bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chorioretinitis following Bacillus Calmette-Guerin Treatment for Bladder Cancer
Authors: Boopathiraj Nithya , Wagner Isabella V. , Powers Ross , Mashayekhi Arman 
Published: February 2025

Purpose:
To report a rare case of multifocal chorioretinitis subsequent to intravesical Bacillus Calmette-Guerin (BCG) therapy for bladder cancer.

Methods:
Case report.

Results:
A 74-year-old man presented with ill-defined visual changes in his right eye (RE), along with constitutional symptoms such as low-grade fever, chills with rigors, night sweats, headache, dry cough, memory problems, and unintentional weight loss. These symptoms occurred 11 months after receiving intravesical BCG treatment for bladder cancer. His visual acuity in the RE was 20/30. Examination of his RE revealed multiple yellow white chorioretinal lesions, and optical coherence tomography imaging showed focal involvement of the choroid and overlying neurosensory retina. Blood-based testing utilizing next generation sequencing for detection of microbial cell free DNA (Karius test ®) was positive for Mycobacterium tuberculosis complex. The patient was treated with 12 months of triple therapy consisting of isoniazid, rifampin, and ethambutol. The chorioretinal lesions showed complete regression to flat scars, with no evidence of recurrence 15 months after discontinuation of systemic treatment.

Conclusion:
Despite being rare, the possibility of mycobacterial chorioretinitis should be considered in patients with new-onset visual symptoms following intravesical BCG for treatment of bladder cancer.
Serum and Urine Gadolinium Reference Intervals in Patients With Normal Renal Function Following Gadobutrol Administration
Authors: McDonald Jennifer S. , Day Patrick L. , Spears Grant M. , Bornhorst Joshua A. , McDonald Robert J. , Jannetto Paul J. 
Published: February 2025

Background
Gadolinium-based contrast agents (GBCAs) increase the sensitivity and clinical utility of magnetic resonance imaging (MRI) examinations and are used extensively worldwide. While concerns remain regarding the potential toxicity of retained gadolinium (Gd) based on “elevated” serum or urinary Gd concentrations, current Gd reference intervals were established in GBCA-naive patients with normal renal function. Therefore, the aim of this study was to determine the serum and urine Gd clearance in patients with normal renal function after being administered intravenous gadobutrol for a contrast-enhanced MRI examination.

Methods
Patients with normal renal function (estimated glomerular filtration rate ≥60 mL/min) with no prior GBCA exposure in the past 6 months were enrolled and had blood and urine collected before and ~1, 3, 7, 14, 28, 56, and 84 days after their gadobutrol-enhanced MRI examination to measure Gd at each time point. Serum and urine Gd were quantified using a clinically validated inductively coupled plasma mass spectrometry–based assay with a limit of quantitation of 0.1 ng/mL (μg/L).

Results
Thirty-one patients who underwent a gadobutrol-enhanced MRI were enrolled, and 24 completed all collection time points. The pharmacokinetic data suggested a multicompartment (5 phase) model of elimination where 95% of patient's serum Gd fell below the unexposed reference interval (<0.5 ng/mL) at ~56 days and 95% of urine Gd would fall below the unexposed reference interval (<0.8 μg/g creatinine) at ~132 days. Based on review of the electronic medical record, none of the patients self-reported any Gd-related toxicity.

Conclusions
Current reference intervals for serum and urinary gadolinium clearance are not applicable for patients in the 5 months following intravenous gadobutrol exposure.
Lung Ultrasound for the Assessment of Patients With Acute Respiratory Failure
Authors: Greenwall Kelly , Kobes Kevin , Buchanan Brian , Fung Christopher 
Published: February 2025

Abstract
Lung ultrasound has become a standard practice in acute care as an adjunct to the physical exam, providing valuable insights to guide clinical decision making at the point of care. Lung ultrasound can rapidly uncover anatomic detail, help resolve undifferentiated respiratory failure, and delineate equivocal findings on standard plain film without the need for transport to access additional diagnostic imaging. In the following review, basic concepts of lung ultrasound are reviewed including its role in detecting and assessing a variety of common problems.
RarePANK2Variants and Pantothenate Kinase-Associated Neurodegeneration in the Dominican Republic
Authors: Vardarajan Badri N. , Sanchez-Rao Pedro , Kim Christine Y. , Stoeter Peter , Mejia Diones Rivera , Houck Alexander , Chan Amanda , Reyes-Dumeyer Dolly , Piriz Angel , Fee Robert , Blanco-Abinader Francisco , Rice Elizabeth , Christenson Samantha , Chiu Rebecca , Gunasekaran Tamil I , Lantigua Rafael A. , Dalgard Clifton , Przedborski Serge , Mayeux Richard 
Published: February 2025

AbstractPantothenate kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurological disorder characterized by the progressive degeneration of specific regions in the brain and is invariably fatal. Several individuals in families affected by PKAN were known to live in an isolated region in a southwestern province of the Dominican Republic and had been previously studied.Forty-six individuals with PKAN in 34 families were evaluated for disease manifestations using the PKAN-Disease Rating Scale and the Leiter-3 Cognitive and Neuropsychological assessment. We completed whole genome sequencing in the 46 affected individuals and their 80 unaffected relatives. Haplotype analysis was used to identify shared genetic patterns among individuals with the mutation to identify common ancestral and founder effects.The classical form of PKAN was observed in 22 individuals with moderate to severe oromandibular dystonia and limb dystonia and onset in early childhood. The atypical form was observed in 24 individuals with parkinsonism, dystonia, and cognitive impairment and later onset of disease. APANK2variant, chr20:3907977: A:G(c.680A>G, p.Y227C),was homozygous among 42 affected individuals equally divided by disease form. There were 59 heterozygous carriers of this variant among parents and relatives of the affected individuals. Four individuals from two families were compound heterozygotes forc.680A>Gand chr20:3918728: C:T (c.1594C>T).Haplotype analyses revealed shared patterns across families and of African origin consistent with founder effects forc.680A>Gandc.1594C>T, likely introduced to the island 25 to 35 generations earlier. The frequency of heterozygous carriers ofc.680A>Gallele among individuals of Dominican ancestry living in New York was 0.18% but was 0.8% among individuals living in the Dominican Republic, significantly higher than the reported frequency for all causalPANK2mutations worldwide.This investigation confirmed likely founder mutations inPANK2associated with the classical and atypical forms of PKAN in 34 families in an isolated region of the Dominican Republic. Compound heterozygosity was observed in four individuals from two families. The heterozygous frequency ofc.680A>Gwas exceptionally high in the Dominican population compared with worldwide data. Founder mutations in such communities offer a unique opportunity to set up relevant, affordable and accessible genetic counseling and screening.
Algorithm for a multidisciplinary diagnostic and therapeutic approach to abdominal lymphatic malformations
Authors: Holm Annegret , Marckmann Dorian , Tan Jerry Wei Heng , Lagrèze Susanne , Uller Wibke , Puzik Alexander , Misgeld Rainer , Blattmann Claudia , Fichtner-Feigl Stefan , Niemeyer Charlotte M. , Kapp Friedrich G. 
Published: February 2025

ABSTRACTObjectiveAbdominal lymphatic malformations (ALM) are benign macro-, microcystic or mixed lesions that originate from defects in vascular development. Depending on size and location, clinical symptoms vary from asymptomatic to potentially life-threatening. Standardized diagnostic and therapeutic guidelines for ALM do not exist. Current literature focuses on imaging characteristics rather than symptoms for indication of invasive treatment strategies, including sclerotherapy and surgery. Sirolimus is evolving as a medical treatment option, while a watchful waiting approach for asymptomatic and low-risk ALM patients is not yet established as a conservative strategy.MethodsWe retrospectively characterized a multicenter cohort of 21 ALM treated 1996 - 2024. Items included clinical symptoms, imaging findings, and management strategies, including resection, sclerotherapy, sirolimus or a watchful waiting approach.ResultsALM patients were categorized based on symptoms and lesion characteristics with potentially associated complications depending on lesion size and anatomical location: 9/21 (43%) patients were observed in the asymptomatic and low-risk group with regular clinical and radiological follow-up intervals. Acutely symptomatic (7/21; 33%), symptomatic or high-risk patients (5/21; 24%) underwent resection (10/21; 48%), sclerotherapy (1/21, 5%), or were treated with sirolimus (1/21, 5%). All patients had favorable long-term outcomes.ConclusionsWe developed a multidisciplinary diagnostic and therapeutic algorithm for ALM based on clinical presentation and lesion characteristics to ensure a standardized, yet patient-centered symptom- and risk-based approach for the most beneficial treatment and outcome. Importantly, our study is the first to demonstrate that watchful waiting is an adequate strategy for asymptomatic ALM patients with a low anticipated risk for complications. Validation of our proposed algorithm is warranted in a prospective study.
Evaluating the inclusion of lesbian, gay, bisexual, transgender, and queer-related content in graduate medical education: a national survey of program directors
Authors: Pregnall Andrew M. , Pesantes Joshua A. , Vulakh Gennady , Chung Youvin , Gooshvar Setareh , Dine C. Jessica 
Published: February 2025

AbstractBackgroundNational organizations have identified incorporation of LGBTQ-health content into graduate medical education programs as key action items; however, there has been no systematic study of LGBTQ-health content in these programs.ObjectiveThe primary objective of this study was to systematically evaluate the quantity of LGBTQ-related didactic and clinical education in graduate medical education programs.MethodsA cross-sectional, internet-based survey study of programs participating in the 2023-2024 Electronic Residency Application System, performed from September 2023-August 2024.ResultsOf 4,512 programs, 1,048 programs responded (23.2%). The median and mean number of didactic hours per year dedicated to LGBTQ-related content was 2.0 (IQR, 1.0–5.0, range, 0.0-200.0) and 4.0 (SD 9.1), respectively. The median and mean number of clinical hours per year dedicated to LGBTQ-related content was 10.0 (IQR, 1.5 – 40.0, range, 0.0 – 2000.0) and 61.0 (SD 188.4), respectively. Multiple programs reported that residents received no exposure to LGBTQ-related health content in either didactic settings (15.8%; 95% CI, 13.5%-18.5%) or clinical settings (19.4%, CI 16.1% – 23.0%). The most covered didactic topics were gender identity (43.6%), sexual orientation (41.6%), and barriers to care (32.0%). The most covered clinical topics were Pre-Exposure Prophylaxis/Post-Exposure Prophylaxis (77.0%) and facial masculinization/feminization surgery (68.4%). The most cited barriers to including LGBTQ-related health topics were the lack of faculty with requisite knowledge/expertise (56.1%, CI 52.3% – 59.9%) and the lack of time (48.3%, CI 44.5% – 52.1%).ConclusionsMultiple programs provide no didactic or clinical exposure to LGBTQ-related health topics, which does not align with the goals outlined by national organizations.
Parameter Efficient Fine-tuning of Transformer-based Masked Autoencoder Enhances Resource Constrained Neuroimage Analysis
Authors: Dhinagar Nikhil J. , Ozarkar Saket S. , Buwa Ketaki U. , Thomopoulos Sophia I. , Owens-Walton Conor , Laltoo Emily , Jagad Chirag , Chen Yao-Liang , Cook Philip , McMillan Corey , Tsai Chih-Chien , Wang J-J , Wu Yih-Ru , Thompson Paul M. 
Published: February 2025

ABSTRACTRecent innovations in artificial intelligence (AI) have increasingly focused on large-scale foundational models that are more general purpose in contrast to conventional models trained to perform specialized tasks. Transformer-based architectures have become the standard backbone in foundation models across data modalities (image, text, audio, video). There has been a keen interest in applying parameter-efficient fine-tuning (PEFT) methods to adapt these models to specialized downstream tasks in language and vision. These methods are particularly essential for medical image analysis where the limited availability of training data could lead to overfitting. In this work, we evaluated different types of PEFT methods on pre-trained vision transformers relative to typical training approaches, such as full fine-tuning and training from scratch. We used a transformer-based masked autoencoder (MAE) framework, to pretrain a vision encoder on T1- weighted (T1-w) brain MRIs. The pretrained vision transformers were then fine-tuned using different PEFT methods that reduced the trainable model parameters to as few as 0.04% of the original model size. Our study shows that: 1. PEFT methods were competitive with or outperformed the reference full fine-tuning approach and outperformed training from scratch, with only a fraction of the trainable parameters; 2. PEFT methods with a 32% reduction in model size boosted Alzheimer’s disease (AD) classification by 3% relative to full fine-tuning and 11% relative to a 3D CNN, with only 258 training scans; and 3. PEFT methods performed well on diverse neuroimaging tasks including AD and Parkinson’s disease (PD) classification, and “brain-age” prediction based on T1-w MRI datasets - a standard benchmark for deep learning models in neuroimaging; 4. smaller model sizes were competitive with larger models in test performance. Our results show the value of adapting foundation models to neuroimaging tasks efficiently and effectively in contrast to training stand- alone special purpose models.
Optimization of the prostaglandin F2αreceptor for structural biology
Authors: Salze Marine , Chrétien Sébastien , Boora Tegvir S. , Macovei Madalina , Barbeau Eric , Blais Véronique , Laporte Stéphane A. , Audet Martin 
Published: February 2025

AbstractProstaglandin F2ɑ(PGF2ɑ) is a bioactive lipid derived from arachidonic acid and is involved in many physiological and pathophysiological processes such as parturition, vascular tone regulation, glaucoma and inflammation. It acts by binding to the Prostaglandin F2ɑreceptor (FP), a G Protein-Coupled Receptor (GPCR) that mediates signaling events by engaging intracellular heterotrimeric G protein effectors. The orthosteric binding site of lipid-binding receptors displays greater efficacy-dependent plasticity that hinders the design of ligands. Solving the structure of FP with ligands of different efficacies at an atomic level is important to fully understand its mechanism of activation and inhibition. Most purified FP-ligand complexes are unstablein vitro. The development of new X-ray crystallography and single particle cryo-electron (cryoEM) strategies to understand receptors’ signal transduction requires improved purification yield andin vitrostability of the receptor. Here, we present a protein engineering effort to optimize the FP protein sequence for use in structural biology. Strategies involve protein insertion sites in the third intracellular loop (ICL3), N-terminal and C-terminal deletions, and single-point mutations that favorably affect receptor purification yield and stabilityin vitro. The best FP construct displays a yield of 1.5 mg/L and a stability of 59°C that constitute a threefold improvement in purification yield and 9°C increase in stability over the wild-type receptor. These modifications in the receptor are suitable for pursuing alternative strategies for improving FP purification yield and for studying FP binding efficacy to its ligands through structural biology approaches.
Water-mediated interactions between glycans are weakly repulsive and unexpectedly long-ranged
Authors: Shin Sucheol , Mugnai Mauro L. , Thirumalai D. 
Published: February 2025

AbstractGlycans, carbohydrates prevalent at the outer cell membrane, play an essential role in mediating cell-cell interactions as well as immune response. Despite their importance, interactions between them have not been characterized. Here, we reveal, using all-atom molecular dynamics simulations and free energy calculations, that watermediated interactions between a pair of N-glycans without net charge are weakly repulsive with a range that exceeds their sizes. Unexpectedly, the effective glycan–glycan interactions decay logarithmically as the separation between them increases. Strikingly, this finding coincides exactly with the predicted interaction, which is entropic in origin, between two star polymers, consisting of long flexible polymers grafted onto colloidal particles. The weak repulsive interaction, which extends beyond the size of a glycan, is sensitive to the relative orientation of the glycans. The effective long-range repulsive interaction vanishes if the charges on water are turned off, thus establishing that electrostatic interactions, arising in part due to the persistent hydrogen bonds between water and the glycans, are responsible for the inter-glycan repulsion.
High efficiency organoid-derived cyst cultures as a drug discovery platform for polycystic kidney disease
Authors: Vanichapol Thitinee , Wangford Ruby , Takemoto Misao , Uesugi Motonari , Davidson Alan J , Sander Veronika 
Published: February 2025

ABSTRACTAutosomal dominant polycystic kidney disease (ADPKD) causes the slow, progressive formation of fluid-filled cysts within the kidney that ultimately leads to renal failure. Despite being the most common genetic kidney disease, the range of therapies for ADPKD is limited. Ureteric bud (UB) organoids derived from human pluripotent stem cells (hPSCs) have been used to model ADPKD. Here, we describe a protocol to generate UB organoids in large-scale suspension culture that is amenable to drug discovery. When differentiated fromPKD2-deficient hPSCs, the UB organoids robustly form cysts within 7 days and reach nearly 100% cyst efficiency within ∼20 days. Cystic UB organoids express ADPKD markers and are responsive to cyst-reducing compounds, such as the BET inhibitor JQ1 and the NF-κB inhibitor QNZ, but not tolvaptan. As proof-of-principle of the platform as a drug discovery tool, we screened a small molecule library comprised of nutrient conjugates and identified M1, a palmitate-glucosamine-glycine conjugate, that reduced cyst formation. These results demonstrate that our scalable method of cystic UB organoid production provides a simple and highly efficient platform for ADPKD drug discovery.TRANSLATIONAL STATEMENTAutosomal dominant polycystic kidney disease (ADPKD) affects over 12 million people worldwide, yet the currently available therapy tolvaptan only moderately delays disease progression and is burdened with adverse effects. Improved treatments that are well tolerated and effective are urgently needed. We established a human ureteric bud organoid platform that enables ADPKD-like cysts to be cultured at large scale and low cost. These cystic organoids resemble human ADPKD cysts and are suitable for drug discovery. Identification of the nutrient conjugate M1 as a new lead molecule for reducing cyst formation highlights the clinical relevance of this model.
Causal associations between gut microbiota and cancers
Authors: Yue Zihan , Yan Junwei , Shen Linyuan , Zhao Chunguang , Yang Xiaopeng , Yao Yiying , Song Dongmei , Xu Chenyang , Bi Chenchen , Xiong Zhongkui , Ma Hongli , Liu Zheng 
Published: February 2025

AbstractBackgroundEmerging evidence suggests that the gut microbiota is associated with various cancer-related outcomes. Recent studies using Mendelian randomization (MR) have indicated a causal relationship between gut microbiota and several types of cancer. However, these conclusions remain controversial. To clarify this relationship, we conducted a systematic review and meta-analysis of MR studies to investigate the potential causal links between gut microbiota and cancer.MethodIn this study, we searched PubMed, Embase, the Cochrane Library, and Web of Science up to May 2024 for eligible MR studies and performed meta-analyses.ResultsOur findings indicate that genetically determined gut microbiota is associated with 12 different types of neoplastic outcomes. We identified nine genera of gut microbiota that are generally associated with a reduced risk of developing cancer. However, we also found that the order Mollicutes RF9 (OR = 1.037, 95% CI 1.013-1.060) may be a potential risk factor for breast and lung cancer. Furthermore, we discovered that the families Alcaligenaceae (OR = 1.034, 95% CI 1.000-1.068), Enterobacteriaceae (OR = 1.077, 95% CI 1.020-1.135), and Lactobacillaceae (OR = 1.033, 95% CI 1.008-1.059) are negatively associated with the risk of breast cancer. On the other hand, the genetically predicted family Lactobacillaceae (OR = 0.892, 95% CI 0.848-0.937), along with other families and genera such as Veillonellaceae, Coprococcus, Dorea, Eubacterium, Lachnospiraceae, Ruminococcus, Ruminococcaceae, and FamilyXIII, were found to be correlated with a lower risk of lung cancer. Additionally, the family Peptostreptococcaceae, Veillonellaceae, Streptococcaceae, and certain genera including Eubacterium, Lachnospiraceae, and Ruminococcaceae, were identified as protective factors against glioblastoma. The evidence from published MR studies supports the notion that the gut microbiota plays a causal role in various neoplastic diseases.ConclusionsIn conclusion, there is a causal relationship between gut microbes and cancer, and it is related to microbial species and tumor type. Further research is necessary to understand the underlying mechanisms and to explore the potential for using gut microbiota in prediction, prevention, and therapeutic strategies for these diseases. Studying changes in the microbiome in cancer has significant implications for developing noninvasive diagnostic tools and innovative interventions that could alter the progression of these diseases.