bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Practice Providers and Western Providers Are Associated With Increased Likelihood of Benign Skin Biopsies: A Cross-sectional Analysis
Authors: Aggarwal Pushkar , DaCunha Matthew , Rismiller Kyle , Neltner Scott , Coldiron Brett , Fleischer Alan B.
Published: December 2024

BACKGROUND AND OBJECTIVE

To identify provider-related characteristics associated with a higher proportion of benign skin biopsies.

PATIENTS AND MATERIALS/METHODS

Medicare Part B database was analyzed, and for each provider, the number of skin biopsies that he/she performed that were benign lesions was estimated.

RESULTS

Increased benign skin biopsies were performed by nurse practitioners and physician assistants (as compared to Doctor of Medicine/Doctor of Osteopathic Medicine) (odds ratio [OR] of 1.9 and 1.6, respectively), providers in the Northeast (OR 1.2), West (OR 1.2), or Midwest (OR 1.1) (as compared to the South), providers in metropolitan cities (OR 1.1), and providers in states with a higher cost of living index. Multivariable regression analysis revealed provider credentials, city size, and the West region to be significant (p < .05) factors in the number needed to biopsy to detect 1 malignant lesion.

CONCLUSION

This analysis is performed only on Medicare patients, which can limit the generalizability of the results over all the population groups. Nurse practitioners and physician assistants (as compared to Doctor of Medicine/Doctor of Osteopathic Medicine), providers practicing in the West (as compared to in the South), and providers practicing in metropolitan cities (as compared to nonmetropolitan cities) were more likely to perform benign skin biopsies than their counterparts.
Evaluation of Responses to Questions About Keratoconus Using ChatGPT-4.0, Google Gemini and Microsoft Copilot: A Comparative Study of Large Language Models on Keratoconus
Authors: Demir Suleyman
Published: December 2024

Objectives:

Large language models (LLMs) are increasingly being used today and are becoming increasingly important for providing accurate clinical information to patients and physicians. This study aimed to evaluate the effectiveness of generative pre-trained transforme-4.0 (ChatGPT-4.0), Google Gemini, and Microsoft Copilot LLMs in responding to patient questions regarding keratoconus.

Methods:

The LLMs' responses to the 25 most common questions about keratoconus asked by real-life patients were blindly rated by two ophthalmologists using a 5-point Likert scale. In addition, the DISCERN scale was used to evaluate the responses of the language models in terms of reliability, and the Flesch reading ease and Flesch–Kincaid grade level indices were used to determine readability.

Results:

ChatGPT-4.0 provided more detailed and accurate answers to patients' questions about keratoconus than Google Gemini and Microsoft Copilot, with 92% of the answers belonging to the “agree” or “strongly agree” categories. Significant differences were observed between all three LLMs on the Likert scale (P<0.001).

Conclusions:

Although the answers of ChatGPT-4.0 to questions about keratoconus were more complex for patients than those of other language programs, the information provided was reliable and accurate.
Medially Migrating Vestibular Schwannomas: A Review of 10 Cases
Authors: Brovold Brooklyn L. , Lohse Christine M. , Mehta Parv M. , Bathla Girish , Lane John I. , Breen Joseph L. , Van Gompel Jamie J. , Carlson Matthew L.
Published: December 2024

Objective

To analyze cases of medial migration of vestibular schwannomas to propose an underlying mechanism.

Study Design

Retrospective chart review.

Patients

Ten patients from one institution with sporadic vestibular schwannomas that demonstrated medial migration toward the cerebellopontine angle on serial imaging were reviewed.

Interventions

Among the 10 patients studied, 8 patients underwent stereotactic radiosurgery and 2 were managed with wait-and-scan. All serial imaging was analyzed throughout follow-up.

Main Outcome Measures

Volumetric and linear measurements were used to assess vestibular schwannoma growth. The fundal fluid cap length was measured from the most lateral end of the neoplasm within the internal auditory canal to the medial end of the cochlea. Pure tone averages of 0.5, 1, 2, and 3 kHz, word recognition scores, and AAO-HNS hearing class were used to assess levels of hearing loss per patient.

Results

Tumor growth exhibited a positive correlation with medial migration. Of the 10 patients studied, 9 exhibited tumor volume growth from initial to most recent imaging. Median changes in tumor volumes and fundal fluid cap lengths from initial diagnosis to the most recent imaging regardless of intervention were 130 mm3 (range 1,400–2,970) and 2.8 mm (range 1.8–6.0), respectively. Migration was noted in 4 patients prior to any intervention, in 4 patients postradiosurgery, and in 2 patients before and after radiosurgery. Therefore, half of the tumors studied migrated before an intervention and half migrated postradiosurgery. No correlation of migration and hearing decline was observed.

Conclusion

Medial migration of vestibular schwannoma is associated with an increase in tumor volume, supporting a “tumor squeeze” mechanism within a conical internal auditory canal toward the wider porus acusticus and cerebellopontine angle.
Aberrant Sylvian Vein Diverticulum and Tegmen Dehiscence–Induced Venous Pulsatile Tinnitus Phenotype Can Be Treated Via Transtemporal Surgery: A Case Report with 4D-Flow Magnetic Resonance Imaging
Authors: Hsieh Yue-Lin , Liu Xu , Dai Fei , Wang Shenjiang , Gao Xiuli , Wen Deyuan , Wang Wuqing
Published: December 2024

Objective

To report the first successful surgical treatment of a rare subtype of venous pulsatile tinnitus (PT) caused by aberrant sylvian vein and tegmen dehiscence (SVTD) with a diverticulum and soft tissue enclosing the middle ear ossicles.

Patients

A 35-year-old female participant presented with more than 10-year left-side PT due to SVTD diverticulum.

Intervention(s)

The participant underwent transtemporal surgery with a lateral minimally invasive approach to the epitympanum and aditus ad antrum after finding SVTD and diverticulum.

Main Outcome Measures

Contrast-enhanced CT, various magnetic resonance (MR) techniques, including the 4D-flow MR method, and transcanal recording examinations were utilized. The Tinnitus Handicap Inventory (THI) was employed to quantify the surgical efficacy in treating PT.

Results

PT was successfully resolved following resurfacing of the diverticulum located on the medial wall of the epitympanic space, with the patient achieving a THI score of 0. The 4D-flow MR indicated that the mean and largest velocities at the dehiscence area were 20.8 cm/s and 54.9 cm/s, respectively. The main frequency of PT fluctuated below 750 hz.

Conclusion

SVTD diverticulum–induced venous PT can be successfully treated via the transtemporal pathway. Additionally, this finding underscores the importance to carefully examine tegmen dehiscence and the exposed vasculature when managing venous PT.
Hypertrophy of the Annular Ligament as a Cause of Painful Elbow Snapping
Authors: Pan Tommy , Sneddon Jacob , Tang Peter
Published: December 2024

Snapping annular ligament is an uncommon cause of lateral elbow pain. Due to the limited literature, snapping annular ligament is often misdiagnosed as lateral epicondylitis. Recognition of this uncommon condition is important as early surgical intervention is recommended to prevent erosion of articular cartilage caused by the hypertrophic synovial fold and early-onset arthritis. We present a 37-year-old male with left lateral elbow pain and clicking for 5 years. MRI of the elbow revealed hypertrophy of the annular ligament with associated lateral epicondylitis. After failing conservative management, the patient underwent open resection of the hypertrophied annular ligament in addition to lateral epicondylitis surgery. The patient demonstrated complete relief of symptoms. Our aim is to increase the nurse’s and hand surgeon’s awareness of hypertrophy of the annular ligament as an uncommon cause of lateral elbow snapping and pain. We also review the literature, pathophysiology, nursing and surgical management and outcomes of treatment for this rare condition.
Methods to Manage Edema and Reduce Flap Compression in Postoperative Nursing Care Following Trauma to the Lower Extremity
Authors: Rancu Albert L. , Darby Fabrizio A. , Averbukh Leon D. , Nicholson Allen , Myrick Karen M. , Leslie Michael P. , Wiznia Daniel H.
Published: December 2024

Lower extremity edema and compression are potential causes of poor soft tissue healing and flap failure for patients who suffer lower extremity trauma. This review summarizes techniques aimed at reducing edema and mechanical pressure in these patients as well as those undergoing soft tissue coverage techniques. We conducted a literature review for postoperative nursing management to reduce edema in the lower extremity, following traumatic injury. To assist orthopaedic nurses in acute care settings, this review presents techniques for reducing edema and mechanical pressure in patients recovering from lower extremity trauma. The accompanying figures demonstrate how to apply these techniques. Techniques such as rope suspension, mini water mattresses, and pillow or blanket stacking were identified as measures that can reduce edema and compression for patients recovering from lower extremity trauma as well as those requiring soft tissue coverage procedures.
Effective Motivational Interviewing-Based Counseling for Knee Osteoarthritis
Authors: Küçük Öztürk Gülhan , Muz Gamze , Özdil Kamuran , Öztürk Ramazan İlter
Published: December 2024

Objective:

This research was conducted to determine the effect on pain, psychosocial adjustment and self-care management of motivational interview-based counseling for individuals with a diagnosis of knee osteoarthritis.

Methods:

This study was conducted as a randomized controlled experimental study. The sample size for the study was calculated as 60 individuals (29 intervention, 31 controls) diagnosed with osteoarthritis. Study data were collected using a Personal Information Form, Visual Analogue Scale (VAS) for measuring pain intensity, Psychosocial Adjustment to Illness Self-Report Scale, and Self-Care Management Scale in Chronic Diseases. The intervention group received motivational interview-based counseling for four weeks and standard care was administered to the control group. At the end of four weeks, the post-test was applied to participants.

Results:

Motivational interview-based counseling for the intervention group lasting four weeks significantly decreased the mean scores for the Psychosocial Adjustment to Illness Self-Report Scale, indicating increased psychosocial adjustment levels. It significantly decreased VAS scores, and significantly increased mean scores for the Self-Care Management Scale in Chronic Diseases, indicating self-care management increased (P < .001).

Conclusion:

Motivational interview-based counseling for individuals with knee osteoarthritis reduces pain and increases psychosocial adjustment and self-care management.

Practice Implementation:

Health professionals can use motivational interviewing during the treatment, care and rehabilitation of individuals with knee osteoarthritis.
Multicenter Clinical Performance Evaluation of the NeuMoDx™ CT/NG Assay 2.0
Authors: Van Der Pol B. , Avery A. , Taylor S.N. , Miller J. , Emery C.L. , English A. , Lazenby G.B , Lillis R. , Ruth J. , Young D. , Young S. , Chavoustie S. , Crane L. , Reid V. , Wall G. , Johnson S.
Published: December 2024

Background

Given the continued increases in rates of both Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection, additional diagnostic assays may be useful in increasing access to testing for these sexually transmitted infections. We evaluated the performance of the NeuMoDx™ CT/NG Assay 2.0 on the NeuMoDx-96 and NeuMoDx-288 Molecular Systems.

Methods

The clinical sensitivity and specificity of the assay was assessed when used with: 1) endocervical swabs; 2) self-, and clinician-collected vaginal swabs; and 3) first-catch urine specimens (female and male). Results were compared to a patient infection status based on US Food and Drug Administration (FDA)-cleared assays.

Results

The NeuMoDx CT/NG Assay 2.0 demonstrated high sensitivity and specificity in both symptomatic and asymptomatic participants. All specimen types other than endocervical swabs had >95% sensitivity and > 99% specificity for both pathogens. For endocervical samples, sensitivity was 93.2% and 93.3% for CT and NG, respectively. There was no difference in performance based on platform. The frequency of invalid results was low (<1%).

Conclusions

The NeuMoDx CT/NG Assay 2.0 demonstrated performance similar to currently FDA-cleared assays, with the added choice of a moderate- (96-sample) or a high-throughput (288-sample) platform. The system therefore offers solutions to laboratories running lower volumes of testing that may obviate the need for outsourcing to larger reference laboratories.
Alignment of PrEP Use With Potential HIV Exposure in Young Women and Men in Uganda
Authors: Wu Linxuan , Ssebuliba Timothy , Muwonge Timothy R. , Bambia Felix , Stein Gabrielle , Nampewo Olivia , Sapiri Oliver , Goetz B. Jay , Penrose Kerri J. , Parikh Urvi M. , Mujugira Andrew , Heffron Renee
Published: December 2024

Background:

Despite high oral pre-exposure prophylaxis (PrEP) uptake among young heterosexual cisgender women, early discontinuation is frequent. It is unclear whether this aligns with potential HIV exposure.

Methods:

Young women aged 16–25 years and ≥1 of their male partners were enrolled in separate but linked longitudinal HIV PrEP studies in Kampala, Uganda, from 2018 to 2021. Data on sexual behavior, PrEP use, sexually transmitted disease positivity, and Y chromosome DNA (Yc DNA; a marker for condomless sex) were collected at enrollment and quarterly visits. Potential HIV exposure was defined as one of the following in the past 3 months: any sexually transmitted disease, detection of Yc DNA, condomless vaginal sex, or multiple sex partners. Alignment between potential HIV exposure and PrEP use by participants was examined using generalized estimating equation (GEE) regression.

Results:

Eighty-eight young women (median age = 20.6 years, interquartile range 19.5–22.0) and 124 male partners (median age = 23.5 years, interquartile range 21.0–26.0) were included. Women and men were dispensed PrEP in 66.9% and 60.5% of their first linked visits, respectively. PrEP dispensation was more common when women or men self-reported condomless vaginal sex and multiple sex partners or when women had Yc DNA detected in vaginal swabs. Men's self-report of multiple partners (adjusted prevalence ratio = 1.56, P = 0.012) and the detection of Yc DNA (adjusted prevalence ratio = 1.52, P = 0.040) were significantly associated with women's PrEP dispensation.

Conclusions:

Women and their male partners may align their PrEP use with their HIV risk behaviors, providing some reassurance that PrEP discontinuation in young people often aligns with sexual behavior. Greater attention to measurement of and mismatches in PrEP discontinuation and potential HIV exposure is needed.
Impact of Age of Sexual Debut on HIV Care Engagement Among Sexual and Gender Minorities in Nigeria
Authors: Volpi Connor , Adebiyi Ruxton , Chama John , Ononaku Uche , Aka Abayomi , Mitchell Andrew , Shutt Ashley , Kokogho Afoke , Tiamiyu Abdulwasiu B. , Baral Stefan D. , Charurat Man , Adebajo Sylvia , Crowell Trevor A. , Nowak Rebecca G. ,   on behalf of the TRUST/RV368 Study Group
Published: December 2024

Background:

Sexual and gender minorities (SGM) bear a high burden of HIV. The age of anal sexual debut may influence HIV care engagement. Our objective was to evaluate this relationship to help health care providers promote and anticipate future HIV care engagement among at-risk SGM.

Methods:

The TRUST/RV368 study provided HIV testing and treatment at SGM-friendly clinics in Abuja and Lagos, Nigeria. Self-reported age of sexual debut was dichotomized as <16 or ≥16 years. Multivariable logistic models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the association of sexual debut with (1) HIV testing history, (2) HIV testing at the clinics, (3) initiation of antiretroviral therapy (ART) within 6 months of a clinic diagnosis, and (4) viral suppression within 12 months of ART initiation.

Results:

Of the 2680 participants, 30% (n = 805) reported a sexual debut <16 years. Those with an <16-year debut had significantly more receptive sex partners, condomless sex, and transactional sex (all P < 0.01) and were 24% less likely to have tested for HIV before enrollment (aOR: 0.76; CI: 0.62 to 0.93). However, <16-year debut was not associated with HIV testing, receiving ART, or achieving viral suppression once engaged with TRUST/RV368 (all P > 0.05).

Conclusions:

SGM with <16-year debut engaged in behaviors that could increase HIV risk and were less likely to have a history of HIV testing. However, once enrolled in SGM-friendly clinics, uptake of HIV care was not associated with <16-year debut, suggesting that SGM-friendly care models may promote HIV care engagement.
Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators
Authors: Goldberg Jason F. , deFilippi Christopher R. , Lockhart Christopher , McNair Erick R. , Sinha Shashank S. , Kong Hyesik , Najjar Samer S. , Lohmar Brendan J. , Tchoukina Inna , Shah Keyur , Feller Erika , Hsu Steven , Rodrigo Maria E. , Jang Moonkyoo , Marboe Charles C. , Berry Gerald J. , Valantine Hannah A. , Agbor-Enoh Sean , Shah Palak
Published: December 2024

Background.

Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods.

Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results.

Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR). Differential expression was found in 2 proteins during ACR (inflammatory proteins CXCL10 and CD5) and 73 proteins during AMR. The most abundant AMR proteins were the heart failure biomarkers N-terminal pro-B-type natriuretic peptide and suppression of tumorigenicity 2. In univariate logistic regression, odds of identifying ACR on endomyocardial biopsy increased with doubling of CXCL10 (odds ratio [OR] 2.2 [95% confidence interval (CI), 1.3-3.6]) and CD5 (OR 4.7 [95% CI, 1.7-12.9]) concentrations, and odds of AMR increased with doubling of N-terminal pro-B-type natriuretic peptide (OR 13.0 [95% CI, 2.7-62.7) and suppression of tumorigenicity 2 (OR 4.8 [95% CI, 2.1-10.7]) concentrations. After multivariable analysis with clinical covariates, these proteins showed similar odds of ACR or AMR on biopsy. Pathway analysis identified T cell–receptor signaling and cell differentiation as key pathways in ACR and cardiovascular disease and cell turnover in AMR.

Conclusions.

Proteomic analysis reveals unique biomarkers and biological pathway expression in ACR and AMR. Cardiac injury-associated biomarkers were more pronounced in AMR, whereas inflammatory biomarkers were more pronounced in ACR. Proteomic analysis may provide insights into rejection pathophysiology, detection, and therapy.
Geometrical frustration in nonlinear mechanics of screw dislocation
Authors: Kobayashi Shunsuke , Tarumi Ryuichi
Published: December 2024

The existence of stress singularities and reliance on linear approximations pose significant challenges in comprehending the stress field generation mechanism around dislocations. This study employs differential geometry and calculus of variations to mathematically model and numerically analyse screw dislocations. The kinematics of the dislocation are expressed by the diffeomorphism of the Riemann–Cartan manifold, which includes both the Riemannian metric and affine connection. The modelling begins with a continuous distribution of dislocation density, which is transformed into torsion

τ

through the Hodge duality. The plasticity functional is constructed by applying the Helmholtz decomposition to bundle isomorphism, which is equivalent to the Cartan first structure equation for the intermediate configuration

B

. The current configuration is derived by the elastic embedding of

B

into the standard Euclidean space

ℝ
3

. The numerical analysis reveals that the elastic stress fields effectively eliminate the singularity along the dislocation line and exhibit excellent conformity with Volterra’s theory beyond the dislocation core. Geometrical frustration is the direct source of dislocation stress fields, as demonstrated through the multiplicative decomposition of deformation gradients. By leveraging the mathematical properties of the Riemann–Cartan manifold, we demonstrate that the Ricci curvature determines the symmetry of stress fields. These results substantiate a long-standing mathematical hypothesis: the duality between stress and curvature.
Scaling of the extended phenotype: convergent energetics from diverse spider web geometries
Authors: Greenberg-Pines Gabriel , Straus Samantha , Bennett Robb , Avilés Leticia
Published: December 2024

Organisms capture energy to support growth, survival and reproduction in diverse ways. Larger metazoans require less energy per unit time and mass than smaller ones. Thus, structures animals build to capture energy need not scale isometrically with body size. Web-building spiders use silk structures of diverse geometries to capture energy, including two-dimensional orbs in some families or three-dimensional tangles or sheet-and-tangles, in others. Despite this diversity, we show that energy consumption rate per unit mass scaled identically with body size across all web geometries with a less than 1 : 1 relationship to body size, as expected for metazoans from metabolic theory. Spiders thus appear to adjust the size and shape of their webs in precise ways to attain this relationship, including, as we show here, creating a hollow space within certain three-dimensional web types to maintain a constant prey capture surface area per unit spider mass as they grow in size without requiring more silk. Our findings show how the allometric relationship between energetic traits and body size can be mediated by extended phenotypes and suggest an equivalence paradigm akin to the equal fitness paradigm whereby the diverse adaptive strategies of organisms allow them to perform equally well in supplying a unit of mass the energy needed across a lifetime.
Blood Omics Models for System-Specific Mortality Risk Estimation
Authors: Fuentealba Matías , Arpawong Thalida Em , Schneider Kevin , Crimmins Eileen M , Furman David
Published: December 2024

Traditional blood-based aging clocks provide an estimate of a person’s overall biological age. However, physiological systems and organs age at different rates in an individual, and anti-aging interventions often target specific physiological systems. Therefore, there is a growing need for methods capable of assessing biological age at the level of specific physiological systems. Here, we used blood chemistry and cell count data from 456,180 individuals in the UK Biobank (UKB) to develop mortality-based predictors of biological age across 9 physiological systems matching WHO’s International Classification of Disease (ICD-10) chapters (DiseaseAge). We applied DiseaseAge to the Health and Retirement Study (HRS) cohort and validated its ability to identify biologically older systems in individuals diagnosed or deceased from age-related diseases affecting those systems. For instance, individuals diagnosed with high blood pressure, heart attack, congestive heart failure, or angina exhibited a biologically older circulatory system than other systems. Similarly, individuals with accelerated aging in the circulatory, musculoskeletal, or respiratory systems displayed higher risk of mortality from conditions associated with these systems. Additionally, we showed that individuals within the top 5% biologically older metabolic, circulatory, respiratory and mental systems exhibited increased risk of developing diabetes, high blood pressure, lung disease and dementia, respectively. Finally, we used metabolomics and proteomics data in the UKB and epigenomics and transcriptomics in HRS to generate omics surrogates of DiseaseAge for all physiological systems and created an online resource for their calculation.
Flow-Induced Vascular Remodeling On-Chip: Implications for Anti-VEGF Therapy
Authors: Mirzapour-Shafiyi Fatemeh , Huber Elias , Karr Leonie , Tong Johnny , Bausch Andreas R. , Simmel Friedrich C. , Alim Karen
Published: December 2024

Impaired vascular remodeling is linked to tumor progression, impacting the efficacy of anti-vascular therapies. However, the interplay between blood flow and vascular endothelial growth factor (VEGF) in driving vascular remodeling remains unclear. We optimized a human vasculature-on-chip system for long-term perfusion to quantify vascular remodeling under physiologically low and tumor-mimicking high VEGF conditions. Live imaging shows that at low VEGF levels, flow-conditioned vascular networks remodeled like animal models, en-hancing flow velocities. Conversely, static networks lacking flow exhibited continuous growth, loss of network hierarchy, and decreased flow velocities. At tumor-mimicking high VEGF levels, flow-conditioned vessels showed aberrant overgrowth, which was blocked by the anti-VEGF tumor drug bevacizumab, restoring flow-induced remodeling. Without flow, however, high VEGF slowed vessel growth compared to low VEGF, while anti-VEGF treatment restored continuous growth. These findings provide valuable insights into optimizing anti-angiogenic therapies by exploiting VEGF modulation and flow conditions for vascular remodeling and improved tumor treatment.
Farming with Alternative Pollinators for Increased Biodiversity and Smallholder Incomes in Zimbabwe
Authors: Allebone-Webb Sophie , Gossrau Felix , Orland Chloé , Bara Gracian , Fioekou Cédric , Matsika Annah , Riber Karl , Dioula Bader Mahaman
Published: December 2024

1.

Pollinator populations have dramatically declined over the past 50 years, with over 40% of invertebrate pollinator species at risk of extinction largely due to intensive agriculture, pesticide use, habitat loss and climate change. Pollinators provide an essential ecosystem service, with about 75% of global crops relying on pollination by animals. It is therefore essential to reconsider conventional farming practices, which are largely responsible for this decline. By cultivating flowering crops “Marketable Habitat Enhancement Plants”, (MHEPs), alongside the edges of pesticide-free fields, the Farming with Alternative Pollinators (FAP) approach aims to enhance the presence of wild pollinators. In this study, we compared the performance of smallholder farmer plots using the FAP approach with plots following conventional approaches, for pollinator abundance and diversity, yield and income for 43 plots in Zimbabwe. We found significantly higher pollinator abundance and richness in FAP plots compared to control plots. There was significantly higher income and higher value of yields for all offtake in FAP plots for both crop cycles measured. Plots with higher pollinator abundance showed significantly higher income from all crops and significantly higher value of yields, showing a clear link between pollinator populations, crop production and income.
A mathematical model clarifies the ABC Score formula used in enhancer-gene prediction
Authors: Nasser Joseph , Nam Kee-Myoung , Gunawardena Jeremy
Published: December 2024

Enhancers are discrete DNA elements that regulate the expression of eukaryotic genes. They are important not only for their regulatory function, but also as loci that are frequently associated with disease traits. Despite their significance, our conceptual understanding of how enhancers work remains limited. CRISPR-interference methods have recently provided the means to systematically screen for enhancers in cell culture, from which a formula for predicting whether an enhancer regulates a gene, the Activity-by-Contact (ABC) Score, has emerged and has been widely adopted. While useful as a binary classifier, it is less effective at predicting the quantitative effect of an enhancer on gene expression. It is also unclear how the algebraic form of the ABC Score arises from the underlying molecular mechanisms and what assumptions are needed for it to hold. Here, we use the graph-theoretic linear framework, previously introduced to analyze gene regulation, to formulate thedefault model, a mathematical model of how multiple enhancers independently regulate a gene. We show that the algebraic form of the ABC Score arises from this model. However, the default model assumptions also imply that enhancers act additively on steady-state gene expression. This is known to be false for certain genes and we show how modifying the assumptions can accommodate this discrepancy. Overall, our approach lays a rigorous, biophysical foundation for future studies of enhancer-gene regulation.
Beta cells are essential drivers of pancreatic ductal adenocarcinoma development
Authors: Garcia Cathy C. , Venkat Aarthi , McQuaid Daniel C. , Agabiti Sherry , Tong Alex , Cardone Rebecca L. , Starble Rebecca , Sogunro Akin , Jacox Jeremy B. , Ruiz Christian F. , Kibbey Richard G. , Krishnaswamy Smita , Muzumdar Mandar Deepak
Published: December 2024

Pancreatic endocrine-exocrine crosstalk plays a key role in normal physiology and disease. For instance, endocrine islet beta (β) cell secretion of insulin or cholecystokinin (CCK) promotes progression of pancreatic adenocarcinoma (PDAC), an exocrine cell-derived tumor. However, the cellular and molecular mechanisms that govern endocrine-exocrine signaling in tumorigenesis remain incompletely understood. We find that β cell ablation impedes PDAC development in mice, arguing that the endocrine pancreas is critical for exocrine tumorigenesis. Conversely, obesity induces β cell hormone dysregulation, alters CCK-dependent peri-islet exocrine cell transcriptional states, and enhances islet proximal tumor formation. Single-cell RNA-sequencing,in silicolatent-space archetypal and trajectory analysis, and genetic lineage tracingin vivoreveal that obesity stimulates postnatal immature β cell expansion and adaptation towards a pro-tumorigenic CCK+ state via JNK/cJun stress-responsive signaling. These results define endocrine-exocrine signaling as a driver of PDAC development and uncover new avenues to target the endocrine pancreas to subvert exocrine tumorigenesis.
The Product neutrality function defining genetic interactions emerges from mechanistic models of cell growth
Authors: Fuentes Valenzuela Lucas , Francois Paul , Skotheim Jan
Published: December 2024

Genetic analyses, which examine the phenotypic effects of mutations both individually and in combination, have been fundamental to our understanding of cellular functions. Such analyses rely on a neutrality function that predicts the expected phenotype for double mutants based on the phenotypes of the two individual non-interacting mutations. In this study, we examine fitness, the most fundamental cellular phenotype, through an analysis of the extensive colony growth rate data for budding yeast. Our results confirm that the Product neutrality function describes the colony growth rate, or fitness, of a double mutant as the product of the fitnesses of the individual single mutants. This Product neutrality function performs better than additive or minimum neutrality functions, supporting its continued use in genetic interaction studies. Furthermore, we explore the mechanistic origins of this neutrality function by analyzing two theoretical models of cell growth. We perform a computational genetic analysis to show that in both models the product neutrality function naturally emerges due to the interdependence of cellular processes that maximize growth rates. Thus, our findings provide mechanistic insight into how the Product neutrality function arises and affirm its utility in predicting genetic interactions affecting cell growth and proliferation.
An integrative approach for profiling antibody responses in bats to human pathogens
Authors: Toshkova Nia , Zhelyzkova Violeta , Koseva Kaloyana , Dimitrova Katrin , Elshaer Farida , Lacombe Robin V. , Lecerf Maxime , Pashov Anastas , Dimitrov Jordan D.
Published: December 2024

Serological analyses are a fundamental tool for identifying infections by a wide range of pathogens. They offer a current overview of pathogen prevalence and insight into past infections. This is particularly relevant for bats, given their high capacity to tolerate pathogens and their role as reservoirs of zoonotic diseases. At present, serological studies in bats have predominantly employed traditional techniques such as enzyme-linked immunosorbent assay (ELISA). However, these techniques have several limitations, including low throughput and the lack of bat-specific detection antibodies. To address these limitations, we developed an integrative approach for systemic serological analyses based on microarray technology, which enables the simultaneous detection of bat IgG antibodies against >190 human pathogens (viruses, bacteria, protists). The results of our analyses demonstrated an antibody response in bats targeting multiple epitopes from different pathogens, thereby proving the method’s high-throughput capability. Furthermore, this approach does not rely on the use of IgG detection reagents, thereby allowing for its application to a diverse range of bat species. This assay offers insights into the infections of bats with pathogens, thereby enhancing our comprehension of zoonotic disease dynamics and facilitating targeted pathogen surveillance.
From Micro to Macro: Avian Chromosome Evolution is Dominated by Natural Selection
Authors: Alfieri James M. , Bolwerk Kevin , Hu Zhaobo , Blackmon Heath
Published: December 2024

Birds display striking variation in chromosome number, defying the traditional view of highly conserved avian karyotypes. However, the evolutionary drivers of this variability remain unclear. To address this, we fit probabilistic models of chromosome number evolution across birds, enabling us to estimate rates of evolution for total chromosome number and the number of microchromosomes and macrochromosomes while simultaneously accounting for the impact of other evolving traits. Our analyses revealed higher rates of chromosome fusion than fission across all bird lineages. Notably, much of this signal was driven by Passeriformes, where migratory species showed a particularly strong bias towards fusions compared to sedentary counterparts. Furthermore, a robust correlation between the rearrangement rates of microchromosomes and macrochromosomes suggests that genome-wide processes drive rates of structural evolution. Additionally, we found that lineages with larger population sizes exhibited higher rates of both fusion and fission, indicating that positive selection plays a dominant role in driving divergence in chromosome number. Our findings illuminate the evolutionary dynamics of avian karyotypes and highlight that, while the fitness effects of random structural mutations are often deleterious, beneficial mutations may dominate karyotype divergence in some clades.
AtSDR4L and paralog promote seed-to-seedling transition in multiple seed compartments
Authors: Lu Bailan , Go Dongeun , Shan Jiayi , Song Liang
Published: December 2024

Arabidopsis thalianaSEED DORMANCY 4-LIKE (AtSDR4L) and its paralog Dynamic Influencer of Gene Expression 2 (DIG2) act as transcriptional co-repressors to promote seed-to-seedling phase transition. Their regulatory roles at the temporal and tissue-specific scales remain elusive. Here, we show thatAtsdr4l dig2seeds over-accumulate multiple hormones, and the mutant phenotypes are alleviated by abscisic acid (ABA) antagonists and gibberellin (GA). Dissected mutant embryos exhibit stunted growth due to reduced cell differentiation and expansion. The double mutant results in extensive changes in gene expression in both the seed coat and the embryo, including many transcription factors genes, with a subset of the genes differentially expressed tissue-specifically. Transcriptomes ofAtsdr4l-5 dig2seed compartments form a distinct cluster from those of the mutant seedlings ofAtsdr4land Polycomb Repressive Complex (PRC)-related genes, suggesting developmental stage-specific role of these regulators. Together, these results demonstrated that AtSDR4L and DIG2 work in concert to launch the growth potential in the embryo and alleviate the constraints in the seed coat to prepare seeds for germination.
Hypoxia inducible factors drive miRNA-mediated downregulation ofL2HGDHandHIF1Ain clear cell renal cancer independent of 14q deletion
Authors: Seal Soma , Luchtel Rebecca A. , Akram Talia , Isaila Bogdan , Perry Kent T. , Procissi Daniele , Hafizi Sassan , Shenoy Niraj K.
Published: December 2024

Clear cell renal cell carcinoma (ccRCC) is characterized by pseudohypoxic signaling as well as metabolic and epigenetic aberrations of increasing severity during its pathogenesis and progression. Upon identifying that the markedly lower expression ofL2HGDHandHIF1Ain ccRCC tumors is not explained only by 14q deletion (⁓40% of ccRCC), we sought to elucidate the mechanisms underscoring their down-regulation independent of 14q deletion, given the marked translational and scientific importance. While lowerL2HGDHexpression was found to portend a strikingly worse prognosis in a multivariate survival analysis of ccRCC patients (n=509; TCGA) highlighting its translational importance, the paradoxical downregulation ofHIF1AmRNA in ccRCC despite the upregulation of HIF1α protein (secondary to VHL loss) is of significant scientific interest. Using a comprehensive array of in vitro assays, clinicogenomic bioinformatic analyses of large ccRCC datasets, and theCdh16-CreVhl-fl mouse model with kidney specificVhl-loss, we show that the hypoxia-inducible factors upregulate miR21-3p and miR155-5p, which subsequently targetL2HGDHandHIF1Arespectively, during ccRCC pathogenesis and progression. In doing so, we unveil a conserved inhibitory feedback loop forHIF1Ain ccRCC (HIFs→miR155→HIF1A), providing a mechanistic explanation forHIF1Adownregulation despite elevated HIF1α protein. Furthermore- and most importantly-we show that inhibition of hypoxia-inducible factors reverses the adverse loss ofL2HGDHand hydroxymethylcytosine in ccRCC, implicating both HIF2α (primarily) and HIF1α in these metabolic-epigenetic aberrations.

Graphical Abstract
Beyond Stimulus Onset: Ongoing Fixations Within an Object Do Not Re-evoke Category Representations During Free-Viewing
Authors: Auerbach-Asch Carmel Ruth , Deouell Leon Y
Published: December 2024

Human visual perception in natural conditions involves multiple fixations within single objects. While traditional studies focus on transient neural responses to initial stimuli, this study investigates how object-category representations evolve across sequential fixations on an object. Using electroencephalography (EEG) and eye-tracking, we analyzed fixation-related potentials (FRPs) and applied multivariate pattern analysis (MVPA) to decode neural representations of faces and watches during prolonged viewing. Results revealed robust category-selective responses, including the N170 component, at stimulus onset, with sustained representations persisting throughout object presentation. Temporal signal deconvolution showed that subsequent fixations did not re-evoke the N170 but elicited transient occipital responses, likely reflecting low-level differences. These findings underscore the dynamic interplay between transient and sustained neural processes during naturalistic vision and highlight the importance of disentangling overlapping neural signals during free viewing.
Cortical dynamics in hand/forelimb S1 and M1 evoked by brief photostimulation of the mouse’s hand
Authors: Novo Daniela Piña , Gao Mang , Yu Jianing , Barrett John M. , Shepherd Gordon M. G.
Published: December 2024

Spiking activity along synaptic circuits linking primary somatosensory (S1) and motor (M1) areas is fundamental for sensorimotor integration in cortex. Circuits along the ascending somatosensory pathway through mouse hand/forelimb S1 and M1 were recently described in detail (Yamawaki et al., 2021). Here, we characterize the peripherally evoked spiking dynamics in these two cortical areas in the same system. Brief (5 ms) optogenetic photostimulation of the hand generated short (∼25 ms) barrages of activity first in S1 (onset latency 15 ms) then M1 (10 ms later). The estimated propagation speed was 20-fold faster from hand to S1 than from S1 to M1. Response amplitudes in M1 were strongly attenuated to approximately a third of those in S1. Responses were typically triphasic, with suppression and rebound following the initial peak. Parvalbumin (PV) inhibitory interneurons were involved in each phase, accounting for three-quarters of the initial spikes generated in S1, and their selective photostimulation sufficed to evoke suppression and rebound in both S1 and M1. Partial silencing of S1 by PV activation during hand stimulation reduced the M1 sensory responses. These results provide quantitative measures of spiking dynamics of cortical activity along the hand/forelimb-related transcortical loop; demonstrate a prominent and mechanistic role for PV neurons in each phase of the response; and, support a conceptual model in which somatosensory signals reach S1 via high-speed subcortical circuits to generate characteristic barrages of cortical activity, then reach M1 via densely polysynaptic corticocortical circuits to generate a similar but delayed and attenuated profile of activity.
Detection and characterization of Langya virus inCrocidura lasiura, Republic of Korea
Authors: Natasha Augustine , Pye Sarah E. , Park Kyungmin , Rajoriya Shivani , Yang Intae , Park Jieun , Pangestu Haryo Seno , Kim Jongwoo , Oh Yeonsu , López Carolina B. , Song Jin-Won , Kim Won-Keun
Published: December 2024

This study reports the identification of Langya virus Korea (LayV KOR) during the surveillance of shrews in the Republic of Korea. LayV KOR represents the first identification of LayV outside of China, exhibiting approximately 80% and 95.5% homologies at nucleotide and amino acid levels.
Best practice mass photometry: A guide to optimal single molecule mass measurement
Authors: Kratochvíl Jiří , van Wee Raman , Loewenthal Dan , Thiele Jan Christoph , Bardzil Jack , Iqbal Kishwar , Thorpe Stephen , Kukura Philipp
Published: December 2024

Mass photometry (MP) has emerged as a powerful approach to study biomolecular structure, dynamics and interactions. The capabilities of the method ultimately hinge on the ability to accurately measure the tiny optical contrast generated by individual molecules landing at a glass-water interface, which enables mass-resolved quantification of biomolecular mixtures. Ideally, this capability is only limited by shot noise inherent to photon detection, but in practice depends on additional parameters and details of the assay. Here, we focus on the key parameters affecting MP performance, and present simple steps that can be taken to achieve optimal MP performance in terms of mass resolution, quantitative detection limit and analyte concentration range without compromising the ease and simplicity of the technique.
The respiratory phase modulates task-related neural representations of visual stimuli
Authors: Stetza Lisa , Hehemann Lena , Kayser Christoph
Published: December 2024

We investigate how respiration influences cognition by examining the interaction between respiratory phase and task-related brain activity during two visual categorization tasks. While prior research shows that cognitive performance varies along the respiratory cycle, the underlying neurophysiological mechanisms remain poorly understood. Though some studies have shown that large-scale neural activity reflecting changes in the excitation-inhibition balance is co-modulated with the respiratory cycle, it remains unclear whether respiration directly shapes the quality by which task-relevant sensory information is encoded. We address this gap by applying single-trial multivariate analyses to EEG data obtained in humans, allowing us to track how respiration modulates the sensory evidence in this neurophysiological signal. Confirming previous studies, our data show that participant’s performance varies with the respiratory phase prior and during a trial. Importantly, they also suggest that respiration directly influences the sensory evidence carried by parieto-occipital processes emerging around 300 to 200 ms prior to participant’s responses. Hence, respiration and sensory-cognitive processes are not only highly intertwined but respiration directly facilitates the representation of behaviourally-relevant signals in the brain.
Exploring mitonuclear interactions in the regulation of cell physiology: insights from interspecies cybrids
Authors: Gaertner Kateryna , Tapanainen Riikka , Saari Sina , Fekete Zsófia , Goffart Steffi , Pohjoismäki Jaakko L. O. , Dufour Eric
Published: December 2024

Brown hares (Lepus europaeus) and mountain hares (Lepus timidus) frequently hybridize in regions where their range overlaps, producing fertile offspring and enabling gene flow between the species. Despite this, no hybrid species has emerged, suggesting that hybrid backcrosses may incur fitness costs. One potential mechanism for such costs involves the interactions between mitochondrial and nuclear gene products, where incompatibilities between species-specific alleles may reinforce species barriers and lead to hybrid breakdown. However, direct experimental evidence for this hypothesis remains limited.

In this study, we used fibroblasts derived from skin biopsies of wild-caught hares to generate cytoplasmic hybrid (cybrid) cell lines, wherein mitochondria and mtDNA from one species were transferred to mitochondria-depleted cells of the other species, creating novel mitonuclear gene combinations while preserving the original diploid nuclear background. Employing a range of techniques – including transcriptomics, metabolomics, microscopy, and respirometry – we explored the consequences of mitochondrial transfer between these hare species. Our results reveal that in the studied species mitonuclear incompatibilities exhibit strong effects on cellular fitness but are limited to specific genotypes. We propose mechanisms of cellular-level incompatibility and their potential consequences for interspecific hybrids, offering new insights into the complexity of mitonuclear interactions.