bluuebunny/crossref_metadata_2025 huggingface dataset:
Health risk and germ cell toxicity of five commercially available sachet waters in Nigeria: a public health concern
Authors: Alabi Okunola Adenrele , Lawrence Olufunbi Esther , Ayeni Funmilayo Esther , Olumurewa John A V
Published: July 2024

Background

Sachet water is the most common form of portable water commercially available in Nigeria.

Methodology

Using the murine sperm count and sperm abnormality assay, the germ cell toxicity of five common commercially available sachet waters in Nigeria was assessed in this study. The levels of hormones such as Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH) and Total Testosterone (TT); and activities of catalase (CAT), alanine aminotransferase (ALT), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated. The heavy metal and physicochemical parameters of the sachet waters were also analyzed. Healthy male mice were allowed to freely drink the sachet waters for 35 days after which they were sacrificed.

Results

The findings indicated that the concentrations of some heavy metals (As, Cr, and Cd) in the sachet waters exceeded the limit by regulatory organizations. The data of the total carcinogenic risk (TCR) and total non-carcinogenic risk (THQ) of some heavy metals associated with the ingestion of sachet water for adults and children showed that the values exceeded the acceptable threshold, and thus, is indicative of a high non-carcinogenic and carcinogenic risks. The data of the sperm abnormality assay showed that in the exposed mice, the five sachet waters induced a statistically significant (P < 0.05) increase in abnormal sperm cells and a significantly lower mean sperm count. Additionally noted were changes in the serum activities of TT, FSH, ALP, AST, ALT, and LH.

Conclusion

Thus, the sachet waters studied contained agents that can induce reproductive toxicity in exposed humans. This is of public health importance and calls for immediate action by regulatory bodies.
High endemic freshwater mussel (Bivalvia: Unionida) diversity in western Borneo, with description of three new species
Authors: Zieritz Alexandra , Pfeiffer John , Rahim Khairul Adha A , Prayogo Hari , Anwari Muhammad Sofwan , Diba Farah , Froufe Elsa , Blackwell Tabitha , Hartikainen Hanna , Lopes-Lima Manuel
Published: July 2024

The freshwater mussels (Bivalvia: Unionida) of the biodiversity hotspot Sundaland are experiencing severe anthropogenic threats, whilst their diversity and distribution remain poorly understood. Here, we present the first modern-day data on Unionida diversity and distribution across western Borneo. Mussels were surveyed and collected in the upper Kapuas and Pawan river basins in West Kalimantan, Indonesia, and the Sambas Besar, Sarawak and Batang Sadong river basins in Sarawak, Malaysia. DNA sequencing (COI + 16S + ND1 + 18S + 28S) and morphological analyses were conducted to delineate and identify species, and reconstruct phylogenetic relationships and population genetics. Specimens belonged to six native genera and nine species, of which seven are endemic to Borneo and three are new to science, i.e. Ctenodesma mawonae Zieritz et al., sp. nov., Sarawak basin, and Ctenodesma bersinara Zieritz et al., sp. nov., and Rectidens lauris Zieritz et al., sp. nov., both Pawan basin. The monotypic genera Caudiculatus and Discomya were phylogenetically highly divergent from other known Gonideinae taxa, potentially indicating a separate tribe (for Caudiculatus) and subfamily (for Discomya). In addition, we report new records of the non-native Sinanodonta pacifica Heude, 1878 in the Batang Sadong and Kapuas river basins.
The Development and Characteristics of Planetary Health in Medical Education: A Scoping Review
Authors: Visser Eva H. , Oosterveld Berdien , Slootweg Irene A. , Vos Hedwig M.M. , Adriaanse Marieke A. , Schoones Jan W. , Brakema Evelyn A.
Published: July 2024

Purpose

Climate change, biodiversity loss, and other ecological crises threaten human health globally. The interrelation between human health and ecosystems is addressed in the emerging field of planetary health. Ecological crises have created an urgency to integrate planetary health, including sustainable health care, into medical education. To facilitate integration and guide future research, this review aims to provide an overview of the existing literature about planetary health in medical education.

Method

The authors conducted a scoping review using the conventional methodological framework for scoping studies. They performed a comprehensive search in 7 databases without language restrictions in March 2022. Two researchers independently extracted data. The team analyzed the data using data-driven thematic analysis, content analysis, and qualitative summarizing. Data were structured according to the Curriculum Development for Medical Education: A Six-Step Approach.

Results

The authors identified 3,703 unique publications, of which 127 were included. Articles predominantly (71%, n = 90) covered the call to integrate planetary health in medical education (step 1: general needs assessment). Many publications (24%, n = 31) proposed learning objectives (step 3); these mainly concerned raising awareness, while few concerned action perspectives. Publications limitedly reported on the final steps of curriculum development. Only 2 covered a full cycle of curriculum development. Most were published recently, with first authors mainly from Europe and North America.

Conclusions

Planetary health in medical education is an urgent and hot topic. Literature focused predominantly on why planetary health should be integrated in medical education and what should be covered. The authors recommend future research and education development to shift to how to do so, especially in evaluation and feedback. Research and education development needs to be conducted and reported on systematically and underpinned by educational principles. Lastly, it would benefit from perspectives beyond “Western-based” ones.
Perioperative Infection Prophylaxis With Vancomycin is a Significant Risk Factor for Deep Surgical Site Infection in Spine Surgery
Authors: Kazarian Gregory S. , Mok Jung K. , Johnson Mitchell , Jordan Yusef Y. , Hirase Takashi , Subramanian Tejas , Brause Barry , Kim Han Jo
Published: July 2024

Study Design.

Retrospective cohort.

Objective.

The purpose of this study was to compare the efficacy of cefazolin versus vancomycin for perioperative infection prophylaxis.

Summary of Background Data.

The relative efficacy of cefazolin alternatives for perioperative infection prophylaxis is poorly understood.

Materials and Methods.

This study was a single-center multisurgeon retrospective review of all patients undergoing primary spine surgery from an institutional registry. Postoperative infection was defined by the combination of three criteria: irrigation and debridement within 3 months of the index procedure, clinical suspicion for infection, and positive intraoperative cultures. Microbiology records for all infections were reviewed to assess the infectious organism and organism susceptibilities. Univariate and multivariate analyses were performed.

Results.

A total of 10,122 patients met inclusion criteria. The overall incidence of infection was 0.78%, with an incidence of 0.73% in patients who received cefazolin and 2.03% in patients who received vancomycin (OR: 2.83, 95% CI: 1.35–5.91, P=0.004). Use of IV vancomycin (OR: 2.83, 95% CI: 1.35–5.91, P=0.006), BMI (MD: 1.56, 95% CI: 0.32–2.79, P=0.014), presence of a fusion (OR: 1.62, 95% CI: 1.04–2.52, P=0.033), and operative time (MD: 42.04, 95% CI: 16.88–67.21, P=0.001) were significant risk factors in the univariate analysis. In the multivariate analysis, only noncefazolin antibiotics (OR: 2.48, 95% CI: 1.18–5.22, P=0.017) and BMI (MD: 1.56, 95% CI: 0.32–2.79, P=0.026) remained significant independent risk factors. Neither IV antibiotic regimen nor topical vancomycin significantly impacted Gram type, organism type, or antibiotic resistance (P>0.05). The most common reason for antibiosis with vancomycin was a penicillin allergy (75.0%).

Conclusions.

Prophylactic antibiosis with IV vancomycin leads to a 2.5 times higher risk of infection compared with IV cefazolin in primary spine surgery. We recommend the routine use of IV cefazolin for infection prophylaxis, and caution against the elective use of alternative regimens like IV vancomycin unless clinically warranted.
Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder
Authors: Moga Lucile , Paradis Valérie , Ferreira-Silva Joel , Gudavalli Koushik , Indulti Federica , Dajti Elton , Nicoara-Farcau Oana , Tosetti Giulia , Antonenko Antonina , Fodor Andreea , Vidal-González Judit , Turco Laura , Capinha Francisco , Elkrief Laure , Monllor-Nunell Teresa , Goria Odile , Balcar Lorenz , Lannes Adrien , Mallet Vincent , Poujol-Robert Armelle , Thabut Dominique , Houssel-Debry Pauline , Wong Yu Jun , Ronot Maxime , Vilgrain Valérie , Rampally Sai Prasanth , Payancé Audrey , Castera Laurent , Reiberger Thomas , Ferrusquía-Acosta José , Noronha Ferreira Carlos , Vitale Giovanni , Simon-Talero Macarena , Procopet Bogdan , Berzigotti Annalisa , Caccia Riccardo , Turon Fanny , Schepis Filippo , Ravaioli Federico , Colecchia Antonio , Valsan Arun , Macedo Guilherme , Plessier Aurélie , Rautou Pierre-Emmanuel ,   on behalf of the ERN RARE-LIVER; a study of VALDIG, an EASL consortium
Published: July 2024

Background and Aims:

Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension.

Approach and Results:

We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without a history of variceal bleeding, who underwent an SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. One hundred fifty-four patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value. In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% negative predictive value.

Conclusions:

This study gathering a total of 309 patients with PSVD showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared.
Long-term outcomes of extensive thoracoabdominal aortic aneurysm repair utilizing normothermic iliac perfusion: a retrospective cohort study with 10-year single-center experience
Authors: Wang Luchen , Liu Yanxiang , Gao Haoyu , Xie Mingxin , Zhang Bowen , Zhou Sangyu , Qian Xiangyang , Yu Cuntao , Sun Xiaogang
Published: July 2024

Background:

Normothermic iliac perfusion has been increasingly utilized for thoracoabdominal aortic aneurysm repair; however, the long-term outcomes in large samples are lacking. This study was designed to assess the perioperative and long-term results of thoracoabdominal aortic repair using normothermic iliac perfusion.

Methods:

The authors retrospectively analyzed 156 patients having Crawford extent II or III thoracoabdominal aortic aneurysm replacement with normothermic iliac perfusion from 2012 to 2022. Primary endpoints were composite adverse events and long-term survival, which encompassed 30-day mortality, persistent stroke, persistent paraplegia, and acute renal failure needing continuous dialysis. The cohort was divided into two subgroups based on the use of selective visceral and cold renal perfusion techniques.

Results:

The combined adverse event rate was 14.1%. Specific rates were: 30-day mortality (4.5%), persistent stroke (1.9%), persistent paraplegia (4.5%), and renal failure requiring persistent dialysis (3.2%). The median follow-up time was 67 months. Overall survival rates at 1, 3, 5, 7, and 10 years were 91.6, 90.0, 85.4, 77.6, and 69.7%, respectively. Subgroup analysis showed the visceral and renal perfusion group had a significantly reduced adverse event incidence compared to the nonperfusion group (6.5 vs. 19.1%, P=0.026). Multivariable logistic regression analysis confirmed selective visceral and cold renal perfusion techniques as protective factors against postoperative adverse events (OR 0.30, 95% CI: 0.09–0.94; P=0.038). Multivariable Cox regression analysis identified age ≥50 years (HR 2.63, 95% CI: 1.10–6.27; P=0.029) and NYHA grade ≥III (HR: 3.20, 95% CI: 1.04–9.87; P=0.043) as independent risk factors predicting overall survival.

Conclusions:

Normothermic iliac perfusion is a feasible option for thoracoabdominal aortic repair with cost benefits and simpler management, and selective visceral and cold renal perfusion techniques may further improve its safety and effectiveness. However, enhanced vigilance and meticulous care are essential, particularly for elderly patients and those with cardiac insufficiency.
Reoperation for ipsilateral local recurrence following prior nephron-sparing surgery: innovative surgical insights from a high-volume urological center with cross-sectional study
Authors: Ma Wenming , Xu Wenlong , Meng Jialin , Chen Lei , Tai Sheng , Yang Cheng , Chen Jinhu , Shi Haoqiang , Liang Chaozhao
Published: July 2024

Background:

The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), the authors aim to propose novel surgical strategies that offer practical recommendations to surgeons.

Methods:

Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. The authors conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, the authors developed our surgical strategies.

Results:

In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in five cases (33.3%), laparoscopic surgery in six cases (40%), and open surgeries in four cases (26.7%). While four (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 min (IQR: 135–300), and the median estimated blood loss was 50 ml (IQR: 50–100). The median length of postoperative hospitalization was 6 days (IQR: 5–9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution.

Conclusion:

Reoperation following the pNSS is a secure and effective surgical approach. The authors introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in the current study.
Cross-circulation combined with rapidly deployable venovenous bypass grafts for multiorgan biosystemic support in liver failure: experimental studies
Authors: Liu Peng , Yang Lifei , Lu Qiang , Qian Yerong , Shi Aihua , Liu Xin , Wei Shasha , Fan Shujuan , Lv Yi , Xiang Junxi
Published: July 2024

Background:

Liver failure remains a critical clinical challenge with limited treatment options. Cross-circulation, the establishment of vascular connections between individuals, has historically been explored as a potential supportive therapy but with limited success. This study investigated the feasibility of combining cross-circulation with a rapidly deployable venovenous bypass (VVB) graft for multiorgan support in a rat model of total hepatectomy, representing the most severe form of liver failure.

Materials and methods:

A Y-shaped VVB graft was fabricated using coaxial electrospinning of PLCL/heparin nanofibers and magnetic rings for rapid anastomosis. After total hepatectomy in rats, the VVB graft was implanted to divert blood flow. Cross-circulation was then established between anhepatic and normal host rats. Hemodynamics, biochemical parameters, blood gases, and survival were analyzed across three groups: hepatectomy with blocked vessels (block group), hepatectomy with VVB only (VVB group), and hepatectomy with VVB and cross-circulation (VVB/cross-circulation group).

Results:

The VVB graft exhibited suitable mechanical properties and hemocompatibility. VVB rapidly restored hemodynamic stability and mitigated abdominal congestion posthepatectomy. Cross-circulation further ameliorated liver dysfunction, metabolic derangements, and coagulation disorders in anhepatic rats, significantly prolonging survival compared to the VVB group (mean 6.56±0.58 vs. 4.05±0.51 h, P<0.05) and the block group (mean 1.01±0.05 h, P<0.05).

Conclusion:

Combining cross-circulation with a rapidly deployed VVB graft provided effective multiorgan biosystemic support in a rat model of total hepatectomy, substantially improving the biochemical status and survival time. This approach holds promise for novel liver failure therapies and could facilitate liver transplantation procedures.
Using Simulation-Based Mastery Learning to Achieve Excellent Learning Outcomes in Physical Therapist Education
Authors: Tappan Rachel S. , Roth Heidi R. , McGaghie William C.
Published: July 2024

Introduction.

The 2 aims of this observational study are (a) to describe the implementation and feasibility of a bed mobility skills simulation-based mastery learning (SBML) curricular module for physical therapist students and (b) to measure learning outcomes and student perceptions of this module.

Review of Literature.

Simulation-based mastery learning is an outcome-based educational approach that has been successful in other health professions but has not been explored in physical therapy education.

Subjects.

Eighty-seven students in a single cohort of a Doctor of Physical Therapy program.

Methods.

The SBML module in this pretest–posttest study included a pretest, instruction, initial posttest, and additional rounds of instruction and assessment as needed for all learners to achieve the minimum passing standard (MPS) set using the Mastery Angoff and Patient Safety methods. Outcome measures were bed mobility assessment pass rates and scores, additional student and faculty time compared with a traditional approach, and student perceptions of their self-confidence and the module.

Results.

All students achieved the MPS after 3 rounds of training and assessment beyond the initial posttest. Mean Total Scores improved from 67.6% (12.9%) at pretest to 91.4% (4.8%) at mastery posttest (P < .001, Cohen's d = 1.8, 95% CI [1.4–2.1]); mean Safety Scores improved from 75.2% (16.0%) at pretest to 100.0% (0.0%) at mastery posttest (P < .001, Cohen's d = 1.5, 95% CI [1.2–1.9]). Students who did not achieve the MPS at the initial posttest (n = 30) required a mean of 1.2 hours for additional instruction and assessment. Survey results revealed an increase in student confidence (P < .001) and positive student perceptions of the module.

Discussion and Conclusion.

Implementation of this SBML module was feasible and resulted in uniformly high levels of bed mobility skill acquisition. Based on rigorous learning outcomes, feasible requirements for implementation, and increased student confidence, SBML offers a promising approach for wider implementation in physical therapy education.
Quantification of Cephalometric Changes in Gonial Angle Morphology Following Facial Feminization Surgery
Authors: Ihnat Jacqueline M. , Hu Kevin G. , Parikh Neil , Almeida Mariana N. , Williams Mica , Hauc Sacha C. , Alperovich Michael
Published: July 2024

Facial feminization surgery (FFS) is a type of gender-affirming surgery aimed at bringing masculine facial features more in line with typically feminine characteristics. Specifically, mandibular contouring can create a softer jawline and help create a more round, feminine face. As the popularity of FFS continues to increase, improving surgical techniques and patient satisfaction is imperative. However, no quantitative measurement system currently exists to measure these changes. In this study, the authors describe the use of a novel segmentation technique using computerized tomography imaging to quantify the bony changes that occur during gonial angle reduction. Further, authors utilize this technique to describe changes in a cohort of 13 patients, and how these changes correlate with patient satisfaction. The authors found that gonial angle volume and surface area significantly decreased, as well as the intergonial:interzygomatic ratio, with a smaller ratio associated with more feminine features. In addition, patient satisfaction significantly increased post-operatively both specifically regarding jawline appearance (P = 0.0014) and regarding overall social and psychological function (P = 0.0021 and P = 0.0032, respectively), as captured by the FACE-Q and World Health Organization Quality of Life (WHOQOL) surveys. Patients with greater changes in surface area reported greater improvements in WHOQOL psychological scores (P = 0.0086), and patients with greater changes in the intergonial:interzygomatic ratio reported greater improvements in WHOQOL social scores (P = 0.0299). Overall, our novel technique captures significant changes in gonial angle shape and can be applied to a wide range of future studies to improve the quality and accessibility of FFS.
Blue Ribbon Committee II Faculty Development
Authors: Damewood Richard , Michelassi Fabrizio , Mansour Ashraf , Shabahang Moshen , Sharp Kenneth , Farmer Diana
Published: July 2024

The American College of Surgeons, the American Board of Surgery, and the American Surgical Association have created a Blue Ribbon Committee II to evaluate the current status of surgical education in the United States. As part of this endeavor, a subcommittee was formed to address issues pertinent to the development of surgical faculty as teachers. This entailed multiple discussions among a group of experienced surgical educators, a review of the literature, and a Delphi analysis of possible suggested improvements for faculty educational support, resulting in a final set of recommendations for improvement for future surgical faculty development. These recommendations include a task force to establish a validated system of compensation for faculty teaching, a task force to determine an accurate assessment of the value of surgical trainees to health systems, a review by the Surgical Residency Review Committee and the Association of Program Directors in Surgery of minimal faculty resources for program accreditation in the area of teaching learners, collaborative efforts across surgical specialties for the definition of a national curriculum for faculty, and development of a tool for evaluation of faculty teaching performance.
Urinary Incontinence Medications: Patient-Initiated Concerns in Primary Care
Authors: Neuner Joan , Schmitt Emily , Winn Aaron , Davidson Emily , O’Connor Robert C. , Marowski Sarah , Luebke Marie , Balza Joanna , Attewell Madeline , Flynn Kathryn E.
Published: July 2024

Importance

Guideline-recommended medications for overactive bladder and urge urinary incontinence (OAB/UUI) are effective but have high costs and side effects. Little is known about patient concerns regarding these medications when prescribed by their primary care providers (PCPs).

Objective

The aim of the study was to describe PCP-patient interactions when prescribing medications for OAB/UUI, specifically clinical concerns, cost and authorization issues, and mode of communication for these interactions.

Study Design

Using electronic health records, we identified a retrospective cohort of women aged 18–89 years who were prescribed a medication for OAB/UUI during a primary care office visit from 2017 to 2018. We examined the electronic health record from initial prescription through 15 subsequent months for documentation of prior authorization requests and patient concerns about cost, side effects, or ineffectiveness. The association of patient demographics, comorbidity, and medication class with these concerns was examined with logistic regression models.

Results

Overall, 46.2% of patients (n = 123) had 1 or more OAB/UUI medication concerns, and 52 reported outside an office visit. Only higher comorbidity was associated with reduced concern of any type. Although the overall percent age of patients reporting concerns was similar by medication type, the patterns of concern type varied. Compared with those taking short-acting antimuscarinics, patients taking long-acting antimuscarinics other than oxybutynin were less likely to have side effect concerns (adjusted odds ratio 0.35, 95% CI 0.16–0.78) and more likely to have cost concerns (adjusted odds ratio 5.10, 95% CI 1.53–17.03).

Conclusions

Patient concerns regarding OAB/UUI medications were common in primary care practices and frequently reported outside of office visits. However, the patterns of concerns (cost vs side effects) varied between medication classes.
Decoupled evolution of ventral and dorsal scales in agamid lizards: ventral keels are associated with arboreality
Authors: Yuan Michael L. , Westeen Erin P.
Published: July 2024

Arboreality has evolved in all major vertebrate lineages and is often associated with morphological adaptations and increased diversification concomitant with accessing novel niche space. In squamate reptiles, foot, claw, and tail morphology are well-studied adaptations shown to be associated with transitions to arboreality. Here, we examined a less well understood trait—the keeled scale—in relation to microhabitat, climate, and diversification dynamics across a diverse lizard radiation, Agamidae. We found that the ancestral agamid had keeled dorsal but not ventral scales; further, dorsal and ventral keels are evolutionarily decoupled. Ventral keeled scales evolved repeatedly in association with arboreality and may be advantageous in reducing wear or by promoting interlocking when climbing. We did not find an association between keeled scales and diversification, suggesting keels do not allow finer-scale microhabitat partitioning observed in other arboreal-associated traits. We additionally found a relationship between keeled ventral scales and precipitation in terrestrial species where we posit that the keels may function to reduce scale degradation. Our results suggest that keeled ventral scales facilitated transitions to arboreality across agamid lizards, and highlight a need for future studies that explore their biomechanical function in relation to microhabitat and climate.
Bio-inspired compensatory strategies for damage to flapping robotic propulsors
Authors: Hooper M. L. , Scherl I. , Gharib M.
Published: July 2024

Natural swimmers and flyers can fully recover from catastrophic propulsor damage by altering stroke mechanics: some fish can lose even 76% of their propulsive surface without loss of thrust. We consider applying these principles to enable robotic flapping propulsors to autonomously repair functionality. However, direct transference of these alterations from an organism to a robotic flapping propulsor may be suboptimal owing to irrelevant evolutionary pressures. Instead, we use machine learning techniques to compare these alterations with those optimal for a robotic system. We implement an online artificial evolution with hardware-in-the-loop, performing experimental evaluations with a flexible plate. To recoup thrust, the learned strategy increased amplitude, frequency and angle of attack (AOA) amplitude, and phase-shifted AOA by approximately 110°. Only amplitude increase is reported by most fish literature. When recovering side force, we find that force direction is correlated with AOA. No clear amplitude or frequency trend is found, whereas frequency increases in most insect literature. These results suggest that how mechanical flapping propulsors most efficiently adjust to damage may not align with natural swimmers and flyers.
Impact of infectious diseases on wild bovidae populations in Thailand: insights from population modelling and disease dynamics
Authors: Horpiencharoen Wantida , Marshall Jonathan C. , Muylaert Renata L. , John Reju Sam , Hayman David T. S.
Published: July 2024

The wildlife and livestock interface is vital for wildlife conservation and habitat management. Infectious diseases maintained by domestic species may impact threatened species such as Asian bovids, as they share natural resources and habitats. To predict the population impact of infectious diseases with different traits, we used stochastic mathematical models to simulate the population dynamics over 100 years for 100 times in a model gaur (
Bos gaurus
) population with and without disease. We simulated repeated introductions from a reservoir, such as domestic cattle. We selected six bovine infectious diseases; anthrax, bovine tuberculosis, haemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis, all of which have caused outbreaks in wildlife populations. From a starting population of 300, the disease-free population increased by an average of 228% over 100 years. Brucellosis with frequency-dependent transmission showed the highest average population declines (−97%), with population extinction occurring 16% of the time. Foot and mouth disease with frequency-dependent transmission showed the lowest impact, with an average population increase of 200%. Overall, acute infections with very high or low fatality had the lowest impact, whereas chronic infections produced the greatest population decline. These results may help disease management and surveillance strategies support wildlife conservation.
Joint exome and metabolome analysis in individuals with dyslexia: Evidence for associated dysregulations of olfactory perception and autoimmune functions
Authors: Nandakumar Rohit , Shi Xiaojian , Gu Haiwei , Kim Yookyung , Raskind Wendy H. , Peter Beate , Dinu Valentin
Published: July 2024

Dyslexia is a learning disability that negatively affects reading, writing, and spelling development at the word level in 5%-9% of children. The phenotype is variable and complex, involving several potential cognitive and physical concomitants such as sensory dysregulation and immunodeficiencies. The biological pathogenesis is not well-understood. Toward a better understanding of the biological drivers of dyslexia, we conducted the first joint exome and metabolome investigation in a pilot sample of 30 participants with dyslexia and 13 controls. In this analysis, eight metabolites of interest emerged (pyridoxine, kynurenic acid, citraconic acid, phosphocreatine, hippuric acid, xylitol, 2-deoxyuridine, and acetylcysteine). A metabolite-metabolite interaction analysis identified Krebs cycle intermediates that may be implicated in the development of dyslexia. Gene ontology analysis based on exome variants resulted in several pathways of interest, including the sensory perception of smell (olfactory) and immune system-related responses. In the joint exome and metabolite analysis, the olfactory transduction pathway emerged as the primary pathway of interest. Although the olfactory transduction and Krebs cycle pathways have not previously been described in dyslexia literature, these pathways have been implicated in other neurodevelopmental disorders including autism spectrum disorder and obsessive-compulsive disorder, suggesting the possibility of these pathways playing a role in dyslexia as well. Immune system response pathways, on the other hand, have been implicated in both dyslexia and other neurodevelopmental disorders.
Metabolic mode estimated by breathing reflects long-term motor memory
Authors: Hayashi Takuji , Nakano Nobuyasu , Washino Sohei , Murai Akihiko
Published: July 2024

Respiration is a crucial metabolic process that converts macronutrients and oxygen (O2) into energy and carbon dioxide (CO2), supporting motor actions. In addition to the energy demands for movements, the brain is a significant energy consumer for neural activity and plasticity. However, it is not known whether breathing patterns can serve as an indicator for them as they can for movement intensity. According to computational theory, motor memory updating involves fast and slow timescales, which may correspond to neural activity and plasticity. To investigate whether breathing patterns reflect these time constants, human experiments assessed short- and long-term memories while recording the O2-CO2 gas exchange. We found that the respiratory exchange ratio (RER), an indicator of metabolic mode, was not influenced by the execution and learning of the reaching movement and was stable within individuals but diverse across individuals. Interestingly, the individual differences in the RER reflect individual variation in long-term memory rather than short-term memory. Furthermore, to manipulate the RER, we provided 200 kcal of glucose immediately before the task. Surprisingly, 24-hour retention increased by 21%. Together, the RER would serve as a remarkable proxy for long-term motor memory and ingesting glucose would shift the neurophysiological “idling state” for learning.
Cellular and Molecular Changes During Aging in MEC: Unveiling the Role of Bglap3 Neurons in Cognitive Aging
Authors: Cao Qichen , Uzeen Sorgog , Cheng Sihui , Liu Yuanjing , Liu Jiangyuan , Wen Shidan , Zhong Meng , Hao Jun , Yao Shuyang , Yang Yikai , Yan Xingyu , Guo Weixiang , Miao Chenglin
Published: July 2024

Aging-correlated cognitive declines, including deficiencies in spatial orientation and memory, may reflect dysfunction in the hippocampus and medial entorhinal cortex (MEC). However, aging-related changes in MEC at the cellular and molecular levels remain unclear. In this study, we found fewer grid cells with reduced spatial stability in old mice. We compared gene expression profiles between young and old mice using 10x Genomics Visium technology. Among 1664 differentially expressed genes, we discovered Bglap3, a marker gene for subpopulation in MEC Layer III with decreased cell number with age. Silencing of Bglap3+ neurons in young mice impaired the spatial tuning of neurons in MEC and the spatial learning of a new platform location in water maze. These findings help us to understand the cellular and molecular changes in the MEC in healthy aging animals and the changes of Bglap3+ cells in old mice indicating a possible cause of aging-related MEC deficiency.
A hypercubic Mk model framework for capturing reversibility in disease, cancer, and evolutionary accumulation modelling
Authors: Johnston Iain G. , Diaz-Uriarte Ramon
Published: July 2024

Accumulation models, where a system progressively acquires binary features over time, are common in the study of cancer progression, evolutionary biology, and other fields. Many approaches have been developed to infer the accumulation pathways by which features (for example, mutations) are acquired over time. However, most of these approaches do not support reversibility: the loss of a feature once it has been acquired (for example, the clearing of a mutation from a tumour or population). Here, we demonstrate how the well-established Mk model from evolutionary biology, embedded on a hypercubic transition graph, can be used to infer the dynamics of accumulation processes, including the possibility of reversible transitions, from data which may be uncertain and cross-sectional, longitudinal, or phylogenetically / phylogenomically embedded. Positive and negative interactions between arbitrary sets of features (not limited to pairwise interactions) are supported. We demonstrate this approach with synthetic datasets and real data on bacterial drug resistance and cancer progression. While this implementation is limited in the number of features that can be considered, we discuss how this limitation may be relaxed to deal with larger systems.
TEtrimmer: a novel tool to automate the manual curation of transposable elements
Authors: Qian Jiangzhao , Xue Hang , Ou Shujun , Storer Jessica , Fürtauer Lisa , Wildermuth Mary C. , Kusch Stefan , Panstruga Ralph
Published: July 2024

Transposable elements (TEs) are repetitive DNA sequences capable of moving within genomes. Accurate annotation and classification of TEs is crucial but challenging due to their sequence diversity and often fragmented occurrence. We present TEtrimmer, a novel tool to automate manual TE curation. TEtrimmer integrates multiple sequence alignment (MSA) clustering, MSA sequence extension, MSA cleaning, TE boundary definition, and TE classification, and provides report plots and a graphical user interface (GUI) application to inspect and improve results. Benchmarked on the genomes of six organisms from various kingdoms of life, TEtrimmer consistently improved the identification of intact TEs compared to established tools.
Disturbance of the Sense of Agency in Obsessive-Compulsive Disorder and its Modulation by Social Context
Authors: Roth Manuel J. , Lindner Axel , Fallgatter Andreas J. , Wittorf Andreas , Jusyte Aiste
Published: July 2024

Executing precise actions and perceiving them as one’s own is a fundamental ability underlying the sense of agency (SoA). The SoA thereby heavily relies on the accuracy and reliability of forward models, capturing sensory movement consequences. Impairments thereof thus represent a promising candidate mechanism contributing to cases of SoA pathogenesis. In obsessive-compulsive disorder (OCD), for example, the feeling of control over one’s actions is perturbed: Compulsive actions are often experienced as uncontrollable and performed without conscious awareness. At the same time, compulsions can be coupled with an inflated sense of illusory control for uncontrollable events. Here we studied self-action perception in virtual reality with and without veridical or rotated visual feedback about subjects’ pointing movements to test whether patients’ internal forward models are indeed less reliable compared to controls. Interestingly, OCD patients did not exhibit deficits in their accuracy and reliability of motor performance and self-action perception in the absence of visual feedback, suggesting intact forward models. Nonetheless, OCD patients weighted rotated visual action-feedback significantly stronger perceptually. Furthermore, they adapted their movement to this false feedback on a trial-by-trial basis. Finally, increasing the social relevance of action consequences led to stronger feedback weighting in all participants while this effect increased with the strength of OCD symptomatology under conditions with strongest social relevance. We suggest that internal forward models are equally reliable in OCD but their weight is pathologically decreased leading to patients’ overreliance on explicit visual action-feedback and, more generally, to their over-attribution of unrelated events to themselves.
Phage display enables machine learning discovery of cancer antigen specific TCRs
Authors: Croce Giancarlo , Lani Rachid , Tardivon Delphine , Bobisse Sara , de Tiani Mariastella , Bragina Maiia , Perez Marta AS , Schmidt Julien , Guillame Philippe , Zoete Vincent , Harari Alexandre , Rufer Nathalie , Hebeisen Michael , Dunn Steven , Gfeller David
Published: July 2024

T cells targeting epitopes in infectious diseases or cancer play a central role in spontaneous and therapy-induced immune responses. T-cell epitope recognition is mediated by the binding of the T-Cell Receptor (TCR) and TCRs recognizing clinically relevant epitopes are promising for T-cell based therapies. Starting from one of the few known TCRs targeting the cancer-testis antigen NY-ESO-1 157-165 epitope, we built large phage display libraries of TCRs with randomized Complementary Determining Region 3 of the β chain. The TCR libraries were panned against the NY-ESO-1 epitope, which enabled us to collect thousands of epitope-specific TCR sequences. We then trained a machine learning TCR-epitope interaction predictor with this data and could identify several epitope-specific TCRs directly from TCR repertoires. Cellular binding and functional assays revealed that the predicted TCRs displayed activity towards the NY-ESO-1 epitope and no detectable cross-reactivity with self-peptides. Overall, our work demonstrates how display technologies combined with machine learning models of TCR-epitope recognition can effectively leverage large TCR repertoires for TCR discovery.
Reversion to metabolic autonomy underpins evolutionary rescue of a bacterial obligate mutualism
Authors: Melero-Jiménez Ignacio J. , Sorokin Yael , Merlin Ami , Couce Alejandro , Friedman Jonathan
Published: July 2024

Populations facing lethal environmental change can avoid extinction by undergoing rapid genetic adaptation, a phenomenon termed evolutionary rescue. While this phenomenon has been the focus of much theoretical and empirical research, our understanding of evolutionary rescue in communities consisting of interacting species is still limited, especially in mutualistic communities, where evolutionary rescue is expected to be constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism in which auxotrophicEscherichia colistrains exchanged essential amino acids reciprocally. We observed that >80% of the communities avoided extinction when exposed to two different types of lethal and abrupt stresses. Of note, only one of the strains survived in all cases. Genetic and phenotypic analyses show that this strain reverted to autonomy by metabolically bypassing the auxotrophy, but we found little evidence of specific adaptation to the stressors. Crucially, we found that the mutualistic partners were substantially more sensitive to both stresses than prototrophs, so that reversion to autonomy was sufficient to alleviate stress below lethal levels. We observed that increased sensitivity was common across several other stresses, suggesting that this may be a general property of obligate mutualisms mediated by amino acid exchange. Our results reveal that evolutionary rescue may depend critically on the specific genetic and physiological details of the interacting partners, adding rich layers of complexity to the endeavor of predicting the fate of microbial communities facing intense environmental deterioration.
In vitro genotoxic and mutagenic potentials of combustion particles from marine fuels with different sulfur contents
Authors: Jeong Seongho , Pantzke Jana , Offer Svenja , Käfer Uwe , Bendl Jan , Saraji-Bozorgzad Mohammad , Huber Anja , Michalke Bernhard , Etzien Uwe , Jakobi Gert , Orasche Jürgen , Czech Hendryk , Rüger Christopher P. , Schnelle-Kreis Jürgen , Streibel Thorsten , Buchholz Bert , Adam Thomas , Sklorz Martin , Bucchianico Sebastiano Di , Zimmermann Ralf
Published: July 2024

Ship emissions cause serious environmental impacts and adverse effects toward human health. Therefore, the International Maritime Organization (IMO) restricted the fuel sulfur content (FSC) of marine fuels: FSC must be <0.5% m/m or <0.1% m/m in sulfur emission control areas, covering a range of fuels from distillate diesel-like fuels to low-sulfur heavy fuel oils (HFOs). As a result, ship emissions, e.g., sulfur oxides and particulate matter (PM) have been reduced. However, how FSC correlates with the toxicological potential of ship emissions is still uncertain. The objective of this study was to understand how the physical and chemical properties of particulate emissions from a marine engine operating on five marine fuels with different FSCs influence their toxicological outcome. For this scope, cytotoxic, genotoxic, mutagenic, and pro-inflammatory potentials of collected particles were evaluated in lung cell model systems. The involvement of intracellular reactive oxygen species and xenobiotic metabolism was also explored. While PM from different fuels’ combustion resulted in up to approximately 20% of reduction of cytotoxicity at the highest concentration, other toxicological outcomes, including clonogenic and genotoxic potentials, showed a stronger trend with the polycyclic aromatic hydrocarbon contents in PM compared with FSC. This trend was supported by evidence of a significant increase in gene mutation frequency and alterations in cellular mechanisms induced by an aromatic-rich HFO with an intermediate FSC. In conclusion, apart from reducing FSC in marine fuels, additional particle abatement systems should be considered to reduce the adverse effects of particulate emissions from shipping operations on human health.
Ultrafast and accurate sequence alignment and clustering of viral genomes
Authors: Zielezinski Andrzej , Gudyś Adam , Barylski Jakub , Siminski Krzysztof , Rozwalak Piotr , Dutilh Bas E. , Deorowicz Sebastian
Published: July 2024

Viromics produces millions of viral genomes and fragments annually, overwhelming traditional sequence comparison methods. We introduce Vclust, a novel approach that determines average nucleotide identity by Lempel-Ziv parsing and clusters viral genomes with thresholds endorsed by authoritative viral genomics and taxonomy consortia. Vclust demonstrates superior accuracy and efficiency compared to existing tools, clustering millions of virus genomes in a few hours on a mid-range workstation.
SCEMENT: Scalable and Memory Efficient Integration of Large-scale Single Cell RNA-sequencing Data
Authors: Chockalingam Sriram P , Aluru Maneesha , Aluru Srinivas
Published: July 2024

Motivation

Integrative analysis of large-scale single cell data collected from diverse cell populations promises an improved understanding of complex biological systems. While several algorithms have been developed for single cell RNA-sequencing data integration, many lack scalability to handle large numbers of datasets and/or millions of cells due to their memory and run time requirements. The few tools which can handle large data do so by reducing the computational burden through strategies such as subsampling of the data or selecting a reference dataset, to improve computational efficiency and scalability. Such shortcuts however hamper accuracy of downstream analyses, especially those requiring quantitative gene expression information.

Results

We present SCEMENT, a SCalablE and Memory-Efficient iNTegration method to overcome these limitations. Our new parallel algorithm builds upon and extends the linear regression model previously applied in ComBat, to an unsupervised sparse matrix setting to enable accurate integration of diverse and large collections of single cell RNA-sequencing data. Using tens to hundreds of real single cell RNA-seq datasets, we show that SCEMENT outperforms ComBat as well as FastIntegration and Scanorama in runtime (upto 214X faster) and memory usage (upto 17.5X less). It not only performs batch correction and integration of millions of cells in under 25 minutes, but also facilitates discovery of new rare cell-types and more robust reconstruction of gene regulatory networks with full quantitative gene expression information.

Availability and implementation

Source code freely available for download athttps://github.com/AluruLab/scement, implemented in C++ and supported on Linux.

Contact

aluru@cc.gatech.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.