bluuebunny/crossref_metadata_2025 huggingface dataset:
Slightly increased level of DNA migration in the comet assay: does statistical significance equal biological significance?
Authors: Møller Peter , Collins Andrew , Rodriguez-Garraus Adriana , Langie Sabine A S , Godschalk Roger , Azqueta Amaya
Published: February 2025

In the comet assay, DNA damage is assessed by differences in DNA migration from gel-embedded nucleoids. Even a small difference in DNA migration between exposure groups can be statistically significant, but may invite speculation about the biological significance of such slight increases in DNA migration. A small difference can be defined as a net difference of 1-2% Tail DNA, but background levels of DNA migration typically vary already more than 1-2% Tail DNA between studies. Here we have used studies on ionizing radiation to assess lowest detectable differences in DNA migration; variation in exposure-effect relationships; variation in central tendencies of DNA migration; unsystematic (residual) variation; and the actual number of lesions detectable with the comet assay. A total of 51 studies on ionizing radiation exposure in mammalian cells have been systematically reviewed, including results from ring-trial studies where the same batch of irradiated cells has been analyzed in different laboratories. Ring-trial studies have shown that unsystematic variation is approximately 4% Tail DNA in studies on ionizing radiation. Studies on ionizing radiation in cell cultures have shown statistically significant effects when the net increase of DNA migration is 0.3-3.1% Tail DNA. Among those experiments, the ones with optimal assay conditions to detect low levels of DNA damage show statistically significant effects with doses of around 0.30 Gy, which corresponds to approximately 350 lesions per diploid cell. However, it has also been shown that the same dose of ionizing radiation can give rise to different levels of DNA migration (i.e. 0.7-7.8% Tail DNA per Gy) in different studies.. In summary, the results show that even a small statistically significant difference in DNA migration has biological significance within the same experiment, but comparisons of DNA migration values between studies have limited biological implications.
SHORT INTERNODE1 regulates the activity of MADS transcription factors during rice floral organ development
Authors: Duan Erchao , Teng Xuan , Xu Huan , Ma Wenyu , Zhang Desheng , Zhang Rushuang , Gu Chuanwei , Zhang Yipeng , Chen Rongbo , Chen Xiaoli , Feng Miao , Lin Qibing , Dong Hui , Zhang Yuanyan , Yang Xue , Zhou Lei , Liu Shijia , Liu Xi , Tian Yunlu , Jiang Ling , Wang Haiyang , Wang Yihua , Wan Jianmin
Published: February 2025

Floral organ identity is fundamental to species diversity and reproductive success in plants and is mainly determined by the combinatorial action of MADS homeotic factors. However, despite their conserved roles in specifying floral organ identity, the regulation of MADS transcription factors remains elusive. Here, we show that the rice (Oryza sativa L.) short internode1 (shi1) mutant displays pleiotropic defects in floral organ development, resulting in severe penalties to yield and grain quality. OsSHI1 mRNA accumulates in each floral organ whorl, and OsSHI1 interacts with multiple MADS transcription factors, especially the Class E members. This physical interaction occurs through the intrinsic MADS domains, thus regulating the transcriptional activity of the MADS transcription factors. This study provides insight into the molecular and genetic regulatory mechanisms underlying the roles of OsSHI1 and MADS transcription factors in rice floral organ development and, consequently, grain yield and quality.
102 ASSESSMENT AND TREATMENT POTENTIAL OF MUSIC INTERVENTION FOR THINKING DISORDERS IN PATIENTS WITH SCHIZOPHRENIA
Authors: Ren Yuan
Published: February 2025

Background

Patients with schizophrenia often show significant thinking disorders, which have a serious impact on their daily life and recovery of social functions. Traditional treatment methods mainly rely on drugs and psychotherapy, and music intervention, as a new non-drug treatment method, has shown its potential in improving the symptoms of schizophrenia. The study aims to evaluate the effect of music intervention on improving thinking disorders and cognitive functions in patients with schizophrenia.

Methods

The study included 60 patients with schizophrenia and randomly divided them into a music intervention group and a control group, with 30 people in each group. The experimental group received 12 weeks of music intervention, 3 times a week, 60 minutes each time, including auditory training, instrumental performance, and rhythm activities. The control group continued to receive conventional drug treatment. The study evaluated the patients before and after using the Positive and Negative Syndrome Scale (PANSS) and the cognitive function test scale to compare the changes in thought disorders, positive symptoms, negative symptoms, and cognitive function between the two groups.

Results

The results showed that the experimental group showed significant improvements in both positive and negative symptom scores, especially in thought disorder symptoms. See Table 1 for specific data.

As can be seen from Table 1, the improvement in thought disorder scores, positive symptoms, and negative symptoms scores in the experimental group was significantly greater than that in the control group. The experimental group’s thinking disorder score improved by 9.5 points, positive symptoms improved by 8.2 points, negative symptoms improved by 7.8 points, and cognitive function score improved by 15.7 points, all of which were statistically significant (P < 0.05). The improvement in various assessments in the control group was smaller and did not reach the significance level. Data show that music intervention has significant therapeutic effects in alleviating thinking disorders and improving cognitive function.

Discussion

Research shows that music intervention can significantly improve the thinking disorders and cognitive functions of patients with schizophrenia, especially showing positive effects in alleviating positive symptoms and negative symptoms. Music intervention is easy to implement and has low side effects, which makes it have good clinical application prospects and provides a valuable supplementary path for the comprehensive treatment of schizophrenia. Future research can further explore the role of music intervention in the long-term recovery of patients with schizophrenia, and combine neuroimaging techniques to further analyze its specific impact on brain function.
106 EFFECT OF PHYSICAL TRAINING COMBINED WITH BASKETBALL ON BEHAVIOR AND MENTAL SYMPTOMS IN SCHIZOPHRENIA
Authors: Bin Enming , Gao* Gan
Published: February 2025

Background

Schizophrenia is a complex mental disorder that affects patients’ behavior, cognition, and emotional regulation, severely impairing their quality of life and social functioning. Although medication can alleviate symptoms, it comes with side effects and has limited effectiveness in improving social adaptability. Therefore, exercise therapy has received attention due to its positive impact on physical and mental health. Basketball not only improves physical fitness, but also promotes social interaction and emotional expression among patients. Studies have shown that moderate exercise can improve mood and cognitive function by increasing neurotransmitter secretion. The study aims to evaluate the effects of physical training and basketball on the behavior and mental symptoms of patients with schizophrenia, in order to provide new evidence for non pharmacological treatment.

Methods

The study included 120 patients with schizophrenia aged 18-45, all of whom met the DSM-5 criteria. Adopting a double-blind randomized controlled design, the participants were divided into an experimental group (physical training and basketball exercise, three times a week, 90 minutes each time) and a control group (conventional treatment only). The intervention of the experimental group includes 30 minutes of physical training and 60 minutes of basketball exercise. Before and after intervention, BPS was used to assess patients’ behavioral problems, PANSS was used to assess psychiatric symptoms, and serum levels of dopamine and BDNF were detected.

Results

The experimental data were analyzed by SPSS 26.0 software, and the specific results are shown in Table 1. Table 1 shows that the experimental group’s BPS score decreased from 42.3 to 28.7, PANSS score decreased from 89.5 to 65.3, and serum dopamine and BDNF levels increased by 23.7% and 18.5%, respectively. The BPS and PANSS scores of the control group only slightly decreased, and the physiological indicators did not show significant changes.

Discussion

Studies have confirmed that physical training combined with basketball has a significant intervention effect on the behavioral and mental symptoms of patients with schizophrenia. Through physical training, physical fitness and confidence are improved; basketball stimulates social participation and emotional expression through team interaction and goal orientation. This integrated intervention not only significantly reduced the behavioral problems and psychiatric symptoms, but also supported the improvement of mental health at the physiological level by promoting the secretion of neurotransmitters and trophic factors. Future studies could further optimize the intervention program with a view to providing more personalized and diverse non-pharmacological approaches for atients with schizophrenia.
A Randomized Controlled Trial Evaluating Traditional versus Extended Techniques of Poly-l-Lactic Acid injection for the Aesthetic Improvement of the Temporal Fossae
Authors: Nikolis Andreas , Rosengaus Frank , Blackburn Geneviève , Safran Tyler , Enright Kaitlyn M.
Published: February 2025

BACKGROUND

Poly-l-lactic acid (PLLA-SCA) can be used to improve the aesthetics of the temporal fossae but is usually only deposited within the visible area of the temporal hollows. However, extending the treatment area posterior to the hairline may provide a greater lifting effect.

OBJECTIVES

Assess the efficacy and safety of 2 techniques (traditional vs extended) of injecting PLLA-SCA for aesthetic improvement of the temporal fossae.

MATERIALS AND METHODS

A prospective, randomized-controlled clinical trial was conducted. Twenty-four subjects were randomized in a 1-to-1 ratio to the traditional or extended injection technique. Subjects received 3 treatments (Baseline, Week 7, Week 14) and were evaluated for follow-up at Weeks 20, 26, and 38. Assessments included the Global Aesthetic Improvement Scale (GAIS), Temple Volume Deficit Scale (TVDS), lifting and volumizing effects, subject satisfaction, and adverse events.

RESULTS

A greater facial lifting effect (p < .001) and mean decrease in TVDS scores were observed with the extended injection technique. Regardless of injection technique, all subjects were at least improved on the GAIS at Week 38, and there was a low frequency of adverse events.

CONCLUSION

Poly-l-lactic acid is a safe and effective treatment for improving the aesthetic appearance of the temporal fossae. Outcomes can be maximized using an extended injection technique.
Addressing Earlobe Elongation: A Systematic Review of Surgical Reduction Techniques in the Aging Population
Authors: Nassar Aref , Nassar Carla , Kassouf Elia , Aoude Marc , El Feghaly Charbel , Nasr Marwan
Published: February 2025

Background:

Aging affects all the components of the face, and the earlobe stands among them. Elongation of the earlobes necessitates surgical correction to restore the youthful ear shape.

Methods:

A comprehensive literature search was conducted across the PubMed, Google Scholar, and Cochrane databases. The quality of the included studies was systematically assessed, and data pertaining to surgical earlobe reduction was extracted.

Results:

Thirteen articles that closely matched the study objectives were included in this systematic review. We regrouped these techniques into 3 categories: those involving inferior margin excision of the earlobe, those involving anterior earlobe resection, and the third group comprising other methods. To aid in clinical decision-making, we created an algorithm to guide the choice of the procedure.

Conclusions:

Proper management of earlobe ptosis and pseudoptosis enhances facial harmony. By outlining the available techniques and providing a treatment algorithm, we emphasize the importance of incorporating earlobe reduction into comprehensive facial rejuvenation strategies.
Epidemiology of Golf-Related Injuries: A 10-Year Analysis of the National Electronic Injury Surveillance System Database and the Impact of Alcohol Consumption
Authors: Swisher Jeremy , Waldrop Matthew , Sitton Zachary , Miles Christopher M.
Published: February 2025

Objective:

The study purpose was to examine epidemiology of golf-related injuries and impact of alcohol consumption.

Design:

Descriptive epidemiologic study.

Setting:

Emergency department injury reports in the United States.

Participants:

Individuals reporting to emergency departments for golf-related injuries.

Methods:

Data (2011–2021) were obtained from National Electronic Injury Surveillance System. Examined trends with pivot tables. Incidence rate ratios and confidence intervals were calculated using χ2. Three hundred seventy-one injuries were removed for not being golf related.

Independent Variables:

Age, gender, alcohol use.

Main Outcome Measures:

Injury type, injury location, injury narrative.

Results:

Mean age 46 years. Men (n = 7605, 71.03%) were injured more frequently. Most common injuries were sprain (n = 1699, 15.87%), laceration (n = 1544, 14.42%), and fracture (n = 1340, 12.52%). Most common locations were trunk (n = 2,417, 22.57%) and head (n = 1866, 17.43%). Most common lower extremity was knee (n = 610, 5.70%), and upper extremity was shoulder (n = 447, 4.17%). With alcohol, the rate of injury being a fracture increased from 12.39% to 18.11% [incidence rate ratio (IRR)], 1.46 [95% CI, 1.05–1.97]; P = 0.018), syncope increased from 2.63% to 9.47% (IRR, 3.51 [95% CI, 2.19–5.38]; P = 0.0001), and internal injury increased from 9.48% to 23.05% (IRR, 2.43 [95% CI, 1.82–3.18]; P = 0.0001). Injury location most common with alcohol was the head, increased from 16.95% to 37.86% (IRR, 2.23 [95% CI, 1.79–2.75]; P = 0.0001).

Conclusions:

Common golf injuries include sprains, lacerations, and fractures. Alcohol is a known risk factor, significantly increasing the risk of severe injuries in golfers, such as fractures and internal injuries. In addition, notable increases in head injuries and syncope were identified.
Realizing the potential of donation after circulatory death requires understanding and resolving tension between end of life decisions and organ donation decisions
Authors: Parent Brendan , Viscusi Summer
Published: February 2025

Purpose of review

Donation after circulatory death (DCD) is one of the most promising methods for expanding the organ pool for transplantation. Yet realizing the promise of DCD depends on careful coordination of end of life treatment with organ donation authorization, organ preservation, and recovery.

Recent findings

As organ procurement organizations (OPO) increase their DCD efforts, challenges regarding timely referral, delays in organ recovery coordination, and the requisite separation of clinical decisions from organ donation decisions are potentially preventing successful organ recovery, and having negative consequences for trust between OPOs, hospital staff, and donor families.

Recent DCD cases should be scientifically studied to understand the variables that lead to successful versus unsuccessful DCD. These variables need to be understood in order to adjust legal, logistical, and ethical approaches to DCD and thus ensure the expansion of the organ pool while preserving trust in organ transplantation.
Selective decline of intact HIV reservoirs during the first decade of ART followed by stabilization in memory T cell subsets
Authors: Nühn Marieke M. , Bosman Kobus , Huisman Terry , Staring Wouter H.A. , Gharu Lavina , De Jong Dorien , De Kort Theun M. , Buchholtz Ninée V.E.J. , Tesselaar Kiki , Pandit Aridaman , Arends Joop , Otto Sigrid A. , Lucio De Esesarte Eduardo , Hoepelman Andy I.M. , De Boer Rob J. , Symons Jori , Borghans José A.M. , Wensing Annemarie M.J. , Nijhuis Monique
Published: February 2025

Objectives:

To investigate the short- and long-term dynamics of intact and defective proviral HIV DNA during ART.

Design:

We evaluated viral reservoir dynamics in a cohort of nine individuals with chronic HIV-1 subtype B infection who initiated first-line ART and were followed for 20 years while continuing ART.

Methods:

PBMCs were obtained before ART (n = 5), during the first year, and after 8.5 and 20 years of treatment. T cell subsets (naive, central-memory, transitional-memory and effector-memory) were sorted at 8.5 and 20 years. DNA was isolated and analyzed using the intact proviral DNA assay (IPDA). Deep-sequencing of the viral env region enabled analysis of viral evolution and cellular mechanisms underlying HIV persistence.

Results:

Initially, defective and intact proviral DNA in PBMCs declined with half-lives of 3.6 and 5.4 weeks, respectively. Over the following 8.5 years, the intact reservoir continued to decrease, with a half-life of 18.8 months in PBMCs, while defective proviral DNA levels stabilized. After 8.5 and 20 years of ART, the intact reservoir showed no further decline, with most intact proviral DNA residing in memory T cell subsets. Phylogenetic analysis revealed no signs of viral evolution over time, both within and between T cell subsets.

Conclusions:

PBMCs containing intact proviral DNA are selectively lost during the first decade of suppressive ART, followed by a decade of stabilization of this reservoir in the memory T cell subsets. In the absence of clear signs of viral evolution and massive clonal expansion, homeostatic proliferation might be an important driver of HIV persistence during long-term ART.
Time to direct-acting antivirals initiation and liver-related events in people with HIV and Hepatitis C virus
Authors: Chalouni Mathieu , Van Santen Daniela K. , Berenguer Juan , Jarrin Inmaculada , Miro José M. , Klein Marina B. , Young Jim , Torgersen Jessie , Rentsch Christopher T. , Gill M John , Epstein Rachel L. , Linas Benjamin , Zangerle Robert , Surial Bernard , Rauch Andri , Touloumi Giota , Papadopoulos Antonios , Wittkop Linda , Van Der Valk Marc , Boyd Anders , Monforte Antonella d’Arminio , Puoti Massimo , Logan Roger W. , Rein Sophia M. , Hernán Miguel A. , Lodi Sara
Published: February 2025

Objective:

People with HIV-HCV co-infection need antiretroviral treatment (ART) to suppress HIV and direct-acting antivirals (DAAs) to cure HCV. ART is typically prioritized, but delays in DAA initiation may increase the risk of liver-related events and HCV transmission to others.

Design:

Target trial emulation with observational data collected in routine clinical practice from a collaboration of cohorts from Europe and North America.

Methods:

We included DAA-naïve adults with HIV-HCV co-infection who achieved HIV virologic suppression (HIV RNA<50 copies/mL) after starting ART between 2013–2020. We 1) estimated the probability of not initiating DAAs at 6 and 36 months after HIV virologic suppression, and 2) emulated a target trial of early (≤6 months after HIV virological suppression) versus delayed (>6 months) DAA initiation and the 36-month risk of liver-related events (liver decompensation or hepatocellular carcinoma).

Results:

Of 862 eligible individuals (median age 46 years; interquartile range 36 to 56), 14% were women, and 52% had a history of injection drug use. The 6 and 36-month probabilities of not initiating DAA were 58% (95% CI: 55, 61) and 24% (21, 27), respectively. The 36-month risk of liver-related events was 1.1% (0.4, 2.0) for early initiation and 1.7% (0.7, 2.5) for delayed initiation; risk difference -0.5% (-1.2, 0.4).

Conclusions:

Almost one-quarter of people with HIV-HCV co-infection on ART had not initiated DAA 3 years after HIV virologic suppression. Because the 3-year risk of liver-related events was low, estimates of the impact of delayed DAA initiation were imprecise.
Barbed Suture Strength in Sacrocolpopexy: Does Pattern Matter?
Authors: Lázaro Weiss José J. , Tomaschke Andrew A. , Hamner Jennifer J. , Hale Douglass S. , Agosta Patrina O. , Ogunmuko Oluwakemi , Reul Olivia , Stewart J. Ryan
Published: February 2025

Importance

Although barbed suture in sacrocolpopexy is becoming increasingly common, an accepted vaginal attachment pattern for barbed suture has not been established.

Objective

This study aimed to compare the structural properties of 3 different barbed suture attachment patterns used to fixate mesh to the vagina during sacrocolpopexy.

Study Design

Segments of type 1 polypropylene mesh (Restorelle; Coloplast, Humlebaek, Denmark) measuring 6 × 3 cm were affixed to rectus abdominis fascia from 5 fresh-frozen female cadavers. Barbed 6-inch 2–0 polydioxanone (Stratafix; Ethicon, Raritan, NJ) with 3 different attachment patterns and nonbarbed 2–0 polydioxanone were used for fixation. Barbed suture attachment patterns included circular, horizontal, and vertical patterns. Mechanical testing was carried out using a uniaxial tensile test to failure.

Results

Tensile testing resulted in similar mechanical properties across all suture attachment pattern groups. Analyses found no significant effect of suture attachment pattern stiffness or the extension at failure. One-way ANOVAs revealed a global effect of suture attachment pattern on the load at failure (P = 0.0188) and energy at failure (P = 0.0435), but this significance was eliminated after controlling for multiple comparisons. A significant (P = 0.0459) increase in ultimate load was found when comparing the horizontal attachment pattern to the vertical attachment pattern.

Conclusions

No difference was observed when comparing suture attachment patterns (circular, horizontal, and vertical). However, a statistically significant difference in ultimate load favored the horizontal attachment over the vertical attachment. Furthermore, there was no difference observed when comparing nonbarbed interrupted suture attachment to the 3 barbed suture attachment patterns.
Novel hot spring Thermoproteota support vertical inheritance of ammonia oxidation and carbon fixation in Nitrososphaeria
Authors: Slosser T , Wenick M , Markert E , Trembath-Reichert E , Ward L M
Published: February 2025

Aerobic ammonia oxidation is crucial to the nitrogen cycle and is only known to be performed by a small number of bacterial lineages (Ammonia Oxidizing Bacteria, or AOB) and a single lineage of archaea belonging to the Nitrosophaeria class of Thermoproteota (Ammonia Oxidizing Archaea, or AOA). Most cultivated AOA originate from marine or soil environments, but this may capture only a limited subset of the full diversity of this clade. Here, we describe several genomes of AOA from metagenomic sequencing of a hot spring microbial mat, representing several poorly characterized basal lineages that may be important for understanding the early evolution of archaeal ammonia oxidation. These genomes include a novel genus most closely related to Nitrososphaera as well as novel species belonging to the genera Nitrosotenuis, Nitrososphaera, and Nitrosotalea. Furthermore, the distributions and phylogenetic relationships of key metabolic genes support a history of vertical inheritance of ammonia oxidation and carbon fixation from the last common ancestor of crown group AOA.
Seroprevalence and Determinants of SARS-Cov-2 Antibodies Among Healthcare Workers in Dar es Salaam, Tanzania
Authors: Mboya Erick , Hawkins Claudia , Kamori Doreen , Amani Davis , Shayo Grace , Sangeda Raphael Z. , Rugemalila Joan , Chiwanga Faraja , Mugusi Sabina , Nkwera Upendo , Mabusi Mangaro , Aboud Said , Mugusi Ferdinand , Sunguya Bruno , Bakari Muhammad , Nagu Tumaini
Published: February 2025

Background

Studies from the Sub-Saharan African (SSA) countries suggest an underestimate of SARS-CoV-2 infections early in the pandemic. To understand and inform infection control strategies to protect key and vulnerable populations, this study investigated the seroprevalence and factors associated with anti-SARS CoV-2 seropositivity among healthcare workers (HCWs) in Dar es Salaam, Tanzania.

Methods

This cross-sectional study was conducted in three tertiary and national hospitals in Dar es Salaam, Tanzania. Employed HCWs aged ≥18 years were enrolled between October 2021 and March 2022. Laboratory testing for Immunoglobulin G (IgG) against SARS-CoV-2 nucleocapsid (N) or spike (S) proteins was performed using WHO/FDA pre-qualified SARS-CoV-2 ELISA test kits, and data were collected on demographics and COVID-19-related exposures. Descriptive statistics were used to determine the SARS-CoV-2 antibody prevalence. Multivariable Modified Poisson regression with robust standard errors accounting for clustering within sites was used to test the independent association between HCW characteristics and SARS-CoV-2 serologic status.

Results

A total of 402 participants [mean age (SD) of 37.9 (9.7) years] were included in this study. 150 (37.3%) reported receiving at least one dose of SARS-CoV-2 vaccine. The overall seroprevalence of anti-SARS-CoV-2 antibodies (anti-SARS-CoV-2 IgG (S or N)) was 90.9% (358/394) among those with valid results. HCWs who reported receiving the SARS-CoV-2 vaccine were 1.14 times more likely to have anti-SARS-CoV-2 antibodies compared to those who reported not being vaccinated (aPR (95% CI) = 1.14 (1.03- 1.26)). HCWs who believed to have contracted COVID-19 previously but never tested had an 11% higher risk of being seropositive for SARS-CoV-2 IgG compared to those who thought never to have contracted COVID-19 before (aPR (95% CI) = 1.11 (1.05- 1.16)). Anesthetists and HCWs working in the laboratory and Obstetrics and Gynecology departments were more likely to have SARS-CoV-2 antibodies than HCWs from the Emergency Medicine Department (EMD).

Conclusion

The seroprevalence of anti-SARS-CoV-2 IgG among HCWs in this study was high in this population indicating high SARS-CoV-2 exposure among HCWs. Our work highlights the need for more effective infection control practices in healthcare settings in future pandemics like these, especially among HCWs at highest risk.
Trichiasis With and Without Tarsal Conjunctival Scarring: a multi-country observational study
Authors: Habtamu Esmael , Mpyet Caleb , Mugume Francis , Atto Gladys , Seife Fikre , Baayenda Gilbert , Backers Sharone , Bakhtiari Ana , Tadesse Zerihun , Nash Scott D. , Callahan E. Kelly , Mcpherson Scott , Harding-Esch Emma M , Macleod David , Kelly Michaela , Millar Tom , Hu Victor , Courtright Paul , Burton Matthew
Published: February 2025

There has been discussion regarding the definition of the clinical sign trachomatous trichiasis (TT) for the purposes of determining elimination of trachoma as a public health problem, and whether the definition should include the presence of trachomatous scarring (TS). A multi-country observational study was conducted in settings with varying TT burdens in Ethiopia, Uganda and Nigeria to determine if the TS grading collected from trichiasis cases by field graders in trachoma surveys using a simplified grading scheme are comparable with tarsal conjunctival scarring (TCS) grading by experts using a detailed grading scheme. The primary outcome was the proportion of eyes that were originally graded in the surveys as “No TS” but had some degree of TCS from expert photographic grading (the negative predictive value, NPV). In Ethiopia, Uganda and Nigeria, 545 (438 cases and 107 comparisons), 256 (156 trichiasis cases and 100 comparisons), and 468 (352 trichiasis cases and 116 comparisons) participants, respectively, were enrolled. In Ethiopia, among 111 trichiatic eyes graded “No TS” in the surveys, 103 (92.8%) had TCS in expert photo grading, NPV 7.2% (95% CI 3.2%– 13.7%). In Uganda, among 28 trichiatic eyes graded “No TS” in the surveys, 19 (67.9%) had TCS in expert photo grading, NPV 32.1% (95% CI 15.9%–52.4%). In Nigeria, among 111 trichiatic eyes graded “No TS” in the surveys, 100 (90.1%) had TCS in expert photo grading, NPV 9.9% (95% CI 5.0%–17.0%). Among eyes misdiagnosed as “No TS” in the survey grading in all the three settings, 174/250 (69.6%) were those with extensive TCS (patches of scarring occupying ≥1/3 of the upper tarsal conjunctiva). Trichiatic eyes with TCS had more severe entropion, trichiasis, conjunctival inflammation, and corneal opacity than those without TCS. In all three settings, including TS to define a trichiasis “trachomatous” in a survey could result in the underestimation of the burden of TT. However, TCS can be effectively used to determine TT severity and management.
Effects of DNA Origami-Based Nanoagent Design on Apoptosis Induction in a Large 3D Spheroid Model
Authors: Weck Johann M. , Nair Riya , Kesici Merve-Z. , Shang Xiaoyue , Monzel Cornelia , Heuer-Jungemann Amelie
Published: February 2025

The extrinsic activation of programmed cell death by FasR/CD95 is a promising minimally invasive strategy for cancer treatment. This can be leveraged using high-precision nanoscale therapeutics: Utilizing DNA origami for precise Fas ligand (FasL) presentation resulted in over 100 times more potent apoptosis induction in single cells. However, treating large, solid tumors poses challenges for DNA origami-based therapeutics, including drug distribution and altered cellular behavior. Here, we addressed these challenges using a 3D spheroid model. First, we assessed DNA origamis’ ability to penetrate tumor tissue, finding that penetration is influenced by the DNA origami size rather its structural flexibility. Second, we evaluated the apoptosis induction efficacy by DNA origami-FasL nanoagents within the spheroid model. The most potent nanoagents were able to completely eradicate all cells in the spheroid. Results indicated that apoptosis induction depended strongly on FasL attachment strategy rather than DNA origami design. Notably, only a rigid neutravidin linker for FasL attachment, rather than a flexible dsDNA linker, halted spheroid growth and fully eradicated all cancer cells. This study offers critical insights into designing DNA-based therapeutics for complex cellular environments and significantly advances DNA origami nanotherapeutic development, highlighting the impact of nanoagent design on cell fate decisions.
Novel Biomolecular techniques in the analysis of Orthopaedic trabecular metal implants produced by additive manufacturing
Authors: Hurst Jack , Oreffo Richard OC , Dunlop Douglas
Published: February 2025

Recent trends have seen an increase in the use of orthopaedic acetabular implants produced by additive manufacturing.

These implants utilise novel trabecular metals with seemingly large variations in their structural designs.

There is no available biomolecular comparisons between these different implants. We have therefore created novel techniques to image and analyse 5 different implants.

Our results have shown differing responses of Human Bone Marrow Stem Cells cultured on these 5 different implants.
Genome Mining ofStreptomycessp. PB17 from Cuatro Ciénegas Basin Reveals Biosynthetic Potential for Novel Neurotherapeutics
Authors: Adriana Martínez-Olivas Martha , Alejandro Melchor-Rangel Silverio , Ángel Mendoza-Cibrian Miguel , Paola Benavides-García , Susana De la Torre-Zavala
Published: February 2025

The Cuatro Ciénegas Basin (CCB), a biodiversity hotspot in Coahuila, Mexico, harbors microbial communities adapted to extreme oligotrophic conditions, making it a promising site for novel bioactive compound discovery.. This study reports the isolation, whole-genome sequencing, and analysis ofStreptomycessp. PB17, a thermotolerant actinomycete retrieved from the karstic Poza La Becerra. Phylogenomic analyses including TYGS and VBCG pipelines, combined with ANI values, support its classification as a putatively novel species.StreptomycesPB17’s genome mining revealed 31 biosynthetic gene clusters (BGCs), with over 10 exhibiting low similarity to known pathways, highlighting its potential for novel bioactive compounds. Among these, ribosomally synthesized and post-translationally modified peptides (RiPPs) demonstrated strong predictive scores for blood-brain barrier penetration properties, representing promising candidates for neurotherapeutic applications. These findings underscore the biotechnological potential of actinomycetes retrieved from extreme sites and emphasize the importance of underexplored ecosystems like the CCB in natural product discovery, including neurotherapeutic research.
Wood ants on the edge: how do the characteristics of linear edges affect the population dynamics of an edge specialist?
Authors: Podesta Jacob A. , Parr Catherine L. , Redeker Kelly R. , Robinson Elva J. H.
Published: February 2025

Landscape structure may facilitate or inhibit the dispersal of species by presenting barriers or opportunities. Slow dispersing edge specialists are likely to be most affected by local topography and land management practices because they require two different adjacent habitats within their limited dispersal range. The northern hairy wood ant,Formica lugubris,requires adjacent forest and open habitats to access aphid honeydew, invertebrate prey, and direct sunlight for thermoregulation. In plantation forest, canopy gaps that provide this combination are often linear and anthropogenic, such as paths, firebreaks, and roads (collectively termed ‘rides’), and their orientation determines shade distribution. Using population data spanning 10 years, we ask how properties of rides, such as bearing and width, affect the distribution and dispersal of wood ant populations in the North York Moors. Regardless of orientation, nests were more abundant on the north side of rides, where they receive more sunlight, and nests were generally larger on narrower rides. Furthermore, we found thatF. lugubrisdispersed approximately 3 times quicker along rides that were oriented north-south or east-west compared to NE-SW or NW-SE. Because wood ants can suppress defoliating pests, these findings have potential forest management implications and may apply to other forest dwelling edge specialists.
Contribution of floral transmission to the assembly and health impact of bacterial communities in watermelon seeds
Authors: Bergmann Gillian E. , Lui Kacie , Lopez Carina , Velasco Alexander , Marais Coralie , Barret Matthieu , Simonin Marie , Vannette Rachel L. , Leveau Johan H.J.
Published: February 2025

Flower-sourced assembly of seed microbiota remains an understudied ecological process. Here, we investigated the floral transmission pathway for bacterial acquisition by developing seeds of watermelon (Citrullus lanatus). Comparison of stigma- and seed-associated bacterial communities from field-grownC. lanatusrevealed significant overlap: up to 40% of the bacterial diversity that was detected in seed was also found on stigmas. In a field pollinator exclusion experiment, honeybee visitation to flower stigmas had no significant effect on bacterial community composition in seeds. Among a collection of bacterial isolates from stigmas and seeds in the field, more than half (57%) were able to transmit to seeds after inoculation onto stigmas under laboratory conditions. Interestingly, for most bacterial strains, fruit set rates increased after floral inoculation, and in some cases even in the absence of transmission to the seed. We also found that bacterial isolates from watermelon stigmas and seeds had variable (i.e. positive or negative) effects on seed germination and seedling emergence. Our findings highlight the contribution of floral transmission to seed microbiota assembly and its consequences for plant fitness.
Myocardial cGMP-PKG1α dysregulation contributes to VT pathogenesis in type II diabetes and metabolic syndrome
Authors: Cao Xuehong , Zhang Yali , Tripp Audrey , Steinhauer Rachel , Liu Pei-wen , Aronovitz Mark J. , Martin Greg L. , Wang Bo , Alissa Abdullah , Aljuaid Mossab , Ho Justin , Phan Tina , Madias Christopher , Blanton Robert M. , Galper Jonas B.
Published: February 2025

Background

Type-II diabetes (DMII) and metabolic syndrome increase ventricular arrhythmia and sudden cardiac death risk.

Objectives

To identify signaling mechanisms through which DMII and metabolic syndrome promote ventricular tachycardia (VT).

Methods

We performed ventricular programmed stimulation on leptin receptor mutant (Db/Db) mice with DMII, high fat high sucrose (HFHS)-fed mice with metabolic syndrome, and cGMP-dependent Protein Kinase 1α (PKG1α) leucine zipper mutant (LZM) mice, which do not have DMII or metabolic syndrome but have disrupted PKG1α signaling.

Results

During ventricular programmed stimulation, Db/Db and HFHS-fed mice displayed increased VT and T-wave alternans. Cardiomyocytes from these mice displayed early afterdepolarizations. Both models demonstrated decreased heart rate response to parasympathetic inhibition, indicating autonomic dysfunction. cGMP, which mediates cardiac parasympathetic stimulation, was reduced in LVs of Db/Db and HFHS-fed mice. Conversely, cGMP augmentation with soluble guanylate cyclase stimulation (riociguat) or phosphodiesterase 5 inhibition (sildenafil) reduced VT inducibility. PKG1α LZM mice had normal autonomic responsiveness, but excess VT inducibility. Db/Db, HFHS, and LZM mice each demonstrated hyperactivated myocardial glycogen synthase kinase3β (GSK3β). Further, GSK3β inhibition with TWS119 abolished inducible VT in these mice. Diastolic cytosolic Ca2+reuptake slope decreased in cardiomyocytes from all models, while GSK3β inhibition with TWS119 reversed this effect. Phospholamban (PLB), which inhibits sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2a-mediated Ca2+reuptake, was hyperactivated/hypophosphorylated in HFHS-fed and LZM mice, and this was reversed by TWS119.

Conclusions

These findings identify cGMP reduction as driving GSK3β hyperstimulation, calcium dyshomeostasis, and VT in DMII and metabolic syndrome. Pharmacological modulation of these pathways opposes VT pathogenesis.
The effect of task demand on EEG responses to irrelevant sound and speech in simulated surgical environments
Authors: Rosenkranz Marc , Uslar Verena N. , Weyhe Dirk , Bleichner Martin G.
Published: February 2025

1

Complex soundscapes in high-stakes environments, such as the operating room (OR), are characterized by a variety of overlapping auditory stimuli and present significant challenges for personnel, particularly during periods of high demand. This study investigates how task demand and an OR soundscape including irrelevant speech, influence perceived work-load, surgical performance, and auditory processing in a simulated surgical environment, using mobile electroencephalography (EEG). Participants performed two simulated surgical tasks, namely peg transfer and suturing, representing a low-demand and high-demand task, respectively. The tasks were performed under two sound conditions: An OR soundscape was presented with irrelevant speech or alone. Neural responses to transient and continuous auditory stimuli were analyzed using event-related potentials (ERPs) and temporal response functions (TRFs), respectively. Results showed that irrelevant speech increased self-reported workload and distraction. EEG analyses revealed reduced neural responses to transient sounds and irrelevant speech under high task demand, reflecting early-stage sensory filtering of auditory distractions. Notably, an inverse relationship was observed between neural responses to speech and self-reported workload, indicating that the speech responses may serve as a marker for perceived workload. Overall, this study demonstrates the potential of EEG to assess irrelevant sound processing in realistic work-like settings and highlights the critical role of task demand in modulating neural responses and self-reported workload to soundscapes.
Characterisation ofMarteilia cocosarumin the Wash Estuary, UK, linked to mass mortalities of cockles (Cerastoderma edule), and its relationship to closely related species
Authors: Tidy Annabel , Jessop Ron , Ward Georgia M. , Green Matthew J. , Bateman Kelly S. , Bass David , Hunt Jasmine E. , Ross Stuart H. , Hooper Chantelle
Published: February 2025

Globally,Marteiliaparasites have been associated with significant mass mortality events in populations of commercially important bivalve molluscs, frequently resulting in large-scale fishery collapses and substantial socio-economic impacts. The Wash Estuary, UK, supports several bivalve fisheries, and among these, common cocklesCerastoderma edulehave suffered unusually high mortalities since 2008. We investigate potential causes of these mortalities, and confirm infection withMarteilia cocosarum, strongly associated with cockle moribundity, also confirming its presence in archived samples collected in 2009. Molecular and light microscopy screening of samples collected during mortality events in 2021, including healthy (buried) and moribund (weak, unable to bury) cockles, indicated high prevalence ofM. cocosarumin moribund cockles (PCR incidence up to 95%) in contrast to healthy cockles (up to 42%), suggesting an association between cockle moribundity andMarteiliainfection. Analysis of the full ribosomal RNA array identified consistently different nucleotides betweenM. cocosaruminfections in The Wash (denoted as genotype WE) and those in Wales (denoted genotype BI). 83% of infections in The Wash could be identified asM. cocosarumWE and 12% asM. cocosarumBI, with both genotypes recovered from 5% of infected animals. Histopathologically,M. cocosarumWE infects the gill, mantle and connective tissues, identical to observations ofM. cocosaruminfecting Welsh cockles. Ongoing cockle mortalities in The Wash raise concerns regarding the sustainability of this resource ecologically and economically. Additional measures may be required to reduce the spread of this pathogen, noting that its distribution beyond The Wash and Wales is currently unknown.
Tissue reassembly with generative AI
Authors: Yu Tingyang , Ekbote Chanakya , Morozov Nikita , Fan Jiashuo , Frossard Pascal , d’Ascoli Stéphane , Brbić Maria
Published: February 2025

The spatial arrangement of cells plays a critical role in determining their functions and interactions within tissues. However, single-cell RNA sequencing (scRNA-seq) dissociates cells from their native tissue context, resulting in a loss of spatial information. Here, we show that complex tissue structures can be reassembled from the gene expression profiles of dissociated cells. To achieve this, we developed LUNA, a generative AI model that reconstructs tissues conditioned solely on gene expressions of cells by learning spatial priors over existing spatially resolved datasets. We show that LUNA effectively reconstructs slices from the MERFISH whole mouse brain atlas with over 1.2 million cells, including cells from cell types never seen during model training. Applying LUNA to the mouse central nervous system scRNA-seq atlas, we show that LUNA is applicable for de novo generation of tissue structures. Additionally, LUNA can infer locations of nuclei lost during cell profiling with Slide-tags technology and correctly places cells belonging to spatially distinct compartments in a human metastatic melanoma sample. We envision that AI-driven tissue reassembly can help to overcome current technological limitations and advance our understanding of tissue organization and function, paving the way towards virtual tissue models.
The role of pathogens in creating and maintaining host polymorphism
Authors: Djahoui Edgard , Loeuille Nicolas , Rohr Rudolf P.
Published: February 2025

Terrestrial and marine ecosystems exhibit remarkable species diversity and richness. Among the hypotheses put forward to explain this diversity —its origins and the forces sustaining it— one prominent hypothesis posits that pathogens could be pivotal in generating and maintaining species diversity within ecosystems. To explore this hypothesis, we analyzed a host-pathogen system, examining the specific conditions that might facilitate pathogen-driven diversification within the host population, with a focus on both the emergence and persistence of diversity. By applying a fecundity-transmission trade-off in which a non-evolving pathogen influences its evolving host, we observed that pathogens only infrequently drive host diversification, and only around intermediate trade-off conditions. Furthermore, while these rare diversification events result in stable coexistence, evolved diversity is low, consisting of two coexisting host morphs. Because the sole evolution of hosts in response to pathogens offers limited opportunity for diversification, we propose additional mechanisms that could foster higher levels of diversity within the system.
CVAE-based Causal Representation Learning from Retinal Fundus Images for Age Related Macular Degeneration(AMD) Prediction
Authors: Kim Dae young
Published: February 2025

Regarding relatively poor prognosis and acute vision impairment, analyzing Age-Related Macular Degeneration, or AMD has been one of the most important tasks in retinal disease analysis. Especially, constructing methods to analyze and predict Wet AMD, which is characterized by rapid RPE damage due to neovascularization, has been a demanding task for many ophthalmologists for decades. Recently, with advancements in ML/DL frameworks and computer vision AI, these previous efforts are now leading to drastic enhancements in AMD prediction and mechanism analysis. Specifically, use of attention mechanism based CNNs or XAI methods are leading to higher performance in predicting AMD status and reliable explanations. Under current success in the usage of cutting-edge techniques, this research implemented a novel latent causal representation learning framework to further enhance AI-based models to comprehend complex causal AMD mechanisms with only access to retinal fundus images, while constructing a more reliable type of AMD prediction model. Results show that valid convolutional VAE and GAE based explicit latent causal modeling can lead to successful causal disentanglements of underlying AMD mechanisms, while returning essential causal factors that can be utilized to reliably distinguish normal fundus and AMD fundus images in downstream tasks such as diagnosis prediction.
Synaptotoxic forms of amyloid-β and α-synuclein act through a common pathway
Authors: Ribe E. , Ghosh A. , Paslawski W. , Savory K. , Ballard C. , Morin P. , Cash D. , Hirth F. , Williams G. , Svenningsson P. , Aarsland D. , Siow R. C. M. , Killick R.
Published: February 2025

It has been suggested that α-synuclein (αSyn), a major player in Parkinson’s disease (PD), plays a role in Alzheimer’s disease (AD). Several reports have also concluded that αSyn and amyloid-β (Aβ) are mechanistically linked, although how is unclear. Synapse loss is an early feature in both PD and AD and held to be the driver of both diseases. We have previously uncovered a signalling pathway required for Aβ-driven dendritic spine loss - a non-canonical branch of Wnt signalling known as the Wnt/Planar Cell Polarity (Wnt/PCP) pathway. We asked if a synaptotoxic form of αSyn known to impact dendritic spines, the A53T autosomal dominant PD mutant form of αSyn (A53T-αSyn), might act on synapses through the same pathway. Here, by blocking all Wnt activity with the porcupine inhibitor IWP2, we show that A53T-αSyn-driven spine loss is Wnt-dependent. By silencingDaam1, which is unique to Wnt/PCP, we show that A53T-αSyn spine loss isDaam1-dependent. Finally, using the pan-ROCK inhibitor fasudil indicates the mechanism also involves ROCK1/2, whichDaam1signals to via RhoA to modulate actin cytoskeletal dynamics within dendritic spines. Together, these observations indicate that A53T-αSyn-driven spine loss involves the Wnt/PCP pathway, the same pathway that mediates Aβ synaptotoxicity. This indicates that Aβ and αSyn are mechanistically connected and that a common pathway is responsible for synapse loss in AD and PD. It also begins to explain why this group of neurodegenerative diseases have many features in common and suggests that drugs which target Wnt/PCP could be of benefit for both AD and PD.