bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it time to use machine learning survival algorithms for survival and risk factors prediction instead of Cox proportional hazard regression? A comparative population-based study
Authors: Morsy Sara , Hieu Truong Hong , Makram Abdelrahman M , Hassan Osama Gamal , Minh Duc Nguyen Tran , Zayan Ahmad Helmy , Nhat-Nam Le-Dong , Huy Nguyen Tien
Published: November 2021

Purpose

Applying machine learning in medical statistics offers more accurate prediction models. In this paper, we aimed to compare the performance of the Cox Proportional Hazard model (CPH), Classification and Regression Trees (CART), and Random Survival Forest (RSF) in short-, and long-term prediction in glioblastoma patients.

Methods

We extracted glioblastoma cancer data from the Surveillance, Epidemiology, and End Results database (SEER). We used the CPH, CART, and RSF for the prediction of 1- to 10-year survival probabilities. The Brier Score for each duration was calculated, and the model with the least score was considered the most accurate.

Results

The cohort included 26473 glioblastoma patients divided into two groups: training (n = 18538) and validation set (n = 7935). The average survival duration was seven months. For the short- and long-term predictions, RSF was the best algorithm followed by CPH and CART.

Conclusion

For big data, RSF was found to have the highest accuracy and best performance. Using the accurate statistical model for survival prediction and prognostic factors determination will help the care of cancer patients. However, more developments of the R packages are needed to allow more illustrations of the effect of each covariate on the survival probability.
Mortality in cancer patients with congenital anomalies across different age groups: trend analysis and prognostic risk factors
Authors: Morsy Sara , Hieu Truong Hong , Ghozy Sherief , Tran Linh , Huy Nguyen Tien
Published: November 2021

Purpose

Congenital anomalies are one of the causes of the high mortality rate in children diagnosed with cancer. However, there is a gap of evidence of the rate of cancer mortality in older patients who had congenital anomalies. The study, therefore, aimed to investigate the epidemiology of cancer mortality in those patients.

Methods

Data were retrieved for patients with cancer and died due to congenital causes throughout 43 years from Surveillance, Epidemiology, and End Results program SEER. The age of patients was divided into nine groups each is formed of 10 years interval. Joinpoint analysis was used to calculate the trends of Cancer mortality and Cox proportional hazard ratio to identify the mortality risk factors.

Results

We have included 2682 patients with death associated with congenital malformation. The mortality of cancer patients due to congenital anomalies greatly enhanced in the last years with the overall average annual percent was 3.8%. Interestingly, congenital anomalies had less mortality risk than other causes reported in SEER. Moreover, age, sex, radiation, chemotherapy, and behavior of tumor were significantly associated with higher survival in patients with congenital anomalies.

Conclusions

Cancer patients with congenital anomalies had less mortality risk than patients with other diseases reported in SEER. The mortality rates decreased recently, with the most mortality in the bone marrow and prostate tumors.

Implications for Cancer Survivors

Congenital anomalies are considered the least studied diseases in cancer patients. In this study, we studied how congenital anomalies did not increase the risk for cancer. However, our analysis implied the congenital anomalies in the male reproductive system were associated with the highest risk of cancer.
Efficacy and safety of pre-exposure of antibiotic prophylaxis for leptospirosis: protocol for a systematic review and meta-analysis
Authors: Rashuamán-Conche Benny , Loli-Guevara Silvana , Rodriguez-López Ethel , Alva-Díaz Carlos
Published: November 2021

Introduction

Leptospirosis is the most widespread zoonosis in the world. It represents a public health problem especially in tropical and subtropical regions, but it is also present in temperate regions. Spirochetes from leptospira genus cause the disease, they affect humans as an intermediate host. About pre-exposure prophylaxis for people at risk, antibiotics such as doxycycline or azithromycin were used to prevent the development of leptospirosis and its related adverse outcomes. However, the evidence about the efficacy and safety of this intervention is limited.

Objectives

To determine whether pre-exposure antibiotic administration prevents infection, hospitalization, or mortality from leptospirosis, without causing severe adverse effects.

Methods

We propose to do a systematic review and meta-analysis. We will search in Pubmed (Medline), Embase.com, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, LILACS and ClinicalTrials.gov. Individual randomized controlled trials, non-randomized controlled trials, cohorts, and cases-control studies will be included according to the inclusion and exclusion criteria set. The flow chart for selecting studies to be included will be presented in accordance with the PRISMA guide. The methodological quality of the studies will be evaluated by duplicate. Subsequently, the qualitative analysis of the data will be carried out and the feasibility of a quantitative meta-analysis will be evaluated. Finally, a summary of findings table will be presented according to the feasibility of the meta-analysis.

Results

The results will be published in a peer-reviewed journal.

Conclusion

This systematic review will sum up-to-date evidence about the efficacy and safety of pre-exposure antibiotic prophylaxis for preventing laboratory-confirmed leptospirosis, hospitalization and mortality.
Patient experience with healthcare: Feedback for a ‘Post COVID-19 clinic’ at a tertiary care center in rural area
Authors: Garg Alpana , Subramain Maran , Barlow Patrick B , Garvin Lauren , Hoth Karin F , Dukes Kimberly , Hoffman Richard M , Comellas Alejandro P.
Published: November 2021

Purpose

Post-acute sequelae of SARS-CoV-2 (PASC) is a complex condition with multisystem involvement. We assessed patients’ perspectives and experience with a PASC clinic established at University of Iowa in June 2020.

Methods

We conducted a mixed-method survey in June 2021 to ask PASC clinic patients about 1) PASC symptoms and their impact on physical and mental health, and cognition using the PROMIS Global Health and Cognitive Function abilities items, and 2) satisfaction with clinic services and referrals, barriers to care, and recommended support resources.

Findings

Ninety-seven patients (97/277, 35% response rate) completed the survey. Most were women (67%, n=65/97), Caucasian (93%, n=90/97) and received outpatient care during acute COVID-19 illness (79%). Fifty percent reported wait time of 1-3 months and 40% traveled >1 hour for appointment. The most common symptoms >3 months from initial infection were fatigue (77%), “brain fog” (73%), exercise intolerance (73%), anxiety (63%), sleep difficulties (56%) and depression (44%). Qualitative analysis of open-ended answers added valuable context to quantitative results. A minority of patients reported significantly reduced functioning (≥1.5 SD below mean) of their physical health (22.5%), mental health (15.9%) and cognitive abilities (17.6%). Satisfaction with clinical services was high though participants identified barriers to care including scheduling delays and financial concerns. Respondents suggested potential strategies for optimizing recovery including continuity of care, a co-located multispecialty clinic and being provided with timely information from emerging research.

Conclusion

Our study reports high PASC symptom burden, its impact on health and patient experience with healthcare. It is important that primary healthcare professionals listen to patients with empathy and support them during recovery. Healthcare systems and policymakers should focus on accessible, comprehensive, and patient-centered integrated care.
Classifying progression status statements from radiology exams among non-small cell lung cancer patients using natural language processing
Authors: Davoudi Anahita , Yu Shun , Doucette Abigail , Gabriel Peter , Miller Mark , Williams Heather , Desai Heena , Le Anh , Stoeckert Christian J , Maxwell Kara , Mowery Danielle L.
Published: November 2021

Although NLP has been used to support cancer research more broadly, the development of NLP algorithms to extract evidence of progression from clinical notes to support lung cancer research is still in its infancy. In this study, we trained supervised machine learning classifiers using rich semantic features to detect and classify statements of progression status from radiology exams. Our progression status classifier achieves high F1-scores for detecting and discerning progression (0.80), stable (0.82), and not relevant (0.92) sentences, demonstrating promising performance. We are actively integrating these extractions with structured electronic health record data using ontologies to instantiate a longitudinal model of progression among non-small cell lung cancer patients.
Homeostatic control of c-di-AMP synthase (MsDisA) and hydrolase (MsPDE) fromMycobacterium smegmatis
Authors: Gautam Sudhanshu , Mahapa Avisek , Yeramala Lahari , Gandhi Apoorv , Krishnan Sushma , Vinothkumar Kutti R. , Chatterji Dipankar
Published: November 2021

Cyclic-di-nucleotide based secondary messengers regulate various physiological processes including the stress responses in bacteria. In the past decade, cyclic diadenosine monophosphate (c-di-AMP) has emerged as a crucial second messenger, implicated in fatty acid metabolism, antibiotic resistance, biofilm formation, virulence, DNA repair, ion homeostasis, sporulation etc. The level of c-di-AMP is maintained in the cell by the action of two opposing enzymes, namely diadenylate cyclase (DAC) and phosphodiesterase (PDE). In mycobacteria, this molecule is essential for its regulatory role in bacterial physiology and host-pathogen interactions. However, such modulation of c-di-AMP remains to be explored inMycobacterium smegmatis. Here, we systematically characterised the c-di-AMP synthase (MsDisA) and a hydrolase (MsPDE) fromM. smegmatisat different pH and osmolytic conditionsin vitro. Our biochemical assays show that the MsDisA activity is enhanced during the alkaline stress and c-di-AMP is readily produced without any intermediates. At pH 9.4, the MsDisA promoter activityin vivoincreases significantly, strengthening this observation. However, under physiological conditions, the activity of MsDisA was moderate with the formation of intermediates. To get further insights into the structural characteristics, we determined the cryo-EM structure of the MsDisA, revealing some interesting features. Biochemical analysis of individual domains shows that the N-terminal minimal region alone can form a functional octamer. Altogether, our results reveal the biochemical and structural regulation of mycobacterial c-di-AMP in response to various environmental stress.
Parapatric speciation with recurrent gene flow of two sexual dichromatic pheasants
Authors: Li Zheng , Zhou Jie , Gao Minzhi , Liang Wei , Dong Lu
Published: November 2021

Background

Understanding speciation has long been a fundamental goal of evolutionary biology. It is widely accepted that speciation requires an interruption of gene flow to generate strong reproductive isolation between species, in which sexual selection may play an important role by generating and maintaining sexual dimorphism. The mechanism of how sexual selection operated in speciation with gene flow remains an open question and the subject of many research. Two species in genus Chrysolophus, Golden pheasant (C. pictus) and Lady Amherst’s pheasant (C. amherstiae), which both exhibit significant plumage dichromatism, are currently parapatric in the southwest China with several hybrid recordings in field.

Methods

In this research, we estimated the pattern of gene flow during the speciation of two pheasants using the Approximate Bayesian Computation (ABC) method based on the multiple genes data. With a new assembled de novo genome of Lady Amherst’s pheasant and resequencing of widely distributed individuals, we reconstructed the demographic history of the two pheasants by pairwise sequentially Markovian coalescent (PSMC).

Results

The results provide clear evidence that the gene flow between the two pheasants were consistent with the prediction of isolation with migration model for allopatric populations, indicating that there was long-term gene flow after the initially divergence (ca. 2.2 million years ago), and further support the secondary contact when included the parapatric populations since around 30 ka ongoing gene flow to now, which might be induced by the population expansion of the Golden pheasant in late Pleistocene.

Conclusions

The results of the study support the scenario of speciation between Golden pheasant (C. pictus) and Lady Amherst’s pheasant (C. amherstiae) with cycles of mixing-isolation-mixing due to the dynamics of natural selection and sexual selection in late Pleistocene that provide a good research system as evolutionary model to test reinforcement selection in speciation.
The annotation and analysis of complex 3D plant organs using 3DCoordX
Authors: Vijayan Athul , Strauss Soeren , Tofanelli Rachele , Mody Tejasvinee Atul , Lee Karen , Tsiantis Miltos , Smith Richard S. , Schneitz Kay
Published: November 2021

A fundamental question in biology concerns how molecular and cellular processes become integrated during morphogenesis. In plants, characterization of 3D digital representations of organs at single-cell resolution represents a promising approach to addressing this problem. A major challenge is to provide organ-centric spatial context to cells of an organ. We developed several general rules for the annotation of cell position and embodied them in 3DCoordX, a user-interactive computer toolbox implemented in the open-source software MorphoGraphX. It enables rapid spatial annotation of cells even in highly curved biological shapes. With the help of 3DCoordX we obtained new insight by analyzing cellular growth patterns in organs of several species. For example, the data indicated the presence of a basal cell proliferation zone in the ovule primordium of Arabidopsis thaliana. Proof-of-concept analyses suggested a preferential increase in cell length associated with neck elongation in the archegonium of Marchantia polymorpha and variations in cell volume linked to central morphogenetic features of a trap of the carnivorous plant Utricularia gibba. Our work demonstrates the broad applicability of the developed strategies as they provide organ-centric spatial context to cellular features in plant organs of diverse shape complexity.
Balancing selection and the crossing of fitness valleys in structured populations: diversification in the gametophytic self-incompatibility system
Authors: Stetsenko Roman , Brom Thomas , Castric Vincent , Billiard Sylvain
Published: November 2021

The self-incompatibility locus (S-locus) of flowering plants displays a striking allelic diversity. How such a diversity has emerged remains unclear. In this paper, we performed numerical simulations in a finite island population genetics model to investigate how population subdivision affects the diversification process at a S-locus, given that the two-genes architecture typical of S-loci involves the crossing of a fitness valley. We show that population structure slightly reduces the parameter range allowing for the diversification of self-incompatibility haplotypes (S-haplotypes), but at the same time also increases the number of these haplotypes maintained in the whole metapopulation. This increase is partly due to a higher rate of diversification and replacement of S-haplotypes within and among demes. We also show that the two-genes architecture leads to a higher diversity in structured populations compared with a simpler genetic architecture where new S-haplotypes appear in a single mutation step. Overall, our results suggest that population subdivision can act in two opposite directions: it renders S-haplotypes diversification easier, although it also increases the risk that the self-incompatibility system is lost.
Unifying Single-Channel Permeability from Rare-Event Sampling and Steady-State Flux
Authors: Lin Yi-Chun , Luo Yun Lyna
Published: November 2021

Various all-atom molecular dynamics (MD) simulation methods have been developed to compute free energies and crossing rates of ions and small molecules through ion channels. However, a systemic comparison across different methods is scarce. Using a carbon nanotube as a model of small conductance ion channel, we computed the single-channel permeability for potassium ion using umbrella sampling, Markovian milestoning, and steady-state flux under applied voltage. We show that a slightly modified inhomogeneous solubility-diffusion equation yields a single-channel permeability consistent with the mean first passage time (MFPT)-based method. For milestoning, applying cylindrical and spherical bulk boundary conditions yield consistent MFPT if factoring in the effective bulk concentration. The sensitivity of the MFPT to the output frequency of collective variables is highlighted using the convergence and symmetricity of the inward and outward MFPT profiles. The consistent transport kinetic results from all three methods demonstrated the robustness of MD-based methods in computing ion channel permeation. The advantages and disadvantages of each technique are discussed, focusing on the future applications of milestoning in more complex systems.
Cohesion in male singing behavior predicts group reproductive output in a social songbird
Authors: Perkes Ammon , Anderson H. Luke , Gros-Louis Julie , Schmidt Marc , White David
Published: November 2021

All social groups require organization to function optimally. Group organization is often shaped by social ‘rules’, which function to manage conflict, discourage cheating, or promote cooperation1–5. If social rules promote effective social living, then the ability to learn and follow these rules may be expected to influence individual and group-level fitness. However, such links can rarely be tested, due to the complexity of the factors mediating social systems and the difficulty of gathering data across multiple groups. Songbirds offer an opportunity to investigate the link between social rules and reproductive output because most of their social interactions are mediated by song, a well-studied and readily quantifiable behavior6,7. Using observations from 19 groups of brown-headed cowbirds (Molothrus ater) studied across 15 years, we find evidence for a previously undocumented social rule: cohesive group transitions between dominance- and courtship-related singing. Comparing across groups, the degree of cohesion in male singing behavior predicts the reproductive output of their group. Experimental manipulation of group structure via the introduction of juvenile males to captive flocks reduced group cohesion and adult male reproductive success. Taken together, these results demonstrate that cohesion in group behavioral states can affect both individual and group-level reproductive success, suggesting that selection can act not only on individual-level traits, but also on an individual’s ability and opportunity to participate effectively in organized social interactions. Social cohesion could therefore be an unappreciated force affecting social evolution in many diverse systems.
Evolutionary and spike-timing-dependent reinforcement learning train spiking neuronal network motor control
Authors: Haşegan Daniel , Deible Matt , Earl Christopher , D’Onofrio David , Hazan Hananel , Anwar Haroon , Neymotin Samuel A
Published: November 2021

Despite being biologically unrealistic, artificial neural networks (ANNs) have been successfully trained to perform a wide range of sensory-motor behaviors. In contrast, the performance of more biologically realistic spiking neuronal network (SNN) models trained to perform similar behaviors remains relatively suboptimal. In this work, we aimed at pushing the field of SNNs forward by exploring the potential of different learning mechanisms to achieve optimal performance. Inspired by biological learning mechanisms operating at multiple timescales, we used spike-timing-dependent reinforcement learning (STDP-RL) and evolutionary strategy (EVOL) with SNNs to solve the CartPole reinforcement learning (RL) control problem. Though the role of STDP-RL in biological systems is well established, several other mechanisms, though not fully understood, work in concert during learning in vivo. Recreating accurate models that capture the interaction of STDP-RL with these diverse learning mechanisms is extremely difficult. EVOL is an alternative method, and has been successfully used in many studies to fit model neural responsiveness to electrophysiological recordings and in some cases for classification problems. One advantage of EVOL is that it may not need to capture all interacting components of synaptic plasticity, and thus provides a better alternative to STDP-RL. Here, we compared the performance of each algorithm after training, which revealed EVOL as a powerful method to training SNNs to perform sensory-motor behaviors. Our modeling opens up new capabilities for SNNs in RL and could serve as a testbed for neurobiologists aiming to understand multi-timescale learning mechanisms and dynamics in neuronal circuits.
A Proteome-Wide Map of Chaperone-Assisted Protein Refolding in the Cytosol
Authors: To Philip , Xia Yingzi , Devlin Taylor , Fleming Karen G. , Fried Stephen D.
Published: November 2021

The journey by which proteins navigate their energy landscapes to their native structures is complex, involving (and sometimes requiring) many cellular factors and processes operating in partnership with a given polypeptide chain’s intrinsic energy landscape. The cytosolic environment and its complement of chaperones play critical roles in granting proteins safe passage to their native states; however, the complexity of this medium has generally precluded biophysical techniques from interrogating protein folding under cellular-like conditions for single proteins, let alone entire proteomes. Here, we develop a limited-proteolysis mass spectrometry approach paired with an isotope-labeling strategy to globally monitor the structures of refolding E. coli proteins in the cytosolic medium and with the chaperones, GroEL/ES (Hsp60) and DnaK/DnaJ/GrpE (Hsp70/40). GroEL can refold the majority (85%) of the E. coli proteins for which we have data, and is particularly important for restoring acidic proteins and proteins with three to five domains, trends that come to light because our assay measures the structural outcome of the refolding process itself, rather than indirect measures like binding or aggregation. For the most part, DnaK and GroEL refold a similar set of proteins, supporting the view that despite their vastly different structures, these two chaperones both unfold misfolded states, as one mechanism in common. Finally, we identify a cohort of proteins that are intransigent to being refolded with either chaperone. The data support a model in which chaperone-nonrefolders have evolved to fold efficiently once and only once, co-translationally, and remain kinetically trapped in their native conformations.
Unsupervised cell functional annotation for single-cell RNA-Seq
Authors: Li Dongshunyi , Ding Jun , Bar-Joseph Ziv
Published: November 2021

One of the first steps in the analysis of single cell RNA-Sequencing data (scRNA-Seq) is the assignment of cell types. While a number of supervised methods have been developed for this, in most cases such assignment is performed by first clustering cells in low-dimensional space and then assigning cell types to different clusters. To overcome noise and to improve cell type assignments we developed UNIFAN, a neural network method that simultaneously clusters and annotates cells using known gene sets. UNIFAN combines both, low-dimensional representation for all genes and cell specific gene set activity scores to determine the clustering. We applied UNIFAN to human and mouse scRNA-Seq datasets from several different organs. As we show, by using knowledge on gene sets, UNIFAN greatly outperforms prior methods developed for clustering scRNA-Seq data. The gene sets assigned by UNIFAN to different clusters provide strong evidence for the cell type that is represented by this cluster making annotations easier.

Software

https://github.com/doraadong/UNIFAN
Incident heart failure and myocardial infarction in sodium-glucose cotransporter 2 versus dipeptidyl peptidase-4 inhibitor users
Authors: Zhou Jiandong , Lee Sharen , Kit Leung Keith Sai , Chung Wai Abraham Ka , Liu Tong , Liu Ying , Chang Dong , Wong Wing Tak , Kei Wong Ian Chi , Yung Cheung Bernard Man , Zhang Qingpeng , Tse Gary
Published: November 2021

Objectives

To compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl-peptidase-4 inhibitors (DPP4I) users in a Chinese population.

Background

SGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction.

Methods

This was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020. Propensity-score matching was performed in a 1:1 ratio based on demographics, past comorbidities, non-SGLT2I/DPP4I medications with nearest-neighbor matching (caliper=0.1). Univariable and multivariable Cox models were used to identify significant predictors for new onset heart failure, new onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. Subgroup age and gender analyses were presented.

Results

A total of 41994 patients (58.89% males, median admission age at 58 years old, interquartile rage [IQR]: 51.2-65.3) were included in the study cohorts with a median follow-up duration of 5.6 years (IQR: 5.32-5.82). After adjusting for significant demographics, past comorbidities, medication prescriptions and biochemical results, SGLT2I users have a significantly lower risk for myocardial infarction (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: [0.28, 0.41], P < 0.0001), cardiovascular mortality (HR: 0.53, 95% CI: [0.38, 0.74], P = 0.0002) and all-cause mortality (HR: 0.21, 95% CI: [0.18, 0.25], P= 0.0001) under multivariable Cox regression. However, the risk for heart failure is comparable (HR: 0.87, 95% CI: [0.73, 1.04], P= 0.1343).

Conclusions

SGLT2 inhibitors are protective against adverse cardiovascular events compared to DPP4I. The prescription of SGLT2I is preferred especially for males and patients aged 65 or older to prevent cardiovascular risks.
Individual Stability of Pain- and Touch-Related Neuronal Gamma Oscillations
Authors: Valentini Elia , Shindy Alina , Witkovsky Viktor , Stankewitz Anne , Schulz Enrico
Published: November 2021

Background

The processing of brief pain and touch stimuli has been associated with an increase of neuronal oscillations in the gamma range (40-90 Hz). However, some studies report divergent gamma effects across single participants.

Methods

In two repeated sessions we recorded gamma responses to pain and touch stimuli using EEG. Individual gamma responses were extracted from EEG channels and from ICA components that contain a strong gamma amplitude.

Results

We observed gamma responses in the majority of the participants. If present, gamma synchronisation was always bound to a component that contained a laser-evoked response. We found a broad variety of individual cortical processing: some participants showed a clear gamma effect, others did not exhibit any gamma. For both modalities, the effect was reproducible between sessions. In addition, participants with a strong gamma response showed a similar time-frequency pattern across sessions.

Conclusions

Our results indicate that current measures of reproducibility of research results do not reflect the complex reality of the diverse individual processing pattern of applied pain and touch. The present findings raise the question of whether we would find similar quantitatively different processing patterns in other domains in neuroscience: group results would be replicable but the overall effect is driven by a subgroup of the participants.
A novel mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein fibrils and recapitulates its pathological diversity
Authors: Kumar Senthil T. , Mahul-Mellier Anne-Laure , Hegde Ramanath Narayana , Moons Rani , Magalhães Pedro , de Opakua Alain Ibáñez , Rivière Gwladys , Rostami Iman , Donzelli Sonia , Zweckstetter Markus , Sobott Frank , Lashuel Hilal A.
Published: November 2021

A novel mutation (E83Q), the first in the NAC domain of alpha-synuclein (aSyn), was recently identified in a patient with dementia with Lewy bodies. We investigated the effects of this mutation on the aggregation of aSyn monomers and the structure, morphology, dynamic, and seeding activity of the aSyn fibrils in neurons. We found that it dramatically accelerates aSyn fibrillization and results in the formation of fibrils with distinct structural and dynamic properties. In cells, this mutation is associated with higher levels of aSyn, accumulation of pS129, and increased toxicity. In a neuronal seeding model of Lewy bodies (LB) formation, the E83Q mutation significantly enhances the internalization of fibrils into neurons, induce higher seeding activity and results in the formation of diverse aSyn pathologies, including the formation of LB-like inclusions that recapitulate the immunohistochemical and morphological features of brainstem LBs observed in PD patient brains.

Teaser

A novel mutation (E83Q) exacerbates alpha-synuclein aggregation and toxicity and reproduces PD pathological diversity.
Best practices for multi-ancestry, meta-analytic transcriptome-wide association studies: lessons from the Global Biobank Meta-analysis Initiative
Authors: Bhattacharya Arjun , Hirbo Jibril B. , Zhou Dan , Zhou Wei , Zheng Jie , Kanai Masahiro ,   the Global Biobank Meta-analysis Initiative, Pasaniuc Bogdan , Gamazon Eric R. , Cox Nancy J.
Published: November 2021

The Global Biobank Meta-analysis Initiative (GBMI), through its genetic and demographic diversity, provides a valuable opportunity to study population-wide and ancestry-specific genetic associations. However, with multiple ascertainment strategies and multi-ethnic study populations across biobanks, the GBMI provides a distinct set of challenges in implementing statistical genetics methods. Transcriptome-wide association studies (TWAS) are a popular tool to boost detection power for and provide biological context to genetic associations by integrating single nucleotide polymorphism to trait (SNP-trait) associations from genome-wide association studies (GWAS) with SNP-based predictive models of gene expression. TWAS presents unique challenges beyond GWAS, especially in a multi-biobank and meta-analytic setting like the GBMI. In this work, we present the GBMI TWAS pipeline, outlining practical considerations for ancestry and tissue specificity and meta-analytic strategies, as well as open challenges at every step of the framework. Our work provides a strong foundation for adding tissue-specific gene expression context to biobank-linked genetic association studies, allowing for ancestry-aware discovery to accelerate genomic medicine.
Gut metabolites predict Clostridioides difficile recurrence
Authors: Dawkins Jennifer J. , Allegretti Jessica R. , Gibson Travis E. , McClure Emma , Delaney Mary , Bry Lynn , Gerber Georg K.
Published: November 2021

Background

Clostridioides difficile infection (CDI) is the most common hospital acquired infection in the U.S., with recurrence rates >15%. Although primary CDI has been extensively linked to gut microbial dysbiosis, less is known about the factors that promote or mitigate recurrence. Moreover, previous studies have not shown that microbial abundances in the gut measured by 16S rRNA amplicon sequencing alone can accurately predict CDI recurrence.

Results

We conducted a prospective, longitudinal study of 53 non-immunocompromised participants with primary CDI. Stool sample collection began pre-CDI antibiotic treatment at the time of diagnosis, and continued up to eight weeks post-antibiotic treatment, with weekly or twice weekly collections. Samples were analyzed using: (1) 16S rRNA amplicon sequencing, (2) liquid chromatography/mass-spectrometry metabolomics measuring 1387 annotated metabolites, and (3) short-chain fatty acid profiling. The amplicon sequencing data showed significantly delayed recovery of microbial diversity in recurrent participants, and depletion of key anaerobic taxa at multiple time-points, including Clostridium cluster XIVa and IV taxa. The metabolomic data also showed delayed recovery in recurrent participants, and moreover mapped to pathways suggesting distinct functional abnormalities in the microbiome or host, such as decreased microbial deconjugation activity, lowered levels of endocannabinoids, and elevated markers of host cell damage. Further, using predictive statistical/machine learning models, we demonstrated that the metabolomic data, but not the other data sources, can accurately predict future recurrence at one week (AUC 0.77 [0.71, 0.86; 95% interval]) and two weeks (AUC 0.77 [0.69, 0.85; 95% interval]) post-treatment for primary CDI.

Conclusions

The prospective, longitudinal and multi-omic nature of our CDI recurrence study allowed us to uncover previously unrecognized dynamics in the microbiome and host presaging recurrence, and, in particular, to elucidate changes in the understudied gut metabolome. Moreover, we demonstrated that a small set of metabolites can accurately predict future recurrence. Our findings have implications for development of diagnostic tests and treatments that could ultimately short-circuit the cycle of CDI recurrence, by providing candidate metabolic biomarkers for diagnostics development, as well as offering insights into the complex microbial and metabolic alterations that are protective or permissive for recurrence.
Changes in antidepressant use in Australia: A nationwide analysis prior to and during the COVID-19 pandemic (2015-2021)
Authors: de Oliveira Costa Juliana , Gillies Malcolm B. , Schaffer Andrea L. , Peiris David , Zoega Helga , Pearson Sallie-Anne
Published: November 2021

Background

Depression and anxiety affect 4% to 14% of Australians every year; symptoms may have been exacerbated during the COVID-19 pandemic. We examined recent patterns of antidepressant use in Australia in the period 2015 to 2021, which includes the first year of the pandemic.

Methods

We used national dispensing claims for people aged ≥10 years to investigate annual trends in prevalent and new antidepressant use (no antidepressants dispensed in the year prior). We conducted stratified analyses by sex, age group and antidepressant class. We report outcomes from 2015 to 2019 and used time series analysis to quantify changes during the first year of the COVID-19 pandemic (March 2020 to February 2021).

Results

In 2019 the annual prevalence of antidepressant use was 170.4 per 1,000 women and 101.8 per 1,000 men, an increase of 7.0% and 9.2% from 2015, respectively. New antidepressant use also increased for both sexes (3.0% for women and 4.9% for men) and across most age groups, particularly among adolescents (aged 10-17 years; 46%-57%). During the first year of the COVID-19 pandemic, we observed higher than expected prevalent use (+2.2%, 95%CI 0.3%, 4.2%) among females, corresponding to a predicted excess of 45,217 (95%CI 5,819, 84,614) females dispensed antidepressants. The largest increases during the first year of the pandemic occurred among female adolescents for both prevalent (+11.7%, 95%CI 4.1%, 20.5%) and new antidepressant use (+15.6%, 95%CI 8.5%, 23.7%).

Conclusion

Antidepressant use continues to increase in Australia overall and especially among young people. We found a differential impact of the COVID-19 pandemic in treated depression and anxiety, greater among females than males, and greater among young females than other age groups, suggesting an increased mental health burden in populations already on a trajectory of increased use of antidepressants prior to the pandemic. Reasons for these differences require further investigation.
Population density and plant availability interplay to shape browsing intensity by roe deer in a deciduous forest
Authors: Gaudry William , Gaillard Jean-Michel , Saïd Sonia , Mårell Anders , Baltzinger Christophe , Rocquencourt Agnès , Bonenfant Christophe
Published: November 2021

Browsing damage in forests relies on a complex interaction between herbivore density and both forest understory composition and relative availability. Although variation in the amount of browsed twigs is sometimes used to assess abundance of large herbivores, the potential confounding effect of resource availability on this relationship has not yet been investigated. To fill the gap, we measured how browsing intensity of the woody plants varied in response to changes in both roe deer (Capreolus capreolus) abundance and vegetation availability from an intensive long-term monitoring. We estimated plant availability and consumption by roe deer from a modified Aldous method throughout a 14 yearlong period during which we experimentally manipulated population density. The functional response was strongly non-linear and density-dependent. When plant availability was low (< 12.5%), browsing intensity strongly increased with plant availability with an increasing rate with roe deer density, whereas beyond this threshold, browsing intensity slightly increased with both plant availability and population density in an additive way. Thus, forest susceptibility to browsing increases with increasing competition for food, especially when plant availability is low. Moreover, the interplay between browsing intensity and population density at low plant availability prevents the use of browsing intensity to monitor roe deer abundance when plant availability is low. Our findings provide clear evidence that relying on key ecological concepts such as functional responses improves the accuracy of management tools when monitoring changes of the herbivore-plant system over time.
DeepSpot: a deep neural network for RNA spot enhancement in smFISH microscopy images
Authors: Bouilhol Emmanuel , Lefevre Edgar , Dartigues Benjamin , Brackin Robyn , Savulescu Anca Flavia , Nikolski Macha
Published: November 2021

Detection of RNA spots in single molecule FISH microscopy images remains a difficult task especially when applied to large volumes of data. The small size of RNA spots combined with high noise level of images often requires a manual adaptation of the spot detection thresholds for each image. In this work we introduce DeepSpot, a Deep Learning based tool specifically designed to enhance RNA spots which enables spot detection without need to resort to image per image parameter tuning. We show how our method can enable the downstream accurate detection of spots. The architecture of DeepSpot is inspired by small object detection approaches. It incorporates dilated convolutions into a module specifically designed for the Context Aggregation for Small Object (CASO) and uses Residual Convolutions to propagate this information along the network. This enables DeepSpot to enhance all RNA spots to the same intensity and thus circumvents the need for parameter tuning. We evaluated how easily spots can be detected in images enhanced by our method, by training DeepSpot on 20 simulated and 1 experimental datasets, and have shown that more than 97% accuracy is achieved. Moreover, comparison with alternative deep learning approaches for mRNA spot detection (deepBlink) indicated that DeepSpot allows more precise mRNA detection. In addition, we generated smFISH images from mouse fibroblasts in a wound healing assay to evaluate whether DeepSpot enhancement can enable seamless mRNA spot detection and thus streamline studies of localized mRNA expression in cells.
Resolving the time course of visual and auditory object categorization
Authors: Iamshchinina Polina , Karapetian Agnessa , Kaiser Daniel , Cichy Radoslaw M.
Published: November 2021

Humans can effortlessly categorize objects, both when they are conveyed through visual images and spoken words. To resolve the neural correlates of object categorization, studies have so far primarily focused on the visual modality. It is therefore still unclear how the brain extracts categorical information from auditory signals. In the current study we used EEG (N=47) and time-resolved multivariate pattern analysis to investigate (1) the time course with which object category information emerges in the auditory modality and (2) how the representational transition from individual object identification to category representation compares between the auditory modality and the visual modality. Our results show that (1) that auditory object category representations can be reliably extracted from EEG signals and (2) a similar representational transition occurs in the visual and auditory modalities, where an initial representation at the individual-object level is followed by a subsequent representation of the objects‘ category membership. Altogether, our results suggest an analogous hierarchy of information processing across sensory channels. However, we did not find evidence for a shared supra-modal code, suggesting that the contents of the different sensory hierarchies are ultimately modality-unique.
Design, implementation and academic perspectives on authentic assessment for applied business higher education in a top performing Asian economy
Authors: Akbari Mohammadreza , Nguyen Hung Manh , McClelland Robert , Van Houdt Kristof
Published: November 2021

Purpose

The purpose of authentic assessment can enrich students with a set of skills that can have a significant impact on their employability. The key aim of these actions is to equip students with the practical skills to be work ready. The focus here is to demonstrate effects on student satisfaction and observations from teaching staff accrued over several semesters in an educational institution after introducing authentic assessments.

Design/methodology/approach

This paper used a set of scaffolded authentic assessments for students in logistics and supply chain management (LSCM). A combination of literature and expert input was used to design and implement the authentic assessment. A multi-phase systematic approach using cyclical model steps articulated the course learning outcomes (CLOs).

Findings

Reinforced evidence that authentic assessments create options for divergent learners and provide opportunities for applying practical and higher-order cognitive skills in tertiary education system of an emerging economy. With the focus on student ability in doing things, students with diversified backgrounds and abilities in Asia can be encouraged to take an active role in their own learning. The formats of the newly redesigned assessments allow multidimensional cognitive capabilities such as art development (posters and video tasks) and reflective exercises. Importantly, formative types of authentic assessments help to decrease the level of anxiety by emphasising the aspect of doing and lead to better student satisfaction with the courses. All of these effects are shown to be repeatable in an Asian economy.

Practical implications

Authentic assessments prepare students for the new world of work through a more focused scaffolding of their learning.

Originality/value

Stimulation of deeper learning in tertiary education students is relevant for a top performing Asian economy.
Dietary composition and overlap among small‐ and medium‐sized carnivores in Flanders, Belgium
Authors: Van Den Berge Koen , van der Veken Timo , Gouwy Jan , Verschelde Pieter , Eeraerts Maxime
Published: November 2021

There are increasing concerns about the status and population trends of carnivores around the world. Carnivores play an important role in terrestrial ecosystems, as their interactions influence the composition and function of ecological communities. In the context of global change, it is essential to understand the interactions and resource use of carnivores. In this study, we explore the dietary ecology of six small‐ and medium‐sized carnivores (red fox, European badger, European polecat, stoat, stone marten and least weasel) to determine their main food resources and the degree of food overlap in Flanders, Belgium. The studied species differed in their food consumption pattern with some being generalist and some more specialist. The dietary composition among the species was clearly different, although certain species showed considerable overlap for different food types. We also conclude that the differences and overlap in the dietary habits among the species were consistent across seasons. Understanding these relationships among species' populations and their dietary ecology is essential for biodiversity conservation and nature management.
Too big, too young, too risky: How diagnosis of the foetal body determines trajectories of care for the pregnant woman in pre‐viability second trimester pregnancy loss
Authors: Middlemiss Aimee L.
Published: November 2021

Women in the English National Health Service facing pre‐viability second trimester pregnancy loss through foetal death, premature labour or termination of pregnancy for foetal anomaly find themselves in a particular trajectory of care. This usually involves the requirement to labour and birth the foetal body and may involve undergoing feticide in cases of termination. Drawing on ethnographic research investigating women's experiences of second trimester pregnancy loss, I argue that the determining factor affecting care trajectories for the pregnant body is the biomedically diagnosed status of the foetal body. Foetal size, non‐viability and the potential for live birth during terminations all structure the healthcare options for the woman facing pregnancy loss in the second trimester. As such, the diagnostic classification of the foetal body in the context of gestational time determines the medical care afforded to the pregnant body. This results in specific consequences for women, whose experiences of, and choices around, second trimester pregnancy loss are constrained by diagnostic and classificatory decisions around the status of the foetal being before legal viability.
Replacement feeding and the HIV Diaspora: A case of ontological multiplicity and fluid technologies
Authors: McKnight Ulla
Published: November 2021

Breastmilk is a transmission source of HIV. Therefore, mothers living with HIV are able to avoid exposing their infants to HIV‐contaminated breastmilk if they replacement feed them. This article draws on an ethnographic study of an acute National Health Service HIV specialist antenatal clinic in London and explores the ontological multiple HIVs that the practice of replacement feeding takes part in enacting within the fluid space of the HIV diaspora. The term articulates the circumstances of racialised people affected by HIV who are originally from countries where access to life sustaining medication, care and resources—that enable a decoupling of the illness from death—are not readily accessible, and who have (temporarily) relocated themselves to geographical places where these resources are on offer. Arguing that Black African and Caribbean migrant women's ability to benefit from the technologies and care that have turned HIV into a chronic illness in England is delimited by race and their diasporic positionality. In so doing, the article contributes to Sociology by showing how race is part of practice–ethnographic research and medical care even when it is seemingly absent.