bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled Mesoscopic Growth of Polymeric Fibers Using Liquid Crystal Template
Authors: Han Jeong Yeon , Kim Kyuhwan , Lee Changjae , Yoon Dong Ki
Published: July 2023

Orientation‐controlled polymeric fiber is one of the most exciting research topics to rationalize the multifunctionality for various applications. In order to realize this goal, the growth of polymeric fibers should be controlled using various techniques like extrusion, molding, drawing, and self‐assembly. Among the various candidates to fabricate the orientation‐controlled polymeric fibers, the template‐assisted assembly guided by a liquid crystal (LC) matrix is the most promising because the template can be manipulated easily with various methods like surface anchoring, rubbing, geometric confinement, and electric field. This review introduces the recent progress toward the directed growth of polymeric fibers using the LC template. Three representative LC‐templated polymerization techniques to fabricate fibers include chemical or physical polymerization from the monomers mixed in LC matrix, patterned fibers formed from LC‐templated reactive mesogens, and orientation‐controlled nanofibers by infiltrating vaporized monomers between LC molecules. The orientation‐controlled polymeric fibers will be used in electro‐optical switching tools, tunable hydrophilic or hydrophobic surfaces, and control of phosphorescence, which can open a way to design, fabricate, and modulate nano‐ to micron‐scale fibers with various functions on demand.
A general decay criterion for a viscoelastic equation with nonlinear distributed delay and damping effects
Authors: Feng Baowei , Park Sun‐Hye
Published: July 2023

In this paper, a viscoelastic equation with nonlinear distributed delay and nonlinear damping effects is considered. Under very general conditions that do not involve differential inequalities for the kernel function, a general decay criterion is established through the perturbed energy method and properties of convex functions. We extend the stability result of wave equation with linear delay and linear damping to the nonlinear case.
The association between perfectionism and academic procrastination among undergraduate nursing students: The role of self‐efficacy and resilience
Authors: Huang Haitao , Ding Yueming , Liang Yipei , Wan Xiao , Peng Qianwen , Zhang Yiming , Kong Deren , Chen Chaoran
Published: July 2023

Aims

This study aimed to investigate the associations between perfectionism and undergraduate nursing students' academic procrastination, the mediating effects of self‐efficacy and the moderating role of resilience.

Design

A cross‐sectional survey.

Methods

The survey was conducted from March to May 2022 with a sample of 587 undergraduate nursing students in two undergraduate universities in China. A descriptive statistical approach, Pearson's correlation analysis and the Hayes' PROCESS Macro model 4 and 14 were used to analyse the available data.

Results

Adaptive perfectionism and maladaptive perfectionism negatively and positively predicted academic procrastination in nursing undergraduates, respectively. Self‐efficacy played a partially mediating role in the association between adaptive perfectionism and academic procrastination. Furthermore, resilience played a moderating role in the association between adaptive perfectionism and academic procrastination.

Conclusions

Maladaptive perfectionism and low levels of resilience and self‐efficacy may increase the risk of academic procrastination among nursing undergraduates. Nursing educators can take measures to decrease the risk of academic procrastination among nursing undergraduate students by guiding them to cultivate adaptive perfectionism tendencies and improve their self‐efficacy and resilience.

Impact

The findings of this study can be used to develop targeted coping and prevention measures for nursing educators to reduce the incidence of academic procrastination among nursing undergraduates.

Patient or Public Contribution

Five hundred eighty‐seven undergraduate nursing students from two undergraduate universities participated in the study and responded to questions on perfectionism and academic procrastination, etc.
Sex‐specific incidence of hepatitis B virus flares among Bcr‐Abl tyrosine kinase inhibitor users in Taiwan
Authors: Wang Ling‐Yi , Chu Sung‐Chao , Chang I‐Yun , Chan K. Arnold
Published: July 2023

Background

The use of Bcr‐Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr‐Abl TKI users, to estimate sex‐specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr‐Abl TKI.

Methods

Bcr‐Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case–control analysis was used to evaluate the cumulative effect of Bcr‐Abl TKI use on HBV flare.

Results

Among 415 patients with chronic HBV infection treated with Bcr‐Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr‐Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person‐years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr‐Abl TKI on HBV flare was not observed.

Conclusion

Approximately 10% of HBV carriers who used Bcr‐Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.
Real‐world evidence of outcomes of oligometastatic hormone‐sensitive prostate cancer patients treated with metastasis‐directed therapy
Authors: Wenzel Mike , Garcia Cristina C. , Hoeh Benedikt , Jorias Charlotte , Humke Clara , Koll Florestan , Tselis Nikolaos , Rödel Claus , Graefen Markus , Tilki Derya , Chun Felix K. H. , Mandel Philipp
Published: July 2023

Objective

To investigate characteristics and outcomes of oligometastatic hormone‐sensitive prostate cancer (mHSPC) patients undergoing metastases‐directed therapy (MDT) with external beam radiation therapy (EBRT).

Materials and Methods

We relied on an institutional tertiary‐care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration‐resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as ≤3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20–27 Gy).

Results

Overall, 37 patients treated with EBRT as MDT were identified. The median follow‐up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo‐metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high‐grade adverse events were recorded during MDT.

Conclusion

Our real‐world data suggest that MDT represents a safe treatment option for well‐selected oligometastatic mHSPC patients.
Trace Tungsten Microalloying PtCuCo Medium Entropy Alloys: Substructure Reconstruction‐Triggered High‐Performance for PEMFC
Authors: Chen Zhiming , Wang Qiheng , Jin Chun , Liu Jingjun
Published: July 2023

Refractory metals (W, Nb, or Mo) microalloying Pt‐based alloys with unprecedented performance may serve as advanced electrocatalysts for proton exchange membrane fuel cells (PEMFCs). These alloys are endowed with unique stabilizing substructures or lattice defects through the microalloying effect. Herein, trace W microalloying PtCuCo medium entropy alloys (W‐PtCuCo) are reported via a stepwise synthesis strategy, starting with home‐made Cu nanowires as sacrificial templates by anhydrous solid‐phase milling route, and then followed by galvanic replacement‐assisted solvothermal in ethylene glycol (EG). In PEMFC tests, the obtained W‐PtCuCo exhibits an ultrahigh peak power density and mass power density (relative to cathode) reaching 2.09 W cm−2 and 20.9 W mgPt−1, respectively. During the accelerated degradation test (ADT), the mass activity just lost only 3% after 30 k cycles, much better than the above benchmark catalyst. The microalloying‐dependent performances shall be attributed to the presence of abundant stepped surfaces, twisted edges, and other lattice defects terminated by W via substructure reconstruction that indeed alters the electronic structure and strain level of the alloys. This work first provides an atomic‐level insight into the microalloying‐dependent electrocatalytic performance of Pt‐based alloys, which is of great significance for developing next‐generation efficient catalysts for PEMFC.
Innovative suture technique for robotic hepaticojejunostomy: double-layer interrupted sutures
Authors: Takagi Kosei , Umeda Yuzo , Yoshida Ryuichi , Fuji Tomokazu , Yasui Kazuya , Yagi Takahito , Fujiwara Toshiyoshi
Published: July 2023

Purpose

Biliary reconstruction remains a technically demanding and complicated procedure in minimally invasive hepatopancreatobiliary surgeries. No optimal hepaticojejunostomy (HJ) technique has been demonstrated to be superior for preventing biliary complications. This study aimed to investigate the feasibility of our unique technique of posterior double-layer interrupted sutures in robotic HJ.

Methods

We performed a retrospective analysis of a prospectively collected database. Forty-two patients who underwent robotic pancreatoduodenectomy using this technique between September 2020 and November 2022 at our center were reviewed. In the posterior double-layer interrupted technique, sutures were placed to bite the bile duct, posterior seromuscular layer of the jejunum, and full thickness of the jejunum.

Results

The median operative time was 410 (interquartile range [IQR], 388–478) min, and the median HJ time was 30 (IQR, 28–39) min. The median bile duct diameter was 7 (IQR, 6–10) mm. Of the 42 patients, one patient (2.4%) had grade B bile leakage. During the median follow-up of 12.6 months, one patient (2.4%) with bile leakage developed anastomotic stenosis. Perioperative mortality was not observed. A surgical video showing the posterior double-layer interrupted sutures in the robotic HJ is included.

Conclusions

Posterior double-layer interrupted sutures in robotic HJ provided a simple and feasible method for biliary reconstruction with a low risk of biliary complications.
Meta-analysis of second language research with complex research designs
Authors: Norouzian Reza , Bui Gavin
Published: July 2023

Meta-analyses play an instrumental role in informing second language (L2) theory and practice. However, current (i.e., classic) approaches to meta-analysis are limited in their ability to do so because they often fail to capture the complexity inherent in primary studies’ research designs. As we argue in this article, when complex L2 studies are represented by simplistic meta-analyses, the latter cannot reach its potential to contribute to the development of cumulative knowledge. To mitigate this issue, we first discuss the fundamental problems of the classic approaches to meta-analysis of complex L2 research. Second, we introduce an alternative meta-analytic framework that will address those problems. Third, we apply the meta-analytic framework discussed to a complex L2 domain. Fourth, we offer free software to facilitate the conduct of the alternative meta-analytic approach described. Finally, we discuss the implications of this alternative framework for making evidence-based recommendations to the relevant stakeholders.
High‐Resolution Mantle Flow Models Reveal Importance of Plate Boundary Geometry and Slab Pull Forces on Generating Tectonic Plate Motions
Authors: Saxena Arushi , Dannberg Juliane , Gassmöller Rene , Fraters Menno , Heister Timo , Styron Richard
Published: July 2023

Mantle convection models based on geophysical constraints have provided us with a basic understanding of the forces driving and resisting plate motions on Earth. However, existing studies computing the balance of underlying forces are contradicting, and the impact of plate boundary geometry on surface deformation remains unknown. We address these issues by developing global instantaneous 3‐D mantle convection models with a heterogeneous density and viscosity distribution and weak plate boundaries prescribed using different geometries. We find that the plate boundary geometry of the Global Earthquake Model (GEM, Pagani et al., 2018, https://doi.org/10.1177/8755293020931866), featuring open plate boundaries with discrete lithospheric‐depth weak zones in the oceans and distributed crustal faults within continents, achieves the best fit to the observed GPS data with a directional correlation of 95.1% and a global point‐wise velocity residual of 1.87 cm/year. A good fit also requires plate boundaries being 3 to 4 orders of magnitude weaker than the surrounding lithosphere and low asthenospheric viscosities between 5 × 1017 and 5 × 1018 Pa s. Models without asthenospheric and lower mantle heterogeneities retain on average 30% and 70% of the plate speeds, respectively. Our results show that Earth's plate boundaries are not uniform and better described by more discrete plate boundaries within the oceans and distributed faults within continents. Furthermore, they emphasize the impact of plate boundary geometry on the direction and speed of plate motions and reaffirm the importance of slab pull in the uppermost mantle as a major plate driving force.
Risk factors in acquiring multidrug-resistant Klebsiella pneumoniae infections in a hospital setting in Saudi Arabia
Authors: Ibrahim Mutasim E.
Published: July 2023

Over the last decades, the prevalence of multidrug-resistant (MDR) Klebsiella pneumoniae in clinical settings has increased progressively. This study determined the prevalence and risk factors associated with MDR K. pneumoniae infection among hospitalized patients in a referral hospital located in southern Saudi Arabia. A prospective cross-sectional study was conducted in King Abdullah Hospital from April 2021 to March 2022. K. pneumoniae (n = 211) bacteria were recovered from clinical samples of adult patients and examined for antibiotic susceptibility. Univariate and multivariate logistic regressions were applied to determine the factors associated with MDR K. pneumoniae infection. MDR K. pneumoniae strains was found in 66.8% (142/211) of the patients. Among MDR K. pneumoniae, the highest resistance rate was determined for ampicillin (100%), cefuroxime (97.9%), ceftriaxone (94.3%), and aztreonam (92.2%). The lowest resistance rate was determined for colistin (16.3%), and tigecycline (6.4%). Further, the patients’ gender, age group, intensive care unit (ICU) admission, invasive medical devices, and chronic illness were found to be significantly associated with MDR K. pneumoniae infection. The independent risk factors associated with MDR K. pneumoniae infection were the male gender (adjusted odds ratio [AOR] 2.107, 95% confidence interval CI 1.125‒3.945, p = 0.02), patients ≥ 65 years of age (AOR 1.905; CI 1.003‒3.616, p = 0.049), ICU admission (AOR 1.963; CI 1.033‒3.732, p = 0.04), diabetes (AOR 1.95; CI 1.02‒3.727, p = 0.043) and chronic obstructive pulmonary disease (AOR 7.172; CI 1.557‒33.032, p = 0.011). The study offered a vision of MDR K. pneumoniae infection in our setting and provided essential indications for further studies that may lead to the prevention and reduction of MDR bacteria.
Status of Patient Safety Culture in Community Pharmacy Settings: A Systematic Review
Authors: Kwon Kyoung-Eun , Nam Dal Ri , Lee Mo-Se , Kim Su-Jin , Lee Jae-Eun , Jung Sun-Young
Published: July 2023

Objectives

This systematic aimed to understand the global status using the results of survey studies based on the Community Pharmacy Survey on Patient Safety Culture and set the directions of development in terms of the patient safety culture of community pharmacies.

Methods

Electronic searches were performed in EMBASE, MEDLINE, PubMed, and CINAHL databases by using the words “patient safety,” “culture,” and “community pharmacy” with synonyms or associated words in the original English language research articles published between January 1, 2012, and March 2, 2023. This systematic review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Eleven surveys from 10 countries were selected. Five studies were conducted on pharmacists, whereas 6 studies were carried out on all pharmacy staff members such as pharmacists, technicians, clerks, and pharmacy students on apprenticeship. There was a considerable variation in the positive response rates across the dimensions of all the surveys. The highest positive response score was demonstrated for “teamwork” and “patient counseling,” whereas the “staffing, work pressure, and pace” dimension was essential for improving patient safety culture in community pharmacy settings. For overall rating of the pharmacy on patient safety, 84.8% of pharmacy staff members gave good, very good, or excellent as their responses.

Conclusions

Despite the differences among studies, findings of this study are expected to be used as valuable evidence to develop patient safety improvement strategies after reflecting each country’s health care setting or community pharmacy practice. Furthermore, the results would offer meaningful assistance to achieve the goals of global campaigns such as the World Health Organization Patient Safety Challenge.
Socioeconomic and Demographic Barriers Associated with Delays in Pancreatic Cancer Germline Genetic Testing
Authors: Zou Xianghui , Sidiqi Baho , Patruni Sunita , Rezak Leora , Hollweg Christopher , Kauff Noah , King Daniel
Published: July 2023

Background

Germline genetic testing is recommended for patients with pancreatic ductal adenocarcinoma (PDAC) and pre-diagnostic testing is offered to patients with a significant family history. However, only 41% of patients in our institution obtained genetic testing. We identified associations between patient social profiles and delays in obtaining germline genetic testing from New York’s largest healthcare system.

Methods

Patients with PDAC were identified using our EMR between Mar 2016 and Feb 2022 with an IRB-approved protocol. Median income was extrapolated using zip code. Date of diagnosis (DOD) was recorded as the date of biopsy. Delays of testing was calculated as the difference between DOD and the date of germline test. Social work needs and insurance were captured by EMR review of social work notes.

Results

329 patients with PDAC were identified, with 135 (41%) having reports found. Availability of germline testing did not vary by median income. Pearson analysis between income and delays showed a negative correlation (r=-0.258, p=0.0025). Patients who received social security and were unemployed/disabled had significant delays (167d) in testing compared to patients receiving social security (13d) and retired or patients receiving salaries (30d).

African Americans and Hispanics, classified as underserved minority, had significant delays in testing (66d) compared to not underserved patients (22.5d, p=0.021). In addition, African American patients had significant delays in testing (66d) compared to White patients (20d, p=0.0076).

Patients with social work needs had significant delays in testing (104d) compared to patients without SW needs (20.5d, p=0.0002). Of the twelve patients who required SW, six required home care, three required transportation, and two required financial assistance. In addition, patients with Medicare and supplementary insurances had significant decreases in delays (10d) of germline testing compared with patients with Medicare alone (32d, p=0.0077), Medicaid (57d, p=0.020), or commercial insurances (21d, p=0.021).

We identified 12 patients who had germline mutation reports before PDAC diagnosis. For patients with pre-diagnostic testing, 5 had Medicare with supplementary insurances. For the rest of patients with germline testing after the diagnosis of PDAC, 10 had supplementary insurances (p=0.0043).

Conclusion

The analysis of our 329-patient cohort showed a striking and concerning negative correlation between patient income and delays in germline testing. Under-represented minority patients had significant delays in germline testing and did not obtain any pre-diagnostic testing. Social work needs and insurance may be barriers as well. Interprofessional collaborations may be required to prompt germline testing.
Microenvironment of metastasis reveals key predictors of PD-1 blockade response in renal cell carcinoma
Authors: Jeanneret Florian , Bazelle Pauline , Schoch Sarah , Pillet Catherine , Um In Hwa , Bouzit Assilah , Evrard Bertrand , Seffar Evan , Chalmel Frédéric , Alfaro Javier A , Pesquita Catia , Zanzotto Fabio Massimo , Stares Mark , Symeonides Stefan N , Laird Alexander , Long Jean-Alexandre , Descotes Jean Luc , Pflieger Delphine , Harrison David J , Filhol Odile , Axelson Håkan , Battail Christophe
Published: July 2023

Immune checkpoint blockade (ICB) therapies have improved the overall survival (OS) of many patients with advanced cancers. However, the response rate to ICB varies widely among patients, exposing non-responders to potentially severe immune-related adverse events. The discovery of new biomarkers to identify patients responding to ICB is now a critical need in the clinic. We therefore investigated the tumor microenvironment (TME) of advanced clear cell renal cell carcinoma (ccRCC) samples from primary and metastatic sites to identify molecular and cellular markers of response to ICB. We revealed a significant discrepancy in treatment response between subgroups based on cell fractions inferred from metastatic sites. One of the subgroups was enriched in non-responders and harbored a lower fraction of CD8+ T cells and plasma cells, as well as a decreased expression of immunoglobulin genes. In addition, we developed the Tumor-Immunity Differential (TID) score which combines features from tumor cells and the TME to accurately predict response to anti-PD-1 immunotherapy (AUC-ROC=0.88, log-rank tests for PFS P < 0.0001, OS P = 0.01). Finally, we also defined TID-related genes (YWHAE,CXCR6andBTF3), among whichYWHAEwas validated as a robust predictive marker of ICB response in independent cohorts of pre- or on-treatment biopsies of melanoma and lung cancers. Overall, these results provide a rationale to further explore variations in the cell composition of metastatic sites, and underlying gene signatures, to predict patient response to ICB treatments.

One Sentence Summary

Tumor microenvironment balance of metastasis and associated genes are key predictors of immunotherapy patient response in kidney cancer.
Effect of sample preprocessing and extraction methods on the physical and molecular profiles of extracellular vesicles
Authors: Alexandre Lucile , Shen Molly L. , de Araujo Lorenna Oliveira Fernandes , Renault Johan , DeCorwin-Martin Philippe , Martel Rosalie , Ng Andy , Juncker David
Published: July 2023

Extracellular vesicles (EVs) are nanometric lipid vesicles that shuttle cargo between cells. Their analysis could shed light on health and disease conditions, but EVs must first be preserved, extracted and often pre-concentrated. Here we firstly compare plasma preservation agents, and secondly, using both plasma and cell supernatant, four EV-extraction methods including (i) ultracen-trifugation (UC), (ii) size exclusion chromatography (SEC), (iii) centrifugal filtration (LoDF), and (iv) accousto-sorting (AcS). We benchmarked them by characterizing integrity, size-distribution, concentration, purity and the expression profiles for nine proteins of EVs, as well as overall throughput, time-to-result and cost. We found that the difference between EDTA and citrate anticoagulants vary with the extraction method. In our hands, ultracentrifugation produced a high yield of EVs with low contamination; SEC is low-cost, fast, and easy to implement, but the purity of EVs is lower; LoDF and AcS are both compatible with process automation, small volume requirement, and rapid processing times. When using plasma, the LoDF was susceptible to clogging and sample contamination, while the AcS featured high purity but a lower yield of extraction. Analysis of protein profiles suggest that extraction methods extract different sub-population of EVs. Our study highlights the strength and weakness of sample preprocessing methods, and the variability in concentration, purity, and EV expression profiles of the extracted EVs. Pre-analytical parameters such as collection or pre-processing protocols must be considered as part of the entire process in order to address EV diversity and their use as clinically actionable indicators.
Optical Control of G-Actin with a Photoswitchable Latrunculin
Authors: Vepřek Nynke A. , Cooper Madeline H. , Laprell Laura , Yang Emily Jie-Ning , Folkerts Sander , Bao Ruiyang , Oertner Thomas G. , Pon Liza A. , Zuchero J. Bradley , Trauner Dirk H.
Published: July 2023

Actin is one of the most abundant proteins in eukaryotic cells and a key component of the cytoskeleton. A range of small molecules have emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin to stabilize or destabilize filaments or prevent their formation and growth, respectively. Amongst these, the latrunculins, which bind to G-actin and affect polymerization, are widely used as tools to investigate actin-dependent cellular processes. Here, we report a photoswitchable version of latrunculin, termed opto-latrunculin (OptoLat), which binds to G-actin in a light-dependent fashion and affords optical control over actin polymerization.OptoLatcan be activated with 390 – 490 nm pulsed light and rapidly relaxes to the inactive form in the dark. Light activatedOptoLatinduced depolymerization of F-actin networks in oligodendrocytes and budding yeast, as shown by fluorescence microscopy. Subcellular control of actin dynamics in human cancer cell lines was demonstrated by live cell imaging. Light-activatedOptoLatalso reduced microglia surveillance in organotypic mouse brain slices while ramification was not affected. Incubation in the dark did not alter the structural and functional integrity of microglia. Together, our data demonstrate thatOptoLatis a useful tool for the elucidation of G-actin dependent dynamic processes in cells and tissues.
Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins
Authors: Vakirlis Nikolaos , Kupczok Anne
Published: July 2023

Species-specific genes, also known as orphans, are ubiquitous across life’s domains. In prokaryotes, species-specific orphan genes (SSOGs) are mostly thought to originate in external elements such as viruses, followed by horizontal gene transfer, while the scenario of native origination, through rapid divergence or de novo, is mostly dismissed. However, quantitative evidence supporting either scenario is lacking. Here, we systematically analyzed genomes from 4,644 human gut microbiome species and identified over 600,000 unique SSOGs, representing an average of 2.6% of a given species’ pangenome. These sequences are mostly rare within each species yet show signs of purifying selection. Overall, SSOGs use optimal codons less frequently, and their proteins are more disordered than those of conserved genes (i.e., non-SSOGs). Importantly, across species, the GC content of SSOGs closely matches that of conserved ones. In contrast, the ∼5% of SSOGs that share similarity to known viral sequences have distinct characteristics, including lower GC content. Thus, SSOGs with similarity to viruses differ from the remaining SSOGs, contrasting an external origination scenario for most SSOGs. By examining the orthologous genomic region in closely related species, we show that a small subset of SSOGs likely evolved natively de novo and find that these genes also differ in their properties from the remaining SSOGs. Our results challenge the notion that external elements are the dominant source of prokaryotic genetic novelty and will enable future studies into the biological role and relevance of species-specific genes in the human gut.
Natural disaster alters the adaptive benefits of sociality in a primate
Authors: Testard C. , Shergold C. , Acevedo-Ithier A. , Hart J. , Bernau A. , Negron-Del Valle JE. , Phillips D. , Watowich MM. , Sanguinetti-Scheck JI. , Montague MJ. , Snyder-Mackler N. , Higham JP. , Platt ML. , Brent LJN.
Published: July 2023

Weather-related disasters can radically alter ecosystems. When disaster-driven ecological damage persists, the selective pressures exerted on individuals can change, eventually leading to phenotypic adjustments. For group-living animals, social relationships are believed to help individuals cope with environmental challenges and may be a critical mechanism enabling adaptation to ecosystems degraded by disasters. Yet, whether natural disasters alter selective pressures on patterns of social interactions and whether group-living animals can, as a result, adaptively change their social relationships remains untested. Here, we leveraged unique data collected on rhesus macaques from 5 years before to 5 years after a category 4 hurricane, leading to persistent deforestation which exacerbated monkeys’ exposure to intense heat. In response, macaques increased tolerance for and decreased aggression toward other monkeys, facilitating access to scarce shade critical for thermoregulation. Social tolerance predicted individual survival for 5 years after the hurricane, but not before it, revealing a clear shift in the adaptive function of social relationships in this population. We demonstrate that an extreme climatic event altered selection on sociality and triggered substantial and persistent changes in the social structure of a primate species. Our findings unveil the function and adaptive flexibility of social relationships in degraded ecosystems and identify natural disasters as potential evolutionary drivers of sociality.

One-Sentence Summary

Testard et al.show that a natural disaster altered selection on sociality in group-living primates triggering persistent changes in their social structure.
Effects of sex and gonadal hormones on manually segmented hypothalamic and pituitary gland volumes in young healthy adults
Authors: Jones Sherri Lee , Anastassiadis Chloe , Dupuis Matthieu , Pruessner Jens
Published: July 2023

The hypothalamus and pituitary regulate, amongst other functions, third order endocrine systems, and their volumes have been associated with normal and pathological outcomes. Yet, there are very few studies that examine their combined structural variationsin vivo. This is due, in part, to their small size and a lack of comprehensive image segmentation protocols. In the current project we acquired high-resolution T1- (1mm isotropic) and T2-weighted (0.4mm in plane resolution) 3T magnetic resonance images (MRI) of the hypothalamus and pituitary gland, as well as salivary estradiol and testosterone from 31 (17M, 14F) young healthy adults. Women reported oral contraceptive use. Image preprocessing included non-uniformity correction, signal intensity normalization and standard stereotaxic space registration. We applied a comprehensive manual segmentation protocol of the whole hypothalamus, with detailed segmentation of the pituitary stalk, the anterior and posterior pituitary gland, and the posterior bright spot. We also propose a novel medial-lateral hypothalamic parcellation into medial preoptic, periventricular (PVN), and lateral hypothalamic regions. The protocol yielded good inter- (range: 0.78-0.92) and intra-rater (range: 0.79-0.94) Dice kappa overlap coefficients. We detected sex differences of the whole hypothalamus and each hemisphere, and a trend for the right preoptic region to be larger in males than in females, with a moderate effect size. Sex differences were maintained or enhanced when covarying for estradiol, but not when covarying for testosterone. In addition, testosterone was associated with the volume of the PVN, but only in women. In summary, these results suggest that there are morphometric differences at the level of the pituitary and hypothalamus that are likely driven by central regulation of gonadal hormones. The here described protocol allows the structural investigation of neuroendocrine effects in the central nervous system.
cycle_finder:de novoanalysis of tandem and interspersed repeats based on cycle-finding
Authors: Tanaka Yoshiki , Kajitani Rei , Itoh Takehiko
Published: July 2023

Repeat sequences in the genome can be classified into interspersed and tandem repeats, both of which are important for understanding genome evolution and important traits such as disease. They are also noteworthy as regions of high frequency of genome rearrangement in somatic cells and high inter-individual diversity. Existing repeat detection tools have limitations in that they targets only one of the two types and/or require reference sequences. In this study, we developed a novel tool: cycle_finder, which constructs a graph structure (de Bruijn graph) from low-cost short-read data and constructs units of both types of repeats. The tool can detect cycles with branching and corresponding tandem repeats, and can also construct interspersed repeats by exploring non-cycle subgraphs. Furthermore, it can estimate sequences with large copy-number differences by using two samples as input. Benchmarking with simulations and actual data from the human genome showed that this tool had superior recall and precision values compared to existing methods. In a test on the roundworm data, in which large-scale deletions occur in somatic cells, the tool succeeded in detecting deletion sequences reported in previous studies. This tool is expected to enable low-cost analysis of repeat sequences that were previously difficult to construct.
Recognition of sounds by ensembles of proteinoids
Authors: Mougkogiannis Panagiotis , Adamatzky Andrew
Published: July 2023

Proteinoids are artificial polymers that imitate certain characteristics of natural proteins, including self-organization, catalytic activity, and responsiveness to external stimuli. This paper investigates the potential of proteinoids as organic audio signal processors. We convert sounds of English alphabet into waveforms of electrical potential, feed the waveforms into proteinoid solutions and record electrical responses of the proteinoids. We also undertake a detailed comparison of proteinoids’ electrical responses (frequencies, periods, and amplitudes) with original input signals. We found that responses of proteinoids are less regular, lower dominant frequency, wider distribution of proteinoids and less skewed distribution of amplitudes compared with input signals. We found that letter of English alphabet uniquely maps onto a pattern of electrical activity of a proteinoid ensemble, that is the proteinoid ensembles recognise spoken letters of English alphabet. The finding will be used in further designs of organic electronic devices, based on ensembles of proteinoids, for sound processing and speech recognition.
The MEK-ERK signaling pathway promotes maintenance of cardiac chamber identity
Authors: Yao Yao , Yelon Deborah
Published: July 2023

Ventricular and atrial cardiac chambers have unique structural and contractile characteristics that underlie their distinct functions. Intriguingly, the maintenance of chamber-specific features requires active reinforcement, even in differentiated cardiomyocytes. Prior studies in zebrafish have shown that sustained FGF signaling acts upstream ofnkx2.5to maintain ventricular identity, but the rest of this maintenance pathway remains unclear. Here, we show that MEK1/2-ERK1/2 signaling acts downstream of FGF and upstream ofnkx2.5to promote ventricular maintenance. Inhibition of MEK signaling, like inhibition of FGF signaling, results in ectopic atrial gene expression and reduced ventricular gene expression in ventricular cardiomyocytes. FGF and MEK signaling both influence ventricular maintenance over a similar timeframe, when phosphorylated ERK (pERK) is present in the myocardium. However, the role of FGF-MEK activity seems to be context-dependent: some ventricular regions are more sensitive than others to inhibition of FGF-MEK signaling. Additionally, in the atrium, although endogenous pERK does not induce ventricular traits, heightened MEK signaling can provoke ectopic ventricular gene expression. Together, our data reveal chamber-specific roles of MEK-ERK signaling in the maintenance of ventricular and atrial identities.

SUMMARY STATEMENT

The MEK-ERK signaling pathway plays distinct roles in the maintenance of ventricular and atrial cardiomyocyte identities.
Longitudinal Variability ofBifidobacteriumSpecies in the Infant Gut is Independent of Maternal Milk HMO Composition
Authors: Ennis Dena , Shmorak Shimrit , Jantscher-Krenn Evelyn , Yassour Moran
Published: July 2023

The development of the infant gut microbiome is primarily influenced by the infant feeding type, with breast milk serving as the optimal source of nutrition. Breast milk contains human milk oligosaccharides (HMOs) that act as nourishment for the developing gut microbiome, potentially conferring advantages to specific bacterial species. Previous studies have demonstrated the ability of certainBifidobacteriumspecies to utilize individual HMOs, however a longitudinal study examining the evolving microbial community at a high resolution in the context of mothers’ milk HMO composition is lacking. Here, we explored the relationship between the HMO composition in mothers’ milk and the abundance ofBifidobacteriumspecies in the infant gut throughout the course of early life. To enable subspecies taxonomic classification, we developed a high-throughput method for quantifying the abundance ofBifidobacterium longumsubsp.infantis(BL. infantis; the best known HMO-utilizer) from metagenomic sequencing. We applied this method to a longitudinal cohort consisting of 21 mother-infant dyads, from whom we collected matched breast milk and infant stool samples at multiple time points during the first year of life. We observed substantial changes in the infant gut microbiome over the course of several months, while the HMO composition in mothers’ milk remained relatively stable.Bifidobacteriumspecies were a prominent factor contributing to the variation observed among samples; however, no significant associations were found between specific HMOs in mothers’ milk and the abundance ofBifidobacteriumspecies. Finally, the longitudinal nature of our cohort enabled us to characterize the dynamic colonization ofBL. infantisin the infant gut, which surprisingly began late in the breastfeeding period. Applying ourBL. infantisquantification method to additional datasets from various geographical locations, we found similar, late-colonization byBL. infantis, highlighting the importance of quantifyingBL. infantisin the infant gut.
Model connectivity: leveraging the power of encoding models to overcome the limitations of functional connectivity
Authors: Meschke Emily X. , Castello Matteo Visconti di Oleggio , Tour Tom Dupré la , Gallant Jack L.
Published: July 2023

Functional connectivity (FC) is the most popular method for recovering functional networks of brain areas with fMRI. However, because FC is defined as temporal correlations in brain activity, FC networks are confounded by noise and lack a precise functional role. To overcome these limitations, we developed model connectivity (MC). MC is defined as similarities in encoding model weights, which quantify reliable functional activity in terms of interpretable stimulus- or task-related features. To compare FC and MC, both methods were applied to a naturalistic story listening dataset. FC recovered spatially broad networks that are confounded by noise, and that lack a clear role during natural language comprehension. By contrast, MC recovered spatially localized networks that are robust to noise, and that represent distinct categories of semantic concepts. Thus, MC is a powerful data-driven approach for recovering and interpreting the functional networks that support complex cognitive processes.
Climate and geography shape hybrid zone dynamics across space and time: insights fromPopulus trichocarpaxP. balsamifera
Authors: Bolte Constance E. , Phannareth Tommy , Fitzpatrick Matthew C. , Holliday Jason A. , Keller Stephen R. , Hamilton Jill A.
Published: July 2023

Quantifying the mechanisms underlying hybrid zone formation requires an evaluation of both neutral and nonneutral evolutionary processes. Population demographic changes, alongside landscape heterogeneity and climate adaptation, can influence the timing, stability, and extent of introgression where species hybridize. Thus, quantifying interactions across diverged lineages, and the relative contributions of interspecific genetic exchange and selection to divergence at the genome-wide level is needed.

We quantified the contributions of climate and geography to the genetic structure across replicate contact zones betweenPopulus trichocarpaandP. balsamifera,evaluating the demographic context of hybridization and the role of genetic connectivity over time.

We found genomic structure differed among the seven latitudinally arrayed transects. While ancestry was strongly structured by climate, geography appears to have restricted gene flow in certain regions of the hybrid zone. The best fitting demographic model indicated high rates of gene flow alongside selection have likely influenced the establishment and maintenance of the hybrid zone.

Our results point towards the importance of climate in structuring the contact zones betweenP. trichocarpaandP. balsamiferaand emphasize the value of sampling replicated zones of contact to understand how neutral and non-neutral processes influence hybrid zone formation across space and time.
C9orf72gene networks in the human brain correlate with cortical thickness in C9-FTD and implicate vulnerable cell types
Authors: Broce Iris J. , Sirkis Daniel W. , Nillo Ryan M. , Bonham Luke W. , Lee Suzee E. , Miller Bruce , Castruita Patricia , Sturm Virginia E. , Sugrue Leo S. , Desikan Rahul S. , Yokoyama Jennifer S.
Published: July 2023

Introduction

A hexanucleotide repeat expansion (HRE) intronic to chromosome 9 open reading frame 72 (C9orf72) is recognized as the most common genetic cause of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and ALS-FTD. Identifying genes that show similar regional co-expression patterns toC9orf72may help identify novel gene targets and biological mechanisms that mediate selective vulnerability to ALS and FTD pathogenesis.

Methods

We leveraged mRNA expression data in healthy brain from the Allen Human Brain Atlas to evaluateC9orf72co-expression patterns. To do this, we correlated averageC9orf72expression values in 51 regions across different anatomical divisions (cortex, subcortex, cerebellum) with average gene expression values for 15,633 protein-coding genes, including 50 genes known to be associated with ALS, FTD, or ALS-FTD. We then evaluated whether the identifiedC9orf72co-expressed genes correlated with patterns of cortical thickness in symptomaticC9orf72pathogenic HRE carriers (n=19). Lastly, we explored whether genes with significantC9orf72radiogenomic correlations (i.e., ‘C9orf72gene network’) were enriched in specific cell populations in the brain and enriched for specific biological and molecular pathways.

Results

A total of 1,748 genes showed an anatomical distribution of gene expression in the brain similar toC9orf72and significantly correlated with patterns of cortical thickness inC9orf72HRE carriers. ThisC9orf72gene network was differentially expressed in cell populations previously implicated in ALS and FTD, including layer 5b cells, cholinergic motor neurons in the spinal cord, and medium spiny neurons of the striatum, and was enriched for biological and molecular pathways associated with multiple neurotransmitter systems, protein ubiquitination, autophagy, and MAPK signaling, among others.

Conclusions

Considered together, we identified a network ofC9orf72-associated genes that may influence selective regional and cell-type-specific vulnerabilities in ALS/FTD.
SPLASH: a statistical, reference-free genomic algorithm unifies biological discovery
Authors: Chaung Kaitlin , Baharav Tavor Z. , Henderson George , Zheludev Ivan N. , Wang Peter L. , Salzman Julia
Published: July 2023

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2022/497555. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi:https://doi.org/10.1101/2022.06.24.497555
Comparative metagenomic analysis of diarrheal and non-diarrheal gut microbiome delineating the prospective development of prognostic markers and probiotics to protect from diarrhea
Authors: De Rituparna , Kanungo Suman , Mukhopadhyay Asish K. , Dutta Shanta
Published: July 2023

A cross-sectional gut microbiome analysis of 23 non-diarrheal and 5 diarrheal fecal samples was conducted by employing 16s rRNA amplicon sequencing and subsequent analysis for taxonomic profiling of OTUs and abundance interpretation of reads. Significant differences in the structural composition of the two groups were observed. In both Firmicutes was the most abundant phylum in majority of the samples. B/F ratio was consistently <1 in all diarrheal samples. Significant difference in mean B/F ratio of the two groups was found. Proteobacteria was significantly more abundant in the diarrheal group.Prevotellaceaewas the most abundant family in non-diarrheal samples and was suppressed significantly in diarrheal samples.Streptococcaceaewas the most abundant family in 60% diarrheal samples and whereStreptococcaceaewas suppressed,BacteroideaceaeandNocardeaceaewere the most abundant. In non-diarrheal samples whereStreptococcaceaewas almost completely suppressedBifidobacteriaceaewas the most abundant and suppressed other families significantly. A negative correlation was observed betweenPrevotellaceaeandBacteroideaceaein the non-diarrheal group.Prevotella copriwas the most abundant species in 70% non-diarrheal samples and was significantly suppressed in diarrheal samples.Proteus mirabiliswas identified in all the non-diarrheal samples while they were absent in diarrheal samples. The OTUs associated with diarrheal dysbiosis can serve as prognostic markers. This is the first report on the comparative analysis of diarrheal and non-diarrheal microbiome, to our knowledge, and distinctly addressing the gut microbiome dysbiosis from the context that can lead to the development of prognostic markers and probiotics for protecting the endemic population from diarrhea.