy and safety of onabotulinumtoxinA in adults with upper-limb or lower-limb post-stroke spasticity (n = 273), and the addition of onabotulinumtoxinA to the existing standard of care demonstrated improvements in passive goal-oriented activities compared with placebo, as well as additional benefits in active functional goals with no new safety signals (14).IncobotulinumtoxinA (Xeomin^®, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) is a BoNTA approved for the treatment of upper-limb spasticity at doses up to 400 Units (U) at intervals no sooner than every 12 weeks in the USA (15); while in Europe doses of up to 500 U at intervals of at least 12 weeks are approved, enabling treatment of a greater number of muscles (16). Two Phase 3 studies have confirmed the efficacy and safety of incobotulinumtoxinA in subjects with upper-limb post-stroke spasticity (17, 18); both studies included a placebo-controlled main period (MP) comprising a single injection cycle, followed by an open-label extension (OLEX) period with 3 fixed, 12-week incobotulinumtoxinA injection cycles (study 3001) (17), or a maximum of 5 flexible-duration injection cycles (study 0410) (19), respectively. Compared with placebo, incobotulinumtoxinA resulted in significant improvements in muscle tone (Ashworth Scale; AS) and functional disability (Disability Assessment Scale, DAS, for the principal target domain) 4 weeks post-treatment in the MP of both studies (17, 18). These improvements were sustained during the OLEX period of both studies (19–21) and associated with significant improvement in caregiver burden from the study baseline to the end of the OLEX period in study 3001 (21).We report here the results of a post hoc analysis, using data pooled from the MP and the first 3 OLEX injection cycles of both studies, to assess the efficacy of incobotulinumtoxinA in a large subject population using the AS sumscore; a novel approach that allows for a holistic clinical assessment of arm spasticity. In addition, we assess the impact of repeated incobotulinumtoxinA injections on caregiver burden in this large population.     

REHABILITATION IN PATIENTS WITH LYMPHOMA: AN OVERVIEW OF SYSTEMATIC REVIEWS

ObjectiveTo evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation interventions in patients with lymphoma.Data sourcesA comprehensive literature search was conducted using medical/health science databases up to 1 October 2020. Bibliographies of pertinent articles, journals and grey literature were searched.Data extraction and synthesisTwo reviewers independently selected and reviewed potential reviews for methodological quality and graded the quality of evidence for outcomes using validated tools. Any discrepancies were resolved by final group consensus.ResultsTwelve systematic reviews (n = 101 studies, 87,132 patients with lymphoma) evaluated 3 broad categories of rehabilitation interventions (physical modalities, nutrition and complementary medicine). Most reviews were of moderate-to-low methodological quality. The findings suggest: moderate-quality evidence for exercise programmes for improved fatigue and sleep disturbance; low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and an inverse association between sunlight/ultraviolet radiation exposure and incidence of non-Hodgkin’s lymphoma; and very low-quality evidence for beneficial effects of yoga for sleep disturbances. Association between physical activity and lymphoma risk is indistinct.ConclusionDespite a range of rehabilitation modalities used for patients with lymphoma, high-quality evidence for many is sparse. Beneficial effects of exercise programmes were noted for fatigue, psychological symptoms and quality of life. More research with robust study design is required to determine the effective rehabilitation approaches.LAY ABSTRACTLymphoma and its treatment cause significant disability and morbidity, often requiring comprehensive rehabilitation. Currently, a range of rehabilitation interventions are applied in patients with lymphoma. This review systematically evaluated evidence from published systematic reviews of clinical trials to determine the effectiveness of rehabilitation interventions in patients with lymphoma. The findings suggest that there is moderate-quality evidence for exercise programmes in improving fatigue and sleep disturbance. There was low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and very low-quality evidence for beneficial effects of yoga for sleep disturbances. The evidence for association of vitamin D or physical activity and lymphoma risk is limited.Key words: lymphoma, rehabilitation, systematic review, critical appraisal

Lymphomas are a heterogeneous group of malignant neoplasms of the haematopoietic system, characterized by the aberrant proliferation of mature lymphoid cells or their precursors (1). Traditionally lymphoma is classified broadly into 2 major groups: non-Hodgkin’s lymphoma (NHL, 90%) and Hodgkin’s lymphoma (HL) (1); however, lymphomas can also be stratified by cell of origin, as in the World Health Organization (WHO) classification (B-cell, T-cell/natural killer-cell (T/NK) and HL), or clinical behaviour (aggressive or indolent) (2, 3). An estimated 590,000 new cases of lymphoma (3.2% of all cancers) were diagnosed worldwide in 2018, the majority being NHLs (509,590 cases, 2.8% of all cancers) (4). NHL is a leading cause of death amongst the haematological malignancies globally, estimated to cause over 248,000 deaths (2.6% of all cancers) in 2018 (4). The incidence of lymphoma is increasing, with total worldwide incidence projected to reach approximately 919,000 by 2040 (5).The total global economic burden of lymphoma is unknown; however, treatments and supportive care requirements are resource-intensive and associated with significant financial costs for patients/families and healthcare systems. Productivity losses arise from disease and treatment-associated morbidity and premature mortality (6). In 2018, the mean monthly healthcare and utilization costs per patient for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the USA were approximately US$11,890 and $10,460, respectively (6). In Spain, in 2017 lymphoma represented 45.4% of productivity losses due to haematological malignancies, resulting in €121 million in losses due to premature mortality (7).Current therapeutic advances and cancer detection/diagnosis have improved survival rates for patients with lymphoma (PwL). The age-standardized 5-year net survival of lymphoid malignancies in adults ranges from 40% to 70% globally in 2010–14, with a 5–10% increase in trend for the period 2000–04 (8). The 5-year survival rate in the US in 2010–16 was estimated to be 72.7% for NHL and 87.4% for HL (9). As the incidence of NHL is strongly associated with increasing age, improved supportive care and availability of reduced intensity chemotherapy regimens (such as prednisone, etoposide, procarbazine, and cyclophosphamide – ‘PEP-C’; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone – ‘R-miniCHOP’, rituximab, cyclophosphamide, vincristine, prednisolone – ‘R-CVP’) are critical to facilitate deliverable therapy to older patients. Despite these factors, certain lymphomas and their treatment are associated with short- and medium-term residual neurological deficits, leading to physical, cognitive, psychosocial and behavioural impairments, limiting activities of daily living (ADL) and participation (10–13). Treatment procedures can be extensive (e.g., radiotherapy, chemotherapy and/or surgery), and associated with a range of side-effects/complications, such as neuropathy, cardiotoxicity, cachexia, fatigue, deconditioning, myopathy, etc. (14–16). Furthermore, in the transitional period, various adjustment issues are reported, such as increased care needs, inability to drive and return to work, financial constraints, relationship stress, and limitation in societal participation (11, 14, 17, 18). Distressing symptoms, such as fatigue, is a major complaint, reported in 60–100% of patients during or after cancer treatment, which persists for several years after treatment (19–21). Therefore, patients require routine surveillance to monitor complications and relapse and integrated longer-term management, including rehabilitation (22–24).Rehabilitation is an integral part of any cancer management, and there is evidence suggesting the beneficial effect of comprehensive rehabilitation (25–31). Furthermore, a major limitation of delivery of chemotherapy and predictor of inferior outcome is poor performance status (32). As the incidence of older patients treated for lymphoma requiring rehabilitation before or after anti-lymphoma therapy increases, effective evidence-based rehabilitation strategies are expected to play critical and expanding roles in best practice. Currently, a range of rehabilitation interventions are trialled in the management of lymphoma pre-treatment, during adjuvant therapies, and late phases of care, and, for the longer-term, care continuum in the community. The aim is to maximize patient function, promote independence and participation, and improve psychological well-being and quality of life (QoL) (28, 29). Reports suggest that patients with haematological malignancies, including lymphomas, can make functional gains in inpatient rehabilitation settings (31). Maximal exercise capacity seems to decrease before treatment in PwL, especially in patients with advanced disease, and tends to return to close to normal during and/or after treatment (33). Furthermore, comprehensive exercise programmes were found to be effective in reducing disability and symptoms (depression, anxiety, fatigue, pain, etc.), improving functional capacity, muscular strength and QoL (19, 31, 34, 35). One systematic review reported that NHL survivors who met public health exercise guidelines defined by the American College of Sports Medicine (i.e. engaging in >30 min/day of at least moderate physical activity (PA) on ≥ 5 days/week, or > 150 min a week) reported a clinically important better health-related quality of life (HRQoL) than their counterparts who did not meet exercise guidelines (11). Aerobic exercise training interventions were associated with positive effects on cardiorespiratory fitness, fatigue and self-reported physical functioning, and were feasible and safe in PwL (33). Other complementary and alternative therapies, such as mindfulness-based cognitive therapy, meditation, yoga, and tai chi, have shown improvement in cognitive function and QoL (36–38). Another recent systematic review reported that a combination of PA together with mental exercise may be more beneficial to PwL (39). There remains, however, an unmet need in the cancer population, and only a limited number of survivors receive the appropriate rehabilitation intervention that they need (40, 41). Furthermore, despite acknowledging rehabilitation as an integral component of the management of cancer patients, rehabilitation-specific guidelines for many cancer groups are limited, and many general cancer guidelines do not incorporate recommendations for specific rehabilitation interventions (42–44).As mentioned above, various systematic reviews have evaluated the current evidence regarding the effectiveness and safety of different rehabilitation interventions in PwL. However, these published reviews vary in scope, methodology and quality, with diverse, and occasionally discordant, conclusions. The heterogeneity of the lymphoma rehabilitation literature warrants a comprehensive review, with a focus on the evidence for efficacy and potential harm of various rehabilitative strategies. A systematic review of systematic reviews is a new approach to synthesize current evidence across the same or similar interventions, to summarize treatment effect in a much broader concept (45). This approach allows comparison of results from multiple reviews, thereby providing a comprehensive evidence-based summary (45, 46). To our knowledge, systematic reviews of rehabilitation strategies for PwL have not been thoroughly and qualitatively appraised to date. Therefore, this review aimed to systematically evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation strategies for improved function, impairments and participation in PwL. Specific questions addressed include: Are rehabilitation interventions effective in minimizing impairment, activity limitation, participation restriction and treatment-related complications in PwL?, and: What specific types of rehabilitation interventions are effective in PwL, and in which setting?     

Organocatalytic sulfa-Michael/aldol cascade: constructing functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter

A practical sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylates has been developed, which allows efficient access to functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter in moderate to good yields with high enantioselectivities.

A sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylate has been developed, which allows access to 2,5-dihydrothiophenes bearing a quaternary carbon center in moderate to good yields with high enantioselectivities.

Among the various classes of heterocycles, members of the thiophene family have received particular attention from the chemical community because of their widespread occurrence as ubiquitous motifs in natural products, pharmaceuticals, agrochemicals as well as materials.¹ In this context, the 2,5-dihydrothiophene ring is a common structural feature of many bioactive compounds and a potential intermediate for various synthetic applications.² Over the decades, only a few examples of the assembly of optically active 2,5-dihydrothiophenes have been documented.³ For instance, the Spino^3b group successfully prepared non-racemic dihydrothiophenes using an efficient chiral auxiliary. The first gold-catalyzed cycloisomerization of α-hydroxyallenes to 2,5-dihydrothiophenes was reported by Krause^3c and co-workers. Then in 2010, the Xu^3e group developed a highly stereoselective domino thia-Michael/aldol reaction between 1,4-dithiane-2,5-diol and α,β-unsaturated aldehyde catalyzed by a chiral diphenylprolino TMS ether, which provided a new avenue for the synthesis of functionalized 2,5-dihydrothiophenes.Quaternary carbon stereocenters are often contained in natural products and pharmaceuticals.⁴ Compared with the chiral pool synthesis,⁵ the procedure of chiral materials or catalysts to construct such sterically congested stereogenic centers is more challenging because of the difficulty of orbital overlap.⁶ To date, a lot of progresses have been made in the construction of chiral quaternary carbon centers in cyclic compounds,⁷ which are greatly accelerated by the advancement of transition metal catalysis,⁸ and organocatalysis,⁹ including methods beyond radical initiation.¹⁰ However, only few examples are about the construction of a quaternary carbon in 2,5-dihydrothiophene ring.¹¹ Inspired by the previous work of the Xu group,^3e we describe herein an elegant organocatalytic asymmetric cascade sulfa-Michael/aldol reaction, providing a convenient way for the synthesis of 2,5-dihydrothiophenes bearing a chiral quaternary cabon center.