bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated With Emergency Department Length of Stay and In-hospital Mortality in Intracerebral Hemorrhage Patients
Authors: Davis Nicolle W. , Sheehan Tiffany O. , Guo Yi , Kelly Debra Lynch , Horgas Ann L. , Yoon Saunjoo L.
Published: February 2021

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a medical emergency that requires rapid identification and focused assessment early to ensure the best possible outcomes. The purpose of this study is to evaluate the associations between system and patient factors and emergency department (ED) length of stay and in-hospital mortality in patients given a diagnosis of ICH. METHODS: A sample of 3108 ICH patients was selected from a statewide administrative database for cross-sectional retrospective analysis. System characteristic (hospital stroke certification), patient characteristics (age, sex, and race), and covariate conditions (stroke severity and comorbidities) were analyzed using descriptive statistics and hierarchical logistic regression models to address the study questions. RESULTS: The mean ED length of stay is 2.9 ± 3 hours (range, 0-42 hours) before admission to an inpatient unit. Inpatient mortality is 14.9%. Stroke center certification (P < .000) and stroke severity (P ≤ .000) are significant predictors of ED length of stay, whereas age (P < .000), stroke severity (P < .000), comorbidities (P = .047), and ED length of stay (P = .04) are significant predictors of in-hospital mortality. Most notably, an ED length of stay of 3 hours or longer has a 37% increase in the odds of in-hospital mortality. CONCLUSION: Our findings support age, stroke severity, and ED length of stay as predictors of in-hospital mortality for ICH patients. The importance of timely admission to an inpatient unit is emphasized. Optimal systems of care and expedited inpatient admission are vital to reduce morbidity and mortality for ICH stroke patients.
Understanding Clinical Characteristics of Muscle Weakness
Authors: Bhimani Rozina , Punjani Bisma , Peden-McAlpine Cynthia
Published: February 2021

BACKGROUND: Muscle weakness is a debilitating condition that can lead to frailty, falls, and functional decline. Muscle weakness is found across many diseases; therefore, understanding what constitutes this condition is paramount. The National Library of Medicine provides 2 definitions of muscle weakness, both from a disease perspective. These definitions are narrow and do not account for overlapping causes of muscle weakness. Nurses are holistic practitioners, so they need to understand the clinical characteristics of muscle weakness, regardless of underlying disease processes. METHODS: Secondary analysis of data from an earlier qualitative study. Using content analysis of transcripts of semistructured interviews with a multidisciplinary group of 12 experts in the management of muscle disorders, we identified characteristics of muscle weakness from the clinicians' perspectives. RESULTS: Muscle weakness has characteristics of debility, loss of function, and asymmetry. The characteristics of debility include lack of strength, atrophy, and fatigue. Muscle weakness does coexist with muscle tightness. CONCLUSIONS: The characteristics of muscle weakness identified in our study are markedly different from those included in National Library of Medicine definitions. As a condition, muscle weakness has both subjective and objective traits. Therefore, clinician assessment and patient input combined capture the comprehensive nature of muscle weakness. Nurses' awareness of what constitutes muscle weakness, regardless of diagnosis, is the first step in optimal management of this condition.
Postoperative Pain Management Is Influenced by Previous Cannabis Use in Neurosurgical Patients
Authors: Dupriest Kaitlyn , Rogers Kamryn , Thakur Barsha , Venkatachalam Aardhra M. , Stutzman Sonja E.
Published: February 2021

BACKGROUND: Cannabis use for medical and recreational purposes is growing. Cannabis may have drug-drug interactions for managing pain, anxiety, and seizures. The research regarding cannabis use in patients with craniotomy surgeries is sparse and often conducted in states where cannabis use is legal. This study compared 24-hour postoperative craniotomy pain levels in patients who reported cannabis use in a state where cannabis is not yet legal. METHODS: This is an observational prospective, nonrandomized, pilot study of postoperative craniotomy patients. Patients were consented and given a one-time self-report questionnaire regarding postoperative pain, pain management method, type of pain medication used at home (including cannabis), route of administration, and frequency of use. Subjects scored pain on both the numeric rating scale and the visual analog scale. Demographic data were collected from the electronic medical record. RESULTS: Forty-five patients with a mean age of 57 years, 62% female, participated in this study. There were 33% who reported previous cannabis use. One-way analysis of variance showed a significant difference in the mean postoperative pain scores for the cannabis users (4.58) and nonusers (3.89; P = .0056). There was no significant difference between age (P = .1894) and adequacy of pain control (P = .6584) between users and nonusers. CONCLUSION: In this pilot study, a one-time survey in critical care on the sensitive topic of cannabis use is feasible and seems to generate honest responses. One-third of patients reported home use of cannabis in a state where cannabis is illegal.
What Are We Missing?
Authors: Loza-Avalos Sandra E. , Thompson Ella , Beulah Brianna , Murray Ashlee
Published: February 2021

Objectives

Our study sought to explore and assess pediatric emergency department (ED) health care providers' knowledge, attitudes, and behaviors surrounding an existing intimate partner violence (IPV) screening program 4 years after initial implementation.

Methods

We used anonymous electronic surveys and telephone interviews to obtain provider perspectives using a mixed-methods analysis. We used χ2 tests to analyze the quantitative survey results, and an unstructured qualitative approach to analyze the telephone interviews.

Results

We analyzed 141 survey responses, which correlated to a response rate of about 35% of all the providers reached, and 20 telephone interviews. Our results demonstrate that pediatric ED providers have some knowledge of our existing caregiver IPV screening program in the pediatric ED and universally endorse routine caregiver IPV screening, which both are suggestive of postimplementation cultural shifts. However, reported provider behaviors still indicate selective/targeted screening. For example, many providers reported screening males and nontraditional caregivers less often compared with female caregivers. Reported barriers potentially explaining such screening habits mirror those in existing literature: patient acuity, time, multiple caregivers being present, and more.

Conclusions

Our study indicates that more research must be done to assess root causes of provider barriers to IPV screening in pediatric ED settings because trainings and a long-standing program do not seem to be changing screening practices. Addressing these issues may lead to truly sustainable and effective IPV screening programs in pediatric ED settings.
Wound infection caused by Neisseria zoodegmatis, a zoonotic pathogen: a case report
Authors: Merlino John , Gray Timothy , Beresford Rohan , Baskar Sai Rupa , Gottlieb Thomas , Birdsall Jacob
Published: February 2021

The isolation of

Neisseria zoodegmatis

from a 63-year-old female presenting to the emergency department following a cat bite injury to her right hand is described in this report.

N. zoodegmatis

, also known as Centers for Disease Control (CDC) group EF-4b, is considered to be a zoonotic pathogen, and is usually associated with dog or cat bites. Despite the potential of this organism to cause serious soft tissue infections, it can be overlooked in routine clinical laboratories due to its slow growth characteristics and when the history of animal bite is not provided to the laboratory. This case highlights the importance of appropriate clinical history provision to the microbiology laboratory to help provide important information about potential pathogens and allow microbiologists to optimize culture and identification methods. The introduction of tools such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) into clinical laboratories allows identification and the interpretation of results to be performed within a few minutes of isolation on proper culture media, as opposed to traditional methods, whose slowness may be problematic, as shown in this case report.
Whole-genome comparative analysis of Malaysian Burkholderia pseudomallei clinical isolates
Authors: Ghazali Ahmad-Kamal , Eng Su-Anne , Khoo Jia-Shiun , Teoh Seddon , Hoh Chee-Choong , Nathan Sheila
Published: February 2021

Burkholderia pseudomallei

, a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of

B. pseudomallei

infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across

B. pseudomallei

strains. We previously characterized

B. pseudomallei

strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical

B. pseudomallei

isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in

B. pseudomallei

and

Burkholderia mallei

, but not

Burkholderia thailandensis

. Genes encoding known

B. pseudomallei

virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding

B. pseudomallei

pathogenicity to guide the design of new therapeutics for treating melioidosis.
Naive human B cells engage the receptor binding domain of SARS-CoV-2, variants of concern, and related sarbecoviruses
Authors: Feldman Jared , Bals Julia , Altomare Clara G. , St. Denis Kerri , Lam Evan C. , Hauser Blake M. , Ronsard Larance , Sangesland Maya , Moreno Thalia Bracamonte , Okonkwo Vintus , Hartojo Nathania , Balazs Alejandro B. , Bajic Goran , Lingwood Daniel , Schmidt Aaron G.
Published: February 2021

Exposure to a pathogen elicits an adaptive immune response aimed to control and eradicate. Interrogating the abundance and specificity of the naive B cell repertoire contributes to understanding how to potentially elicit protective responses. Here, we isolated naive B cells from 8 seronegative human donors targeting the SARS-CoV-2 receptor-binding domain (RBD). Single B cell analysis showed diverse gene usage with no restricted complementarity determining region lengths. We show that recombinant antibodies engage SARS-CoV-2 RBD, circulating variants, and pre-emergent coronaviruses. Representative antibodies signal in a B cell activation assay and can be affinity matured through directed evolution. Structural analysis of a naive antibody in complex with spike shows a conserved mode of recognition shared with infection-induced antibodies. Lastly, both naive and affinity-matured antibodies can neutralize SARS-CoV-2. Understanding the naive repertoire may inform potential responses recognizing variants or emerging coronaviruses enabling the development of pan-coronavirus vaccines aimed at engaging germline responses.

One Sentence Summary

Isolation of antibody germline precursors targeting the receptor binding domain of coronaviruses.
Cardiac RyR N-terminal region biosensors for FRET-based high-throughput screening
Authors: Zhang Jingyan , Wong King Yuen Siobhan M. , Schwarz Jacob A. , Treinen Levy M. , Tung Ching-Chieh , Rebbeck Robyn T. , Berg Kaja , Svensson Bengt , Aldrich Courtney C. , Thomas David D. , Van Petegem Filip , Cornea Razvan L.
Published: February 2021

The N-terminal region (NTR) of the ryanodine receptor (RyR) calcium channels is critical to the regulation of Ca2+release during excitation-contraction coupling. NTR hosts numerous mutations linked to skeletal and cardiac myopathies (RyR1 and RyR2, respectively), highlighting its potential as therapeutic target. Here, we labeled the NTR of mouse RyR2 at subdomains A, B, and C with donor and acceptor pairs for fluorescence resonance energy transfer (FRET), obtaining two biosensors. Using fluorescence lifetime (FLT)-detection of intramolecular FRET, we developed high-throughput screening (HTS) assays with the biosensors to identify small-molecule modulators of RyR. We screened a 1280-compound validation library and identified several hits. Hits with saturable FRET dose-response profiles, and previously unreported effects on RyR activity, were further tested using [3H]ryanodine binding to isolated sarcoplasmic reticulum vesicles, to measure their effects on full-length RyR opening in its natural membrane environment. We identified three novel inhibitors of both RyR1 and RyR2, and two RyR1-selective inhibitors at nanomolar Ca2+. These compounds may function as inhibitors of leaky RyRs in muscle. Two of these hits activated RyR1 only at micromolar Ca2+, highlighting them as potential activators of excitation-contraction coupling. These results indicate that large-scale HTS using this platform can lead to compounds with potential for therapeutic development.
PROTOCOL: A cohort study examining the association between mirtazapine and mortality risk in adults with a diagnosis of depression
Authors: Joseph Rebecca M , Jack Ruth H , Morriss Richard , Knaggs Roger David , Hollis Chris , Hippisley-Cox Julia , Coupland Carol
Published: February 2021

This protocol describes a cohort study comparing the risks of mortality and serious self-harm (suicide or near-fatal deliberate self-harm) between adults with depression prescribed mirtazapine, a selective serotonin reuptake inhibitor (SSRI), amitriptyline, or venlafaxine. The study is set within English primary care electronic health records from the Clinical Practice Research Datalink (CPRD) and covers the period 01 January 2005 – 30 November 2018. The study described uses an active comparator new user design: patients are included if they are first prescribed an SSRI before being prescribed mirtazapine, a different SSRI, amitriptyline, or venlafaxine as their second antidepressant. Patients are followed from the initial prescription for the second antidepressant until an outcome (mortality, serious self-harm), end of CPRD follow-up, or study end. Inverse probability of treatment weighting is used to account for confounding variables. The protocol was submitted to the CPRD Independent Scientific Advisory Committee for review and was approved in November 2019 (protocol number 19_241).
Genomic surveillance of SARS-CoV-2 during the first year of the pandemic in the Bronx enabled clinical and epidemiological inference
Authors: Fels J. Maximilian , Khan Saad , Forster Ryan , Skalina Karin A. , Sirichand Surksha , Fox Amy S. , Bergman Aviv , Mitchell William B. , Wolgast Lucia R. , Szymczak Wendy , Bortz Robert H. , Dieterle M. Eugenia , Florez Catalina , Haslwanter Denise , Jangra Rohit K. , Laudermilch Ethan , Wirchnianski Ariel S. , Barnhill Jason , Goldman David L. , Khine Hnin , Goldstein D. Yitzchak , Daily Johanna P. , Chandran Kartik , Kelly Libusha
Published: February 2021

The Bronx was an early epicenter of the COVID-19 pandemic in the USA. We conducted temporal genomic surveillance of SARS-CoV-2 genomes across the Bronx from March-October 2020. Although the local structure of SARS-CoV-2 lineages mirrored those of New York City and New York State, temporal sampling revealed a dynamic and changing landscape of SARS-CoV-2 genomic diversity. Mapping the trajectories of variants, we found that while some became ‘endemic’ to the Bronx, other, novel variants rose in prevalence in the late summer/early fall. Geographically resolved genomes enabled us to distinguish between cases of reinfection and persistent infection in two pediatric patients. We propose that limited, targeted, temporal genomic surveillance has clinical and epidemiological utility in managing the ongoing COVID pandemic.

One sentence summary

Temporally and geographically resolved sequencing of SARS-CoV-2 genotypes enabled surveillance of novel genotypes, identification of endemic viral variants, and clinical inferences, in the first wave of the COVID-19 pandemic in the Bronx.
An optimized MRI and PET based clinical protocol for improving the differential diagnosis of Geriatric Depression and Alzheimer’s Disease
Authors: Emsell Louise , Vanhaute Heleen , Vansteelandt Kristof , De Winter François-Laurent , Christiaens Danny , Van den Stock Jan , Vandenberghe Rik , Van Laere Koen , Sunaert Stefan , Bouckaert Filip , Vandenbulcke Mathieu
Published: February 2021

OBJECTIVE

MRI derived hippocampal volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer’s Disease (AD). Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants.

METHOD

Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid.

RESULTS

Both HV(χ2(1) = 6.46: p= 0.011) and amyloid (χ2(1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%).

CONCLUSION

Hippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available.
Confirmed forecasts for the expansion of the COVID-19 epidemic in the largest Brazilian City
Authors: Celaschi Sergio
Published: February 2021

Objective

A SEIR compartmental model was previously selected to estimate future outcomes to the dynamics of the Covid-19 epidemic breakout in Brazil.

Method

Compartments for individuals vaccinated, and prevalent SARS-Cov-2 variants were not included. A time-dependent incidence weight on the reproductive basic number accounted for Non Pharmaceutical Interventions (NPI). A first series of published data from March 1st to May 8, 2020 was used to adjust all model parameters aiming to forecast one year of evolutionary outbreak. The cohort study was set as a city population-based analysis.

Analysis

The population-based sample, 25,366 during the study period, was the number of confirmed cases on exposed individuals. The analysis was applied to predict the consequences of holding for posterior NPI releases, and indicates the appearance of a second wave starting last quarter of 2020.

Findings

By March 1st2021, the number of confirmed cases was predicted to reach 0.47Million (0.24-0.78), and fatalities would account for 21 thousand (12-33), 5 to 95% CRI. A second series of data published from May 9, 2020 to March 1st, 2021 confirms the forecasts previously reported for the evolution of infected people and fatalities.

Novelty

By March 1st 2021, the number of confirmed cases reached 527,710 (12% bellow predicted average of accumulated cases), and fatalities accounted for 18,769 (10% above the accumulated average of estimated fatalities). After March 1st, new peaks on reported numbers of daily new infected and new fatalities appeared as a combined result to the appearance of the prevalent SARS-CoV-2 P1 variant, and the increased number of vaccinated individuals.
Avian influenza A viruses reassort and diversify differently in mallards and mammals
Authors: Ganti Ketaki , Bagga Anish , DaSilva Juliana , Shepard Samuel S. , Barnes John R. , Shriner Susan , Koelle Katia , Lowen Anice C.
Published: February 2021

Reassortment among co-infecting influenza A viruses (IAVs) is an important source of viral diversity and can facilitate expansion into novel host species. Indeed, reassortment played a key role in the evolution of the last three pandemic IAVs. Observed patterns of reassortment within a coinfected host are likely to be shaped by several factors, including viral load, the extent of viral mixing within the host and the stringency of selection. These factors in turn are expected to vary among the diverse host species that IAV infects. To investigate host differences in IAV reassortment, here we examined reassortment of two distinct avian IAV within their natural host (mallards) and a mammalian model system (guinea pigs). Animals were co-inoculated with A/wildbird/California/187718-36/2008 (H3N8) and A/mallard/Colorado/P66F1-5/2008 (H4N6) viruses. Longitudinal samples were collected from the cloaca of mallards or the nasal tract of guinea pigs and viral genetic exchange was monitored by genotyping clonal isolates from these samples. Relative to those in guinea pigs, viral populations in mallards showed higher frequencies of reassortant genotypes and were characterized by higher genotype richness and diversity. In line with these observations, analysis of pairwise segment combinations revealed lower linkage disequilibrium in mallards as compared to guinea pigs. No clear longitudinal patterns in richness, diversity or linkage disequilibrium were present in either host. Our results reveal mallards to be a highly permissive host for IAV reassortment and suggest that reduced viral mixing limits avian IAV reassortment in a mammalian host.
Using Adaptive Psychophysics to Identify the Neural Network Reset Time in Sub-second Interval Timing
Authors: Sadibolova Renata , Sun Stella , Terhune Devin B.
Published: February 2021

State dependent network models of sub-second interval timing propose that duration is encoded in states of neuronal populations that need to reset prior to a novel timing operation in order to maintain optimal timing performance. Previous research has shown that the approximate boundary of this reset interval can be inferred by varying the interstimulus interval between two to-be-timed intervals. However, the estimated boundary of this reset interval is broad (250-500ms) and remains underspecified with implications for the characteristics of state dependent network dynamics subserving interval timing. Here we probed the interval specificity of this reset boundary by manipulating the interstimulus interval between standard and comparison intervals in two sub-second auditory duration discrimination tasks (100 and 200ms) and a control (pitch) discrimination task using adaptive psychophysics. We found that discrimination thresholds improved with the introduction of a 333ms interstimulus interval relative to a 250ms interstimulus interval in both duration discrimination tasks, but not in the control task. This effect corroborates previous findings of a breakpoint in the discrimination performance for sub-second stimulus interval pairs as a function of an incremental interstimulus delay but more precisely localizes the minimal interstimulus delay range. These results suggest that state dependent networks subserving sub-second timing require approximately 250-333ms for the network to reset in order to maintain optimal interval timing.

New & Noteworthy

The state-dependent-network model considers interval timing as an intrinsic ability of neuronal populations to track the temporal evolution of their collective state. However, the time-dependent nature of neuronal properties imposes constraints on a maximum encodable interval and on the processing of intervals that are presented before the network resets to its baseline state. Investigating temporal discrimination thresholds as a function of variable inter-stimulus-intervals, we showed that the network reset time is between 250 and 333ms.
On the application of BERT models for nanopore methylation detection
Authors: Zhang Yao-zhong , Hatakeyama Sera , Yamaguchi Kiyoshi , Furukawa Yoichi , Miyano Satoru , Yamaguchi Rui , Imoto Seiya
Published: February 2021

Motivation

DNA methylation is a common epigenetic modification, which is widely associated with various biological processes, such as gene expression, aging, and disease. Nanopore sequencing provides a promising methylation detection approach through monitoring abnormal signal shifts for detecting modified bases in target motif regions. Recently, model-based approaches, especially those with deep learning models, have achieved significant performance improvements on nanopore methylation detection. In this work, we explore using bidirectional encoder representations from transformers (BERT) for doing the task, which can provide non-recurrent neural structures for fast parallel computation.

Results

We find original BERT architecture does not work as well as the bidirectional recurrent neural network (biRNN) on the nanopore methylation prediction task. Through further analysis, we observe recurrent patterns of positional-signal-shift in the context window surrounding target 5-methylcytosine (5mC) and N6-methyladenine (6mA) motifs. We propose a refined BERT with relative position representation and center hidden units concatenation, which takes account of task-specific characters into modeling. We perform systematic evaluations in-sample and cross-sample. The experiment results show that the refined BERT model can achieve competitive or even better results than the state-of-the-art biRNN model, while the model inference speed is about 6x faster. Besides, on the cross-sample evaluation of datasets from the different research groups, BERT models demonstrate a good generalization performance.

Availability

The source code and data are available athttps://github.com/yaozhong/methBERT

Contact

yaozhong@ims.u-tokyo.ac.jp
Modeling features of addiction with an oral oxycodone self-administration paradigm
Authors: Murphy Caitlin A. , Chang Yu-Hsuan , Pareta Rajesh , Li Jun-Nan , Slivicki Richard A. , Earnest Tom , Tooley Jessica , Abiraman Kavitha , Vachez Yvan M. , Gereau Robert W. , Copits Bryan A. , Kravitz Alexxai V. , Creed Meaghan C.
Published: February 2021

Prescription opioid use is an initiating factor driving the current opioid epidemic. There are several challenges with modeling prescription opioid addiction. First, prescription opioids such as oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl. This oral route of administration determines the pharmacokinetic profile, which is critical for establishing reliable drug-reinforcement associations in animals. Moreover, the pattern of intake and environment in which addictive drugs are self-administered intake are critical determinants of the levels of drug intake, sensitization and relapse behavior. This is an important consideration with prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we present an oral oxycodone self-administration paradigm that is administered in the home cage. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and exhibit preference for oxycodone, escalation of intake, physical signs of dependence, reinstatement of seeking after withdrawal, and a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model could be useful for studying the neurobiological substrates specifically relevant to prescription opioid abuse.
Finger somatotopy is preserved after tetraplegia but deteriorates over time
Authors: Kikkert Sanne , Pfyffer Dario , Verling Michaela , Freund Patrick , Wenderoth Nicole
Published: February 2021

Following spinal cord injury (SCI), the motor output flow to the limb(s) and sensory input to the brain is largely lost. While attempted movements with the paralysed and sensory deprived body part can still evoke signals in the sensorimotor system, this task-related “net” brain activity of SCI patients differs substantially from healthy controls. Such reorganised and/or altered activity is thought to reflect abnormal processing. It is however possible that this altered ‘net’ sensorimotor activity in SCI patients conceals preserved somatotopically-specific representations of the paralysed and sensory deprived body parts that could be exploited in a functionally meaningful manner (e.g. via neuroprosthetics).

In this cross-sectional study, we investigated whether a functional connection between the periphery and the brain is necessary to maintain somatosensory representations. We used functional MRI and an (attempted) finger movement task to characterise the somatotopic hand layout in the primary somatosensory cortex and structural MRI to assess spared spinal tissue bridges. We tested 14 tetraplegic SCI patients (mean age ± s.e.m.=55 ± 3.6; 1 female) who differed in terms of lesion completeness, retained sensorimotor functioning, and time since injury, as well as 18 healthy control participants (mean age ± s.e.m.=56 ± 3.6 years; 1 female).

Our results revealed somatotopically organised representations of patients’ hands in which neighbouring clusters showed selectivity for neighbouring fingers in contralateral S1, qualitatively similar to those observed in healthy controls. To quantify whether these representations were normal in tetraplegic SCI patients we correlated each participant’s intricate representational distance pattern across all fingers (revealed using representational similarity analysis) with a canonical inter-finger distance pattern obtained from an independent sample. The resulting hand representation typicality scores were not significantly different between patients and controls. This was even true when considering two individual patients with no sensory hand functioning, no hand motor functioning, and no spared spinal tissue bridges. However, a correlational analysis revealed that over years since SCI the hand representation typicality in primary somatosensory cortex deteriorates.

We show that somatosensory representations can be maintained for several years following SCI even in the absence of perhiperhal inputs. Such preserved cortical hand representations could therefore be exploited in a functionally meaningful way by rehabilitation approaches that attempt to establish new functional connections between the hand and the brain after an SCI (e.g. through neuroprosthetics). However, time since injury may critically influence the somatotopic representations of SCI patients and might thereby impact the success of such rehabilitation approaches.
Maternal obesity programs white and brown adipose tissue transcriptome and lipidome in offspring in a sex-dependent manner
Authors: Savva Christina , Helguero Luisa A. , González-Granillo Marcela , Melo Tânia , Couto Daniela , Buyandelger Byambajav , Gustafsson Sonja , Liu Jianping , Domingues Maria Rosário , Li Xidan , Korach-André Marion
Published: February 2021

The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational epigenetic regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. In this work, we investigated the sex-dependent programming of maternal obesity in visceral, subcutaneous and brown adipose tissues of offspring using magnetic resonance imaging and spectroscopy and a lipidomic approach combined with a Smart-Seq2 differential sequencing analysis. We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. Our results demonstrate for the first time that a sex-dependent gene programming exists in visceral, subcutaneous and brown adipose tissues. Maternal obesity differentially programs gene expression in adipose depots of female and male offspring, which may contribute to the sex-dependent metabolic complications later in life.

Graphical abstract
Tiara: Deep learning-based classification system for eukaryotic sequences
Authors: Karlicki Michał , Antonowicz Stanisław , Karnkowska Anna
Published: February 2021

Motivation

With a large number of metagenomic datasets becoming available, the eukaryotic metagenomics emerged as a new challenge. The proper classification of eukaryotic nuclear and organellar genomes is an essential step towards the better understanding of eukaryotic diversity.

Results

We developed Tiara, a deep-learning-based approach for identification of eukaryotic sequences in the metagenomic data sets. Its two-step classification process enables the classification of nuclear and organellar eukaryotic fractions and subsequently divides organellar sequences to plastidial and mitochondrial. Using test dataset, we have shown that Tiara performs similarly to EukRep for prokaryotes classification and outperformed it for eukaryotes classification with lower calculation time. Tiara is also the only available tool correctly classifying organellar sequences.

Availability and implementation

Tiara is implemented in python 3.8, available athttps://github.com/ibe-uw/tiaraand tested on Unix-based systems. It is released under an open-source MIT license and documentation is available athttps://ibe-uw.github.io/tiara. Version 1.0.1 of Tiara has been used for all benchmarks.
RNF43 inhibits WNT5A driven signaling and suppresses melanoma invasion
Authors: Radaszkiewicz Tomasz , Nosková Michaela , Gömöryová Kristína , Vondálová Blanářová Olga , Radaszkiewicz Katarzyna Anna , Picková Markéta , Víchová Ráchel , Gybel’ Tomáš , Kaiser Karol , Demková Lucia , Kučerová Lucia , Potěšil David , Zdráhal Zbyněk , Souček Karel , Bryja Vítězslav
Published: February 2021

RNF43 is a E3 ubiquitin ligase and known negative regulator of WNT/β-catenin signaling. We demonstrate that RNF43 is also regulator of noncanonical WNT5A-induced signaling in human cells. Analysis of the RNF43 interactome using BioID and immunoprecipitation showed that RNF43 can interact with the core receptor complex components dedicated to the noncanonical Wnt pathway such as ROR1, ROR2, VANGL1 and VANGL2. RNF43 triggers VANGL2 ubiquitination and proteasomal degradation and clathrin-dependent internalization of ROR1 receptor. This activity of RNF43 is physiologically relevant and blocks pro-metastatic WNT5A signaling in melanoma. RNF43 inhibits responses to WNT5A, which results in the suppression of invasive properties of melanoma cells. Furthermore, RNF43 prevented WNT5A-assisted development of resistance to BRAF V600E inhibitor. In line with these findings,RNF43expression decreases during melanoma progression and RNF43-low patients have worse prognosis. We conclude that RNF43 is a newly discovered negative regulator of WNT5A-mediated biological responses that desensitizes cells to WNT5A.
Wavelength-dependent effects of artificial light at night on phytoplankton growth and community structure
Authors: Diamantopoulou Christina , Christoforou Eleni , Dominoni Davide M. , Kaiserli Eirini , Czyzewski Jakub , Mirzai Nosrat , Spatharis Sofie
Published: February 2021

Artificial light at night (ALAN) is increasingly recognised as a disruptive form of environmental pollution, impacting many physiological and behavioural processes that may scale up to population and community-level effects. Mounting evidence from animal studies show that the severity and type of the impact depends on the wavelength and intensity of ALAN. This knowledge has been instrumental for informing policy-making and planning for wildlife-friendly illumination. However, most of this evidence comes from terrestrial habitats, while research testing alternative wavelength illumination in marine environments is lagging behind. In this study we investigated the effect of such alternative ALAN colours on marine primary producers. Specifically, we tested the effect of green, red, and natural white LED illumination at night, compared to a dark control, on the growth of a green microalgae as well as the biomass, diversity and composition of a phytoplankton assemblage. Our findings show that green ALAN boosted chlorophyll production at the exponential growth stage, resulting in higher biomass production in the green algaeTetraselmis suesica.All ALAN wavelengths affected the biomass and diversity of the assemblage with the red and green ALAN having the stronger effects, leading to higher overall abundance and selective dominance of specific diatom species compared to white ALAN and the dark control.

Synthesis

Our work indicates that the wavelength of artificial light sources in marine areas should be carefully considered in management and conservation plans. In particular, green and red light should be used with caution in coastal areas, where there might be a need to strike a balance between the strong effects of green and red light on marine primary producers with the benefit they bring to other organisms.
C1q binding to surface-bound IgG is stabilized by C1r2s2proteases
Authors: Zwarthoff Seline A. , Widmer Kevin , Kuipers Annemarie , Strasser Jürgen , Ruyken Maartje , Aerts Piet C. , de Haas Carla J.C. , Ugurlar Deniz , Vidarsson Gestur , Van Strijp Jos A. G. , Gros Piet , Parren Paul W.H.I. , van Kessel Kok P.M. , Preiner Johannes , Beurskens Frank J. , Schuurman Janine , Ricklin Daniel , Rooijakkers Suzan H.M.
Published: February 2021

Complement is an important effector mechanism for antibody-mediated clearance of infections and tumor cells. Upon binding to target cells, the antibody’s constant (Fc) domain recruits complement component C1 to initiate a proteolytic cascade that generates lytic pores and stimulates phagocytosis. The C1 complex (C1qr2s2) consists of the large recognition protein C1q and a heterotetramer of proteases C1r and C1s (C1r2s2). While interactions between C1 and IgG-Fc’s are believed to be mediated by the globular heads of C1q, we here find that C1r2s2proteases affect the capacity of C1q to form an avid complex with surface-bound IgG molecules (on various DNP-coated surfaces and pathogenicStaphylococcus aureus). The extent to which C1r2s2contribute to C1q-IgG stability strongly differs between human IgG subclasses. Using antibody engineering of monoclonal IgG we reveal that hexamer-enhancing mutations improve C1q-IgG stability, both in absence and presence of C1r2s2. In addition, hexamer-enhanced IgGs targetingS. aureusmediate improved complement-dependent phagocytosis by human neutrophils. Altogether, these molecular insights into complement binding to surface-bound IgGs could be important for optimal design of antibody therapies.
The desert green algaeChlorella ohadiithrives at excessively high light intensities by exceptionally enhancing the mechanisms that protect photosynthesis from photoinhibition
Authors: Levin Guy , Kulikovsky Sharon , Liveanu Varda , Eichenbaum Benjamin , Meir Ayala , Isaacson Tal , Tadmor Yaakov , Adir Noam , Schuster Gadi
Published: February 2021

Although light is the driving force of photosynthesis, excessive light can be harmful. One of the main processes that limits photosynthesis is photoinhibition, the process of light-induced photodamage. When the absorbed light exceeds the amount that is dissipated by photosynthetic electron flow and other processes, damaging radicals are formed that mostly inactivate photosystem II (PSII). Damaged PSII must be replaced by a newly repaired complex in order to preserve full photosynthetic activity.Chlorella ohadiiis a green micro-alga, isolated from biological desert soil crusts, that thrives under extreme high light and is highly resistant to photoinhibition. Therefore,C. ohadiiis an ideal model for studying the molecular mechanisms underlying protection against photoinhibition. Comparison of the thylakoids ofC. ohadiicells that were grown under low light versus extreme high light intensities, found that the alga employs all three known photoinhibition protection mechanisms:i)massive reduction of the PSII antenna size;ii)accumulation of protective carotenoids; andiii)very rapid repair of photo-damaged reaction center proteins. This work elucidated the molecular mechanisms of photoinhibition resistance in one of the most light-tolerant photosynthetic organisms and shows how photoinhibition protection mechanisms evolved to marginal conditions, enabling photosynthesis-dependent life in severe habitats.

One Sentence Highlight

Analysis of the photosynthetic properties of a desert algae that thrives at extreme high light intensities revealed protection from photoinhibition driven by the remarkable enhancement of three protection mechanisms.
Quantitative proteomics identifies secreted diagnostic biomarkers as well as tumor-dependent prognostic targets for clear cell Renal Cell Carcinoma
Authors: Senturk Aydanur , Sahin Ayse Tugce , Armutlu Ayse , Kiremit Murat Can , Acar Omer , Erdem Selcuk , Bagbudar Sidar , Esen Tarik , Tuncbag Nurcan , Ozlu Nurhan
Published: February 2021

Clear cell Renal Cell Carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified 4 putatively secreted biomarker candidates, namely PLOD2, FERMT3, SPARC and SIRPα, as highly expressed proteins that are not affected by intra- and inter-tumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of ccRCC patients, making it a promising marker for clinical screening assays. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared to cluster 2 tumors. Moreover, among the most significant clustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC.
Recognition of N6-methyladenosine by the YTHDC1 YTH domain studied by molecular dynamics and NMR spectroscopy: The role of hydration
Authors: Krepl Miroslav , Damberger Fred Franz , von Schroetter Christine , Theler Dominik , Pokorná Pavlína , Allain Frédéric H.-T. , Šponer Jiří
Published: February 2021

The YTH domain of YTHDC1 belongs to a class of protein “readers”, recognizing the N6-methyladenosine (m6A) chemical modification in mRNA. Static ensemble-averaged structures revealed details of N6-methyl recognition via a conserved aromatic cage. Here, we performed molecular dynamics (MD) simulations along with nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC) to examine how dynamics and solvent interactions contribute to the m6A recognition and negative selectivity towards unmethylated substrate. The structured water molecules surrounding the bound RNA and the methylated substrate’s ability to exclude bulk water molecules contribute to the YTH domain’s preference for m6A. Intrusions of bulk water deep into the binding pocket disrupt binding of unmethylated adenosine. The YTHDC1’s preference for the 5′-Gm6A-3′ motif is partially facilitated by a network of water-mediated interactions between the 2-amino group of the guanosine and residues in the m6A binding pocket. The 5′-Im6A-3′ (where I is inosine) motif can be recognized too but disruption of the water network lowers affinity. The D479A mutant also disrupts the water network and destabilizes m6A binding. Our interdisciplinary study of YTHDC1 protein/RNA complex reveals an unusual physical mechanism by which solvent interactions contributes towards m6A recognition.
Rapid spread of a symbiotic virus in a major crop pest following wide-scale adoption of Bt-cotton in China
Authors: Xiao Yutao , Li Wenjing , Yang Xianming , Xu Pengjun , Jin Minghui , Yuan He , Zheng Weigang , Soberón Mario , Bravo Alejandra , Wilson Kenneth , Wu Kongming
Published: February 2021

Bacillus thuringiensis(Bt) crops have been widely planted and the effects of Bt-crops on populations of the target and non-target insect pests were well studied. However, the effects of Bt-crops exposure on microorganisms that interact with crop pests haven’t previously been quantified. Here, we use laboratory and field data to show that infection ofHelicoverpa armigerawith a symbiotic densovirus (HaDV2) is associated with its enhanced growth and resistance to Bt-cotton. Moreover, field monitoring showed a much higher incidence of cotton bollworm infection with HaDV2 in regions cultivated with Bt-cotton than in regions without it, with the rate of densovirus infection increasing with increasing use of Bt-cotton. RNA-seq suggested resistance to both baculovirus and Cry1Ac were enhanced via the immune-related pathways. These suggest that the exposure to Bt-crops has selected for beneficial interactions between the target pest and a symbiotic microorganism that enhances its performance on Bt-crops under field conditions.
Machine learning reveals cryptic dialects that guide mate choice in a songbird
Authors: Wang Daiping , Forstmeier Wolfgang , Farine Damien , Maldonado-Chaparro Adriana A. , Martin Katrin , Pei Yifan , Alarcón-Nieto Gustavo , Klarevas-Irby James A. , Ma Shouwen , Aplin Lucy M. , Kempenaers Bart
Published: February 2021

Culturally transmitted communication signals – such as human language or bird song – can change over time through a process of cultural drift, and may consequently enhance the separation of populations, potentially leading to reproductive isolation1–4. Local song dialects have been identified in bird species with relatively simple songs where individuals show high cultural conformity5–10. In contrast, the emergence of cultural dialects has been regarded as unlikely11–13for species with more variable song, such as the zebra finch (Taeniopygia guttata). Instead, it has been proposed that selection for individual recognition and distinctiveness may lead to a complete spread across the space of acoustic and syntactical possibilities11–15. However, another possibility is that analytical limitations have meant that subtle but possibly salient group differences have not yet been discovered in such species. Here we show that machine learning can distinguish the songs from multiple captive zebra finch populations with remarkable precision, and that these ‘cryptic song dialects’ drive strong assortative mating in this species. We studied mating patterns across three consecutive generations using captive populations that have evolved in isolation for about 100 generations. Cross-fostering eggs within and between these populations and quantifying social interactions of the resulting offspring later in life revealed that mate choice primarily targets cultural traits that are transmitted during a short developmental time window. Detailed social networks showed that females preferentially approached males whose song resembled that of their adolescent peers. Our study shows that birds can be surprisingly sensitive to cultural traits for mating that have hitherto remained cryptic, even in this well-studied species that is used as a model for song-learning13,14,16–28.