Viral co‐infections are associated with increased rates of hospitalization in those with influenza

BackgroundInfluenza causes significant morbidity and mortality in the United States. Among patients infected with influenza, the presence of bacterial co‐infection is associated with worse clinical outcomes; less is known regarding the clinical importance of viral co‐infections. The objective of this study was to determine rates of viral co‐infections in emergency department (ED) patients with confirmed influenza and association of co‐infection with disease severity.MethodsSecondary analysis of a biorepository and clinical database from a parent study where rapid influenza testing was implemented in four U.S. academic EDs, during the 2014–2015 influenza season. Patients were systematically tested for influenza virus using a validated clinical decision guideline. Demographic and clinical data were extracted from medical records; nasopharyngeal specimens from influenza‐positive patients were tested for viral co‐infections (ePlex, Genmark Diagnostics). Patterns of viral co‐infections were evaluated using chi‐square analysis. The association of viral co‐infection with hospital admission was assessed using univariate and multivariate regression.ResultsThe overall influenza A/B positivity rate was 18.1% (1071/5919). Of the 999 samples with ePlex results, the prevalence of viral co‐infections was 7.9% (79/999). The most common viral co‐infection was rhinovirus/enterovirus (RhV/EV), at 3.9% (39/999). The odds of hospital admission (OR 2.33, 95% CI: 1.01–5.34) increased significantly for those with viral co‐infections (other than RhV/EV) versus those with influenza A infection only.ConclusionPresence of viral co‐infection (other than RhV/EV) in ED influenza A/B positive patients was independently associated with increased risk of hospital admission. Further research is needed to determine clinical utility of ED multiplex testing.     

Correlation between Serum 25-Hydroxyvitamin D Level and Peripheral Arterial Stiffness in Chronic Kidney Disease Stage 3–5 Patients

Vitamin D deficiency and high brachial-ankle pulse wave velocity (baPWV) are each independently associated with higher incidence of mortality and cardiovascular (CV) disease or CV events, respectively. This study aimed to evaluate the relationship between serum 25-hydroxyvitamin D levels and baPWV in non-dialysis patients with stage 3–5 chronic kidney disease (CKD). We enrolled 180 CKD patients. A commercial enzyme-linked immunosorbent assay was used to measure 25-hydroxyvitamin D levels. BaPWV values were measured using an automatic pulse wave analyzer. Either left or right baPWV > 18.0 m/s was considered indicative of peripheral arterial stiffness (PAS). In this study, 73 (40.6%) patients were found to have PAS. Compared to those without PAS (control group), patients with PAS were older and had higher incidence of diabetes mellitus, higher systolic and diastolic blood pressure, higher levels of intact parathyroid hormone, and C-reactive protein, and lower levels of 25-hydroxyvitamin D. Multivariate logistic regression analysis found 25-hydroxyvitamin D levels (odds ratio [OR]: 0.895, 95% confidence interval [CI] 0.828–0.968, p = 0.005) and old age (OR: 1.140, 95% CI 1.088–1.194, p < 0.001) to be independently associated with PAS in patients with stage 3–5 CKD. Lower serum 25-hydroxyvitamin D levels and older age were associated with PAS in these patients.     

Wettability and Surface Roughness of Parylene C on Three-Dimensional-Printed Photopolymers

The use of poly-(para-chloro-xylylene) (Parylene C) in microelectromechanical systems and medical devices has increased rapidly. However, little research has been conducted on the wettability and surface roughness of Parylene C after being soaked in solutions. In this study, the contact angle and surface roughness (arithmetic average of roughness) of Parylene C on three-dimensional (3D)-printed photopolymer in 10% sodium hydroxide, 10% ammonium hydroxide, and 100% phosphate-buffered saline (PBS) solutions were investigated using a commercial contact angle measurement system and laser confocal microscope, respectively. The collected data indicated that 10% ammonium hydroxide had no major effect on the contact angle of Parylene C on a substrate, with a Shore A hardness of 50. However, 10% sodium hydroxide, 10% ammonium hydroxide, and 100% PBS considerably affected the contact angle of Parylene C on a substrate with a Shore A hardness of 85. Substrates with Parylene C coating exhibited lower surface roughness than uncoated substrates. The substrates coated with Parylene C that were soaked in 10% ammonium hydroxide exhibited high surface roughness. The aforementioned results indicate that 3D-printed photopolymers coated with Parylene C can offer potential benefits when used in biocompatible devices.     

Detecting spontaneous deception in the brain

Deception detection can be of great value during the juristic investigation. Although the neural signatures of deception have been widely documented, most prior studies were biased by difficulty levels. That is, deceptive behavior typically required more effort, making deception detection possibly effort detection. Furthermore, no study has examined the generalizability across instructed and spontaneous responses and across participants. To explore these issues, we used a dual‐task paradigm, where the difficulty level was balanced between truth‐telling and lying, and the instructed and spontaneous truth‐telling and lying were collected independently. Using Multivoxel pattern analysis, we were able to decode truth‐telling versus lying with a balanced difficulty level. Results showed that the angular gyrus (AG), inferior frontal gyrus (IFG), and postcentral gyrus could differentiate lying from truth‐telling. Critically, linear classifiers trained to distinguish instructed truthful and deceptive responses could correctly differentiate spontaneous truthful and deceptive responses in AG and IFG with above‐chance accuracy. In addition, with a leave‐one‐participant‐out analysis, multivoxel neural patterns from AG could classify if the left‐out participant was lying or not in a trial. These results indicate the commonality of neural responses subserved instructed and spontaneous deceptive behavior as well as the feasibility of cross‐participant deception validation.     

Entanglement-assisted concatenated quantum codes

Entanglement-assisted concatenated quantum codes (EACQCs), constructed by concatenating two quantum codes, are proposed. These EACQCs show significant advantages over standard concatenated quantum codes (CQCs). First, we prove that, unlike standard CQCs, EACQCs can beat the nondegenerate Hamming bound for entanglement-assisted quantum error-correction codes (EAQECCs). Second, we construct families of EACQCs with parameters better than the best-known standard quantum error-correction codes (QECCs) and EAQECCs. Moreover, these EACQCs require very few Einstein–Podolsky–Rosen (EPR) pairs to begin with. Finally, it is shown that EACQCs make entanglement-assisted quantum communication possible, even if the ebits are noisy. Furthermore, EACQCs can outperform CQCs in entanglement fidelity over depolarizing channels if the ebits are less noisy than the qubits. We show that the error-probability threshold of EACQCs is larger than that of CQCs when the error rate of ebits is sufficiently lower than that of qubits. Specifically, we derive a high threshold of 47% when the error probability of the preshared entanglement is 1% to that of qubits.

Quantum error-correction codes (QECCs) are necessary to realize quantum communications and to make fault-tolerant quantum computers (1, 2). The stabilizer formalism provides a useful way to construct QECCs from classical codes, but certain orthogonality constraints are required (3). The entanglement-assisted (EA) QECC (EAQECC) (4–6) generalizes the stabilizer code. By presharing some entangled states between the sender (Alice) and the receiver (Bob), EAQECCs can be constructed from any classical linear codes without the orthogonality constraints. Therefore, the construction could be greatly simplified. As an important physical resource, entanglement can boost the classical information capacity of quantum channels (7–12). Recently, it has been shown that EAQECCs can violate the nondegenerate quantum Hamming bound (13) or the quantum Singleton bound (14).Compared to standard QECCs, EAQECCs must establish some amount of entanglement before transmission. This preshared entanglement is the price to be paid for enhanced communication capability. In a sense, we need to consider the net transmission of EAQECCs—i.e., the number of qubits transmitted minus that of ebits preshared. Further, it is difficult to preserve too many noiseless ebits in EAQECCs at present. Thus, we have to use as few ebits as possible to conduct the communication—e.g., one or two ebits are preferable (15–18). In addition, EAQECCs with positive net transmission and little entanglement can lead to catalytic quantum codes (4, 6), which are applicable to fault-tolerant quantum computation (FTQC). In ref. 4, a table of best-known EAQECCs of length up to 10 was established through computer search or algebraic methods. Several EAQECCs in ref. 4 have larger minimum distances than the best-known standard QECCs of the same length and net transmission. However, for larger code lengths, the efficient construction of EAQECCs with better parameters than standard QECCs is still unknown.In classical coding theory, concatenated codes (CCs), originally proposed by Forney in the 1960s (19), provide a useful way of constructing long codes from short ones. CCs can achieve very large coding gains with reasonable encoding and decoding complexity (20). Moreover, CCs can have large minimum distances since the distances of the component codes are multiplied. As a result, CCs have been widely used in many digital communication systems—e.g., the NASA standard for the Voyager program (21) and the compact disc (20). Similarly, in QECCs, the concatenated quantum codes (CQCs), introduced by Knill and Laflamme in 1996 (22), are also effective for constructing good quantum codes. In particular, it has been shown that CQCs are of great importance in realizing FTQC (23–25).Moreover, there exists a specific phenomenon in QECCs, called “error degeneracy,” which distinguishes quantum codes from classical ones in essence. It is widely believed that degenerate codes can correct more quantum errors than nondegenerate ones. Indeed, there are some open problems concerning whether degenerate codes can violate the nondegenerate quantum Hamming bound (26) or can improve the quantum-channel capacity (27, 28). Many CQCs have been shown to be degenerate, even if the component codes are nondegenerate—e.g., Shor’s [[9,1,3]] code and the [[25,1,9]] CQC (23, 29). If we introduce extra entanglement to CQCs, it is possible to improve the error-degeneracy performance of CQCs.In this article, we generalize the idea of concatenation to EAQECCs and propose EACQCs. We show that EACQCs can beat the nondegenerate quantum Hamming bound, while standard CQCs cannot. Several families of degenerate EACQCs that can surpass the nondegenerate Hamming bound for EAQECCs are constructed. The same conclusion could be reached for asymmetric error models, in which the phase-flip errors (Z errors) happen more frequently than the bit-flip errors (X errors) (30, 31). Furthermore, we derive a number of EACQCs with better parameters than the best-known QECCs and EAQECCs. In particular, we see that many EACQCs have positive net transmission, and each of them consumes only one or two ebits. Thus, they give rise to catalytic EACQCs with little entanglement and better parameters than the best-known QECCs. Further, we show that the EACQC scheme makes EA quantum communication possible, even if the ebits are noisy. We compute the entanglement fidelity (EF) of the [[15,1,9;10]] EACQC by using Bowen’s [[3,1,3;2]] EAQECC (32) or the [[3,1,3;2]] EA repetition code (4, 6) as the inner code. The outer code is the standard [[5,1,3]] stabilizer code. We show that the [[15,1,9;10]] EACQC performs much better than the [[25,1,9]] CQC over depolarizing channels if the ebits suffer a lower error rate than the qubits. Moreover, we compute the error-probability threshold of EACQCs, and we show that EACQCs have much higher thresholds than CQCs when the error rate of ebits is sufficiently lower than that of qubits.     

Association of Albumin and Globulin with Mortality Risk in Incident Peritoneal Dialysis Patients

Background: Nutrition and inflammation have been implicated in predicting mortality in patients on peritoneal dialysis (PD). Serum albumin and globulin can be regarded for the nutritional and inflammatory status. However, there is lack of data to evaluate the synergistic effect of albumin and globulin on mortality prediction. Methods: In 554 patients initiating PD from January 2001 to July 2016, we divided them into four groups by the combination of two categories of low vs. high albumin and low vs. high globulin. The median values for albumin and globulin were chosen to classify them into low or high groups. Their associations with all-cause and cardiovascular (CV) mortality were examined in Cox regression models adjusted for confounding clinical and laboratory data. Results: Patients, 52.91 ± 15.2 years old and 47.8% men, had a median (interquartile range) value of 3.3 (2.9–3.8) g/dL for albumin and 2.8 (2.5–3.2) g/dL for globulin, respectively. Patients with low albumin and high globulin had the highest all-cause mortality and CV mortality, with adjusted hazard ratios of 3.87 (95% CI 1.83–8.20, p < 0.001) and 5.65 (95% CI 2.23–14.34, p < 0.001), respectively, compared with those with a high albumin and low globulin having the lowest mortality rate. Sensitivity analyses further confirmed this relationship. Conclusions: A patient profile of either low albumin or high globulin is linked to a higher risk for mortality, particularly for a profile of both low albumin and high globulin compared with one without either of them. Further studies are needed to explore the mechanisms underlying this phenomenon and how to improve clinical outcomes in those high-risk patients.     

Combination of CRAFITY score with Alpha-fetoprotein response predicts a favorable outcome of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.     

Extensive sampling of Saccharomyces cerevisiae in Taiwan reveals ecology and evolution of predomesticated lineages

The ecology and genetic diversity of the model yeast Saccharomyces cerevisiae before human domestication remain poorly understood. Taiwan is regarded as part of this yeast''s geographic birthplace, where the most divergent natural lineage was discovered. Here, we extensively sampled the broadleaf forests across this continental island to probe the ancestral species’ diversity. We found that S. cerevisiae is distributed ubiquitously at low abundance in the forests. Whole-genome sequencing of 121 isolates revealed nine distinct lineages that diverged from Asian lineages during the Pleistocene, when a transient continental shelf land bridge connected Taiwan to other major landmasses. Three lineages are endemic to Taiwan and six are widespread in Asia, making this region a focal biodiversity hotspot. Both ancient and recent admixture events were detected between the natural lineages, and a genetic ancestry component associated with isolates from fruits was detected in most admixed isolates. Collectively, Taiwanese isolates harbor genetic diversity comparable to that of the whole Asia continent, and different lineages have coexisted at a fine spatial scale even on the same tree. Patterns of variations within each lineage revealed that S. cerevisiae is highly clonal and predominantly reproduces asexually in nature. We identified different selection patterns shaping the coding sequences of natural lineages and found fewer gene family expansion and contractions that contrast with domesticated lineages. This study establishes that S. cerevisiae has rich natural diversity sheltered from human influences, making it a powerful model system in microbial ecology.

The yeast genus Saccharomyces, which includes S. cerevisiae, is a powerful model system for revealing patterns of genomic variation underlying reproductive isolation and adaptation in eukaryotic microorganisms. Surveys of population genetic data have been used in S. cerevisiae to date the origin of key domestication events (Gallone et al. 2016; Duan et al. 2018; Peter et al. 2018), to determine life cycle frequencies in nature (Tsai et al. 2008), to determine the genomic basis of adaptation at continental scale (Duan et al. 2018; Peter et al. 2018), and, more recently, to establish its geographical origin and dispersal history (Xia et al. 2017). Phylogenomic analyses of the Saccharomyces sensu stricto complex and extensive sequencing of collections across the world suggest that S. cerevisiae originated in East Asia (Duan et al. 2018; Peter et al. 2018). The 1011 Genome Project—the most broad large-scale yeast population genomic study—discovered that three wild isolates from Taiwan showed an unprecedented high genetic diversity compared with populations from the rest of the world (Peter et al. 2018). Population genomics of 266 domestic and wild isolates in China revealed six wild lineages from primeval forests. The newly identified CHN-IX group represents the most diverged lineage (Duan et al. 2018). Isolates from this group and the three Taiwanese isolates were grouped into a single lineage that showed a disjunct geographic distribution (Bendixsen et al. 2021). Although considerable knowledge is available on the biogeography and population genetics of plants and animals across continents (Whittaker et al. 2017), little is known about how eukaryotic microorganisms such as S. cerevisiae disperse, establish, reproduce, and persist in nature (Liti 2015).Most S. cerevisiae biology has been based on experiments on a handful of laboratory domesticated strains, but comprehensive analyses of the ecology and evolutionary biology of S. cerevisiae in the wild are still unavailable. In nature, S. cerevisiae have been isolated from the bark, fruits, surrounding soil, and leaves of plants belonging to several different families (Naumov et al. 2013), with early reports suggesting that the yeast is most successfully isolated from the oak family Fagaceae (Sniegowski et al. 2002; Sampaio and Gonçalves 2008; Wang et al. 2012). S. cerevisiae contains high genetic diversity in certain populations, including lineage-specific variants that display clear population structures (Barnett 1992; Wang et al. 2012; Cromie et al. 2013; Strope et al. 2015; Gallone et al. 2016; Gonçalves et al. 2016; Zhu et al. 2016; Duan et al. 2018; Legras et al. 2018; Peter et al. 2018) and explain phenotypic variance similar to common variants (Fournier et al. 2019). Samples from natural habitats tend to be homozygous diploids forming unique populations with minimal genetic admixture, whereas lineages associated with human activities were likely heterozygous, containing higher ploidy and greater genetic admixture leading to a mosaic genome makeup (Diezmann and Dietrich 2009; Liti et al. 2009; Wang et al. 2012; Almeida et al. 2015). The diverse natural lineages of S. cerevisiae present in East Asia provide an excellent opportunity to study the natural diversity of this species, which was previously believed to be fully domesticated (Fay and Benavides 2005).Taiwan is a continental shelf island with the fifth highest tree density in the world (Crowther et al. 2015). Among the 13 climate-related forests types in Taiwan, five are Fagaceae-dominated natural forests on low- and mid-elevation mountains (Li et al. 2013), thus a potentially ideal natural habitat for S. cerevisiae. Taiwan also harbors a high phylogenetic diversity of flowering plants (53 out of 64 angiosperm orders present under the APG IV classification system) (Lin and Chung 2017) and endemism compared with other oceanic islands (Hsieh 2002), raising the possibility that the associated microbial populations are genetically different from their continental counterparts. Here, we set out to characterize the intra-genetic diversity, relative abundance, and distribution of S. cerevisiae in Taiwanese forests over 4 yr of broad sampling. Our study provides novel insights of the predomestication phase of S. cerevisiae and broadens our understanding of the ecological and biogeographic implications before anthropogenic impacts.