bluuebunny/crossref_metadata_2025 huggingface dataset:
Is radiofrequency ablation effective in treating patients with chronic knee osteoarthritis? A meta-analysis of randomized controlled trials
Authors: Chen Bingkeng , Yang Yang , Wang Hui , Guo Xuefang , Wu Zhiqiang , Lan Zhibin
Published: November 2023

Background and aims:

This meta-analysis aimed to evaluate the short-term and long-term efficacy of radiofrequency ablation (RFA) and explore the role of diagnostic genicular nerve blocks in predicting treatment outcomes.

Methods:

A comprehensive literature search was conducted, and nine randomized controlled trials involving 714 participants were included in the analysis. Data extraction, risk of bias assessment, and subgroup analyses were performed. The primary outcome measures were pain scores at 6 and 12 months, assessed using visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Results:

The meta-analysis revealed that RFA demonstrated a significant short-term efficacy in reducing pain compared to the control group at 6 months, as indicated by the pain scores [weighted mean difference (WMD): −2.69, 95% CI: −3.99, −1.40]. Similarly, WOMAC scores at 6 months favored the RFA group (WMD: −4.40, 95% CI: −7.12, −1.68). However, the long-term efficacy of RFA at 12 months remained uncertain for both pain scores (WMD: −0.88, 95% CI: −2.36, 0.61) and WOMAC (WMD: 0.03, 95% CI: −0.25, 0.32). Subgroup analysis suggested that a positive result from the diagnostic genicular nerve blocks test was associated with a more favourable short-term outcome.

Conclusion:

This meta-analysis provides moderate-quality evidence supporting the short-term efficacy of RFA in reducing pain in patients with knee osteoarthritis. The inclusion of a diagnostic genicular nerve blocks test prior to RFA may help identify patients likely to benefit from the procedure. But it still needs more large sample studies to verify the results. However, further research is needed to determine the long-term efficacy of RFA in managing knee osteoarthritis pain.
Accuracy of imaging grading in comparison to open laminectomy to evaluate pedicle screws positioning
Authors: Rosa Filezio Marina , Peiro-Garcia Alejandro , Parsons David Llewellyn , Thomas Kenneth , Ferri-de-Barros Fabio
Published: November 2023

Study design:

Prospective experimental study.

Objective:

To compare the accuracy of O-Arm-acquired radiographic and computed tomography (CT) evaluation of thoracic pedicle screw placement with open laminectomy in a simulation laboratory.

Summary of background data:

Improving surgical safety and procedural efficiency during thoracic posterior spine instrumentation is essential for decreasing complication rates and possible related risks. The most common way of verifying the position of pedicle screws during the surgical procedure and immediately postoperatively is to acquire intraoperative fluoroscopic images and plain radiographs of the spine, respectively. Laboratory simulated surgery is a valuable tool to evaluate the accuracy of those exams.

Methods:

Twenty simulation models of scoliosis from T3 to T7 were instrumented by five spine fellows (total of 200 pedicle screws), followed by radiographic and CT images acquired with the assistance of the O-Arm which were evaluated by three independent raters. A fellowship-trained spine neurosurgeon performed laminectomies on the instrumented levels and assessed pedicle integrity (gold standard).

Results:

Forty-eight breaches were identified in the axial direct view after laminectomy. Of those, eighteen breaches were classified as unacceptable. Regarding the sagittal direct view, four breaches were observed, three of which were classified as unacceptable. Overall, both O-arm radiographic and CT evaluations had a significantly high negative predicted value but a low positive predicted value to identify unacceptable breaches, especially in the sagittal plane. The frequency of missed breaches by all three examiners was high, particularly in the sagittal plane.

Conclusion:

Postoperative evaluation of pedicle screws using O-arm-acquired radiographic or CT images may underdiagnose the presence of breaches. In our study, sagittal breaches were more difficult to diagnose than axial breaches. Although most breaches do not have clinical repercussions, this study suggests that this modality of postoperative radiographic assessment may be inaccurate.

Level of evidence:

4.
Scope and Suction: Hysteroscopic-Guided Suction Evacuation of Cesarean Scar Pregnancy—A Safe and Efficacious Treatment for Selected Patients
Authors: Hameed Mohamed Siraj Shahul , Wright Ann , Chern Bernard Su Min
Published: November 2023

(Abstracted from Gynecol Minim Invasive Ther 2023;12:72–76)

A continual rise of cesarean rates indicates a need to further study the possible development of lower uterine niches or cesarean scar defects, which can be described by adjacent myometrial thickness and residual myometrial thickness (RMT). Pregnancy complications such as placenta accreta spectrum disorders and uterine rupture are associated with RMTs of <2.2 mm.
Cost-Utility Analysis of Midurethral Sling Timing Among Women Undergoing Prolapse Surgery
Authors: Sassani Jessica C. , Giugale Lauren E. , Lavelle Erin Seifert , Shepherd Jonathan P.
Published: November 2023

(Abstracted from Urogynecology 2023; doi: 10.1097/SPV.0000000000001384)

Approximately 25% of women in the United States are affected by pelvic floor disorders, with estimates pointing to a 50% increase in urinary incontinence prevalence and pelvic organ prolapse (POP) by 2050. Surgery for stress urinary incontinence (SUI) is also often required, which adds to economic burdens of pelvic floor disorders. Determining the POP patients who would benefit most from concomitant midurethral slings (MUSs) remains a clinical challenge.
Maternal and Fetal Cardiovascular Responses to Acute High-Intensity Interval and Moderate-Intensity Continuous Training Exercise During Pregnancy: A Randomized Crossover Trial
Authors: Wowdzia J. B. , Hazell T. J. , Vanden Berg E. R. , Labrecque L. , Brassard P. , Davenport M. H.
Published: November 2023

(Abstracted from Sports Med 2023;53(9):1819–1833)

Current recommendations for exercise during pregnancy largely refer to moderate-intensity continuous training (MICT), which has been shown by many studies to be beneficial to both mother and fetus by reducing preeclampsia, gestational diabetes, and depression. Although MICT has been shown to be effective, only 15% of individuals meet the recommended 150-minutes-a-week threshold for MICT; many individuals report their main obstacle as lack of time.
Subtypes of complex regional pain syndrome—a systematic review of the literature
Authors: Knudsen Lone , Santoro Lana , Bruehl Stephen , Harden Norman , Brunner Florian
Published: November 2023

To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.
Value of Quantitative Salivary Gland SPECT/CT for the Detection of Saliva Leakage
Authors: Kim Ji-Young , Kim Han Su , Kang Seo Young , Moon Byung Seok , Kim Bom Sahn , Yoon Hai-Jeon
Published: November 2023

A 47-year-old woman presented to our emergency department with a 10-day history of pain, halitosis, and swelling below the left jaw. The patient was diagnosed with left sialadenitis and left submandibular abscess by tissue biopsy. An otolaryngologist performed transcervical incision and drainage of the abscess 1 day after admission. Postoperatively, the patient complained of a sensation of fluid leakage from the mouth, and a continuous purulent discharge was observed. One month postoperatively, a salivary gland scan and SPECT/CT were performed to investigate the sialorrhea and the cause of the discharge. Salivary gland SPECT/CT images localized the saliva leakage site.
Incidental Tongue Cancer Detected With Total-Body 13N-NH3 PET/CT
Authors: Yu Xiaofeng , Xu Lian , Zhu Lijing , Liu Jianjun , Chen Yumei
Published: November 2023

A 68-year-old man with chest tightness underwent cardiac blood perfusion imaging on total-body 13N-NH3 PET/CT. Incidentally, mildly increased 13N-NH3 activity was observed in the left side of the body of the tongue. Pathological diagnosis proved to be mucosal squamous cell carcinoma.
The Life Cycle of Orofacial Cleft Operations
Authors: Koh Daniel J. , Gong Jung Ho , Sobti Nikhil , Soliman Luke , King Victor , Woo Albert S.
Published: November 2023

Patients with cleft lip and palate must undergo various surgical interventions at appropriate times to achieve optimal outcomes. While guidelines for the timing of these operations are well known, it has not yet been described if national surgical practice reflects these recommendations. This study evaluates whether orofacial operations are performed in time frames that align with advised timing. Time-to-event analyses were performed using the 2012–2020 Pediatric National Surgical Quality Improvement Program database on the ages at time of orofacial operations. Outliers with an absolute Z-score of 3.29 or greater were excluded. Cleft lip (N=9374) and palate (N=13,735) repairs occurred earliest at mean ages of 200.99±251.12 and 655.08±694.43 days, respectively. Both operations clustered along the later end of recommended timing. 69.0% of lip versus 65.1% of palate repairs were completed within the advised age periods. Cleft lip (N=2850) and palate (N=1641) revisions occurred at a mean age of 7.73±5.02 and 7.00±4.63 years, respectively. Velopharyngeal insufficiency operations (N=3026), not including palate revision, were performed at a delayed mean age of 7.58±3.98 years, with only 27.7% of operations occurring within the recommended time frame. Finally, 75.8% of alveolar bone grafting cases (N=5481) were found to happen within the advised time period, with a mean age of 10.23±2.63 years. This study suggests that, with the exception of VPI procedures, orofacial operations reliably cluster near their recommended age periods. Nevertheless, primary lip repair, palatoplasty, and velopharyngeal insufficiency procedures had a mean age that was delayed based on advised timing.
Challenges in Managing Post-Radiation TMJ Pseudoankylosis
Authors: Bangun Kristaninta , Widayanti Nurina , Menna Clara
Published: November 2023

This study demonstrates the outcomes of post-radiation temporomandibular joint (TMJ) pseudoankylosis management and its challenges. A rare maxillary squamous cell carcinoma was treated with subtotal maxillary resection. Subsequent radiation therapy, failure of free flap reconstruction, and 1 year of jaw hypomobility instigated TMJ pseudoankylosis with a maximal mouth opening (MMO) of less than 5 mm. Bilateral coronoidectomy was done simultaneously with maxillary reconstruction, followed up with buccal fibrosis release and extensive jaw exercises. At 16 months of follow-up, the patient’s MMO was 20 mm. Although bilateral coronoidectomy released the attachment of the atrophic temporalis muscle, it did not correct the other causes of trismus, specifically the progressive fibrosis of masticatory muscles, loss of elasticity of the TMJ ligaments, and other soft tissue abnormalities. Radiotherapy-induced–trismus refractory to physical exercise may require further management to achieve satisfactory MMO.
Cervical Necrotizing Fasciitis: A Severe Sequela of Open Mandibular Fracture and Delay in Treatment
Authors: Jinka Sanjay K.A. , Davidson Edward H. , Wang Howard D.
Published: November 2023

Cervical necrotizing fasciitis (CNF) is a rare condition in the United States, with very few cases reported as a sequela of mandibular fracture. The authors describe the case of a 40-year-old man with poor oral health and no significant past medical history who developed CNF following delayed treatment of an open mandibular fracture, leading to life-threatening septic shock, thrombophlebitis of the internal jugular vein, and septic emboli to the lungs. Successful management of this patient was accomplished by serial surgical debridement, the administration of broad-spectrum antibiotics, and hemodynamic support. Eventual reconstruction was performed with external fixation of the mandible fracture and split-thickness skin grafting for the left neck and chest wound. The authors recommend early treatment of open mandibular fractures for immunocompromised patients or patients with poor oral hygiene to avoid the rare but potentially fatal complication of CNF and highlight external fixation as a useful technique in select cases of complex mandibular fractures.
Suicidality and nonsuicidal self-injury in females diagnosed with attention-deficit hyperactivity disorder - a narrative review
Authors: Todzia-Kornaś Agata , Szczegielniak Anna , Gondek Tomasz M.
Published: November 2023

Purpose of review

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder and is associated with an increased risk of suicidal behavior, especially in females. The differences in the presentation of ADHD in females, factors contributing to suicidality and the effects of therapeutic interventions are presented in this review to highlight the relationship between ADHD and suicidality and self-harm behavior.

Recent findings

Impulsivity, an inherent symptom of ADHD, commonly acts as a risk factor of suicidality and is associated with both suicidal behavior and nonsuicidal self-injury. The combined subtype of ADHD, which typically is characterized by significant impulsivity, is linked with the highest vulnerability to suicide attempts. Female gender, lower educational attainment, comorbid substance abuse, a history of depression, and experience of childhood maltreatment were singled out as distinct factors that were independently linked to lifetime suicide attempts.

The association of the ADHD and suicidality is gaining an increasing interest in recent years. Active suicide prevention is required in this population and it is crucial for clinicians and researchers to have access to the most current information in this field.
Investigating the impact of temperature on growth rate of the root rot fungus, Gymnopus fusipes
Authors: Pettifor Bethany J , Kajamuhan Anparasy , Denman Sandra , McDonald James E.
Published: November 2023

Gymnopus fusipes is an understudied root rot pathogen associated with multiple tree species and is linked to episodes of oak decline across the UK and Europe. The reported distribution of G. fusipes potentially spans most of the northern hemisphere, however many of these observations are based on visual identification of fruiting bodies only, which might not always be correct, and there is a lack of confirmatory molecular and/or isolation data to validate this ecological range. Given the paucity of information regarding the true ecological distribution of G. fusipes, it is difficult to predict and model the potential distribution of the species under both current and future climate scenarios. In this study, to determine the growth capabilities of G. fusipes across a range of ecologically relevant temperatures, five geographically diverse isolates of G. fusipes were grown at five different temperatures (ranging from 4˚C to 37˚C), in order to determine the optimal incubation temperature for G. fusipes growth, and to establish whether geographically diverse isolates showed any signs of local adaptation to temperature tolerance, by having different growth rates at different temperatures. G. fusipes isolates grew with varying success at 4˚C, 10˚C, 20˚C and 25˚C, with minimal growth observed with incubation at 37˚C. Statistical analysis, and a generalised linear mixed-effects model fitted to the growth data, illustrated that incubation temperature had a significant effect on G. fusipes growth rate, with 25˚C found to be the optimum (P < 0.001). Isolates were found to have different growth rates at each of the temperatures, with a UK isolate (originating from the south of England) having the highest overall growth rate across all five temperatures tested (P < 0.001), increasing by a mean value of over 4915 mm2 over the 28-day experimental period (at the optimal growth temperature of 25˚C). Local adaptation to temperature was not found in the isolates tested, as there was no significant interaction between temperature and isolate. These data demonstrate the optimal incubation temperature for future laboratory studies on G. fusipes and provide the first data on the growth rate of this pathogen across ecologically relevant climate ranges that may inform land managers, modellers, and policy makers in predicting the current and potentially future geographical limits of this widespread root rot pathogen.
Assessment of an AI virtual staining model performance across same and serial tissue sections using CD3+T cell ground truth
Authors: Azam Abu Bakr , Wee Felicia , Väyrynen Juha P. , Yim Willa Wen-You , Xue Yue Zhen , Chua Bok Leong , Lim Jeffrey Chun Tatt , Tan Daniel Shao Weng , Takano Angela , Chow Chun Yuen , Khor Li Yan , Lim Tony Kiat Hon , Yeong Joe , Lau Mai Chan , Cai Yiyu
Published: November 2023

Immunophenotyping via multi-marker assays significantly contributes to patient selection, therapeutic monitoring, biomarker discovery, and personalized treatments. Despite its potential, the multiplex immunofluorescence (mIF) technique faces adoption challenges due to technical and financial constraints. Alternatively, hematoxylin and eosin (H&E)-based prediction models of cell phenotypes can provide crucial insights into tumor-immune cell interactions and advance immunotherapy. Current methods mostly rely on manually annotated cell label ground truths, with limitations including high variability and substantial labor costs. To mitigate these issues, researchers are increasingly turning to digitized cell-level data for accurate in-situ cell type prediction. Typically, immunohistochemical (IHC) staining is applied to a tissue section serial to one stained with H&E. However, this method may introduce distortions and tissue section shifts, challenging the assumption of consistent cellular locations. Conversely, mIF overcomes these limitations by allowing for mIF and H&E staining on the same tissue section. Importantly, the multiplexing capability of mIF allows for a thorough analysis of the tumor microenvironment by quantifying multiple cell markers within the same tissue section. In this study, we introduce a Pix2Pix generative adversarial network (P2P-GAN)-based virtual staining model, using CD3+T-cells in lung cancer as a proof-of-concept. Using an independent CD3 IHC-stained lung cohort, we demonstrate that the model trained with cell label ground-truth from the same tissue section as H&E staining performed significantly better in both CD3+and CD3-T-cell prediction. Moreover, the model also displayed prognostic significance on a public lung cohort, demonstrating its potential clinical utility. Notably, our proposed P2P-GAN virtual staining model facilitates image-to-image translation, enabling further spatial analysis of the predicted immune cells, deepening our understanding of tumor-immune interactions, and propelling advancements in personalized immunotherapy. This concept holds potential for the prediction of other cell phenotypes, including CD4+, CD8+, and CD20+cells.
Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons
Authors: Wang Guoqiang , Guasp Ryan , Salam Sangeena , Chuang Edward , Morera Andrés , Smart Anna J , Jimenez David , Shekhar Sahana , Friedman Emily , Melentijevic Ilija , Nguyen Ken C , Hall David H , Grant Barth D , Driscoll Monica
Published: November 2023

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading to neurodegenerative disease. Factors that regulate extrusion of large vesicles, such as exophers produced by proteostressedC. eleganstouch neurons, are poorly understood. Here we document that mechanical force can significantly potentiate exopher extrusion from proteostressed neurons. Exopher production from theC. elegansALMR neuron peaks at adult day 2 or 3, coinciding with theC. elegansreproductive peak. Genetic disruption ofC. elegansgermline, sperm, oocytes, or egg/early embryo production can strongly suppress exopher extrusion from the ALMR neurons during the peak period. Conversely, restoring egg production at the late reproductive phase through mating with males or inducing egg retention via genetic interventions that block egg-laying can strongly increase ALMR exopher production. Overall, genetic interventions that promote ALMR exopher production are associated with expanded uterus lengths and genetic interventions that suppress ALMR exopher production are associated with shorter uterus lengths. In addition to the impact of fertilized eggs, ALMR exopher production can be enhanced by filling the uterus with oocytes, dead eggs, or even fluid, supporting that distention consequences, rather than the presence of fertilized eggs, constitute the exopher-inducing stimulus. We conclude that the mechanical force of uterine occupation potentiates exopher extrusion from proximal proteostressed maternal neurons. Our observations draw attention to the potential importance of mechanical signaling in extracellular vesicle production and in aggregate spreading mechanisms, making a case for enhanced attention to mechanobiology in neurodegenerative disease.
High quality, high throughput, and low-cost simultaneous video recording of 60 animals in operant chambers using PiRATeMC
Authors: Ramborger Jarryd , Kalra Sumay , Smith Alexander C.W. , George Olivier
Published: November 2023

Background

The development of Raspberry Pi-based recording devices for video analyses of drug self-administration studies has shown to be promising in terms of affordability, customizability, and capacity to extract in-depth behavioral patterns. Yet, most video recording systems are limited to a few cameras making them incompatible with large-scale studies.

New Method

We expanded the PiRATeMC (Pi-based Remote Acquisition Technology for Motion Capture) recording system by increasing its scale, modifying its code, and adding equipment to accommodate large-scale video acquisition, accompanied by data on the throughput capabilities, video fidelity, synchronicity of devices, and comparisons between the Raspberry Pi 3B+ and 4B models.

Results

Using PiRATeMC default recording parameters resulted in minimal storage (∼350MB/h), high throughput (< ∼120 seconds/Pi), high video fidelity, and synchronicity within ∼0.02 seconds, affording the ability to simultaneously record 60 animals in individual self-administration chambers at a fraction of current commercial costs. No consequential differences were found between Raspberry Pi 3B+ and 4B models.

Comparison with Existing Method(s)

This system allows greater acquisition of video data simultaneously than other video recording systems by an order of magnitude with less storage needs and lower costs. Additionally, we report in-depth quantitative assessments of throughput, fidelity, and synchronicity, displaying real-time system capabilities.

Conclusions

The system presented is able to be fully installed in a month’s time by a single technician and provides a scalable, low cost, and quality-assured procedure with a high-degree of customization and synchronicity between recording devices, capable of recording a large number of subjects with high turnover in a variety of species and settings.
Population size shapes trade-off dilution and adaptation to a marginal niche unconstrained by sympatric habitual conditions
Authors: Chavhan Yashraj , Malusare Sarthak , Dey Sutirth
Published: November 2023

Niche expansion remains significantly understudied in sympatric scenarios where marginal and habitual niches are simultaneously available. Devoid of spatial constraints, such conditions impose selection to maintain fitness in habitual (high-productivity) niches while adapting to marginal (low-productivity) niches. Hence, habitual niche composition should constrain adaptation to marginal niches. This remains untested. Similarly, it is unknown if larger populations expand their niches better. We tested these hypotheses using experimental evolution withEscherichia coliand found that larger populations consistently adapted better to both marginal and habitual niches. Whereas the habitual niche composition (constant versus fluctuating environments; environmental fluctuations varying in both predictability and speed) significantly shaped fitness in habitual niches, surprisingly, it failed to constrain adaptation to the marginal niche. Curiously, two negatively correlated habitual niches can still each be positively correlated with the marginal niche. This allows the marginal niche to dilute trade-offs between habitual niches, thereby enabling costless niche expansion.
Modeling recent positive selection in Americans of European ancestry
Authors: Temple Seth D. , Waples Ryan K. , Browning Sharon R.
Published: November 2023

Recent positive selection can result in an excess of long identity-by-descent (IBD) haplotype segments. The statistical methods that we propose here address three major objectives in studying classical selective sweeps: scanning for regions of interest, identifying possible sweeping alleles, and estimating a selection coefficients. First, we implement a selection scan to locate regions of excess IBD rate. Second, we develop a statistic to rank alleles in strong linkage disequilibrium with a putative sweeping allele. We aggregate these scores to estimate the allele frequency of the sweeping allele, even if it is not genotyped. Lastly, we propose an estimator for the selection coefficient and quantify uncertainty using the parametric bootstrap. Comparing against state-of-the-art methods in extensive simulations, we show that our methods are better at pinpointing alleles at low frequency and estimatings≥ 0.015. We apply these methods to study positive selection in inferred European ancestry samples from the TOPMed project. We find twelve loci where their IBD rates exceed four standard deviations above the population median. The excess IBD rate at LCT is thirty-five standard deviations above the population median, and our estimates of its selection coefficient imply strong selection within the past 120 to 163 generations. Overall, we present robust and accurate new approaches to study very recent adaptive evolution under mild assumptions.
A neural geometry theory comprehensively explains apparently conflicting models of visual perceptual learning
Authors: Cheng Yu-Ang , Sanayei Mehdi , Chen Xing , Jia Ke , Li Sheng , Fang Fang , Watanabe Takeo , Thiele Alexander , Zhang Ru-Yuan
Published: November 2023

Visual perceptual learning (VPL), defined as long-term improvement in a visual task, is considered a crucial tool for elucidating underlying visual and brain plasticity. However, the identification of a unified theory of VPL has long been controversial. Multiple existing models have proposed diverse mechanisms, including improved signal-to-noise ratio, changes in tuning curves, and reduction of noise correlations, as major contributors to improved neural representations associated with VPL. However, each model only accounts for specific aspects of the empirical findings, and there exists no theory that can comprehensively explain all empirical results. Here, we argue that all neural changes at single units can be conceptualized as geometric transformations of population response manifolds in a high-dimensional neural space. This approach enables conflicting major models of VPL to be quantitatively tested and compared within a unified computational theory. Following this approach, we found that changes in tuning curves and noise correlations, as emphasized by previous models, make no significant contributions to improved population representations by visual training. Instead, we identified neural manifold shrinkage due to reduced trial-by-trial neural response variability, a previously unexplored factor, as the primary mechanism underlying improved population representations. Furthermore, we showed that manifold shrinkage successfully accounts for learning effects across various domains, including artificial neural responses in deep neural networks trained on typical VPL tasks, multivariate BOLD signals in humans, and multi-unit activities in monkeys. These converging results suggest that our neural geometry theory offers a quantitative and comprehensive approach to explain a wide range of empirical results and to reconcile previously conflicting models of VPL.
The effects of inhaled corticosteroids on healthy airways
Authors: Marchi Emanuele , Hinks Timothy S.C. , Richardson Matthew , Khalfaou Latifa , Symon Fiona A. , Rajasekar Poojitha , Clifford Rachel , Hargadon Beverley , Austin Cary D. , MacIsaac Julia L. , Kobor Michael S. , Siddiqui Salman , Mar Jordan S. , Arron Joseph R. , Choy David , Bradding Peter
Published: November 2023

Rationale

The effects of inhaled corticosteroids (ICS) on healthy airways are poorly defined.

Objectives

To delineate the effects of ICS on gene expression in healthy airways, without confounding caused by changes in disease-related genes and disease-related alterations in ICS-responsiveness.

Methods

Randomised open-label bronchoscopy study of high dose ICS therapy in 30 healthy adult volunteers randomised 2:1 to i) fluticasone propionate 500 mcg bd or ii) no treatment, for 4 weeks. Laboratory staff were blinded to allocation. Biopsies and brushings were analysed by immunohistochemistry, bulk RNA sequencing, DNA methylation array and metagenomics.

Measurements and main results

ICS induced small between-group differences in blood and lamina propria eosinophil numbers, but not in other immunopathological features, blood neutrophils, FeNO, FEV1, microbiome or DNA methylation. ICS treatment upregulated 72 genes in brushings and 53 genes in biopsies, and downregulated 82 genes in brushings and 416 genes in biopsies. The most downregulated genes in both tissues were canonical markers of type-2 inflammation (FCER1A, CPA3, IL33, CLEC10A, SERPINB10 and CCR5), T cell-mediated adaptive immunity (TARP, TRBC1, TRBC2, PTPN22, TRAC, CD2, CD8A, HLA-DQB2, CD96, PTPN7), B cell immunity (CD20, immunoglobulin heavy and light chains), and innate immunity, including CD48, Hobit, RANTES, Langerin and GFI1. An IL-17-dependent gene signature was not upregulated by ICS.

Conclusions

In healthy airways, 4-week ICS exposure reduces gene expression related to both innate and adaptive immunity, and reduces markers of type-2 inflammation. This implies that homeostasis in health involves tonic type-2 signalling in the airway mucosa, which is exquisitely sensitive to ICS.
ChatGPT Exhibits Gender and Racial Biases in Acute Coronary Syndrome Management
Authors: Zhang Angela , Yuksekgonul Mert , Guild Joshua , Zou James , Wu Joseph C.
Published: November 2023

Recent breakthroughs in large language models (LLMs) have led to their rapid dissemination and widespread use. One early application has been to medicine, where LLMs have been investigated to streamline clinical workflows and facilitate clinical analysis and decision-making. However, a leading barrier to the deployment of Artificial Intelligence (AI) and in particular LLMs has been concern for embedded gender and racial biases. Here, we evaluate whether a leading LLM, ChatGPT 3.5, exhibits gender and racial bias in clinical management of acute coronary syndrome (ACS). We find that specifying patients as female, African American, or Hispanic resulted in a decrease in guideline recommended medical management, diagnosis, and symptom management of ACS. Most notably, the largest disparities were seen in the recommendation of coronary angiography or stress testing for the diagnosis and further intervention of ACS and recommendation of high intensity statins. These disparities correlate with biases that have been observed clinically and have been implicated in the differential gender and racial morbidity and mortality outcomes of ACS and coronary artery disease. Furthermore, we find that the largest disparities are seen during unstable angina, where fewer explicit clinical guidelines exist. Finally, we find that through asking ChatGPT 3.5 to explain its reasoning prior to providing an answer, we are able to improve clinical accuracy and mitigate instances of gender and racial biases. This is among the first studies to demonstrate that the gender and racial biases that LLMs exhibit do in fact affect clinical management. Additionally, we demonstrate that existing strategies that improve LLM performance not only improve LLM performance in clinical management, but can also be used to mitigate gender and racial biases.
Image guided construction of a common coordinate framework for spatial transcriptome data
Authors: Lais Peter , Mishra Shawn , Xiong Kun , Atwal Gurinder S. , Bai Yu
Published: November 2023

Spatial transcriptomics is a powerful technology for high-resolution mapping of gene expression in tissue samples, enabling a molecular level understanding of tissue architecture. The acquisition entails dissecting and profiling micron-thick tissue slices, with multiple slices often needed for a comprehensive study. However, the lack of a common coordinate framework (CCF) among slices, due to slicing and displacement variations, can hinder data analysis, making data comparison and integration challenging, and potentially compromising analysis accuracy. Here we present a deep learning algorithm STaCker that unifies the coordinates of transcriptomic slices via an image registration process. STaCker derives a composite image representation by integrating tissue image and gene expressions that are transformed to be resilient to noise and batch effects. Trained exclusively on diverse synthetic data, STaCker overcomes the training data scarcity and is applicable to any tissue type. Its performance on various benchmarking datasets shows a significant increase in spatial concordance in aligned slices, surpassing existing methods. STaCker also successfully harmonizes multiple real spatial transcriptome datasets. These results indicate that STaCker is a valuable computational tool for constructing a CCF with spatial transcriptome data.
Diverse rhizosphere-associatedPseudomonasgenomes isolated along the marine-terrestrial transition zone of a Wadden island salt march
Authors: Mei Siyu , Wang Miao , Falcão Salles Joana , Hackl Thomas
Published: November 2023

Soil microbes are key drivers of ecosystem processes promoting nutrient cycling, system productivity, and resilience. While much is known about the roles of microbes in established systems, their impact on soil development and the successional transformation over time remains poorly understood. Here, we provide 67 diverse, rhizosphere-associatedPseudomonasdraft genomes from an undisturbed salt march primary succession spanning >100 years of soil development.Pseudomonasare cosmopolitan bacteria with a significant role in plant establishment and growth. We obtained isolates associated withLimonium vulgareandArtemisia maritima, two typical salt marsh perennial plants with roles in soil stabilization, salinity regulation, and biodiversity support. We anticipate that our data, in combination with the provided physiochemical measurements, will help identify genomic signatures associated with the different selective regimes along the successional stages, such as varying soil complexity, texture, and nutrient availability. Such findings would not only advance our understanding ofPseudomonas’role in natural soil ecosystems but also provide the basis for a better understanding of the roles of microbes throughout ecosystem transformations.
DeepMRG: a multi-label deep learning classifier for predicting bacterial metal resistance genes
Authors: Emon Muhit Islam , Zhang Liqing
Published: November 2023

The widespread misuse of antibiotics has escalated antibiotic resistance into a critical global public health concern. Beyond antibiotics, metals function as antibacterial agents. Metal resistance genes (MRGs) enable bacteria to tolerate metal-based antibacterials and may also foster antibiotic resistance within bacterial communities through co-selection. Thus, predicting bacterial MRGs is vital for elucidating their involvement in antibiotic resistance and metal tolerance mechanisms. The “best hit” approach is mainly utilized to identify and annotate MRGs. This method is sensitive to cutoff values and produces a high false negative rate. Other than the best hit approach, only a few antimicrobial resistance (AMR) detection tools exist for predicting MRGs. However, these tools lack comprehensive annotation for MRGs conferring resistance to multiple metals. To address such limitations, we introduce DeepMRG, a deep learning-based multi-label classifier, to predict bacterial MRGs. Because a bacterial MRG can confer resistance to multiple metals, DeepMRG is designed as a multi-label classifier capable of predicting multiple metal labels associated with an MRG. It leverages bit score-based similarity distribution of sequences with experimentally verified MRGs. To ensure unbiased model evaluation, we employed a clustering method to partition our dataset into six subsets, five for cross-validation and one for testing, with non-homologous sequences, mitigating the impact of sequence homology. DeepMRG consistently achieved high overall F1-scores and significantly reduced false negative rates across a wide range of datasets. It can be used to predict bacterial MRGs in metagenomic or isolate assemblies. The web server of DeepMRG can be accessed athttps://deepmrg.cs.vt.edu/deepmrgand the source code is available athttps://github.com/muhit-emon/DeepMRGunder the MIT license.
Small in size but huge as reservoir – insights into the virome of European white-toothed shrews
Authors: Haring Viola C. , Litz Benedikt , Jacob Jens , Brecht Michael , Bauswein Markus , Sehl-Ewert Julia , Heroldova Marta , Hoffmann Donata , Ulrich Rainer G. , Beer Martin , Pfaff Florian
Published: November 2023

While the virome and immune system of bats and rodents have been extensively studied, comprehensive data are lacking for insectivores. Anthropogenic land use and outdoor recreational activities may lead to an expansion of the human-shrew interface with the risk of zoonotic infections, as reported for Borna disease virus 1. We investigated the virosphere of four white-toothed shrew species from Central Europe, addressing the One Health concept of spillover prevention. A high diversity of viruses was identified, including several co-infections. Whole genomes were generated for novel species of paramyxoviruses (n=3), nairoviruses (n=2) and hepevirus. Phylogenetically, they are closely related to WHO priority diseases, such as henipaviruses. High viral loads of orthoparamyxoviruses were detected in kidneys, in well-perfused organs for orthonairoviruses, and an association with liver and intestine was identified for orthohepevirus. Our study highlights the virus diversity present in shrews, not only in biodiversity hotspots but also in industrialised countries.
Natural variability and individuality of walking behavior inDrosophila
Authors: Godesberg Vincent , Bockemühl Till , Büschges Ansgar
Published: November 2023

Insects use walking behavior in a large number of contexts, such as exploration, foraging, escape and pursuit, or migration. A lot is known on how nervous systems produce this behavior in general and also how certain parameters vary with regard to walking direction or speed, for instance. An aspect that has not received much attention is if and how walking behavior varies across individuals of a particular species. To address this, we created a large corpus of kinematic walking data of many individuals of the fruit flyDrosophila. We only selected instances of straight walking in a narrow range of walking speeds to minimize the influence of these high-level parameters, aiming to uncover more subtle aspects of variability. Using high-speed videography and automated annotation we captured the positions of the six leg tips for thousands of steps and used principal components analysis to characterize the postural space individuals used during walking. Our analysis shows that the largest part of walking kinematics can be described by five principal components (PCs). Separation of these five PCs into a 2-dimensional and a 3-dimensional subspace was found to divide the description of walking behavior into invariant features shared across individuals and features that relate to the specifics of individuals; the latter features can be regarded as idiosyncrasies. We also demonstrate that this approach can detect the effects of experimental interventions in an unbiased manner and that general aspects of individuality, such as the average width of the individual walking posture, can be described.

Summary statement

The kinematics of walking behavior inDrosophilacan be decomposed into general aspects of motor output and idiosyncrasies of individual flies.
VaxSeer: Selecting influenza vaccines through evolutionary and antigenicity models
Authors: Shi Wenxian , Wohlwend Jeremy , Wu Menghua , Barzilay Regina
Published: November 2023

Current vaccines provide limited protection against rapidly evolving viruses. For example, the flu vaccine’s effectiveness has averaged below 40% for the past five years. Today, clinical outcomes of vaccine effectiveness can only be assessed retrospectively. Since vaccine strains are selected at least six months ahead of flu season, prospective estimation of their effectiveness is crucial but remains under-explored. In this paper, we propose anin-silicomethod named VaxSeer that selects vaccine strains based on their coverage scores, which quantifiesexpectedvaccine effectiveness in future seasons. This score considers both the future dominance of circulating viruses and antigenic profiles of vaccine candidates. Based on historical WHO data, our approach consistently selects superior strains than the annual recommendations. Finally, the prospective coverage score exhibits a strong correlation with retrospective vaccine effectiveness and reduced disease burden, highlighting the promise of this framework in driving the vaccine selection process.
Capturing cell heterogeneity in representations of cell populations for image-based profiling using contrastive learning
Authors: van Dijk Robert , Arevalo John , Babadi Mehrtash , Carpenter Anne E. , Singh Shantanu
Published: November 2023

Image-based cell profiling is a powerful tool that compares perturbed cell populations by measuring thousands of single-cell features and summarizing them into profiles. Typically a sample is represented by averaging across cells, but this fails to capture the heterogeneity within cell populations. We introduce CytoSummaryNet: a Deep Sets-based approach that improves mechanism of action prediction by 30-68% in mean average precision compared to average profiling on a public dataset. CytoSummaryNet uses self-supervised contrastive learning in a multiple-instance learning framework, providing an easier-to-apply method for aggregating single-cell feature data than previously published strategies. Interpretability analysis suggests that the model achieves this improvement by downweighting small mitotic cells or those with debris and prioritizing large uncrowded cells. The approach requires only perturbation labels for training, which are readily available in all cell profiling datasets. CytoSummaryNet offers a straightforward post-processing step for single-cell profiles that can significantly boost retrieval performance on image-based profiling datasets.
AI-Driven Insights into the complexities of Chinese hamster ovary cells death in order to optimize production processes
Authors: Moshfeghnia Mohammad
Published: November 2023

Chinese hamster ovary (CHO) cells are a multipurpose and high-performance cell line for recombinant protein production in biopharmaceutical industry. They have proven their ability to produce a wide range of therapeutic proteins with high efficiency and quality. Designing novel and high-performance CHO cell lines has an incredible impact in biopharmaceutical industry that can reduce prices and increase product efficiency. One of the best ways is to prevent CHO cells death during Bioprocessing. Apoptosis is the most common form of CHO cells death during Bioprocessing. Analyzing Apoptosis and cell-cycle complex signaling pathways are necessary for the control of cell growth, efficiency, and the death of CHO cells. Therefore, analyzing and understanding interactions of these pathways and their interactions with other cellular processes can help optimize the performance and quality of CHO cell lines. AI-driven insight solutions and Advanced machine learning algorithms like GAT (Graph Attention Network) used in this project indicate most important Targets in complex signaling pathways. Pathways such as the TNF signaling pathway, and also viruses like: Hepatitis C, HIV1 and Bacteria like: Salmonella have High intersection size and Low P-value with complex signaling pathways. These microorganisms should be used to design high-performance CHO cell lines because they are master in these pathways. This method can be used to find novel and high efficiency targets for curing cancer in humans.