bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Outcomes of Amniotic Membrane Transplantation in Impending or Full-Thickness Corneal Perforation
Authors: Zatarain-Barrón Naomi C. , Vera-Duarte Guillermo Raul , Velasco-Sepulveda Braulio , Ramirez-Miranda Arturo , Navas Alejandro , Garfias Yonathan , Graue-Hernandez Enrique O.
Published: January 2025

Purpose:

The aim of this study was to determine the efficacy and surgical outcomes of cryopreserved amniotic membrane transplantation in impending (ie, descemetocele) or full-thickness corneal perforation.

Methods:

A retrospective chart review that included patients who underwent AMT because of impending or full-thickness corneal perforation. Data collected were preoperative diagnosis, surgical indication, pre- and postoperative uncorrected (UCVA) and best-corrected visual acuity (LogMAR), intraocular pressure (IOP) (mm Hg), postoperative complications, and their resolutions. The primary outcome was defined as a complete closure of the corneal wound.

Results:

A total of 33 eyes from 31 patients were included, of which 29 were in the full-thickness perforation group, and 4 in the descemetocele group. Mean follow-up period was 15.84 ± 13.43 months. Preoperative UCVA and best-corrected visual acuity improved slightly postoperative, and IOP levels were maintained. There were no intraoperative complications. Postoperative complications were found in 11 eyes, with recurrent perforation the most common, predominantly in patients with autoimmune disease diagnosis versus nonautoimmune etiologies (P < 0.002). Eleven patients from the full-thickness corneal perforation group required surgical reintervention. Complete closure of the corneal wound was achieved in 25 eyes overall.

Conclusions:

AMT is a safe procedure that can be performed to manage corneal imminent or full-thickness perforation, with successful surgical outcomes, and stability in visual acuity and IOP levels. Patients with autoimmune diagnoses have a worse prognosis compared with those with nonautoimmune etiologies. Further research is needed to help predict surgical failure and prevent unfavorable results.
Access to non-physician led Exercise Stress Echocardiography reduces wait times and improves consumer engagement.
Authors: Whitman Mark , Jenkins Carly , Challa Prasad
Published: January 2025

The performing of non-physician led exercise stress testing with and without echocardiography has shown similar diagnostic utility and safety as physician led models. While diagnostic accuracy and relative safety have been the focus of previous research, the current study aims to demonstrate efficiencies not previously reported such as reduction in wait times for testing and improved service attendance. A non-physician led exercise stress echocardiography (ESE) service was implemented on 01/01/2018, prior to this all tests were performed under a physician led model. Retrospective data was retrieved from both models (physician led model from 01/01/2015 to 31/12/2017 and the non-physician led model from 01/01/2018 to 31/12/2023). Comparisons were made between the models regarding the number of tests performed, the average wait time to access testing, and the did not attend (DNA) rates. On average 212 tests were performed in the physician led model per year, with average wait times to access testing of 11.3 weeks and a DNA rate of 15.3%. In contrast, the non-physician led model performed on average 501 tests per year (135% increase) (p<0.001) with average wait times of 6 weeks (47% decrease) (p<0.01) and DNA rate of 4.8% (69% decrease). Despite the physician led group displaying an overall higher cardiovascular (CV) disease risk, there were no adverse CV events at the time of testing in either model. Non-physician led ESE remains as safe as physician led models but demonstrates service improvements including significant reductions in wait times and lower DNA rates.
Prevalence of some cardiovascular risk factors: obesity, hypertension, and smoking among medical students
Authors: Alrasheed Asayil A. , Alabdullatif Norah I. , AlOmair Aljawhara W. , Almutairi Atheer K. , Moria Abdulaziz H. , Amjad Zainab , Elsheikh Eman
Published: January 2025

Introduction:

Cardiovascular diseases (CVDs) are the principal cause of worldwide mortality, with 17.9 million deaths reported in 2019. In Saudi Arabia, CVDs account for 42% of all deaths, occurring on average 10 years earlier than in Western populations. Medical students are particularly susceptible to Cardiovascular disease CVD risk factors due to demanding academic schedules and lifestyle changes. This study aims to identify cardiovascular risk factors (CVRF) among medical students at King Faisal University, highlighting the need for preventive measures and curriculum modifications.

Methods:

This prospective cross-sectional study was conducted from February to April 2024 at King Faisal University, focusing on undergraduate medical students. Participants not enrolled in the College of Medicine, those who declined to complete the survey, or those who submitted incomplete responses were excluded. A total of 313 students participated in the study. Data collection involved physical evaluations and a validated questionnaire covering demographics, medical history, lifestyle, and diet. Measurements included waist circumference, weight, height, blood pressure, and pulse. Data was analyzed using IBM SPSS Statistics version 19.

Results:

Among participants, 52.4% had a normal body mass index BMI, while 19.5% were overweight and 11.2% obese. Blood pressure measurements showed 45.7% had normal BP, but 44.4% were prehypertensive. A family history of CVDs was reported by 55.6% of students, with hypertension (HTN) and diabetes being the most common. Smoking was infrequent, with only 5.1% reporting regular habits. Dietary analysis showed moderate consumption of unhealthy foods, with 80% maintaining a moderately healthy diet. Physical activity assessment indicated significant portions engaged in light or moderate activities, but only a minority met recommended levels for vigorous activities. Significant associations were found between physical activity levels and academic year, personal history of diseases, and smoking behavior.

Conclusion:

Most students had normal body weight, but many were overweight or pre-hypertensive. Family histories of CVDs, particularly (HTN) and diabetes, were common. Smoking was rare, but diets included frequent unhealthy foods. These findings underscore the need for targeted health programs to reduce cardiovascular risks in this population.
Scleral Tattooing Complications: Surgical Management of Granulomas in a Cosmetic Procedure
Authors: Ortiz-Morales Gustavo , Haro-Morlett Luis , Eskenazi-Betech Ruth , Navas Alejandro , Ramirez-Miranda Arturo , Perezpeña-Diazconti Mario , Graue-Hernandez Enrique O.
Published: January 2025

Purpose:

To report the surgical management and outcomes of a patient with granulomatous inflammation following scleral tattooing, emphasizing the associated risks and clinical implications.

Methods:

A 26-year-old woman with a history of multiple body modifications, including scleral tattooing, presented with bilateral ocular pain and discomfort. Clinical examination revealed corneal dellen and subconjunctival granulomas. The patient underwent surgical excision of the granulomas, with efforts to preserve the black conjunctival pigmentation. Histopathological analysis was performed on the excised tissue. The patient's visual acuity and ocular condition were monitored for 12 months postoperatively.

Results:

Preoperative best-corrected visual acuity was 20/50 in the right eye and 20/60 in the left. Surgical excision of the granulomas was successfully performed, resulting in symptomatic relief and preservation of the black scleral coloration. Histopathological analysis confirmed the presence of exogenous pigment without hemosiderin or melanin deposits. Twelve months after surgery, the patient maintained a best-corrected visual acuity of 20/20 in both eyes, with no recurrence of granulomas or additional complications.

Conclusions:

This case highlights the serious risks associated with scleral tattooing, including granulomatous reactions and corneal complications. Surgical intervention effectively addressed the ocular issues while preserving the desired cosmetic outcome. Greater public awareness and stronger regulations are critical to prevent such complications, and to prepare ophthalmologists for managing cases of scleral tattooing–related injuries.
Prospective Fumarate Hydratase Tumor Predisposition Syndrome Screening in Patients With Uterine Smooth Muscle Tumors
Authors: McHenry Austin , Monsrud Ashley , Pors Jennifer , Folkins Ann , Longacre Teri , Hodan Rachel
Published: January 2025

Fumarate hydratase tumor predisposition syndrome (FHTPS) is caused by germline fumarate hydratase (FH) pathogenic variants (PVs). Most women with FHTPS develop FH-deficient (FHD) uterine leiomyomas (ULs), which arise 10 to 15 years earlier than aggressive FHD–renal cell carcinoma. We evaluate a previously proposed FHTPS screening strategy for women with ULs. This 5-year, prospective and retrospective study performed FH and later S-(2-succino) cysteine immunohistochemistry (IHC) on all uterine smooth muscle (USM) tumors in patients 40 (later ≤30) years or younger and on all USM tumors with suggestive FHD morphology regardless of age. Patients with FHD tumors by IHC were referred to genetic counseling. Of 840 USM tumors, 112 FHD-tumors by IHC (13%) were identified, all with suggestive FHD-morphology; 44 patients (39%) underwent germline testing, and 15 harbored germline FH PVs (34.1% of germline tested, 13.4% of all FHD-tumors). While FHD tumors were seen across a wide age range (24 to 73 y), those with germline FH PVs were significantly younger (median 33 vs 44 years wild-type, P = 0.0032). Few (12.5%) patients ≥40 and no patients ≥50 had a germline FH PV, whereas a majority (60%) of patients <40 (86% of those <30) had a germline FH PV. We demonstrate that previously proposed resource-conscious screening involving morphology and IHC is effective for identifying women with FHTPS. We provide prospective data confirming patients presenting with FHD-ULs over age 50 are unlikely to harbor germline FH PVs and argue that for germline testing without consideration of other factors, a threshold of younger than 50 years may be appropriate.
Purulent  pleurisy  caused  by  Salmonella choleraesuis : A case report

Authors: Amri Amine , BOUGHALEM Youssra , BENAISSA Elmostafa , BENLAHLOU Yassine , CHADLI Mariama
Published: January 2025

Introduction: Salmonellosis typically presents as typhoid fever or gastroenteritis, with complications being relatively rare. Pleural complications, in particular, are exceptionally uncommon. We report a rare case of purulent pleurisy caused by Salmonella choleraesuis ssp. arizonae.
Case report: A 50-year-old woman, with a history of breast cancer treated with chemotherapy, radiotherapy, and ongoing hemodialysis for chronic renal insufficiency, was admitted to the medical-surgical emergency department due to hemodynamic instability. On clinical examination, she presented with acute chest pain, dyspnea, hypotension, bradycardia, and a fever of 39°C. Thoracic CT angiography excluded proximal pulmonary embolism but revealed a large pleural effusion associated with adjacent passive atelectasis. A pleural puncture allowed drainage of cloudy fluid, which was sent for bacteriological and biochemical analysis. Blood tests showed leukocytosis (12,000/mm³), normochromic normocytic anemia, and thrombocytopenia (27,000/mm³), with elevated CRP (236.4 mg/L) and procalcitonin (29.02 ng/L). Microscopic examination of the pleural fluid revealed leukocytosis (64,000/ mm³), predominantly polymorphonuclear cells (87%), and Gram-negative bacilli. Biochemical analysis indicated an exudate, with total proteins at 36 g/L.
The Api20E gallery (Bio-Mérieux) allowed the identification of Salmonella choleraesuis ssp. arizonae (99.7%). Antibiotic susceptibility testing was performed using the diffusion method on Mueller-Hinton agar and interpreted according to the 2024 EUCAST guidelines
Conclusion: Although pleural complications due to Salmonella remain exceptionally rare, this case highlights the importance of a thorough diagnostic and therapeutic approach to salmonellosis to improve clinical outcomes and reduce associated complications
The utility of 8-Hydroxydeoxyguanosine and 8-Oxoguanine DNA glycosylase as a novel diagnostic marker for autistic children
Authors: Ismael Hawnaz Mohammad , Ismail Parween Abdulsamad
Published: January 2025

Autism spectrum disorder (ASD) is a neurodevelopmental condition that develops in childhood. Although genetics are a key factor in its development, neurological, environmental, and immunological influences also play significant roles. This study investigated the oxidative DNA damage (ODD) biomarker 8-hydroxy-2-deoxyguanosine (8OHdG) in children with autism, exploring its connection to disease severity and the DNA repair enzyme oxoguanine glycosylase 1 (OGG1). This study investigated the oxidative DNA damage (ODD) biomarker, 8-hydroxy-2-deoxyguanosine (8OHdG), in children with autism, examining its relationship with disease severity and the DNA repair enzyme oxoguanine glycosylase 1 (OGG1). The study included 89 children with ASD and 29 typically developing children in an observational controlled cross-sectional design. Autism severity was assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). ELISA was used to measure serum levels of 8-OHdG and OGG1.The results showed that children with autism had significantly higher serum 8-OHdG levels compared to healthy children (P=0.04), with a significant positive correlation with autism severity (P=0.02). Additionally, serum OGG1 levels were significantly lower in children with autism than in their healthy counterparts (P=0.0004), with a notable positive association with disease severity (P=0.0001). These findings indicate that elevated serum 8-OHdG levels may play a key role in oxidative DNA damage in ASD. Higher levels of 8-OHdG in children with severe ASD symptoms could serve as a potential biomarker for diagnosis. Furthermore, the reduced levels of the repair enzyme OGG1, associated with increased 8-OHdG levels, contribute to the observed DNA damage in ASD.
Frequent lncRNA-derived fusions in pediatric neuroblastoma identified byLncFusion: potential biomarker and therapeutic implications
Authors: Li Zixiu , Wu Joae , Zhou Peng , Zhou Chan
Published: January 2025

Despite growing interest in the onco-fusion proteins and long noncoding RNAs (lncRNAs) in cancers, lncRNA-derived fusion transcripts in pediatric cancers remain understudied. To address this gap, we first developedLncFusion, a novel computational pipeline that systematically detects lncRNA-derived fusion transcripts from RNA-seq data. Leveraging our previously publishedFlnc(for comprehensive lncRNA identification) as a foundation and applyingLncFusion, we identified over 900 high-confidence lncRNA-derived fusions (lnc-fusions) in pediatric neuroblastoma by analyzing the transcriptomics datasets from three major pediatric cancer cohorts—TARGET, Gabriella Miller Kids First, and St. Jude Cloud. The number of lnc-fusions exceeds the number of mRNA-derived fusions (mRNA-fusions) in neuroblastoma. Whole genome sequencing analyses revealed that approximately 40% of these lnc-fusions result from chromosomal rearrangements, while over 60% may arise from aberrant splicing events. Among these high-confidence lnc-fusions, 61 are enriched in pediatric neuroblastoma compared to healthy controls; and 20s exhibit subtype-specific expressions in pediatric neuroblastoma patients, which would be categorized into three groups: MYCN-amplified patients, c-MYC-highly expressed patients and the remaining (MYCN-unamplified and c-MYC not high expression). Subtype-specific enrichment of certain lnc-fusions, particularly in MYCN-amplified and c-MYC-high subgroups, underscores distinct oncogenic roles. Further functional studies implicated lnc-fusions in key pathways related to neuron development, translation, and energy metabolism, suggesting potential contributions to neuroblastoma pathogenesis. Additionally, We found several novel fusions might serve as potential diagnostic or prognostic biomarkers in neuroblastoma. A few candidates correlate with either favorable histology and lower-risk patient subsets, or poorer survival outcomes, indicating strong prognostic biomarker potential. Experiments in cell line further confirmed the presence of a few key lnc-fusions discovered from patient samples. Our findings provide the first comprehensive insight into lncRNA-derived fusions in pediatric neuroblastoma, providing the promise of lnc-fusions as novel biomarkers and therapeutic targets. TheLncFusiontool developed can also be applied to explore lnc-fusions in other pediatric and adult cancers.
Embryonic macrophages in brown adipose tissue are spatially associated with developing nerves
Authors: Félix Inês , Ollikainen Janni , Haque Afra , Karhula Joonas , Salmi Marko , Jokela Heli , Rantakari Pia
Published: January 2025

Brown adipose tissue (BAT) is a specialized adipose tissue that produces heat through sympathetic nerve-dependent thermogenesis and influences glucose and triglyceride metabolism, making it a potential target for obesity-related diseases. In mice, interscapular BAT (iBAT) emerges on embryonic days (E)14.5-15.5, with extensive vessel and nerve networks still maturing postnatally. These developmental stages are critical for BAT, impacting long-term BAT function. In adult mice, macrophages regulate sympathetic innervation and thermogenesis. However, research on BAT macrophage characters, ontogeny, and functions in early life is lacking. Using single-cell genomics and proteomics, fate-mapping techniques, and 3D imaging, we analyzed iBAT macrophages during early development. We discovered the presence of fetal liver-derived macrophages as early as E15.5, which are later fully replaced by bone marrow-derived macrophages. Transcriptomics data highlight mononuclear phagocyte subpopulations, from which most express macrophage-associated genes (Adgre1, Fcgr1, Csf1r) and monocytic markers (Ccr2,Ly6c2) together. Embryonic macrophages interact closely with developing neural networks, while postnatal bone marrow-derived macrophages associate with blood vessels. Lack of fetal liver-derived macrophages disrupts nerve and vessel development and causes downregulation of genes related to neuronal diseases and protein digestion pathways. Our data suggest that fetal liver-derived macrophages, interacting with BAT’s developing sympathetic neural network, guide the development of tissue morphology. Understanding further the mechanism behind these events can unravel novel targets for BAT immunomodulation.
Crop genotype modulates root rot resistance-associated microbial community composition and abundance of key taxa
Authors: Gfeller Valentin , Schneider Michael , Bodenhausen Natacha , Horton Matthew W. , Wille Lukas , Oldach Klaus H. , Studer Bruno , Hartmann Martin , Messmer Monika M. , Hohmann Pierre
Published: January 2025

Plants are constantly challenged by pathogens, which can cause substantial yield losses. The aggressiveness of and damage by pathogens depends on the host-associated microbiome, which might be shaped by plant genetics to improve resistance. How different crop genotypes modulate their microbiota when challenged by a complex of pathogens is largely unknown. Here, we investigate if and how pea (Pisum sativum L.) genotypes shape their root microbiota upon challenge by soil-borne pathogens and how this relates to a genotype’s resistance. Building on the phenotyping efforts of 252 pea genotypes grown in naturally infested soil, we characterized root fungi and bacteria by ITS region and 16S rRNA gene amplicon sequencing, respectively. Pea genotype markedly affected both fungal and bacterial community composition, and these genotype-specific microbiota were associated with root rot resistance. For example, genotype resistance was correlated (R2= 19%) with root fungal community composition. Further, several key microbes, showing a high relative abundance, heritability, connectedness with other microbes, and correlation with plant resistance, were identified. Our findings highlight the importance of crop genotype-specific root microbiota under root rot stress and the potential of the plant to shape its associated microbiota as a second line of defense.
Reefal regions were biodiversity hotspots throughout the Phanerozoic
Authors: Close Roger A. , Benson Roger B.J. , Kiessling Wolfgang , Saupe Erin E.
Published: January 2025

Reefs are important hotspots of marine biodiversity today, and acted as cradles of diversification in the geological past. However, we know little about how the diversity of reef-supporting regions varied through deep time, and how this differed from other regions. We quantified regional diversity patterns in reef-supporting and non-reef-supporting regions in the fossil record of Phanerozoic marine invertebrates. Diversity in reef-supporting regions is on average two- to three-fold higher than in non-reef-supporting regions, and has been remarkably stable over timescales of tens to hundreds of millions of years. This signal is present in both reefal and non-reefal facies within reef-supporting regions, suggesting that reefs enriched diversity in surrounding environments. Sepkoski’s ‘Modern Fauna’, an assemblage of higher taxa that includes gastropods, bivalves and echinoids, has been a key component of reef-supporting regions since the Paleozoic, contrasting with its later rise to dominance in non-reef-supporting regions during the later Mesozoic–Cenozoic.

One-Sentence Summary

Regions of the globe that supported reefal environments have been key hotspots of marine animal diversity for over 400 million years.
Telomeric G-quadruplex Intermediates unveiled by Complex Markov Network Analysis
Authors: Sáinz-Agost A. , Falo F. , Fiasconaro A.
Published: January 2025

G-quadruplexes are secondary, non-canonical RNA/DNA structures formed by guanine-rich sequences assembled into four-stranded helical structures by the progressive stacking of G-Tetrads, planar arrangements of guanines stabilised by monovalent ions such as K+or Na+. Their stability plays a very important role in the prevention of DNA degradation, leading to the promotion or inhibition of specific biological pathways upon formation. In this work we study the different conformations of these structures through their Free Energy Landscape at different temperatures. All-atom simulations are adopted according to a mesoscopic G-quadruplex model previously developed by our group. We use a small number of significant reaction coordinates to analyze the evolution of the system by applying two dimensionality reduction techniques: Principal Component Analysis (PCA) and time-Independent Component Analysis (tICA). The data of the trajectories of the system in this reduced space are encoded into a Complex Markov Network which, in conjunction with an Stochastic Steepest Descent, provides an hierarchical organization of the different nodes into basins of attraction, so revealing the main intermediate states and the most relevant transitions the system undergoes in its denaturation path.

Author summary

G-quadruplexes are fascinating structures formed in guanine-rich regions of DNA and RNA, and they are key players in gene regulation and genome stability. Their ability to promote or block biological processes makes them potential targets for therapies.

In this study, we explored how G-quadruplexes evolve and melt at different temperatures. Through different data analyses of our molecular simulations, we mapped out their observed denaturation pathways together with their occurrence of their intermediate states. Specifically, with the use of Complex Markov Networks we encoded the trajectories into networks able to clearly reveal the main intermediates and quantify the most relevant connections between them, providing detailed information about the structural denaturation pathway.
Mathematical Modeling and Simulation of Tumor-Induced Angiogenesis in Retinal Hemangioblastoma
Authors: Pradelli Franco , Minervini Giovanni , Venkatesh Pradeep , Azad Shorya , Gomez Hector , Tosatto Silvio C.E.
Published: January 2025

Retinal Hemangioblastoma (RH) is the most frequent manifestation of the von Hippel-Lindau syndrome (VHL), a rare disease associated with the germline mutation of the von Hippel-Lindau protein (pVHL). An emblematic feature of RH is the high vascularity, which is explained by the overexpression of angiogenic factors (AFs) arising from the pVHL impairment. The introduction of Optical Coherence Tomography Angiography (OCTA) allowed observing this feature with exceptional detail. Here, we combine OCTA images and a mechanistic model to investigate tumor growth and vascular development in a patient-specific way. We derived our model from the agreed pathology for RH and focused on the earliest stages of tumor-induced angiogenesis. Our simulations closely resemble the medical images, proving the capability of our model to recapitulate vascular patterning in actual patients. Our results also suggest that angiogenesis in RH occurs upon reaching a critical dimension (around 200 μm), followed by the rapid formation of stable vascular networks. These findings open a new perspective on the crucial role of time in antiangiogenic therapy in RH, which has resulted in ineffective control. Indeed, it might be that when RH is diagnosed, angiogenesis is already too advanced to be effectively targeted with any effective means. Moreover, our simulations suggest that vascularization in RH is not a continuous process but an inconstant development with long, stable phases and rapid episodes of vascular sprouting.

AUTHOR SUMMARY

Tumor-induced angiogenesis is a survival strategy commonly exploited by solid tumors to access further nutrients and sustain their growth. The recent introduction of Optical Coherence Tomography Angiography (OCTA) enables scientists and physicians to observe vascular patterning in the retina, non-invasively and with unprecedented detail. Here, we exploit direct observations on a vascular retinal tumor, Retinal Hemangioblastoma (RH), and a mathematical model to investigate the earliest stages of tumor-induced angiogenesis. Our simulations closely match reality and provide critical insights into the role of time in anti-angiogenic therapy for this neoplasm.
Metabolic shifts in the heart of hypothyroid mice — insights from untargeted metabolomics
Authors: Guan Heng , Yang Yujie , Xiao Wenping , Wan Sha , Liu Fang
Published: January 2025

ABSTRACTS

Introduction

Hypothyroidism is a prevalent disorder that affect all systems of body, including the cardiovascular system and control of cardiac function. However, much remains unknown about the metabolic pathways and disorders in the heart induced by hypothyroidism, as well as the metabolic mechanisms involved.

Objectives

This work aims to investigate the impacts of hypothyroidism on the heart and explore its underlying mechanisms through untargeted metabolomics analysis.

Methods

An experimental model of hypothyroidism was established by giving water containing 0.1% methimazole and 1% potassium perchlorate to 12-week-old C57BL/6J mice for six consecutive weeks.

Results

After treatment, hypothyroidism significantly reduced mice’s heart weight and heart rate. Metabolomics analysis revealed that the different metabolites (DEMs) primarily concentrated in Phospholipids, Lipids or Lipids-like, Carbohydrates and Carbohydrate conjugates. These specific metabolites were mainly enriched in pathways related to lipid metabolism. The hearts of hypothyroid mice exhibited significantly lower levels of lipoyl-carnitine compared to controls, along with markedly higher levels of glycolysis and pentose phosphate pathway (PPP) intermediates. Furthermore, carnitine palmitoyltransferase 1B (CPT1B) and carnitine palmitoyltransferase 2 (CPT2) expressions were significantly decreased in the hypothyroid mouse heart, while lactate dehydrogenase A (LDHA) expressions was significantly increased, according to the immunoblotting assay.

Conclusions

Research indicates that hypothyroidism triggers disruptions in both cardiac energy metabolism and phospholipid metabolism in adult mice, which in turn results in myocardial atrophy. These findings could pave the way for novel therapeutic strategies aimed at treating hypothyroidism-induced myocardial atrophy.
Predicting the structures of cyclic peptides containing unnatural amino acids by HighFold2
Authors: Zhu Cheng , Cao Sen , Shang Tianfeng , Guo Jingjing , Su An , Li Chengxi , Duan Hongliang
Published: January 2025

Cyclic peptides containing unnatural amino acids possess many excellent properties and have become promising candidates in drug discovery. Therefore, accurately predicting the three-dimensional structures of cyclic peptides containing unnatural residues will significantly advance the development of cyclic peptide-based therapeutics. Although deep learning-based structural prediction models have made tremendous progress, these models still cannot predict the structures of cyclic peptides containing unnatural amino acids. To address this gap, we introduce a novel model, HighFold2, built upon the AlphaFold-Multimer framework. HighFold2 first extends the pre-defined rigid groups and their initial atomic coordinates from natural amino acids to unnatural amino acids, thus enabling structural prediction for these residues. Then, it incorporates an additional neural network to characterize the atom-level features of peptides, allowing for multi-scale modeling of peptide molecules while enabling the distinction between various unnatural amino acids. Besides, HighFold2 constructs a relative position encoding matrix for cyclic peptides based on different cyclization constraints. Except for training using spatial structures with unnatural amino acids, HighFold2 also parameterizes the unnatural amino acids to relax the predicted structure by energy minimization for clash elimination. Extensive empirical experiments demonstrate that HighFold2 can accurately predict the three-dimensional structures of cyclic peptide monomers containing unnatural amino acids and their complexes with proteins, with the median RMSD for Calpha reaching 1.891 angstroms. All these results indicate the effectiveness of HighFold2, representing a significant advancement in cyclic peptide-based drug discovery.
SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals
Authors: Dadonaite Bernadeta , Burrell Allison R. , Logue Jenni , Chu Helen Y. , Payne Daniel C. , Haslam David B. , Staat Mary A. , Bloom Jesse D.
Published: January 2025

The immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain. Here we compare the neutralizing antibody specificities of imprinted individuals versus infants infected with a recent strain. Specifically, we use pseudovirus-based deep mutational scanning to measure how spike mutations affect neutralization by the serum antibodies of adults and children imprinted by the original vaccine versus infants with a primary infection by a XBB* variant. While the serum neutralizing activity of the imprinted individuals primarily targets the spike receptor-binding domain (RBD), serum neutralizing activity of infants only infected with XBB* mostly targets the spike N-terminal domain (NTD). In these infants, secondary exposure to the XBB* spike via vaccination shifts more of the neutralizing activity towards the RBD, although the specific RBD sites targeted are different than for imprinted adults. The dramatic differences in neutralization specificities among individuals with different exposure histories likely impact SARS-CoV-2 evolution.
Short-term Outcomes of Trabeculectomy with Mitomycin-C in a Tertiary Eye Hospital in Nepal: A Prospective Descriptive Study
Authors: Thinley  , Paudyal Indhira , Joshi Pratibha Lama
Published: January 2025

Objective

This study evaluated the short-term outcomes of trabeculectomy with mitomycin-C in glaucoma patients at Tilganga Institute of Ophthalmology, Kathmandu, Nepal, between June 2021 and May 2022.

Methods

This was a prospective descriptive study, conducted on 56 eyes of 51 consecutive glaucoma patients who underwent trabeculectomy with mitomycin-C (0.02%). Follow-up assessments were carried out on postoperative day 1, week 1, month 1, month 3, and month 6. Statistical analysis was done using SPSS version 20 software.

Results

The study included 38 male (74.5%) and 13 female (25.5%) patients with an average age of 43.50 ± 15.45 years. A significant reduction in median intraocular pressure (IOP) from 24.33 mmHg preoperatively to 12.00 mmHg at 6 months postoperatively was observed (P < 0.01). The median number of anti-glaucoma medications decreased from 3.0 preoperatively to 0.0 at all postoperative visits. Complete surgical success was achieved in 85.7% of eyes. Common complications included shallow anterior chamber, hypotony, and IOP elevation.

Conclusion

Trabeculectomy with mitomycin-C demonstrated high surgical success rate with low complication rates in the short term, making it an effective and safe treatment option for glaucoma patients not medically controlled. It may benefit glaucoma patients facing challenges with long-term anti-glaucoma medication use and frequent follow-up visits, thus improving the management outcomes of this chronic condition.
The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults
Authors: Chen Yu , Li Huey-Ting , Luo Xingguang , Li Guangfei , Ide Jaime S. , Li Chiang-Shan R.
Published: January 2025

Genetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. Here, we employed the Human Connectome Project data of neurotypical adults (n = 995; age 22-35; 618 women) and, with voxel-based morphometry analysis, computed the GMVs of 166 regions in the automated anatomical atlas 3. Alcohol use behaviors were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures. Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects using the Psychiatric Genomics Consortium study of alcohol dependence as the base sample. With age, sex, race, and total intracranial volume as covariates, we evaluated the relationships of regional GMVs with PC1 and PRS together in a linear regression. PC1 was negatively correlated with GMVs of right insula and Heschl’s gyrus, and PRS was positively correlated with GMVs of left posterior orbitofrontal cortex, bilateral intralaminar nuclei of the thalamus and lingual gyri. These findings suggest distinct volumetric neural markers of drinking severity and genetic risks of alcohol misuse. Notably, in contrast to volumetric reduction, the genetic risks of dependent drinking may involve larger regional volumes in the reward, emotion, and saliency circuits.
Evaluation of plasma p-tau217 for detecting amyloid pathology in a diverse and heterogeneous community-based cohort
Authors: Rudolph Marc D. , Sutphen Courtney L. , Register Thomas C. , Lockhart Samuel N. , Rundle Melissa M. , Hughes Timothy M. , Bateman James R. , Solingapuram Sai Kiran K. , Whitlow Christopher T. , Craft Suzanne , Mielke Michelle M.
Published: January 2025

INTRODUCTION

Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints.

METHODS

Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (n=598) and/or cerebrospinal fluid (CSF;n=154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer’s Disease Research Center (WFADRC). Participants (n=598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive; 29% overweight/obese; and 64% with mild-to-moderate kidney disease. Gaussian-mixture models, logistic regression, and receiver operating curve analyses were performed.

RESULTS

Plasma p-tau217 was associated with elevated Aβ deposition and accurately classified Aβ-positive participants (PET: AUC: 94%-97%, cutpoint≥.338 pg/mL; CSF: AUC = .84, cutpoint ≥.307 pg/mL).

DISCUSSION

Plasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort, and superior to other plasma biomarkers assessed. Longitudinal analyses assessing impact of comorbidities on p-tau217 utility for disease progression are underway.

HIGHLIGHTS

The WFADRC is a diverse and heterogeneous cohort.

P-tau217 levels were lower, on average, in cognitively unimpaired participants, females, and Black participants.

Plasma p-tau217 classified amyloid PET positive individuals with high precision and performed better than p-tau181.

Cutpoints and reference ranges of plasma p-tau217 were lower compared to recently published thresholds.

Combining cutpoint approaches, a 4-tier system captured cohort heterogeneity.
Static and dynamic intracerebral signal analysis reveals protective networks against seizures in drug-resistant focal epilepsy
Authors: Di Giacomo Roberta , Núñez Pablo , Poza Jesús , Rodríguez-González Victor , Gómez Carlos , Burini Alessandra , Castana Laura , de Curtis Marco , Tassi Laura , Varotto Giulia
Published: January 2025

Background

Epilepsy research increasingly emphasizes the role of brain network dynamics in seizure generation and propagation. This study explores static and dynamic functional networks in subjects with drug-resistant epilepsy, to identify mechanisms that enhance or inhibit seizure initiation. To this aim, we analyzed functional connectivity of brain networks preceding ictal minor electrical discharges and major seizures in epileptogenic and non-epileptogenic zones explored with intracerebral electrodes.

Material and methods

Stereo-electroencephalographic signals were recorded from 39 patients with focal drug-resistant epilepsy during presurgical monitoring. Static functional connectivity was analyzed using graph theory metrics, whereas dynamic connectivity through the analysis of the complexity and dwell times of brain meta-states activations.

Results

Static connectivity analysis revealed significant alterations in network centrality, integration, and segregation properties, with distinct patterns observed in resting conditions just ahead minor electrical discharges and major seizures. Specifically, network analysis before minor electrical discharges exhibited increased nodal strength and reduced betweenness centrality in the epileptogenic zone, associated with increased integration and reduced segregation in non-epileptogenic zones. Dynamic connectivity analysis showed lower complexity and longer stability of meta-states before minor electrical discharges, particularly in high-frequency signals of non-epileptogenic zones.

Conclusions

Our findings provide novel and valuable insights into the dynamic reconfiguration of brain networks before epileptic seizures, suggesting an inhibitory/protective mechanism mainly involving the non-epileptogenic zones. Understanding these network changes is pivotal for improving epilepsy treatment strategies targeting dynamic network alterations.
GacA regulates symbiosis and mediates lifestyle transitions inPseudomonas
Authors: Luo Youqing , Srinivas Apsara , Guidry Casey , Bull Carolee , Haney Cara H. , Hamilton Corri
Published: January 2025

Through horizontal gene transfer, closely related bacterial strains have assimilated distinct sets of genes, resulting in significantly varied lifestyles. However, it is not clear how strains are able to properly regulate horizontally transferred virulence genes. We hypothesized that strains may use components of the core genome to regulate diverse horizontally acquired genes. To investigate how closely related bacteria assimilate and activate horizontally acquired DNA, we used a model ofPseudomonas fluorescenssubspeciesbrassicacearumstrains, N2E2 and N2C3, which exhibit contrasting lifestyles on the model plant Arabidopsis.P. brassicacearumstrain N2E2 is a plant commensal and contains the genes that encode biosynthetic enzymes for the anti-fungal compound 2,4-Diacetylphloroglucinol (DAPG). In contrast, N2C3 lacks DAPG biosynthesis and has gained a pathogenic island encoding syringomycin (SYR)-and syringopeptin (SYP)-like toxins from the plant pathogenP. syringae.This causes a transition in lifestyle from plant-protective N2E2 to plant pathogenic N2C3. We found that N2E2 and N2C3 share a highly conserved two-component system GacA/S, a known regulator of DAPG and SYR/SYP. Using knockout mutations, we found that aΔgacAmutation resulted in loss of expression of SYR/SYP virulence genes and returned pathogenic N2C3 to a plant commensal lifestyle. Our study further explored the conservation of regulatory control across strains by demonstrating that GacA genes from both distant and closely relatedPseudomonasstrains could functionally complement one another across the genus.

IMPORTANCE

Emerging pathogens represent a significant threat to humans, agriculture, and natural ecosystems. Bacterial horizontal gene transfer aids in the acquisition of novel genes that facilitate bacterial adaptation to new environments. Our work shows a novel role for GacA in orchestrating the regulatory changes necessary for virulence and lifestyle transitions facilitated by HGT. These findings suggest that the GacA/S system plays a key role in mediating transitions across diversePseudomonassymbiotic lifestyles. It provides insights into the mechanisms that drive the emergence of pathogenic strains and highlights potential targets for managing bacterial threats to plant health.
Mapping the complete influenza A virus infection cycle through single vRNP imaging
Authors: Rabouw Huib H. , Schokolowski Janin , Müller Micha , Baars Matthijs J.D. , Dost Antonella F.M. , Bestebroer Theo M. , Püschel Jakob , Clevers Hans , Fouchier Ron A.M. , Tanenbaum Marvin E.
Published: January 2025

Cell-to-cell heterogeneity is a common feature of viral infection that can generate enormous complexity, complicating understanding of infection progression and interpretation of differences between viral variants. To overcome these challenges, we developed a technology to visualize the infection cycle of human influenza A virus (IAV) from start-to-finish in individual living cells with unprecedented spatial and temporal resolution, which identified numerous distinct pathways through which infection can progress. We show that heterogeneous viral gene expression drives infection cycle heterogeneity, and identified genome packaging, vRNP transcriptional activation and host cell division as major determinants of gene expression variability. Our work maps out the complete IAV infection cycle, identifies the origin of infection heterogeneity and provides a broadly-applicable technology for studying IAV and other viruses.
A comparative metagenomic analysis of antibiotic resistance in the fecal microbiome of pigs raised with and without antibiotics
Authors: Pillay Stephanie , Abeel Thomas
Published: January 2025

Purpose

The use of antibiotics in swine production has raised concerns about its impact on animal health, microbial ecology, and the emergence of antibiotic resistance. The gut microbiome, a critical component of animal health, is susceptible to disruptions caused by antibiotic use. The fecal microbiome can provide a snapshot of changes in the gut microbiome and provide information on the spread of antibiotic resistance from pig feces to the environment.

Methods

We investigated the differences between the fecal microbiome of pigs raised with (AB+) and without (AB-) antibiotics to assess how antibiotic exposure influenced the microbial community, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs).

Results

Our findings revealed that the use of antibiotics combined with study-specific conditions alters the fecal microbiome. Antibiotic usage in pigs explains 20% of the variation in the diversity of bacterial species detected between AB+ and AB- pigs. Similarly, variations in ARGs were observed in the two groups. The RND efflux pump gene family was abundant in both groups. The OXAβ-lactamase gene and associated plasmids were more prevalent in the AB- group. We also identified integrons linked to chloramphenicol resistance and transposon-associated integrative elements that can facilitate the spread of antibiotic resistance genes within and between bacterial species.

Conclusion

These findings highlight that antibiotics influence both the microbial community and the antibiotic resistance gene repertoire, regardless of study-specific or environmental conditions. This emphasises the potential for fecal matter to contribute to the spread of antibiotic resistance in the environment, underscoring the need for more research to fully understand these dynamics in agricultural settings.
OT-Mation: an open-source code for parsing CSV files into python scripts for control of OT-2 liquid handling robotics
Authors: Laverick Alex , Convey Katherine , Harrison Catherine , Tomlinson Jenny , Stach Jem , Howard Thomas P.
Published: January 2025

OT-Mation is an open-source Python script designed to automate the programming of OT-2 liquid handling robots, making combinatorial experiments more accessible to researchers. By parsing user-defined CSV files containing information on labware, reagents, pipettes, and experimental design, OT-Mation generates a bespoke Python script compatible with the OT-2 system. OT-Mation enhances reproducibility, reduces human error, and streamlines workflows, making it a valuable addition to any laboratory utilising OT-2 robotics for liquid handling. While OT-Mation can be used for setting up any type of experiment on the OT-2, its real utility lies in making the connection between multifactorial experimental design software outputs (i.e. Design of Experiments arrays) and liquid-handling robot executable code. As such, OT-Mation helps bridge the gap between code-based flexibility and user-friendly operation, allowing researchers with limited programming skills to design and execute complex experiments efficiently.