bluuebunny/crossref_metadata_2025 huggingface dataset:
The formation of mini-AGN discs around IMBHs and their dynamical implications
Authors: Rozner Mor , Trani Alessandro A , Samsing Johan , Perets Hagai B
Published: January 2025

This study explores the formation and implications of mini-active galactic nucleus (mAGN) discs around intermediate-mass black holes (IMBHs) embedded in gas-rich globular/nuclear clusters (GCs). We examine the parameter space for stable mAGN discs, considering the influence of IMBH mass, disc radius, and gas density on disc stability. The dynamics of stars and black holes within the mAGN disc are modelled, with a focus on gas-induced migration and gas dynamical friction. These dynamical processes can lead to several potentially observable phenomena, including the enhancement of gravitational wave mergers (particularly intermediate-mass ratio inspirals and extreme-mass ratio inspirals), and the occurrence of milli/centi-tidal disruption events with unique observational signatures. We find that gas hardening can significantly accelerate the inspiral of binaries within the disc, potentially leading to a frequency shift in the emitted gravitational waves. Additionally, we explore the possibility of forming accreting IMBH systems from captured binaries within the mAGN disc, potentially resulting in the formation of ultraluminous X-ray sources. The observational implications of such accreting systems, including X-ray emission, optical signatures, and transient phenomena, are discussed. Furthermore, we investigate the possibility of large-scale jets emanating from gas-embedded IMBHs in GCs. While several caveats and uncertainties exist, our work highlights the potential for mAGN discs to provide unique insights into IMBH demographics, accretion physics, and the dynamics of GCs.
Seizure risk factors and management approaches in patients with brain metastases
Authors: Vaios Eugene J , Maingi Spencer , Batich Kristen , Winter Sebastian F , Dietrich Jorg , Mullikin Trey , Floyd Scott R , Kirkpatrick John P , Reitman Zachary J , Peters Katherine B
Published: January 2025

A significant proportion of patients with brain metastases experience a seizure event during their disease course, which can impact morbidity and long-term outcomes. A host of factors elevate the risk for seizures in patients with brain metastases, including patient factors, metabolic imbalances, tumor burden, and treatment modality. While reducing tumor burden via local and systemic therapies remains a critical component to mitigating seizure events, select patients may remain at risk. The use of prophylactic anti-seizure medications may be warranted in a subset of patients, though several clinical trials and guidelines from medical societies currently recommend against prophylactic use. Variability in the use of prophylactic anti-seizure medications in clinical practice underscores the need to update our current understanding of seizure risk in the era of multi-modality treatment and to identify opportunities to improve risk stratification and management. Herein, we provide a comprehensive literature review summarizing the current standard for seizure management in patients with brain metastases and assess the impact of multi-modal therapies on seizure risk. We additionally highlight gaps in the literature and present opportunities for future investigation.
Impact of Policy Changes Expanding Access to Direct-Acting Antivirals on Hepatitis C Virus–Related Hospitalizations in People With HIV: A Population-Based Study
Authors: Antoniou Tony , Ledlie Shaleesa , Wang Tianru , Tadrous Mina , Gomes Tara
Published: January 2025

Background

The burden of hepatitis C virus (HCV)–related hospitalizations is substantial, particularly among people with HIV and HCV. In Ontario, Canada, use of direct-acting antivirals (DAAs) increased following policies removing fibrosis-stage restrictions and approving of pangenotypic agents in 2017 and 2018, respectively. We examined the impact of expanded DAA access on HCV-related hospitalizations in people with HIV.

Methods

We conducted a population-based study using administrative databases between April 2003 and December 2022. We used segmented negative binomial regression to examine changes in level and trend of quarterly HCV-related hospitalization rates in people with HIV following the policy changes and compared predicted rates in the absence of expanded DAA access with observed rates during this period.

Results

We identified 2943 HCV-related hospitalizations among people with HIV during our study period. Rates of HCV-related hospitalizations were substantially higher among people with HIV than individuals without HIV. In the postintervention period, there was an immediate level increase in the rate of HCV-related hospitalizations (rate ratio, 1.23; 95% CI, 1.18–1.29), followed by a decrease in trend (rate ratio, 0.94 per quarter; 95% CI, .93–.94). We estimated that expanding DAA access was associated with 192 fewer hospitalizations in people with HIV between 2019 and 2022.

Conclusions

Policies expanding DAA access have reduced HCV-related hospitalizations in people with HIV. However, rates were higher relative to those in people without HIV. Further research is needed to identify and address disparities in clinical outcomes among people with HIV and HCV.
INSIDE-OUT: Introduction of Speakers at IDWeek Events—Observing for Unconscious Bias Over Time
Authors: Marcelin Jasmine R , Khazanchi Rohan , Lyden Elizabeth , Cawcutt Kelly A , Abdul-Mutakabbir Jacinda C , Ha David R , Florez Narjust , Kullar Ravina , Ristagno Elizabeth H ,   the INSIDE-OUT Study Group (Introduction of Speakers at IDWeek Events—Observing for Unconscious Bias Over Time), Rajapakse Nipunie , Patel Megha , Miller Amy M , Oeltjen Erin N , Semaj Sophie , Sramek Kyle T , Lindeman Christopher J , Daubach Eric C , Akinmoladun Oladapo O , Wurtz Paul J , Yang Yuhong
Published: January 2025

Background

Specialty societies, including the Infectious Diseases Society of America, strive to address gender and racial inequities in professional advancement. Microaggressions remain a persistent and pervasive barrier to these goals. Nonprofessional speaker introductions are a manifestation of race- and gender-based microaggressions, which have not been previously assessed at IDWeek. We assessed disparities in speaker introductions at IDWeek over a 7-year period that included formal gender equity initiatives introduced in 2016.

Methods

We conducted a retrospective observational study of video-recorded IDWeek speaker introductions from 2013 to 2019. Trained coders reviewed presentation video archives to assess a primary outcome of nonprofessional introductions: when a speaker's professional title was not used as the first introduction. We used descriptive statistics, Fisher exact tests, Cochrane-Armitage trend tests, and multivariable logistic regression to characterize relationships between speaker introductions and presentation year, speaker demographics, and speaker-moderator demographic concordance.

Results

Of 1940 videos reviewed, 48.9% of IDWeek speakers received nonprofessional introductions during and before 2016 vs 41.5% of speakers after 2016 (P = .0013). There was an increasing linear trend in the frequency of professional introductions by speaker age group from 47.1% for age <40 years to 65.3% for age >60 years (P < .0001). White moderators more frequently used nonprofessional introductions than moderators from backgrounds underrepresented in medicine (47.7% vs 29.1%, P = .0014). Women-men speaker-moderator pairs had more nonprofessional introductions (54.6%, P < .001).

Conclusions

In the largest assessment of microaggressions in speaker introductions at a national medical specialty conference, we highlighted some progress over time and ample opportunity to further standardize equitable speaker introductions, especially for women and junior speakers
Discovering genetic modulators of the protein homeostasis system through multilevel analysis
Authors: Sarsani Vishal , Aldikacti Berent , Zhao Tingting , He Shai , Chien Peter , Flaherty Patrick
Published: January 2025

Every protein progresses through a natural lifecycle from birth to maturation to death; this process is coordinated by the protein homeostasis system. Environmental or physiological conditions trigger pathways that maintain the homeostasis of the proteome. An open question is how these pathways are modulated to respond to the many stresses that an organism encounters during its lifetime. To address this question, we tested how the fitness landscape changes in response to environmental and genetic perturbations using directed and massively parallel transposon mutagenesis in Caulobacter crescentus. We developed a general computational pipeline for the analysis of gene-by-environment interactions in transposon mutagenesis experiments. This pipeline uses a combination of general linear models, statistical knockoffs, and a nonparametric Bayesian statistical model to identify essential genetic network components that are shared across environmental perturbations. This analysis allows us to quantify the similarity of proteotoxic environmental perturbations from the perspective of the fitness landscape. We find that essential genes vary more by genetic background than by environmental conditions, with limited overlap among mutant strains targeting different facets of the protein homeostasis system. We also identified 146 unique fitness determinants across different strains, with 19 genes common to at least two strains, showing varying resilience to proteotoxic stresses. Experiments exposing cells to a combination of genetic perturbations and dual environmental stressors show that perturbations that are quantitatively dissimilar from the perspective of the fitness landscape are likely to have a synergistic effect on the growth defect.
OP01 MRI is of utility in the evaluation of disease activity in axial Spondyloarthritis- data from a tertiary rheumatology centre
Authors: Weddell Jake , Shah Rahul , Rossi Lara , Robinson Phil , Barr Andrew , Vandevelde Claire , Freeston Jane E , McGonagle Dennis , Marzo-Ortega Helena
Published: January 2025

Background

Assessing disease activity in axial spondyloarthritis (axSpA) is challenging, with heavy reliance on patient reported outcome measures. These measures are subjective and can be influenced by non-inflammatory causes of symptoms, potentially resulting in inappropriate changes to therapy. Despite its unanimous use in the diagnosis of axSpA, the most recent EULAR/ASAS guidelines do not support the use of MRI to assess disease activity due to the lack of evidence and cost implications. However, it is often a pragmatic approach taken in clinical practice.

Aims

To assess current usage of MRI to assess disease activity in axSpA at Leeds Teaching Hospitals NHS Trust (LTHT), particularly in patients experiencing treatment non-response and how findings influence treatment decision making at the bedside.

Methods

As part of a larger service evaluations, MRIs of the whole spine and SIJ requested at LTHT between May 2020 and December 2023 to assess disease activity in patients with previously diagnosed axSpA nr-axSpA, r-axSpA or axial psoriatic spondyloarthritis [axPsA]) were identified. Clinical data was extracted from electronic health records and clinic letters.

Results

In total 237 MRI scans were performed on 231 patients. The average age was 47, 131 (55.3%) were male and 145 (60.3%) were HLA-B27 positive. 109 had a diagnosis of radiographic axSpA, 95 non-radiographic and 27 axial PsA. 167 were on a b/ts-dmard at time of MRI. Overall, 116 (48.9%) had inflammation in spine or SIJ and 137 (57.8%) had non-axSpA related pathology on MRI. Patients with active inflammation were more likely to have their treatment switched or escalated than those without (48% vs 18%). 12 patients were referred to spinal surgical services, 6 to the pain team and 1 to oncology services, based on the results of the MRI scan.

Conclusions

Findings on MRI to assess disease activity influences treatment decisions in a large proportion of patients. Further research into the utility and health economics of MRI to assess disease activity in routine clinical practice, particularly in those experiencing treatment non-response is urgently required.
Unveiling intimacy: sexual dysfunction and marital satisfaction among Pakistani males in Karachi
Authors: Yousefzai Hayat Ali , Ismail Siti Irma Fadhilah , Hussain Sana , Alimuddin Aishah Siddiqah
Published: January 2025

Background

In Asian countries, discussing sex-related issues remains a taboo. Sexual dysfunction is not even considered a serious disorder in Pakistan.

Aim

To explore sexual dysfunction and marital satisfaction within the Pakistani context to develop supportive intervention programs,

Methods

This study entailed a mixed method approach and was carried out in Karachi, Pakistan. The sample comprised 28 married men, and data were gathered by in-depth interviews. Subsequently, data were analyzed through content analysis.

Outcomes

There is a strong relationship between marital dissatisfaction and sexual dysfunction in adult married males aged 25 to 40 years in Pakistan.

Results

The analysis of participants’ perspectives revealed 5 themes: psychosocial issues, rationale of openness in marital life, insufficient sexual knowledge, lack of sexual health service, and individual consequences.

Clinical Implications

The results of this study suggest that it is an important suggestion to the government of Pakistan to introduce sexual health counseling and premarital counseling programs at the university level. The Ministry of Health and Higher Education needs to promote awareness about sexual health, sexual dysfunctions, and marital satisfaction, which will enable men to understand their sexual problems and effectively cope with them.

Strengths and Limitations

The results of this study highlight the biopsychosocial dimensions of human sexuality. In this context, the psychosocial aspects associated with sexual dysfunctions are influenced by cultural and societal norms, where open discussions about sexual issues between male and female partners may be limited due to concerns about maintaining harmony in marital relationships. The limitation of this study is that the sample is not generalized; it is also not a demographic representation of all socioeconomic groups in Pakistan. Participants in low and middle classes reported an inability to seek help from professionals due to the high costs of treatments. Therefore, the results cannot to be extended to all Pakistani males.

Conclusion

In this study, male sexual dysfunction strongly affects marital satisfaction within the couple. As such, marital counseling and psychotherapeutic strategies play an important role to help individuals and couples manage their sexual dysfunctions and enhance their marital satisfaction.
A perspective review on factors that influence mutagenicity in medicinal plants and their health implications
Authors: Fasiku Victoria , Kyagaba Doreen , Hlalele Atlehang , Adegoke Ayodeji , Erukainure Ochuko L , Sekhoacha Mamello
Published: January 2025

Medicinal plants are products from natural sources that have found relevance in medicine for several decades. They are rich in bioactive compounds; thus, they are widely used to treat different ailments globally. Medicinal plants have provided hope for the healthcare industry as most are used to synthesize modern medicines currently used in the treatment of various diseases. However, there are still concerns with respect to the mutagenic properties of medicinal plants. Over the years, researchers have embarked on various studies aimed at investigating the mutagenicity of several medicinal plants found in different regions of the world. In this review, we discussed factors that may influence plant mutagenicity and the findings of in vitro and in vivo mutagenicity studies of several medicinal plants from across the globe. In addition, this review considers the potential health implications of mutagenic medicinal plants and safety measures that can be used to mitigate mutagenesis in medicinal plants. To achieve this, we searched for articles reporting on medicinal plants and mutagenesis on the PubMed, Scopus, and Web of Science databases. Several journal articles reported on the mutagenicity of some medicinal plants; however, it was observed that the majority of the articles reported the nonmutagenicity of medicinal plants. The findings from these studies imply that medicinal plants have good prospects in treating diseases and that they are clinically relevant. However, these reports will require further validation to determine their safety for human use as limited in vivo studies were conducted and there are no clinical safety reports for any of the plants discussed in this review.
Risk factors for noninvasive ventilation failure in preterm infants at less than 30 weeks of gestation with respiratory distress syndrome
Authors: Yazici Aybuke , Buyuktiryaki Mehmet , Sari Fatma Nur , Alyamac Dizdar Evrim
Published: January 2025

This study aimed to identify risk factors for noninvasive ventilation (NIV) failure in <30 weeks’ gestation preterm neonates and compare morbidity in patients with and without NIV failure. This study included preterm neonates <30 weeks’ gestation who received NIV support for respiratory distress syndrome (RDS). Demographic and clinical characteristics were compared between infants with and without NIV failure within the first 72 hours after birth. Of 443 preterm neonates, NIV failure occurred in 101 (22.8%). Of these, initial respiratory support was nasal continuous positive airway pressure (nCPAP) in 76 infants (75.2%) and nasal intermittent positive pressure ventilation (NIPPV) or bilevel positive airway pressure (BiPAP) in 25 infants (24.8%). Gestational age, birth weight, and antenatal steroid exposure were significantly lower in patients with NIV failure. Grade III-IV intraventricular hemorrhage, moderate/severe bronchopulmonary dysplasia, and retinopathy of prematurity requiring laser photocoagulation were significantly more common in the NIV failure group. Multivariate logistic regression analysis showed that antenatal steroid therapy reduced NIV failure [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.29–0.94; P = .03], while nCPAP (OR: 2.61, 95% CI: 1.53–4.48; P < .001), surfactant requirement (OR: 2.40, 95% CI: 1.36–4.25; P = .003), and ≥2 doses of surfactant need (OR: 3.57, 95% CI: 1.89–6.74; P < .001) were associated with greater NIV failure. The results of this study indicated that administering antenatal steroids and using NIPPV or BiPAP instead of nCPAP as initial respiratory support reduced the likelihood of NIV failure in preterm infants with RDS.
Preliminary Development and Validation of Automated Nociception Recognition Using Computer Vision in Perioperative Patients
Authors: Heintz Timothy A , Badathala Anusha , Wooten Avery , Cu Cassandra W , Wallace Alfred , Pham Benjamin , Wallace Arthur W , Cobert Julien
Published: January 2025

Background:

Effective pain recognition and treatment in perioperative environments reduce length of stay and decrease risk of delirium and chronic pain. We sought to develop and validate preliminary computer vision-based approaches for nociception detection in hospitalized patients.

Methods:

Prospective observational cohort study using red-green-blue camera detection of perioperative patients. Adults (≥18 years) admitted for surgical procedures to the San Francisco Veterans Affairs Medical Center (SFVAMC) were included across 2 study phases: (1) algorithm development phase and (2) internal validation phase. Continuous recordings occurred perioperatively across any postoperative setting. We inputted facial images into convolutional neural networks using a pretrained backbone, to detect (1) critical care pain observation tool (CPOT) and (2) numerical rating scale (NRS). Outcomes were binary pain/no-pain. We performed external validation for CPOT and NRS classification on data from University of Northern British Columbia-McMaster University (UNBC) and Delaware Pain Database. Perturbation models were used for explainability.

Results:

We included 130 patients for development, 77 patients for validation cohort and 25 patients from UNBC and 229 patients from Delaware datasets for external validation. Model area under the curve of the receiver operating characteristic for CPOT models were 0.71 (95% confidence interval [CI] 0.70, 0.74) on the development cohort, 0.91 (95% CI 0.90, 0.92) on the SFVAMC validation cohort, 0.91 (0.89, 0.93) on UNBC and 0.80 (95% CI 0.75, 0.85) on Delaware. NRS model had lower performance (AUC 0.58 [95% CI 0.55, 0.61]). Brier scores improved following calibration across multiple different techniques. Perturbation models for CPOT models revealed eyebrows, nose, lips, and foreheads were most important for model prediction.

Conclusions:

Automated nociception detection using computer vision alone is feasible but requires additional testing and validation given small datasets used. Future multicenter observational studies are required to better understand the potential for automated continuous assessments for nociception detection in hospitalized patients.
Flexor Carpi Ulnaris Surgical Approach to the Volar Ulnar Corner of the Distal Radius
Authors: Minaie Arya , Warburton Christopher , Patel Nikhil , Schurhoff Nicolette , Oguayo Christopher , Dodds Seth D.
Published: January 2025

There are many approaches to the wrist both volar and dorsal, depending on the injury at hand. The design of the volar locking plate has created a rise in distal radius fractures being treated using a volar FCR approach and its modifications. It does, however, have limitations in visualization of the volar ulnar corner of the radius. In this paper, we will revisit the flexor carpi ulnaris approach and pose some considerations for its historical context, safety, efficacy, and surgical technique.
Role of Topical 5-Fluorouracil in Demodex-Associated Blepharitis
Authors: Amer Mona M. , Ho Joanne W. , Theotoka Despoina , Wall Sarah , Galor Anat , Cheng Anny , Miller Darlene , Karp Carol L.
Published: January 2025

Purpose:

The aim of this study was to report clinical observations suggesting the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex-associated blepharitis.

Methods:

An observational retrospective review of 13 eyes from 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation that received topical 1% 5-FU eye drops. Patients underwent slit-lamp examination at each follow-up visit. Clinical photographs of the lash line were obtained after treatment initiation. In a subset of patients, lashes were epilated bilaterally and microscopically analyzed for presence of Demodex mites before and after treatment initiation.

Results:

The mean age of the population was 68 ± 14 years (range: 30–84 years) and 92% were male. In all 13 patients, a marked reduction in cylindrical dandruff was noted in the treated eye by slit-lamp examination after 2 cycles of 5-FU. There was complete resolution of cylindrical dandruff in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in untreated eyes (P = 0.0001). In the 6 patients who received epilation, the lashes from the treated eye showed no Demodex, whereas lashes from the fellow untreated eye revealed persistent Demodex.

Conclusions:

Topical 1% 5-FU shows efficacy in treating Demodex-associated blepharitis. Further studies are indicated to reproduce our findings and evaluate the potential use of 5-FU as a treatment ingredient.
La dolce vita: fueling chimeric antigen receptor (CAR) T cells with Glut1 to improve therapeutic efficacy
Authors: Slattery Karen , Finlay David K. , Darcy Phillip K.
Published: January 2025

The approval of chimeric antigen receptor (CAR) T cell therapies for the treatment of hematological cancers has marked a new era in cancer care, with seven products being FDA approved since 2017. However, challenges remain, and while profound effects are observed initially in myeloma, the majority of patients relapse, which is concomitant with poor CAR T cell persistence. Similarly, the efficacy of CAR T cell therapy is limited in solid tumors, largely due to tumor antigen heterogeneity, immune evasion mechanisms, and poor infiltration and persistence. In this recent study, Guerrero et al endeavor to improve the efficacy of human CAR T cells by overexpressing the glucose transporter GLUT1 and show that GLUT1 overexpressing CAR T cells have improved capacity to persist and control tumor burden in vivo.
Full moon capsulorhexis: a novel and safe midperipheral approach, 2-step capsulorhexis technique for intumescent cataract
Authors: Sarma Saurabh Kumar , Bora Sandeep , Wallang Batriti Shympliang , Baishya Bipul , Shullai Wakaru , Bhattacharyya Himashree
Published: January 2025

This article describes a novel 2-step surgical approach to create a continuous curvilinear capsulorhexis (CCC) in an intumescent cataract. While there have been many descriptions for the same, this is unique in that the anterior capsulorhexis is started at the midperiphery. Although this approach may sound counterintuitive to the dreaded peripheral rhexis extensions in such cataracts, it provides a better control over the various mechanical factors contributing toward an increased intralenticular pressure that makes rhexis creation so unpredictable. This technique enables the surgeon to approach the anterior capsule at its strongest point and allows for better equalization of the anterior and posterior intracapsular pressure compartments, as well as easy aspiration of cortical fibers for effective decompression. The full moon capsulorhexis technique is a safe and reproducible technique for the most critical step of CCC, ensuring successful management of intumescent cataract with in-the-bag intraocular lens implantation.
Pediatric Borderline Ovarian Tumors: A Retrospective Study of 15 Cases at a Single Institution
Authors: Laboret Bretton , Scrushy Marinda G. , Pandya Samir , Murphy Joseph T.
Published: January 2025

Borderline ovarian tumors (BOTs) are rare in pediatric populations and typically follow an indolent clinical course with few reported recurrences. Consequently, guidelines for pediatric BOT management are minimal. We retrospectively examined the management of 15 adolescent patients who underwent BOT resection at our institution over 14 years, with a specific focus on recurrence. Data collected include age, symptoms, tumor characteristics, laboratory markers, surgical management, staging, and follow-up. Fifteen patients with BOTs (median age: 16 y) presented with abdominal pain (67%), or distention (33%). Cancer antigen-125 marker was elevated in 10/13 patients. There were 11 (73%) tumors with serous and 4 (23%) with mucinous histology. Most received fertility-preserving surgery (93%) and disease stage was 1A in 7 (47%), 1B/1C in 5 (33%), and stage 2B or higher in 3 (20%) patients. Additional staging procedures, including peritoneal washings (73%), omentectomy (53%), and peritoneal biopsy (47%), varied in use. Four (27%) patients recurred, with 1 case of benign tumor, 1 BOT, and 2 serous carcinomas. Median patient follow-up was 45 months. BOTs can be successfully treated with fertility-preserving surgery but demonstrate a non-negligible rate of recurrence. We recommend surgical staging and posttreatment surveillance for all patients with BOT.
Analysis of Dynamic Mandibular Movement of Patients With Condylar Hyperplasia Treated With Orthognathic Surgery and Condylectomy
Authors: Su Lin , Kang Yanfeng , Guo Chuanbin , Wang Xiaoxia
Published: January 2025

Objective:

To assess the dynamic mandibular movement of patients with condylar hyperplasia before and after simultaneous orthognathic surgery and condylectomy through an intraoral approach.

Methods:

Two groups of patients diagnosed with unilateral condylar hyperplasia were studied: the preoperative group consisted of 23 patients and the postoperative group consisted of 13 patients who had undergone simultaneous orthognathic surgery and condylectomy through an intraoral approach with follow-up for more than 1 year. The normal reference value was obtained from 11 individuals without oral and maxillofacial diseases. Three-dimensional mandibular movement trajectories and electromyography of masticatory muscles were recorded.

Results:

Patients showed no limitation in mandibular border movement before surgery, but the average amplitude of electromyography of the lower head of lateral pterygoid muscle on the affected side was lower than normal reference value. After condylectomy, the maximum mouth opening decreased [32.00 (26.55, 36.20) mm], mandibular movement deviated to the affected side, and the maximum distance in protrusive movement of the mandibular incisal point and the movement to the normal side were both significantly lowered. Amplitude of electromyography of the lateral pterygoid muscle on the normal side increased in the postoperative group compared with the preoperative group.

Conclusions:

Patients with condylar hyperplasia had a restriction in protrusive and to the normal side movement, and mandibular movement deflected to the affected side after condylectomy, which indicates the necessity of postoperative individualized rehabilitation training.
A two-step mechanism for RIG-I activation by influenza virus mvRNAs
Authors: Pitré Emmanuelle , Bisht Karishma , Remick Kaleigh A. , Ghorbani Amir , Yewdell Jonathan W. , Elshina Elizaveta , te Velthuis Aartjan J.W.
Published: January 2025

Influenza A virus (IAV) non-canonical replication products can be bound by host pathogen sensors, such as retinoic acid-inducible gene I (RIG-I). However, innate immune activation is infrequent in cell culture infection, in particular by adapted strains. Moreover, it is not understood why non-canonical IAV RNAs activate RIG-I in a sequence- or RNA structure-dependent manner. We therefore hypothesized that multiple errors need to occur before influenza virus RNA synthesis activates innate immune signaling. To test this idea, we investigated whether RIG-I activation is stimulated by the non-canonical or aberrant transcription of mini viral RNAs (mvRNA), a <125 nt long RNA that is overexpressed in pandemic and highly pathogenic IAV infections. Using mvRNA sequences identified in tissue culture and ferret infections, we find that mvRNAs can cause non-canonical transcription termination through a truncated 5ʹ polyadenylation signal or a 5ʹ transient RNA structure that interrupts polyadenylation. The resulting capped complementary RNAs (ccRNA) can stimulate the release of a template mvRNA in vitro. Finally, we find that both mvRNA and ccRNA sequences can be bound by RIG-I in cell culture and that blocking mvRNA transcription with baloxavir reduces IFN promoter activity. Overall, our findings indicate that sequential rounds of non-canonical or aberrant viral replication and transcription are needed before mvRNAs trigger innate immune signaling in a sequence-dependent manner.
PPIFold: a tool for analysis of Protein-Protein Interaction from AlphaPullDown
Authors: Rouger Quentin , Giudice Emmanuel , Meyer Damien F. , Macé Kévin
Published: January 2025

Protein structure and protein-protein interaction (PPI) predictions based on coevolution have transformed structural biology, but managing pre-processing and post-processing can be complex and time-consuming, making these tools less accessible. Here, we introduce PPIFold, a pipeline built on the AlphaPulldown Python package, designed to automate file handling and streamline the generation of outputs, facilitating the interpretation of PPI prediction results. The pipeline was validated on the bacterial Type 4 Secretion System nanomachine, demonstrating its effectiveness in simplifying PPI analysis and enhancing accessibility for researchers.
T cells are necessary for development of PCOS reproductive symptoms in a letrozole-induced mouse model of PCOS
Authors: Ujagar Naveena , Velez Leandro M. , De Robles Gabriela , Nguyen Christy , Wiggins Kiara , Kim Joshua , Naidu Nandini , Angulo Julio Ayala , Kauffman Alexander S. , Thackray Varykina G. , Banaszewska Beata , Wysocka Ewa , Duleba Antoni , Seldin Marcus , Nicholas Dequina
Published: January 2025

Polycystic ovary syndrome (PCOS) is a complex condition with clear genetic susceptibilities that impact the heterogeneous clinical presentation of symptoms and severity through unknown mechanisms. Chronic inflammation is linked to PCOS, but a clear cause-and-effect relationship has yet to be established. This study used an in depth systems immunology approach and a letrozole-induced PCOS mouse model to identify changes in inflammatory factors associated with PCOS symptoms. By analyzing immune cells and secreted cytokines from 22 different mouse strains, we identified TNF-β as a key T cell-derived cytokine associated with PCOS, regardless of genetic background. We confirmed elevated TNF-β transcripts in immune cells from women with PCOS. Importantly, we used a knockout of TCRα to show that functional T cells are a necessary component of driving PCOS features in letrozole-treated female mice. These findings implicate T cells and specifically TNF-β production in the development of PCOS impairments. T cells are therefore an attractive target for the future development of anti-inflammatory therapeutics to improve PCOS symptoms.

Teaser

TNF-β links T cell inflammation to reproductive dysfunction in PCOS, highlighting new therapeutic targets for this disorder.
Cryopreservation of JuvenileMytilus galloprovincialis: Safeguarding Mollusk Biodiversity and Aquaculture
Authors: Lago A. , Troncoso J. , Paredes E.
Published: January 2025

Mytilus galloprovincialisLamarck, 1819, is a globally significant aquaculture species, contributing 25% of fresh seafood landings and leading EU mussel production. In Spain, it accounted for 255,218 tonnes in 2022, around 60% of the global harvest. This study introduces groundbreaking cryopreservation, being the first to successfully cryopreserve the juvenile stage of a marine organism, the largest marine organism ever cryopreserved. By optimizing feeding strategies, equilibration times, and cryoprotectant concentrations, we extended our initial protocol for young larvae to include complex larval stages (72h–26 days post-fertilization) and juveniles (40–45 days, up to 1 mm). These protocols mark a significant step in biodiversity conservation, seedstock preservation, genetic line maintenance, and sustainability of overexploited mollusk populations.
Atomistic Simulation of Voltage Activation of a Truncated BK Channel
Authors: Jia Zhiguang , Chen Jianhan
Published: January 2025

Voltage-dependence gating of ion channels underlies numerous physiological and pathophysiological processes, and disruption of normal voltage gating is the cause of many channelopathies. Here, long timescale atomistic simulations were performed to directly probe voltage-induced gating transitions of the big potassium (BK) channels, where the voltage sensor domain (VSD) movement has been suggested to be distinct from that of canonical Kv channels but remains poorly understood. Using a Core-MT construct without the gating ring, multiple voltage activation transitions were observed at 750 mV, allowing detailed analysis of the activated state of BK VSD and key mechanistic features. Even though the S4 helix remains the principal voltage sensor in BK, its vertical displacement is only ∼3 Å and accompanied by significant lateral movements. The nature of the predicted VSD movement is in strong agreement with recent Cryo-EM structural studies of mutant BK channels with constitutively activated VSD. Free energy analysis based on the predicted activation transition yielded a total gating charge of 0.44eper VSD, consistent with the experimental range of 0.48 – 0.65e. We further show that the ability of modest physical movements with a small total gating charge to drive effective voltage gating of BK can be attributed to large gradients in the local electric field as reshaped by the protein. Furthermore, the S4 movement is coupled to the pore opening through a non-canonical pathway that involves the tightly packed S4-S5-S6 interface. These distinct mechanistic features may be relevant to voltage gating of other ion channels where VSDs are not domain-swapped with respect to the pore-gate domain.

Significance Statement

The big potassium (BK) channel is the only potassium channel that integrates intracellular calcium signaling with membrane depolarization. It is considered one of the most important channels in cardiovascular and neurological disorders. It has been known that voltage gating of BK channels has distinct features compared to the canonical voltage gating mechanism established through studies of voltage-gated potassium (Kv) channels. Yet, little is known about the molecular nature of voltage sensing and pore activation of BK channels at present. Our work reports the first successful direct simulation of voltage activation of the big potassium (BK) channel, revealing novel voltage sensing and sensor-pore coupling mechanisms that have largely eluded the community until now.
Golgi-associated nuclear import receptor importin-7 targets HPV from the Golgi to the nucleus to promote infection
Authors: Woo Tai-Ting , Takeo Yuka , Harwood Mara C. , Houck Ethan T. , DiMaio Daniel , Tsai Billy
Published: January 2025

During human papillomavirus (HPV) entry, the virus exploits COPI-dependent retrograde transport to cross the trans-Golgi network and Golgi stacks before reaching the nucleus to cause infection. How HPV enters the nucleus after exiting the Golgi is unclear, although mitotic nuclear envelop breakdown (NEB) appears important. Here we show that importin-7 (IPO7), a nuclear pore import receptor, associates with the Golgi and promotes HPV infection. Upon IPO7 knockdown, HPV infection is inhibited and the virus accumulates in the Golgi but does not enter the nucleus, demonstrating that IPO7 promotes Golgi-to-nucleus transport of HPV. We further reveal that the C-terminus of HPV capsid protein L2, which is thought to contain overlapping nuclear localization and cell-penetrating peptide sequences, binds directly to IPO7 in a step that requires COPI-dependent virus trafficking. Together these data identify a role of an importin in HPV infection, raising the possibility that the canonical nuclear pore import machinery plays an unanticipated role in NEB-dependent nuclear entry.

Teaser

HPV, a cancer-causing human pathogen, exploits the Golgi-associated nuclear import receptor IPO7 for Golgi-to-nucleus trafficking to promote infection.
AR-V7 condensates drive androgen-independent transcription in castration resistant prostate cancer
Authors: Massah Shabnam , Pinette Nicholas , Foo Jane , Datta Sumanjit , Guo Maria , Bell Robert , Haegert Anne , Tekoglu Tahsin Emirhan , Terrado Mailyn , Volik Stanislav , Bihan Stephane Le , Bui Jennifer M. , Lack Nathan A. , Gleave Martin E. , Rhie Suhn K. , Collins Colin C. , Gsponer Jörg , Lallous Nada
Published: January 2025

Biomolecular condensates organize cellular environments and regulate key processes such as transcription. We previously showed that full-length androgen receptor (AR-FL), a major oncogenic driver in prostate cancer (PCa), forms nuclear condensates upon androgen stimulation in androgen-sensitive PCa cells. Disrupting these condensates impairs AR-FL transcriptional activity, highlighting their functional importance. However, resistance to androgen deprivation therapy often leads to castration-resistant prostate cancer (CRPC), driven by constitutively active splice variants like AR variant 7 (AR-V7). The mechanisms underlying AR-V7’s role in CRPC remain unclear. In this study, we characterized the condensate-forming ability of AR-V7 and compared its phase behavior with AR-FL across a spectrum of PCa models andin vitroconditions. Our findings indicate that cellular context can influence AR-V7’s condensate-forming capacity. Unlike AR-FL, AR-V7 spontaneously forms condensates in the absence of androgen stimulation and functions independently of AR-FL in CRPC models. However, AR-V7 requires a higher concentration to form condensates, both in cellular contexts andin vitro. We further reveal that AR-V7 drives transcription via both condensate-dependent and condensate-independent mechanisms. Using an AR-V7 mutant incapable of forming condensates, while retaining nuclear localization and DNA-binding ability, we reveal that the condensate-dependent regime activates part of the oncogenic KRAS pathway in CRPC models. Genes under this condensate-dependent regime were found to harbor significantly higher numbers of AR-binding sites and exhibited boosted expression in response to AR-V7. These findings uncover a previously unrecognized role of AR-V7 condensate formation in driving oncogenic transcriptional programs and shed light on its unique contribution to CRPC progression.

Highlights

AR-V7 condensates form independently of both androgens and AR-FL in CRPC models.

AR-V7 mediates condensate-dependent and independent transcription

Condensate-dependent transcription enables boosted expression of oncogenic KRAS genes

Condensate-dependent genes exhibit an exponential increase in expression, with a higher number of AR binding sites potentially playing a key role in their reliance on condensate formation.

Graphical Abstract
Pathogen and pest communities in food security crops across climate gradients: Anticipating future challenges in the Great Lakes region of Africa
Authors: Mouafo-Tchinda Romaric , Plex Sula Aaron , Etherton Berea A , Okonya Joshua , Nakato Gloria Valentine , Xing Yanru , Robledo Buritica Jacobo , Adhikari Ashish , Blomme Guy , Kantungeko Deo , Nduwayezu Anastase , Kreuze Jan Frederik , Kroschel Juergen , Legg James , Garrett Karen A
Published: January 2025

Natural and human-driven disasters are a significant challenge to the sustainable production of food security crops in the Great Lakes region of Africa. A relevant research gap is the effect of climate change on the distribution of pathogens and pests of food security crops in this region. We evaluated the current geographic risk of pathogens and pests in the production of four food security crops - banana, cassava, potato, and sweetpotato - in the region, and the potential future risk under climate change. First, cropland connectivity analysis identified locations likely important in the spread and establishment of crop-specific pathogens and pests for each crop, with locations in Rwanda and Burundi emerging as important across crops. Second, we surveyed 27 economically important pathogens and pests in Rwanda and Burundi, mapping their distribution across landscapes and quantifying patterns of association. Cropland density, cropland connectivity, altitude, and contemporary and long-term temperature and precipitation were strongly associated with disease severity and pest infestation. Among ten machine-learning algorithms evaluated, random forests and support vector machines generally performed best for predicting severity and infestation. Third, an increase in temperature across altitudes is projected under future climate change scenarios in this region. We found evidence that 44% of the pathogen and pest species we studied in banana, potato, and sweetpotato could become more common with warmer temperatures at higher altitudes, while 17% may become less common. Ongoing development of pathogen and pest forecasts can guide strategic surveillance, mitigation and adaptation to future epidemics and pest invasions in high-risk crop locations under climate change.
RETINA: Reconstruction-based Pre-Trained Enhanced TransUNet for Electron Microscopy Segmentation on the CEM500K Dataset
Authors: Xing Cheng , Xie Ronald , Bader Gary D.
Published: January 2025

Electron microscopy (EM) has revolutionized our understanding of cellular structures at the nanoscale. Accurate image segmentation is required for analyzing EM images. While manual segmentation is reliable, it is labor-intensive, incentivizing the development of automated segmentation methods. Although deep learning-based segmentation has shown promise, its accuracy to automatically segment cellular structures in EM data remains insufficient compared to expert manual results. Current approaches usually use either convolutional or transformer-based neural networks for image feature extraction. We developed the RETINA method, which combines pre-training on the large, unlabeled CEM500K EM image dataset with a hybrid neural-network model architecture that integrates both local (convolutional layer) and global (transformer layer) image processing to learn from manual image annotations. RETINA outperformed existing models on cellular structure segmentation on five public EM datasets. This improvement works toward automated cellular structure segmentation for the EM community. Data and code are available at
ZenodoandGitHub.
Tissue imprinting defines functional mosaic of dermal macrophages
Authors: Lohrmann Florens , Sankowski Roman , Schwer Stephan , Neuber Jana , Vlachou Evi P , Westermann Frederike , Troesch Emma , Kolter Julia , Kathrin Lösslein Anne , Das Mahapatra Kunal , Döring Clarissa-Laura , Ghanem Nisreen , Kohnert Eva , Heselich Aileen , Staszewski Ori , Monaco Gianni , Müller Antonia , Eyerich Kilian , Zeiser Robert , Prinz Marco , Becher Burkhard , Zaugg Judith , Kreutz Clemens , Sagar  , Henneke Philipp
Published: January 2025

Dermal macrophages (macs) protect the skin from invading pathogens. They are derived from embryonic as well as hematopoietic progenitors. However, the functional impact of their diverse origin and the control networks defining different subsets remain unclear. Here, using multidimensional analysis of dermal macs, we reveal that the absence of circulating monocytes in interferon regulatory factor 8 (Irf8) deficient mice delays mac renewal during the steady state. Yet, the functional mosaic of dermal macs remains largely intact, i.e., major dermal mac subsets develop independently of monocyte replenishment. Thus, the tissue microenvironment is sufficient to induce alternative differentiation pathways and functional specialization of resident cells. Mycobacterial skin infection induces a steep increase in mac density due to monocyte-derived macs which execute urgent antibacterial functions and differentiate into site-adapted mac subsets in wildtype but notIrf8-/-mice, while long-term resident macs are required to initiate a tissue repair program already in early stages of infection.

In summary, we introduce a model, where an intricate network of specialized mac subsets develops to meet microanatomical needs and external cellular input is required only during immunological emergency situations.

Highlights

Irf8-/--driven monocytopenia has negligible impact on homeostatic dermal macrophage diversity.

Resident dermal macrophages have diverse specializations but remain flexible to adapt to challenges such as lacking monocyte influx

Bone marrow-derived macrophages differentiate into specialized resident cells, with microenvironmental cues overriding origin-dependent programming.

In chronic bacterial infections, distinct specialized bone-marrow-derived macrophages mount the defense, while resident macrophages activate a tissue-modifying program from early on.