bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanism of Death in Electrocution
Authors: Kroll Mark W. , Luceri Richard M. , Efimov Igor R. , Calkins Hugh
Published: August 2024

Our present understanding of electrocution followed a long path of detours and speculation. It is now hard to appreciate how mysterious was an unexpected sudden death—without visible trauma—and we should be sympathetic to the surprising theories that came from well-intentioned attempts to find something in the autopsy of an electrocution victim.

The early hypotheses (1880s) tended to favor effects on the central nervous system, but the emphasis switched to arterial and hematological mechanisms as well as respiratory arrest (ie, asphyxia) along with a widespread publication debate. While careful animal experimentation slowly established that electrocution was due to the induction of VF (ventricular fibrillation), the older hypotheses held sway for many decades. Even today, the neurogenic and asphyxial explanations reappear occasionally.

Despite 170 years of research, the phenomenon of electrocution continues to generate new hypotheses for its mechanism.
No More Excuses: Strategies for Inclusive Pediatric Physical Therapy Education
Authors: Rundell Shawn M. , Wentzell Erin M. , Wynarczuk Kimberly D. , Catalino Tricia , Hernandez Meghan , Lent Kathryn , Young Allison N. , Rapport Mary Jane
Published: August 2024

Purpose:

The purpose of this special communication is to provide practical, evidence-based recommendations and examples of inclusive and accessible teaching practices that can be effectively used in pediatric physical therapy (PT) education to: (1) ensure equity in education, (2) elevate all voices, and (3) facilitate anti-oppressive learning environments.

Summary of Key Points:

Concrete action items and strategies addressing these 3 recommendations are provided at all levels of the ecological model framework.

Statement of Conclusions and Recommendations for Clinical Practice:

Pediatric PT clinical and academic educators must work proactively to ensure learning environments are inclusive of everyone. Pediatric PT educators need to take the time to self-reflect, change their behaviors, and use inclusive, accessible, and anti-oppressive education practices. This will create equitable learning opportunities to successfully meet the needs of our learners, children, and families with whom we engage regularly in our personal and professional lives.
Resection of Fourth-to-Fifth Metacarpal Synostosis and Fascial Interposition for Creation of a Functional Grip/Pinch in the Apert Hand
Authors: Upton Joseph , Khouri Kimberly S.
Published: August 2024

Background:

Fourth-to-fifth metacarpal synostosis, present in a majority of Apert hands, flattens the metacarpal arch, restricts metacarpal descent, may prevent opposition of border rays, and negates any functional flexion. Restoration of position and mobility with arthroplasty changes the plane of flexion and enables both pinch and grip. This report summarizes the evolution of the authors’ technique over 5 decades.

Methods:

In a cohort of 184 Apert patients (368 hands), the presence, anatomy, and level of metacarpal synostosis with a classification was determined. The present technique consists of incision along the ulnar border of the hand, wide excision of the skeletal coalition, release of dorsal structures, and soft-tissue interposition. Data consisted of clinical records, serial molds, radiographs, and occupational therapy records. Follow-up ranged from 3 to 44 years.

Results:

A total of 147 patients (80% of hands) had bilateral fourth-to-fifth metacarpal synostoses, the extent of which correlated with the Apert hand classification. In 72 patients, the synostosis was resected and cadaveric fascia interposed. Synostosis refusion occurred in 38 hands, all of which were treated early in the series and in patients younger than 6 years old. Despite refusion, the position of the fifth digit had improved, and the flat transverse arch was in a more curved or cupped posture. The distance between the opposing border rays was always improved, and a new grip and pinch mechanism created.

Conclusions:

Aggressive ostectomy of synostosis and fascial interposition places the ulnar side of the hand in a much more functional position. In conjunction with thumb lengthening, opposition between the thumb and fifth finger becomes a clinical reality in children with Apert syndrome.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Use of Minimal Important Difference for Patient-Reported Outcome Measures in Plastic Surgery: A Systematic Review
Authors: Zhou Ted , Zeng Aisling , Levit Tal , Gallo Lucas , Kim Patrick , Chen Andrew , Cohen Dalya , Dunn Emily , Thoma Achilles
Published: August 2024

Background:

The minimal important difference (MID) is vital to consider when interpreting the clinical importance of observed changes from surgical interventions assessed by patient-reported outcome measures (PROMs). There is no accepted standard for how to calculate MIDs, and uptake in the plastic surgery literature is unknown, leading to methodologic and interpretation issues.

Methods:

Medline and Embase were searched to identify all plastic surgery randomized controlled trials (RCTs) using PROMs as outcomes and MID estimation studies for PROMs used by RCTs. Included studies were assessed for uptake and application of MIDs, and MID estimation methodology and values were categorized.

Results:

A total of 554 RCTs using PROMs as outcomes were identified. Of these, 419 RCTs had the possibility of incorporating a previously published MID. The uptake rate of MIDs was 11.5% (n = 48 of 419). The most common ways MIDs were applied were to calculate sample size (37.5%) or to determine whether results were clinically important (35.4%). A total of 99 studies estimating MID values for the most common PROMs in plastic surgery, based on our review, were analyzed. The most common estimation methodologies were receiver operating characteristic curve analysis (49%), change difference (31%), and SD (25%).

Conclusions:

This review highlights limited uptake and application of MIDs in plastic surgery. The authors propose 4 major barriers: (1) no repository of published MIDs for PROMs used in plastic surgery exists; (2) available MIDs are not specific to plastic surgery populations; (3) high heterogeneity in MID estimation methodology was present; and (4) there are wide ranges in MID values, with no superior choice identified.
Immune checkpoints and pancreatic beta cell dysfunction in HIV
Authors: Pryke Luke A. , Liu Ziyue , Khaitan Alka K. , Sims Emily K. , Gupta Samir K.
Published: August 2024

We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g. PD-1, CD27+, CD40+) in untreated HIV patients. Notably, soluble TIM-3 correlated positively with improved beta cell function and inversely with beta cell stress, suggesting its potential role in beta cell protection in untreated HIV.
177Lu-PSMA With Olaparib Radiosensitization Potentiates Response and Toxicity in Extensive Castration-Resistant Metastatic Prostate cancer
Authors: Kao Yung Hsiang , Falzone Nadia , Pearson Michael , Pook David , Sivaratnam Dinesh
Published: August 2024

A patient with widespread intensely prostate-specific membrane antigen–expressing, BRCA gene mutation–positive bone metastases at the time of prostate cancer diagnosis had progressed on multiple lines of standard therapy. He received 177Lu–prostate-specific membrane antigen 8.5 GBq augmented by a short course of olaparib radiosensitization and achieved 90% decrease in serum PSA level after a single treatment. His tumor response was much better than expected by predictive dosimetry. However, his marrow radiotoxicity was worse than anticipated and required hospitalization. This suggests radiosensitizing agents to be a double-edged sword that must be carefully considered and balanced during activity prescription.
Medical Students Cannot Assess Robotic Surgeons Performing Radical Prostatectomy
Authors: Olsen Rikke Groth , Konge Lars , Hayatzaki Khalilullah , Mortensen Mike Allan , Røder Andreas , Bjerrum Flemming
Published: August 2024

Introduction

Medical students have previously been shown to be just as effective for video rating as experts. We want to compare medical students to experienced surgeons as video assessors of simulated robot-assisted radical prostatectomy (RARP) performance.

Materials and Methods

Video recordings of three RARP modules on the RobotiX (formerly Simbionix) simulator from a previous study were used. Five novice surgeons, five experienced robotic surgeons, and five experienced robotic surgeons in RARP performed a total of 45 video-recorded procedures. The videos were assessed with the modified Global Evaluative Assessment of Robotic Skills tool as both full-length and an edited edition that only included the first 5 minutes of the procedure.

Results

Fifty medical students and two experienced RARP surgeons (ES) performed a total of 680 video ratings of full-length videos and 5-minute videos (2–9 ratings per video). Medical students and ES showed poor agreement for both full-length videos and 5-minute videos (0.29 and −0.13, respectively). Medical students could not discriminate between the skill level of the surgeons in either full-length videos or 5-minute videos (P = 0.053–0.36 and P = 0.21–0.82), whereas ES could discriminate between novice surgeons and experienced surgeons (full-length, P < 0.001, and 5 minutes, P = 0.007) and intermediate and experienced surgeons (full-length, P = 0.001, and 5 minutes, P = 0.01) in both full-length videos and 5-minute videos.

Conclusion

We found that medical students cannot be used to assess RARP because they showed poor agreement with the ES rating for both full-length videos and 5-minute videos. Medical students could not discriminate between surgical skill levels.
Diagnosis and management of blunt cerebrovascular injuries: What you need to know
Authors: Biffl Walter L. , Moore Ernest E. , Kansagra Akash P. , Flores Bruno C.C.R. , Weiss Jeffrey S.
Published: August 2024

Blunt cerebrovascular injuries are not as rare as they were once thought to be—but they still have the same potential for disastrous outcomes. They may occur following any trauma, but more common with higher energy transfer mechanisms. If stroke occurs, prompt recognition and treatment offers the best chance for optimal outcome. Early diagnosis and provision of antithrombotic therapy may prevent strokes, so screening of asymptomatic patients is recommended. Herein we will present what you need to know to diagnose and manage blunt cerebrovascular injury.
Three-dimensional shape of natural riblets in the white shark: relationship between the denticle morphology and swimming speed of sharks
Authors: Sayama Shotaro , Natsuhara Masahito , Shinohara Gento , Maeda Masateru , Tanaka Hiroto
Published: August 2024

The ridges of the dermal denticles of migratory sharks have inspired riblets to reduce the frictional drag of a fluid. In particular, the dermal denticles of white sharks (
Carcharodon carcharias
) are characterized by a high middle ridge and low side ridges. The detailed morphology of their denticles and their variation along the body, however, have never been investigated. Moreover, the hydrodynamic function of high–low combinations of ridges is unknown. In this article, the ridge spacings and heights of the white shark denticles were three-dimensionally quantified using microfocus X-ray computed tomography. Then, the swimming speed at which the ridges would reduce drag was hydrodynamically calculated with a flat plate body model and previous riblet data. High ridges with a large spacing were found to effectively reduce drag at a migration speed of 2.3 m s
−1
, while adjacent high and low ridges with a small spacing reduced drag at a burst hunting speed of 5.1 m s
−1
. Moreover, the above hydrodynamic calculation method was also applied to the shortfin mako shark and an extinct giant shark (called megalodon) with known ridge spacings, resulting in the estimated hunting speeds of 10.5 m s
−1
and 5.9 m s
−1
, respectively.
How to Set up and Run a Bad Bugs Bookclub group
Authors: Verran Joanna
Published: August 2024

The Bad Bugs Bookclub is a public engagement initiative that enables scientists (microbiologists) and non-scientists to discuss the role of infectious disease and microorganisms in novels of fiction. The bookclub began in 2009 but since 2020 the meetings have taken place online, enabling international membership and occasional author participation. The bookclub has been shown through peer-reviewed publications to have impact and value to its members. For each book (the number now exceeds 100) a reading guide (questions to provoke discussion) and a meeting report (narrative of the discussion) have been produced. Previously hosted on a website, the reading guides from this rich archive and resource are now presented alongside this paper which provides tips on how to run a similar reading group.
Antimicrobial resistance patterns of isolates from bloodstream infections at Jinja Regional Referral Hospital: A cross-sectional study
Authors: Lwigale Fahad
Published: August 2024

Background
Bloodstream infections are common acute syndromes of variable origin with high chances for extreme health effects including death. This underscores the essence for their quick management to expedite better outcomes. In this study settings, therapy is predominantly empirical using majorly cefriaxone and/or metronindazole. Agents for empirical therapy are liable to antimicrobial resistance and their choice ought to be routinely guided by microbiology laboratory data. This study determined the most frequent aetiologic agents responsible for bloodstream infections, their antimicrobial susceptibility patterns, and infection sources in Eastern-central Uganda.
Patients and methods:
The analysis involved all non-duplicate blood culture reports from 2019 to 2021 using World Health Organization Network (WHONET) 2022 desktop software and Microsoft Excel.
Results:
The 1364 reports showed a diagnostic yield of 114(6.8%) and a 1.5% contamination rate. Over 37% and 13% of infections were hospital-acquired and community-acquired respectively. Most etiologic agents were Gram-positive bacteria dominated by Staphylococcus aureus 39(34.2%). Polymicrobial growth existed in 4(0.3%) cases. S. aureus was mainly resistant to penicillin G(100%) but most susceptible to gentamicin(%S=74.1, 95%C.I:53.4-88.1).  Escherichia coli and unspecified Coliforms together showed high resistance to ampicillin(87.5%) and third-generation cephalosporins(100%). The least resistance was to chloramphenicol and carbapenems.
Conclusion:
As the most frequent explanatory for septicaemia, S. aureus suspected cases in this region could have higher success with gentamicin involved in the empirical therapy combination for their management. The heightened resistance against ceftriaxone requires its limited use.  Microbiology services should be routinely utilized to guide targeted antimicrobial use, monitor blood culture contamination rates and resistance trends to strengthen regional antimicrobial stewardship.
Discovering methylation markers and development of a sense-antisense and dual-MGB probe PCR assay in plasma for colorectal cancer early detection
Authors: Zhao Yanteng , Wang Zhijie , Yu Qiuning , Liu Xin , Liu Xue , Dong Shuling , Lv Xianping , Zhang Tiao , Zhou Dihan , Yang Qiankun
Published: August 2024

Screening for colorectal cancer (CRC) using plasma methylation is challenging due to the low abundance of cell-free DNA (cfDNA). Therefore, the development of signal amplification assays based on appropriate markers is essential to increase sensitivity. In this study, we employed an epigenome-wide approach for de novo identification differentially methylated CpGs (DMCs) common to CRC and adenoma using 17 public datasets. A sense-antisense and dual MGB probe (SADMP) assay was then developed. Subsequently, the biomarkers were validated in 712 plasma samples based on SADMP. A total of 2237 DMCs showed overlap between CRC and adenoma. Of these, 75 were hypomethylated in 30 other non-CRC cancers. Following LASSO regression, WBC validation and primer/probe design evaluation,NTMT1andMAP3K14-AS1were identified as the most informative candidate biomarkers. At preset template concentrations, the SADMP assay forNTMT1orMAP3K14-AS1could reduce the cycle threshold by 1. TheNTMT1andMAP3K14-AS1dual-target SADMP assay demonstrated a sensitivity of 84.8% for CRC (stage I: 75.0%), a sensitivity of 32.0% for advanced adenomas (AA), and a specificity of 91.5% in controls. The dual-target assay showed high performance for CRC early detection in plasma, suggesting that it may serve as a promising noninvasive tool for CRC screening.
Investigating the Role of Neighborhood Socioeconomic Status and Germline Genetics on Prostate Cancer Risk
Authors: Judd Jonathan , Spence Jeffrey P. , Pritchard Jonathan K. , Kachuri Linda , Witte John S.
Published: August 2024

Background

Genetic factors play an important role in prostate cancer (PCa) development with polygenic risk scores (PRS) predicting disease risk across genetic ancestries. However, there are few convincing modifiable factors for PCa and little is known about their potential interaction with genetic risk. We analyzed incident PCa cases (n=6,155) and controls (n=98,257) of European and African ancestry from the UK Biobank (UKB) cohort to evaluate the role of neighborhood socioeconomic status (nSES)–and how it may interact with PRS–on PCa risk.

Methods

We evaluated a multi-ancestry PCa PRS containing 269 genetic variants to understand the association of germline genetics with PCa in UKB. Using the English Indices of Deprivation, a set of validated metrics that quantify lack of resources within geographical areas, we performed logistic regression to investigate the main effects and interactions between nSES deprivation, PCa PRS, and PCa.

Results

The PCa PRS was strongly associated with PCa (OR=2.04; 95%CI=2.00-2.09; P<0.001). Additionally, nSES deprivation indices were inversely associated with PCa: employment (OR=0.91; 95%CI=0.86-0.96; P<0.001), education (OR=0.94; 95%CI=0.83-0.98; P<0.001), health (OR=0.91; 95%CI=0.86-0.96; P<0.001), and income (OR=0.91; 95%CI=0.86-0.96; P<0.001). The PRS effects showed little heterogeneity across nSES deprivation indices, except for the Townsend Index (P=0.03).

Conclusions

We reaffirmed genetics as a risk factor for PCa and identified nSES deprivation domains that influence PCa detection and are potentially correlated with environmental exposures that are a risk factor for PCa. These findings also suggest that nSES and genetic risk factors for PCa act independently.
Requirements for the delivery of an Australian Rapid Access Chest Pain Clinic
Authors: Wilson Annika , Sutton Laura , Nash Rose , Black J. Andrew , Jayasinghe Senali , Sharman James E. , Chapman Niamh
Published: August 2024

Background

Rapid Access Chest Pain Clinics (RACPCs) are outpatient cardiac services designed to promptly assess and manage patients experiencing chest pain. Despite the establishment of 25 RACPCs across Australia, a standardised implementation framework has yet to be developed. This study aimed to identify the core components of successful delivery of an existing RACPC.

Methods

A qualitative process evaluation study was conducted at a RACPC in a metropolitan, tertiary hospital in Tasmania, Australia, from November 2022 to July 2023. Clinical observations and semi-structured interviews were conducted with seven RACPC clinicians. Deductive data analysis was undertaken according to a Context-Mechanism-Outcome framework.

Results

Core components of successful RACPC delivery included: (1) a multidisciplinary team-based approach to care with discreet clinical roles; (2) timely patient review by RACPC clinicians within 30 days of referral; (3) embedded patient education; (4) ongoing clinical team training and education; and (5) a shared understanding of the RACPC service’s identity and purpose. Challenges to RACPC delivery were also identified and included resource constraints and administrative burdens.

Conclusions

Successful delivery of a RACPC model of care relies on a range of interrelated factors. These findings align with the broader theme of ongoing health service evaluation as a driver for continuous quality improvement and care standards within RACPCs. Further research aimed at developing and implementing effective strategies to enhance service delivery is needed to determine a national model of care.
Interrupted Time Series Design and Analyses in Health Policy Assessment
Authors: Jiang Huan , Rehm Jürgen , Tran Alexander , Lange Shannon
Published: August 2024

Interrupted time series design is a quasi-experimental study design commonly used to evaluate the impact of a particular intervention (e.g., a health policy implementation) on a specific outcome. Two of the most often recommended analytical approaches to interrupted time series analysis are autoregressive integrated moving average (ARIMA) and Generalized Additive Models (GAM). We conducted simulation tests to determine the performance differences between ARIMA and GAM methodology across different policy effect sizes, with or without seasonality, and with or without misspecification of policy variables. We found that ARIMA exhibited more consistent results under certain conditions, such as with different policy effect sizes, with or without seasonality, while GAM were more robust when the model was misspecified. Given these findings, the variation between the models underscores the need for careful model selection and validation in health policy studies.
Prevalence of Low Visual Acuity in children from public schools in Northeast of Brazil
Authors: Oliveira Lucas Neves de , Costa Matheus Gomes Reis , Pereira Isadora Oliveira Santiago , Tokumoto Isabela Carolina , Moreira Joao Lucas de Magalhaes Leal , Freitas Matheus Carneiro Leal , Sampaio Clarissa Silva , Oliveira Mateus Neves de , Bessa Junior Jose de , Oliveira Neto Hermelino Lopes de
Published: August 2024

OBJECTIVE

To describe the prevalence of Low Visual Acuity (LVA) in public school students in Feira de Santana (FSA), Bahia (BA).

METHODS

This was an observational, cross-sectional, exploratory study. The sample consisted of schoolchildren from the 2nd to the 4th grade of five public schools in FSA/BA. Data collection was carried out in the schools themselves, with a sociodemographic and clinical questionnaire applied and Visual Acuity (VA) measured using the Snellen “E” optotype chart. LVA was defined as uncorrected VA < 20/25 in at least one eye.

RESULTS

The sample consisted of 358 children, with a median age of 9 [8-10] years, of which 189 (52.9%) were female. 248 (69.3%) individuals had never been to an ophthalmologist. LVA was found in 105 (29.3%) schoolchildren, and of these, 7.6% (8/105) current used glasses. Factors associated with LVA were female gender and white ethnicity. LVA was evidenced in 60 (31.7%) schoolchildren with excessive screen use and in 35 (25.5%) without excessive use (OR 1.35; 95% CI 0.83 - 2.19, p = 0.222), and excessive screen use was associated with visual signs/symptoms such as tearing and eye itching.

CONCLUSION

LVA was observed in approximately 30% of children in public schools in the interior of Bahia, and less than 10% of these current used glasses. Our study reinforces the importance of visual screening of schoolchildren through active search in our region and the creation of strategies to facilitate access to ophthalmological consultations and glasses.
Exploring the role of nicotine and smoking in sleep behaviours: A multivariable Mendelian Randomisation study
Authors: Page Stephanie , Gibson Mark , Munafò Marcus R. , Khouja Jasmine , Richmond Rebecca C.
Published: August 2024

Research has shown bidirectional relationships between smoking and adverse sleep behaviours, including late chronotype and insomnia, but the underlying mechanisms are not understood. One potential driver is nicotine, but its role in sleep is unclear. For this study, we estimated the direct effect of nicotine on six sleep behaviours measured in UK Biobank (chronotype, ease of getting up in the morning, insomnia symptoms, napping, daytime sleepiness and sleep duration). We conducted a Mendelian randomisation (MR) study to explore whether nicotine metabolism has a causal effect on these sleep behaviours. We explored whether the effects could be explained by regular nicotine exposure using genetic proxies of the nicotine metabolite ratio (NMR) and cigarettes per day (CPD) in a multivariable MR design. We found a higher NMR (indicating lower levels of circulating nicotine per cigarette smoked) decreased the likelihood of being an evening person when accounting for CPD in current (β = −0.04, 95%CI −0.06 to −0.02, p < 0.001) and ever smokers (β = −0.03 95%CI −0.04 to −0.01, p = 0.003). A higher NMR also increased the ease of getting up (β = 0.02, 95%CI 0.01 to 0.04, p = 0.015) and likelihood of napping (β = 0.02, 95%CI CI 0.002 to 0.03, p = 0.029) in current smokers. Increased nicotine exposure may directly affect sleep and could underlie relationships between smoking and sleep behaviours identified previously. Sleep could also be impacted in individuals using nicotine delivery systems or using nicotine replacement therapies. Further research is warranted to strengthen this conclusion.
Glucagon-Like Peptide 1 Receptor Agonist Use in Hospital: A Multicentre Observational Study
Authors: Ray Prachi , Moggridge Jason A. , Weisman Alanna , Tadrous Mina , Drucker Daniel J. , Perkins Bruce A. , Fralick Michael
Published: August 2024

Introduction

Glucagon-like peptide 1 receptor agonists (GLP-1RA) are effective medications for type 2 diabetes mellitus (T2DM) and obesity, yet their uptake among patients most likely to benefit has been slow.

Methods

We conducted a cross-sectional analysis of medication exposure in adults hospitalized at 16 hospitals in Ontario, Canada between 2015 and 2022. We estimated the proportion with T2DM, obesity, and cardiovascular disease. We identified the frequency of GLP-1RA use, and conducted multivariable logistic regression to identify factors associated with their use.

Results

Across 1,278,863 hospitalizations, 396,084 (31%) patients had T2DM and approximately 327,844 (26%) had obesity. GLP-1RA use (n=1,274) was low among those with T2DM (0.3%) and those with obesity (0.7%), despite high prevalence of cardiovascular disease (36%). In contrast, use of diabetes medications lacking cardiovascular benefits was high, with 60% (n=236,612) receiving insulin and 14% (n=54,885) receiving sulfonylureas. Apart from T2DM (OR=29.6, 95% CI 23.5, 37.2), characteristics associated with greater odds of receiving GLP-1RA were age 50-70 years (OR=1.71, 95% CI 1.38, 2.11) compared to age < 50 years, hemoglobin A1C > 9% (OR=1.83, 95% CI 1.36, 2.47) compared to < 6.5%, and highest income quintile (OR=1.73, 95% CI 1.45, 2.07) compared to lowest income quintile.

Conclusion

Knowledge translation interventions are needed to address the low adoption of GLP-1RA among hospitalized patients with T2DM and obesity, who are the most likely to benefit.
The gut microbiota-immune-brain axis in a wild vertebrate: dynamic interactions and health impacts
Authors: Pereira Hugo , Hoffamn Joseph I. , Krüger Oliver , Czirják Gábor Á. , Rinaud Tony , Ottensmann Meinolf , Gladow Kai-Philipp , Caspers Barbara A. , Maraci Öncü , Kaiser Sylvia , Chakarov Nayden
Published: August 2024

The gut microbiota-immune-brain axis is a feedback network which influences diverse physiological processes and plays a pivotal role in overall health and well-being. Although research in humans and laboratory mice has shed light into the associations and mechanisms governing this communication network, evidence of such interactions in wild, especially in young animals, is lacking. We therefore investigated these interactions during early development in a population of common buzzards (Buteo buteo) and their effects on individual condition. In a longitudinal study, we used a multi-marker approach to establish potential links between the bacterial and eukaryotic gut microbiota, a panel of immune assays and feather corticosterone measurements as a proxy for long-term stress. Using Bayesian structural equation modelling, we found no support for feedback between gut microbial diversity and immune or stress parameters. However, we did find strong relationships in the feedback network. Immunity was negatively correlated with corticosterone levels, and microbial diversity was positively associated with nestling body condition. Furthermore, corticosterone levels and eukaryotic microbiota diversity decreased with age while immune activity increased. The absence of conclusive support for the microbiota-immune-brain axis in common buzzard nestlings, coupled with the evidence for stress mediated immunosuppression, suggests a dominating role of stress-dominated maturation of the immune system during early development. Confounding factors inherent to wild systems and developing animals might override associations known from adult laboratory model subjects. The positive association between microbial diversity and body condition indicates the potential health benefits of possessing a diverse and stable microbiota.
High-Efficiency Capture and Proteomic Analysis of Plasma-Derived Extracellular Vesicles through Affinity Purification
Authors: Zhang Gui-Yuan , Ma Cheng-Xiao , Ma Le , Wei Dong , Wu Ya-Nan , Li Ying , Xu Zhe-Hui , Liu Yu-Feng , Cai Yu-Han , Yu Evan Yi-Wen , Zhu Ye-Fei , Zhang Hao
Published: August 2024

Plasma-derived extracellular vesicles (EVs) are promising sources of biomarkers. It is still a challenge to isolate EVs from a small amount of human plasma for downstream proteomic analysis. The separation process is hindered by contamination with high-abundance blood proteins and lipoprotein particles, which adversely impact proteomic analyses. Moreover, although EVs immune-separation via magnetic beads often integrates with flow sorting and western blotting (WB), it lacks compatibility with nanoparticle tracking analysis (NTA) and proteomic analysis. To address these issues, we have developed a functional affinity magnetic bead, EVlent (ExtracellularVesicles isoLatedEfficiently,Naturally, andTotally), enabling the rapid and efficient separation of EVs from plasma. By optimizing the quantities of magnetic beads and plasma used, we characterized the isolated EVs through WB, NTA, and transmission electron microscopy (TEM), showing a successfully separation of EVs from plasma. Proteomic analysis of these EVs identified over 2,000 proteins and 15,000 peptides from just 100 μL of plasma, and nearly 1,000 proteins from trace samples as small as 5 μL. Additionally, this isolation method significantly reduced contaminants, including plasma proteins and lipoproteins, compared to ultracentrifugation. Finally, we applied this strategy to plasma samples of healthy individuals and those with Parkinson’s disease, identifying four potential biomarkers that provide a promising guidance for clinical diagnosis.
An eye-tracking study of visual attention in chimpanzees and bonobos when viewing different tool-using techniques
Authors: Piao Yige , Brooks James , Yamamoto Shinya
Published: August 2024

Chimpanzees and bonobos are excellent tool users and can socially learn various skills. Previous studies on social learning mainly measure success/failure in acquiring new techniques, with less direct measurement of proximate mechanisms like visual attention during the process. This study investigates how apes observe tool-using demonstrations through eye-tracking. After checking initial techniques, six chimpanzees and six bonobos were shown video demonstrations of human demonstrators using a tube to dip (low-efficiency) or suck (high-efficiency) juice, and then tried the task themselves. Attention to each video was compared to participants’ knowledge. Although no individuals acquired the high-efficiency technique through video demonstrations, eye-tracking results revealed attentional differences between individuals familiar with different techniques. Compared with individuals already familiar with both techniques, individuals knowing only the dipping technique showed less attention to the unfamiliar sucking technique. This result indicates that apes may not attend much to what they do not know well, which aligns with reported interplay of action observation and understanding. Attentional patterns to specific areas was similar between species, though there was a tendency towards more attention to faces in bonobos and food in chimpanzees. This study emphasizes the importance of detailed investigation into social learning process using eye-tracking.
EPInformer: A Scalable Deep Learning Framework for Gene Expression Prediction by Integrating Promoter-enhancer Sequences with Multimodal Epigenomic Data
Authors: Lin Jiecong , Luo Ruibang , Pinello Luca
Published: August 2024

Transcriptional regulation, critical for cellular differentiation and adaptation to environmental changes, involves coordinated interactions among DNA sequences, regulatory proteins, and chromatin architecture. Despite extensive data from consortia like ENCODE, understanding the dynamics of cis-regulatory elements (CREs) in gene expression remains challenging. Deep learning is a powerful tool for learning gene expression and epigenomic signals from DNA sequences, exhibiting superior performance compared to conventional machine learning approaches. However, even the most advanced deep learning-based methods may fall short in capturing the regulatory effects of distal elements such as enhancers, limiting their predictive accuracy. In addition, these methods may require significant resources to train or to adapt to newly generated data. To address these challenges, we present EPInformer, a scalable deep-learning framework for predicting gene expression by integrating promoter-enhancer interactions with their sequences, epigenomic signals, and chromatin contacts. Our model outperforms existing gene expression prediction models in rigorous cross-chromosome validation, accurately recapitulates enhancer-gene interactions validated by CRISPR perturbation experiments, and identifies crucial transcription factor motifs within regulatory sequences. EPInformer is available as open-source software at https://github.com/pinellolab/EPInformer.
MinD proteins regulate CetZ1 localisation inHaloferax volcanii
Authors: Brown Hannah J. , Duggin Iain G.
Published: August 2024

CetZ proteins are archaea-specific homologues of the cytoskeletal proteins FtsZ and tubulin. In the pleomorphic archaeonHaloferax volcanii, CetZ1 contributes to the development of rod shape and motility, and has been implicated in the proper assembly and positioning of the archaellum and chemotaxis motility proteins. CetZ1 shows complex subcellular localization, including irregular midcell structures and filaments along the long axis of developing rods and patches at the cell poles of the motile rod cell type. The polar localizations of archaellum and chemotaxis proteins are also influenced by MinD4, the only previously characterized archaeal member of the MinD family of ATPases, which are better known for their roles in the positioning of the division ring in bacteria. UsingminDmutant strains and CetZ1 subcellular localization studies, we show here that a secondminDhomolog,minD2, has a strong influence on motility and the localization of CetZ1. Knockout of theminD2gene altered the distribution of a fluorescent CetZ1-mTq2 fusion protein in a broad midcell zone and along the edges of rod cells, and inhibited the localization of CetZ1-mTq2 at the cell poles. MinD4 had a similar but weaker influence on motility and CetZ1-mTq2 localization. The MinD2/4 mutant strains formed rod cell shapes like the wildtype at an early log stage of growth. Our results are consistent with distinct roles for CetZ1 in rod shape formation and at the poles of mature rods, that are positioned through the action of the MinD proteins and contribute to the development of swimming motility in multiple ways. They represent the first report of MinD proteins controlling the positioning of tubulin superfamily proteins in archaea.
TowardDe NovoProtein Design from Natural Language
Authors: Dai Fengyuan , Fan Yuliang , Su Jin , Wang Chentong , Han Chenchen , Zhou Xibin , Liu Jianming , Qian Hui , Wang Shunzhi , Zeng Anping , Wang Yajie , Yuan Fajie
Published: August 2024

De novoprotein design represents a fundamental pursuit in protein engineering, yet current deep learning approaches remain constrained by their narrow design scope. Here we present Pinal, a large-scale frontier framework comprising 16 billion parameters and trained on 1.7 billion protein-text pairs, that bridges natural language understanding with protein design space, translating human design intent into novel protein sequences. Instead of a straightforward end-to-end text-to-sequence generation, Pinal implements a two-stage process: first generating protein structures based on language instructions, then designing sequences conditioned on both the generated structure and the language input. This strategy effectively constrains the search space by operating in the more tractable structural domain. Through comprehensive experiments, we demonstrate that Pinal achieves superior performance compared to existing approaches, including the concurrent work ESM3, while exhibiting robust generalization to novel protein structures beyond the PDB database. The online demo is available athttp://www.denovo-pinal.com/.
CRISPR-RNA binding drives structural ordering that primes Cas7-11 for target cleavage
Authors: Lin Calvin P. , Li Harry , Brogan Daniel J. , Wang Tianqi , Akbari Omar S. , Komives Elizabeth A.
Published: August 2024

Type III-E CRISPR-Cas effectors, referred to as Cas7-11 of gRAMPs, are single proteins that cleave target RNAs without nonspecific collateral cleavage, opening new possibilities for RNA editing. Here, biochemical assays combined with amide hydrogen-deuterium exchange (HDX-MS) experiments provide a first glimpse of the conformational dynamics of apo Cas7-11. HDX-MS revealed the backbone comprising the four Cas7 zinc-binding RRM folds are well-folded but insertion sequences are highly dynamic and fold upon binding crRNA. The crRNA causes folding of disordered catalytic loops and β-hairpins, stronger interactions at domain-domain interfaces, and folding of the Cas7.1 processing site. Target RNA binding causes only minor ordering around the catalytic loops of Cas7.2 and Cas7.3. We show that Cas7-11 cannot independently process the CRISPR array and that binding of partially processed crRNA induces multiple states in Cas7-11 and reduces target RNA cleavage. The insertion domain shows the most ordering upon binding of mature crRNA. Finally, we show a crRNA-induced conformational change in one of the TPR-CHAT binding sites providing an explanation for why crRNA binding facilitates TPR-CHAT binding. The results provide the first glimpse of the apo state of Cas7-11 and reveal how its structure and function are regulated by crRNA binding.
CTA and SWGO can discover Higgsino dark matter annihilation
Authors: Rodd Nicholas L. , Safdi Benjamin R. , Xu Weishuang Linda
Published: August 2024

Thermal Higgsino dark matter (DM), with a mass near 1.1 TeV, is one of the most well-motivated and untested DM candidates. Leveraging recent hydrodynamic cosmological simulations that give DM density profiles in Milky Way analog galaxies we show that the linelike gamma-ray signal predicted from Higgsino annihilation in the Galactic Center could be detected at high significance with the upcoming Cherenkov Telescope Array (CTA) and Southern Wide-field Gamma-ray Observatory (SWGO) for all but the most pessimistic DM profiles. We perform the most sensitive search to-date for the linelike signal using 15 years of data from the Fermi Large Area Telescope, coming within an order one factor of the necessary sensitivity to detect the Higgsino for some Milky Way analog DM density profiles. We show that H.E.S.S. has subleading sensitivity relative to Fermi for the Higgsino at present. In contrast, we analyze H.E.S.S. inner Galaxy data for the thermal wino model with a mass near 2.8 TeV; we find no evidence for a DM signal and exclude the wino by over a factor of two in cross section for all DM profiles considered. In the process, we identify and attempt to correct what appears to be an inconsistency in previous H.E.S.S. inner Galaxy analyses for DM annihilation related to the analysis effective area, which may weaken the DM cross-section sensitivity claimed in those works by around an order of magnitude.

Published by the American Physical Society
2024
Energy flow of
λ
in Hořava-Lifshitz cosmology
Authors: Czuchry Ewa , Nilsson Nils A.
Published: August 2024

Hořava-Lifshitz gravity has been proposed as a renormalizable and ghost-free quantum gravity model candidate with an anisotropic UV-scaling between space and time. We present here a cosmological background analysis of two different formulations of the theory, with particular focus on the running of the parameter λ. Using a large dataset consisting of cosmic microwave background data from , Pantheon+supernovae catalog, SH0ES Cepheid variable stars, baryon acoustic oscillations (BAO), cosmic chronometers, and gamma-ray bursts (GRB), we arrive at new bounds on the cosmological parameters, in particular λ, which runs logarithmically with energy and describes deviation from general relativity, which corresponds to λ=1 For the detailed balance scenario we arrive at the bound λ=1.0406±0.0023, and for beyond detailed balance the limit reads λ=1.0064±0.0002. We also study the influence of different datasets and priors, and we find that removing low-redshift data generally moves λ closer toward UV values, while simultaneously widening the error bars. In the detailed balance scenario, this effect is more noticeable, and without prior λ≥1 it takes on values that are significantly below unity.

Published by the American Physical Society
2024
Quantifying local lattice distortions in refractory high-entropy alloys
Authors: Hu Yao , Owen Lewis R. , Playford Helen Y. , Edgren Aina , Guo Sheng , Colliander Magnus Hörnqvist
Published: August 2024

Severe local lattice distortions (LLDs), originating from the size mismatch among atoms, have been proposed as one of the key mechanisms responsible for the excellent mechanical properties of bcc-structured high-entropy alloys (HEAs). They have also been connected to phase stability, as well as physical properties such as electrical conductivity. Experimental measurements of LLDs are, however, difficult and often ambiguous. Analysis of total scattering data in real space has been proposed to provide a uniquely suitable probe of LLDs, but its widespread application and validation are still limited. We conduct a thorough study of LLD measurements in refractory high-entropy alloys (RHEAs) using small-box pair distribution function (PDF) analysis. We start by reexamining existing literature data using a recently proposed coherent theoretical framework to demonstrate that LLDs in RHEAs can indeed be considered as severe and can be reliably measured even in the absence of known thermal components. We perform total scattering experiments of a typical RHEA (HfNbTaTiZr) using both x-rays and neutrons, and show that real-space PDF analysis of data from different types of radiation gives consistent values of LLDs. The results are also in good agreement with the values derived from reciprocal-space data. Finally, through simulation and analysis of theoretical two-phase PDFs, we demonstrate that the effect of the chemical segregation in the investigated RHEA on the measured LLDs is limited when dealing with comparatively large LLDs. The results show that PDF analysis using small-box modeling provides a fast and reliable tool for measuring LLDs in RHEAs, which makes it ideal for analysis of large data sets from time-resolved measurements.

Published by the American Physical Society
2024
Time-domain interferometry of electron weak localization through terahertz nonlinear response
Authors: Li Zi-Long , Li Xiao-Hui , Wan Yuan
Published: August 2024

We study theoretically the nonlinear optical response of disordered electrons in the regime of weak (anti)localization. Our analytical and numerical calculations reveal that in orthogonal/symplectic class systems, two consecutive, phase-coherent optical pulses generate an electric current echo that appears after the second pulse, and at a time equal to the pulse delay time. The current echo reflects the quantum interference between a self-intersecting electron path and its time-reversal partner, and, therefore, provides a time-domain interferometry of weak (anti)localization. Our results can be potentially tested on disordered metal films by using terahertz two-dimensional coherent spectroscopy or ultrafast transport measurements.

Published by the American Physical Society
2024
Fault-Tolerant Quantum Computation by Hybrid Qubits with Bosonic Cat Code and Single Photons
Authors: Lee Jaehak , Kang Nuri , Lee Seok-Hyung , Jeong Hyunseok , Jiang Liang , Lee Seung-Woo
Published: August 2024

Hybridizing different degrees of freedom or physical platforms potentially offers various advantages in building scalable quantum architectures. Here, we introduce a fault-tolerant hybrid quantum computation by building on the advantages of both discrete-variable (DV) and continuous-variable (CV) systems. In particular, we define a CV-DV hybrid qubit with a bosonic cat code and a single photon, which is implementable in current photonic platforms. Due to the cat code encoded in the CV part, the predominant loss errors are readily correctable without multiqubit encoding, while the logical basis is inherently orthogonal due to the DV part. We design fault-tolerant architectures by concatenating hybrid qubits and an outer DV quantum error-correction code such as a topological code, exploring their potential merit in developing scalable quantum computation. We demonstrate by numerical simulations that our scheme is at least an order of magnitude more resource efficient compared to all previous proposals in photonic platforms, allowing us to achieve a record-high loss threshold among existing CV and hybrid approaches. We discuss the realization of our approach not only in all-photonic platforms but also in other hybrid platforms including superconducting and trapped-ion systems, which allows us to find various efficient routes toward fault-tolerant quantum computing.

Published by the American Physical Society
2024