Small Cell Neuroendocrine Carcinoma of the Oropharynx Harbouring Oncogenic HPV-Infection

Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Recently, an association has been reported between oropharyngeal SCNEC and high-risk human papillomavirus (HPV) infection. While HPV infection confers a better prognosis for oropharyngeal squamous cell carcinoma, HPV infection does not appear to influence the biological behaviour of SCNECs, which are generally associated with poor clinical outcomes. We document two cases of SCNEC arising in the oropharynx with evidence of high-risk HPV infection. The cases highlight the expanding range of malignant oropharyngeal neoplasms that harbour oncogenic HPV infection and support the concept that, irrespective of HPV infection, neuroendocrine differentiation portends a poor prognosis.     

Serial changes in myocardial function in preterm infants over a four week period: the effect of gestational age at birth

Background

Myocardial performance is impaired in the first days of life in preterm infants but improves by day 5. Tissue Doppler imaging (TDI) is a novel and reliable means of assessing myocardial performance.

Objective

To investigate myocardial performance using TDI and shortening fraction (SF) in preterm infants of different gestational age groups and serial changes in these parameters in first four weeks of life.Study designInfants less than 36 weeks of gestation were divided into group 1 (24–27 weeks, n = 8), group 2 (28–31 weeks, n = 12) and group 3 (32–35 weeks, n = 13). Infants with severe congenital malformations, a hypoxic insult at birth, and those on inotropic support were excluded. Echocardiograms were performed at 36–48 hours, 2 weeks and 4 weeks of life. Left ventricular (LV) SF, systolic (S′), early diastolic (E′) and late diastolic (A′) TDI velocities were assessed. We analyzed the data using a repeated-measures ANOVA.

Results

Thirty three infants underwent serial TDI and SF measurements. There was an increase in LV S′ (p = .02) and E′ (.01) velocities in group 2 , and in group 3 (p = .03 for S′ and p = .04 for E′), but no significant increase in group 1 (p = .48 for S′ and .32 for E′). At each study point, there was significant difference in myocardial performance between group 1 and 3 for each of the parameters (p < .05). There was no significant increase in SF over time in any of the groups.

Conclusion

We describe a serial increase in myocardial performance in infants of 28 weeks gestation and above. While there was no change in myocardial performance among the most extremely preterm infants, this may have been the result of small sample size of the group.     

Optimisation of Cu+ impregnation of MOF-74 to improve CO/N2 and CO/CO2 separations

Carbon monoxide (CO) purification from syngas impurities is a highly energy and cost intensive process. Adsorption separation using metal–organic frameworks (MOFs) is being explored as an alternative technology for CO/nitrogen (N₂) and CO/carbon dioxide (CO₂) separation. Currently, MOFs'' uptake and selectivity levels do not justify displacement of the current commercially available technologies. Herein, we have impregnated a leading MOF candidate for CO purification, i.e. M-MOF-74 (M = Co or Ni), with Cu⁺ sites. Cu⁺ allows strong π-complexation from the 3d electrons with CO, potentially enhancing the separation performance. We have optimised the Cu loading procedure and confirmed the presence of the Cu⁺ sites using X-ray absorption fine structure analysis (XAFS). In situ XAFS and diffuse reflectance infrared Fourier Transform spectroscopy analyses have demonstrated Cu⁺–CO binding. The dynamic breakthrough measurements showed an improvement in CO/N₂ and CO/CO₂ separations upon Cu impregnation. This is because Cu sites do not block the MOF metal sites but rather increase the number of sites available for interactions with CO, and decrease the surface area/porosity available for adsorption of the lighter component.

We present an in situ study of CO adsorption on Cu impregnated MOF-74 and study the competitive adsorption of CO vs. CO₂ and N₂.     

Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.     

Estimation of Cardiac Depressant Activity of Ten Medicinal Plant Extracts from Pakistan

Ten medicinal plants extracts were pharmacologically screened for their cardiac activity on isolated rabbit heart, and showed significant negative inotropic activity with negative chronotropic effects. In all cases alcohol dried extracts were used and reconstituted in either water or ethyl acetate for these tests. The plant extracts which produced cardiac depression were Cactus grandiflora , Carissa carandas Linn., Duranta repens Linn., Eclipta prostrata Roxb., Heliotropium ophioglossum , Prosopis glandulosa , Scheweinfurthia sphaerocarpa A. Br., Solanum surattense Burm. f., Tephrosia uniflora Pers., Nardostachys jatamansi Dc. (Syn. Valeriana jatamansi ).     

Electronic,mechanical, optical and photocatalytic properties of two-dimensional Janus XGaInY (X,Y ;= S,Se and Te) monolayers

Janus monolayers with breaking out-of-plane structural symmetries and spontaneous electric polarizations offer new possibilities in the field of two-dimensional materials. Due to the depletion of fossil fuels and serious environmental problems, there has been a growing interest in the conversion of water and solar energy into H₂ fuels in recent years. In this research, Janus XGaInY (X, Y = S, Se and Te) monolayers are predicted as promising solar-water-splitting photocatalysts. Based on first-principles calculations, the electronic, mechanical, optical and photocatalytic properties of Janus XGaInY (X, Y = S, Se and Te) monolayers are investigated. These Janus monolayers are structurally stable semiconductors with indirect bandgaps, except for SGaInSe, SGaInTe, TeGaInS and SeGaInTe. Their energy bandgaps extend from 0.74 to 2.66 eV at a hybrid density functional level, which is crucial for broadband photoresponses. Moreover, these Janus monolayers not only show strong light absorption coefficients greater than 10⁴ cm⁻¹ in the visible and ultraviolet regions but possess suitable band edge positions for water splitting. Our findings reveal that these Janus monolayers have a potential for application in the fields of optoelectronic and photocatalysis.

Janus monolayers with breaking out-of-plane structural symmetries and spontaneous electric polarizations offer new possibilities in the field of two-dimensional materials.     

Designing a novel visible-light-driven heterostructure Ni–ZnO/S-g-C3N4 photocatalyst for coloured pollutant degradation

In this study, photocorrosion of ZnO is inhibited by doping Ni in the ZnO nanostructure and electron–hole recombination was solved by forming a heterostructure with S-g-C₃N₄. Ni is doped into ZnO NPs from 0 to 10% (w/w). Among the Ni-decorated ZnO NPs, 4% Ni-doped ZnO NPs (4NZO) showed the best performance. So, 4% Ni–ZnO was used to form heterostructure NCs with S-g-C₃N₄. NZO NPs were formed by the wet co-precipitation route by varying the weight percentage of Ni (0–10% w/w). Methylene blue (MB) was used as a model dye for photocatalytic studies. For the preparation of the 4NZO-x-SCN nanocomposite, 4NZO NPs were formed in situ in the presence of various concentrations of S-g-C₃N₄ (10–50% (w/w)) by using the coprecipitation route. The electron spin resonance (ESR) and radical scavenger studies showed that O₂⁻ and OH free radicals were the main reactive species that were responsible for MB photodegradation.

Ni-doped ZnO/S-g-C₃N₄ nanocomposites were formed as a novel heterostructure photocatalyst.     

One-pot,ligand-free,room-temperature synthesis of Au/Pd/ZnO nanoclusters with ultra-low noble metal loading and synergistically improved photocatalytic performances

Au/Pd/ZnO nanoclusters with ultra-low noble metal loadings were prepared by a one-step and ligand-free method at room temperature. HRTEM, ICP-MS, XPS, and elemental mapping analysis confirmed that the obtained Au/Pd/ZnO nanoclusters were composed of ZnO nanoclusters decorated with well-dispersed AuPd nanoparticles. Au/Pd/ZnO nanoclusters exhibited higher photocatalytic activity compared with those of pristine ZnO, Au/ZnO and Pd/ZnO. Moreover, the high catalytic activity of Au/Pd/ZnO nanoclusters could be maintained even after 5 cycles of photocatalytic reaction. A mechanism for the enhanced photocatalytic performance was also suggested, which was in light of the synergistic effects of the SPR effect from Au and the improved photogenerated charge carrier separation from Pd.

Au/Pd/ZnO nanoclusters with ultra-low noble metal loadings were prepared by a one-step and ligand-free method at room temperature. The obtained Au/Pd/ZnO nanoclusters were composed of ZnO nanoclusters decorated with well-dispersed AuPd NPs with ultra-low noble metal loading.     

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

This study explored the binding patterns of the wild type and B.1.618 variant using which revealed that the B.1.618 variant possess a stronger binding affinity for the host ACE2 and escape the neutralizing antibodies.     

The prognostic and predictive role of 21-gene recurrence scores in hormone receptor-positive early-stage breast cancer

Over the past two decades, gene expression profiling of breast cancer has emerged as an important tool in early-stage breast cancer management. The approach provides important information on underlying biological mechanisms, breast cancer classification, future risk potential of developing recurrent metastatic disease, and provides beneficial clues for adjuvant chemotherapy in hormone receptor (HR) positive breast cancer. Of the commercially available genomic tests for breast cancer, the prognostic and predictive value of 21-gene recurrence score tests have been validated using both retrospective data and prospective clinical trials. In this paper, we reviewed the current evidence on 21-gene expression profiles for HR-positive HER2-negative early-stage breast cancer management. We show that current evidence supports endocrine therapy alone as an appropriate adjuvant systemic therapy for approximately 70% of women with HR-positive, HER2-negative, node-negative breast cancer. Evolving evidence also suggests that 21-gene recurrence scores have predictive values for node-positive breast cancer and that chemotherapy can be avoided in more than half of women with nodes 1 to 3 positive HR-positive breast cancer. Furthermore, retrospective data also supports the predictive role of 21-gene recurrence scores for adjuvant radiation therapy. A prospective trial in this area is ongoing.