bluuebunny/crossref_metadata_2025_split huggingface dataset:
Codesign of a Neurological Physiotherapy Student-Led Clinic With Students and Patients: An Exploratory Qualitative Study
Authors: Wynne Donna , Hancock Elizabeth , Cooper Kay 
Published: October 2024

Introduction.
This study explores students' and patients' views of a UK physical therapy student-led clinic (SLC) for neurological rehabilitation and, using a codesign approach, it proposes an optimal design of a physical therapy SLC for neurological rehabilitation for patient participation and student learning.

Review of Literature.
There is a paucity of literature examining experiences of neurological rehabilitation SLCs. Although research supports the utilization of codesign methodologies with patients and for curriculum development, there remains a gap regarding its application to SLCs in physical therapy for individuals with neurological conditions.

Subjects.
Convenience sampling was used to recruit 4 patient and 4 student participants to take part in the study.

Methods.
This qualitative study employed exploratory codesign based on the participatory action research approach. Three online codesign workshops were facilitated by the research team. Thematic analysis of each workshop informed the outline for the next.

Results.
Patients perceived that the SLC improved their overall well-being, and they highly valued being able to access rehabilitation. Students reported that they developed a range of clinical skills through participation in the SLC but would have liked a more in-depth orientation. The codesign process identified 5 key elements for the optimal design of the physical therapy neurological SLC: student support, continuity, supervision, peer-assisted learning, and orientation.

Discussion.
Findings suggest that the SLC provides both a quality learning experience and a patient service, which is safe, effective, and sustainable. Future research should be undertaken with different stages of students and in different university settings. The codesign approach has been shown to be feasible for students and patients and could be used across other aspects of curriculum design.

Conclusion.
This novel study using codesign methodology provides initial findings of key elements to optimize SLCs in neurological physical therapy, to enhance student learning and patient experience.
Teflon Granuloma With Active Inflammation: A Cause of Recurrent Trigeminal Neuralgia After Microvascular Decompression
Authors: Herber Steven , Zimmerman Richard S. , Chen Alicia , Yang Ming , Martinez Felipe 
Published: October 2024

Abstract
Trigeminal neuralgia (TN) is characterized by excruciating facial pain usually caused by neurovascular compression of the trigeminal nerve roots. TN can be treated medically or invasively. Microvascular decompression is the procedure of choice and usually results in complete symptom relief. During surgical decompression, Teflon can be placed between the offending vessel and the nerve root entry zone. In some cases, chronic Teflon-related inflammation can cause recurrent TN, which might lead to additional surgical intervention. We present imaging and histopathological correlation of a patient presenting with intractable recurrent TN approximately 2 years after microvascular decompression with Teflon implant.
Cutaneous and Subcutaneous Prostate-Specific Membrane Antigen–Avid Lesions
Authors: Rafiei Zahra , Saber Tanha Amin , Tayyebi Meibodi Naser , Zahed Anaraki Siavash , Askari Emran 
Published: October 2024

Abstract
We report the case of a 62-year-old man with metastatic castration-resistant prostate cancer with subcutaneous involvement being treated with 177Lu–prostate-specific membrane antigen (PSMA). Before treatment, he was diagnosed with 2 subcutaneous nodules in the chest wall and soft tissue edema in the pubic and inguinal regions showing PSMA avidity. Biopsy and immunohistochemistry assessment confirmed cutaneous metastases from prostate cancer. He received 3 cycles of 177Lu-PSMA, resulting in a decline in PSA levels and resolution of symptoms. This case underscores the challenging diagnosis of cutaneous metastasis from prostate cancer, especially in atypical presentations. We also reviewed all causes of PSMA-avid lesions in the skin and subcutaneous tissues.
The Surveillance Strategy for Intraductal Pancreatic Mucinous Neoplasms
Authors: McGuigan Mari-Claire , Hadjicosti Rafaella , Cameron Andrew J. , Coats Maria , Chang David , Dickson Euan J. , Holroyd David , McKay Colin J. , Jamieson Nigel B. 
Published: October 2024

Objective:
To review the surveillance of IPMN, the risk of pancreatic cancer and the cost of surveillance.

Background:
The increasing IPMN prevalence and low pancreatic cancer associated with IPMN question the necessity and cost-effectiveness of surveillance. Guidelines favour a ‘watch and wait’ approach, lacking clarity on stopping surveillance. This study aims to identify patients with pancreatic cancer risk equivalent to their age group, create guidelines for stopping surveillance and reduce NHS costs.

Methods:
Retrospective analysis of IPMN patients on surveillance in the WoS. Clinicopathological data were collected. Endpoints included pancreatic cancer development and surveillance pathway cost estimation. Age-matched controls were used for comparison using standardised incidence ratios (SIRs) for pancreatic cancer.

Results:
Of 746 patients, 27 (3.62%) were resected. 3 (0.402%) developed pancreatic cancer and 44 (5.90%) developed worrisome features/ high-risk stigmata after a median surveillance of 48 (IQR 48) months. 221 (29.6%) had a stable cyst for at least 5 years and their SIR was 1.56 (95% CI 0.04-8.71). Patients ≥75 years with stable cysts for ≥5 years, SIR was 1.71 (95% CI 0.03-3.42). Patients ≥65 years with stable cysts of <15 mm for ≥5 years and patients with stable cysts of <10 mm for ≥5 years, had SIRs of 0. The cost of surveillance was £6,330.36 ($8,105.65) per resected patient and £2,032.78 ($2,602.85) per non-resected patient.

Conclusion:
Patients with stable IPMNs have similar pancreatic cancer risk as the general population. Surveillance discontinuation can be considered after 5 years in a cohort of patients, saving £106,211.19 ($136,020.42) per year.
Decoding Non-coding SNPs: Systems Genomics Modelling Dissects the Heterogeneity of IBD
Authors: Módos Dezső , Thomas John P. , Brooks-Warburton Johanne , Poletti Martina , Bohar Balazs , Madgwick Matthew , Csabai Luca , Kang Wen-Xin , Alexander-Dann Benjamin , Zoufir Azedine , Sudhakar Padhmanand , Cozzetto Domenico , Fazekas David , Carding Simon R. , Powell Nicholas , Verstockt Bram , Bender Andreas , Korcsmaros Tamas 
Published: October 2024

AbstractGenome-wide association studies have pinpointed numerous susceptibility loci in complex diseases like chronic immune-mediated inflammatory disorders (IMIDs), yet their impact on pathomechanisms remain poorly understood. Genetic epistasis, low effect sizes, and predominance within non-coding genomic regions, remain major challenges to the functional interpretation of IMID-associated single nucleotide polymorphisms (SNPs). To address this, we present a novel systems genomics approach which models the cumulative impact of non-coding SNPs on downstream cellular signalling and gene regulatory networks (GRNs). Applying this to the prototypical chronic IMIDs of Crohn’s disease (CD) and ulcerative colitis (UC), both forms of inflammatory bowel disease (IBD), we individually analysed 2,636 patient genomes. Signals from non-coding SNPs were found to propagate towards well-established and novel CD- and UC-associated pathogenic pathways through the signalling and gene regulatory layers. The SNP-propagated GRNs stratified CD and UC patients into distinct clusters corresponding to cell type-specific gene dysregulation and therapeutic response. This approach bridges the gap between genotype and phenotype, laying the foundations for accelerating precision medicine in complex diseases.
Locally heterogeneous soil viral and prokaryotic responses to prescribed burn correspond with patchy burn severity in a mixed conifer forest
Authors: Geonczy Sara E. , Hillary Luke S. , Santos-Medellín Christian , Sorensen Jess W. , Emerson Joanne B. 
Published: October 2024

ABSTRACTPrescribed burning, a strategy to mitigate wildfires, imparts physicochemical and biological changes to soil. The effects of burns on soil viruses and virus-host dynamics are largely unexplored, despite known viral and prokaryotic contributions to biogeochemical processes. Using a viromic (<0.2 µm size fraction metagenomic) approach, we assessed how viral communities responded to a spring prescribed burn in a mixed conifer forest and whether soil chemical properties and/or prokaryotic host communities could explain the observed patterns. From 120 soil samples (two per depth at 0-3 and 3-6 cm from four burned and two control plots at five timepoints, two before and three after the burn), 91 viromes and 115 16S rRNA gene amplicon libraries were sequenced. Plot location had the greatest effect on explaining variance in viral communities, over treatment (burned or not), depth, and timepoint. Viral and prokaryotic communities exhibited locally heterogenous responses to the fire, with some burned communities resembling unburned controls. This was attributed to patchy burn severity (defined by soil chemistry). Low viromic DNA yields indicated substantial loss of viral biomass in high-severity locations. The relative abundances of Firmicutes, Actinobacteria, and the viruses predicted to infect them significantly increased along the burn severity gradient, suggesting survival of spore formers and viral infection of these abundant, fire-responsive taxa. Our analyses highlight the importance of a nuanced view of soil community responses to fire, not just to burn overall, but to the specific degree of burn severity experienced by each patch of soil, which differed for nearby soils in the same fire.
Design of Novel Dehalogenases using Protein Large Language Models
Authors: Garcia Lucas , Nauber Willow , Dahlgren Camille , Chung Ray , Reyes Troy , Santos Jael , Kapur Maya , Barsever Monica , Thomson Matt , Lourenço Alec 
Published: October 2024

AbstractPer- and polyfluoroalkyl substances (PFAS) are toxic compounds linked to cancers, infertility, and vaccine resistance at concentrations above 1 part per trillion. Owing to strong carbon-fluorine bonds, they are persistent in the environment, taking centuries to millennia to degrade. As part of the 2024 iGEM competition, several high school students local to the Pasadena area leveraged recently-developed bioinformatic tools and large language models to discover and design novel reductive dehalogenases predicted to degrade perfluorooctanoic acid (PFOA), a long chain PFAS whose manufacture is prohibited, yet still persists in the environment and drinking water. The team identified 68 enzymes with structural similarity toAcidimicrobium sp. Strain A6RdhA, the only specific known PFAS degrading enzyme in nature, expressed and refolded 5 of these enzymes in addition to 1 rational, and 3 large language model designs. These designs all have diverse sequences yet all are predicted to retain key substrate and cofactor binding pockets. These enzymes will be assayed on the ability to defluorinate PFOA.
Exogenous fatty acids inhibit fatty acid synthesis through competition between endogenously- and exogenously-generated substrates for phospholipid synthesis inEscherichia coli
Authors: van den Berg Stefan Pieter Hendrik , Zoumaro-Djayoon Adja , Yang Flora , Bokinsky Gregory 
Published: October 2024

AbstractExogenous fatty acids are directly incorporated into bacterial membranes, heavily influencing bacterial ecology and antibiotic susceptibility. We use liquid chromatography/mass spectrometry to characterize how exogenous fatty acids impact theEscherichia colifatty acid synthesis pathway. We find that acyl-CoA synthesized from exogenous fatty acids rapidly increases long-chain acyl-ACP levels while depleting malonyl-ACP, indicating inhibition of fatty acid synthesis. Contrary to previous assumptions, acyl-CoA does not inhibit FabI in vivo; instead, substrate competition between acyl-CoA and acyl-ACP for phospholipid synthesis enzymes causes long-chain acyl-ACP to accumulate, inhibiting fatty acid synthesis initiation. Furthermore, changes in the acyl-ACP pool driven by acyl-CoA amplify the effects of exogenous fatty acids on the balance between saturated and unsaturated membrane lipids. Transcriptional regulation rebalances saturated and unsaturated acyl-ACP by adjusting FabA and FabB expression. Remarkably, all other fatty acid synthesis enzymes remain at stable levels, maintaining a fixed synthesis capacity despite the availability of exogenous fatty acids. Since all bacterial pathways for exogenous fatty acid incorporation characterized so far converge with endogenous synthesis pathways in a common substrate pool, we propose that the substrate competition-triggered feedback mechanism identified here is ubiquitous across bacterial species.
Lacticaseibacillus rhamnosusGG in a chewable colonizes the nose and facilitates local immune benefits in allergic rhinoconjunctivitis patients
Authors: De Boeck Ilke , Spacova Irina , Cauwenberghs Eline , Eilers Tom , Gehrmann Thies , Van den Bossche Karlien , Martens Katleen , Condori-Catachura Sandra , Michiels Kato , De Winter Fien , Kumar-Singh Samir , Bruffaerts Nicolas , Packeu Ann , Hellings Peter W. , Vroegop Anneclaire , Van Gool Klara , Vanderveken Olivier M. , Lebeer Sarah 
Published: October 2024

AbstractCurrent treatments fall short in managing allergic rhinitis (AR), emphasizing the need for additional strategies. Beneficial bacteria application shows promise in AR, however most studies focus on oral probiotic administration without monitoring the applied strains in the upper respiratory tract (URT) and their local effects. In this randomized, double-blind, placebo-controlled trial, the probioticLacticaseibacillus rhamnosusGG was administered via chewable tablets in seasonal AR patients, randomized to probiotic (n=33) or placebo (n=31) groups. Per-protocol analysis of the URT microbiome, immune markers and AR symptoms was performed.L. rhamnosusGG trafficked from chewables to the oropharynx (77%, p=0.02) and nasopharynx (41%, p<0.0001). Control of self-reported AR symptoms via validated questionnaires under grass pollen exposure was observed after two weeks of probiotic administration and not upon placebo. A local decrease in salivary interleukin-4 (p < 0.05) and nasal IL-13 (p < 0.0001) was observed in the probiotic group. These data indicate thatL. rhamnosusGG chewables can target the URT and exert local effects on key allergy cytokines after temporal probiotic engraftment.ImportanceAllergic rhinitis (AR) or hay fever is a highly prevalent condition, impacting nearly half the population in some countries. Supplementation of beneficial bacteria or probiotics has gained increasing attention in AR, and a key innovative way to do this is direct administration to the upper airways. Our study shows for the first time that the model probiotic strainLacticaseibacillus rhamnosusGG can traffic to the nose in AR patients when administered via a slow-releasing chewable tablet. This trafficking is associated with local benefits in the airways, including on grass pollen-induced nasal symptoms and allergy-related cytokines.
Archaeal tubulin-like proteins CetZ1 and CetZ2 have opposing effects on cell morphology during the growth cycle ofHaloferax volcanii
Authors: Brown Hannah J. , Duggin Iain G. 
Published: October 2024

AbstractCetZs are archaeal tubulin superfamily cytoskeletal proteins implicated in the control of cell shape and motility. In the pleomorphic archaeonHaloferax volcanii, CetZ1 is required for the transformation of a discoid, or plate-like, cell morphology to the rod shape during early-mid log phase cultures and for the development of swimming motility. In this study, we found that the paralog CetZ2 is not required for rod development or reversion to plates in log phase but was strongly upregulated later in stationary phase, where it promotes the maintenance of plate cell shape. CetZ2 cytoskeletal structures visualized through the production of a functional fluorescent tagged CetZ2 were most dynamic specifically in mid-stationary phase, where they showed directional movement around the cell edge and other complex cytomotive-like behaviours. Furthermore, in mid-stationary phase, the dynamics of CetZ1 and CetZ2 cytoskeletal structures were specifically dependent on the presence of one another and their GTPase activities that control the polymerization-depolymerization cycle. Together, the results suggest that CetZ2 counteracts the CetZ1-based rod development pathway to maintain plate shape, and they imply that additional stationary-phase factors are also involved. CetZ1 and CetZ2 are co-conserved in many haloarchaea, suggesting that their coordinated functions at different stages of the growth cycle are widely utilized to control cell shapeshifting. More generally, our findings show that CetZ paralogues can have distinct and non-redundant functions, indicating that diversification and specialisation within the tubulin superfamily has occurred multiple times in archaeal evolution.SignificanceThis study describes the first defined function of a CetZ2 protein, which represents a distinct haloarchaeal protein family within the near-universal tubulin superfamily of cytoskeletal proteins. Using the model archaeal organismHaloferax volcanii, we found that CetZ2 maintains the plate or disk-like cell morphology specifically in the stationary phase of the growth cycle, by counteracting CetZ1-based rod development. We also showed for the first time that CetZ2 can form dynamic cytoskeletal filaments that show directional movement around the cell in mid-stationary phase. The CetZ1-CetZ2 interplay we detected specifically at this stage may represent a paradigm for understanding the evolution of antagonistic cytoskeletal functions, such as those that led to a reliance on active and inactive subunits during the early evolution of microtubules in eukaryotes.
A genome-wide pleiotropy study between atopic dermatitis and neuropsychiatric disorders
Authors: Antonatos Charalabos , Pontikas Alexandros , Akritidis Adam , Mitsoudi Dimitra , Georgiou Sophia , Stratigos Alexander J. , Zacharopoulou Aikaterini , Gregoriou Stamatis , Grafanaki Katerina , Vasilopoulos Yiannis 
Published: October 2024

AbstractComorbidities between atopic dermatitis (AD) and neuropsychiatric disorders are frequently reported, however the extent of shared genetic architecture remains unclear. Here, we performed a large-scale genome-wide pleiotropy approach to investigate the genetic correlations and causal associations between AD and five neuropsychiatric disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia (SCZ). Using genome-wide association (GWAS) data, we explored genetic overlaps, pleiotropic loci and assessed the capacity of pleiotropic associations to identify drug targets. We identified significant positive genetic correlations between AD and ADHD (rg=0.14, P-value=2×10), MDD (rg=0.13, P-value=1.2×10 ³) and BP (rg=0.11, P-value= 4×10 ³). Genome-wide pleiotropy scans identified 37 distinct pleiotropic loci between AD and neuropsychiatric traits, with gene-based analyses highlighting 86 unique genes participating in inflammatory pathways. Pleiotropy-informed target prioritization facilitated the identification of novel pathophysiological mechanisms for AD and putative drug targets, such as members of TNF and JAK-STAT3 signaling. Mendelian randomization provided evidence of a causal relationship between genetic liability to MDD and BP with an increased risk of AD, independent of sample overlap. Collectively, our findings elucidate shared molecular mechanisms between AD and neuropsychiatric disorders, emphasizing immune-related pathways as key contributors to both disease categories, with potential implications for therapeutic interventions targeting common inflammatory mechanisms.
Impact of Cushing’s syndrome on the hypothalamus-pituitary-gonad axis in women
Authors: Yu Anting , Liu Xuan , Chen Yiyu , Li Shuo , Liu Ming 
Published: October 2024

AbstractBackgroundThe reproductive and sexual disorders commonly occur in patient with Cushing’s syndrome (CS), but only few clinical studies focused on the hypothalamus-pituitary-gonad (HPG) axis status in women with CS. A comprehensive spectrum of the impairment on HPG axis in women with CS of different tensity and causes is needed.MethodThis retrospective study analyzed the status of HPG axis in 137 women with different CS causes diagnosed between 2007 and May 2024, and the correlation between reproductive hormones and the tensity of hypercortisolism. Receiver operating characteristic (ROC) analysis was performed in 45 women with available data of plasma steroids by tandem mass spectrometry (LC-MS/MS) as well.ResultsWomen with ectopic adrenocorticotropin (ACTH) secretion (EAS) had significantly higher levels of serum cortisol, 24h urinary-free cortisol (UFC), ACTH, with marked increase in testosterone and decrease in Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) (P<0.001).The serum cortisol and ACTH were positively associated with testosterone, while negatively associated with LH and FSH, especially in postmenopausal women. Further investigation of steroid profiles found plasma androgen including testosterone, Androstenedione (A2), dehydrospiandrostenedione (DHEA) and dehydrospiandrostenedione sulfate (DHEAS) had high sensitivity and specificity in discriminating CD from adrenal CS. Additional analysis of thyroid axis found hypercortisolism had less influence on TSH compared with LH and FSH.ConclusionExcessive cortisol caused by CS can impair the HPG axis in women, which were especially intense in EAS. The degrees of impairment were associated with the intensity and the underlying causes of hypercortisolism.