bluuebunny/crossref_metadata_2025 huggingface dataset:
The modern spiritual affect of perplexed affirmation, or, the David Hume of R. S. Thomas
Authors: Wickman Matthew
Published: October 2024

Long known as a poet of divine silence and Holy Saturday, R. S. Thomas is also a laureate of a modern spiritual affect we may describe as perplexed affirmation. In this state, one has difficulty inhabiting, of being fully present to, an experience of the sacred, an experience of God. In some ways, perplexed affirmation seems to be a product of cultural shifts toward what is spiritual but not religious. Here, openness toward possibilities of sacred encounter finds itself increasingly bereft of theological and liturgical systems that might mediate and at least partly explain experiences of particular intensity. Thomas frequently enacts such states of perplexed affirmation in his poetry. In this essay, I explore how this affect derives partly from Thomas’s reckoning with David Hume. Thomas names Hume in a handful of poems as a figure who complicates and perhaps destroys a traditional vision of the world. But if Hume complicates thought, including theology, he empowers experience. For Thomas, this means that Hume demarcates modern limits the poet implicitly surpasses through faith, or through experiences of the sacred he can no longer fully conceptualize. This dialectic evokes an expansive and counterintuitive vision of spiritual experience that figures in some of Thomas’s most famous religious poems.
A Nomogram for Predicting Late-Onset Neurological Deficits in the Natural Course of Kyphosis or Kyphoscoliosis
Authors: Ni Jiajun , Yan Shi , Li Yangxiao , Chen Zhongqiang , Zeng Yan
Published: October 2024

Study Design.

Retrospective single-center comparative analysis.

Objective.

To develop a nomogram model for predicting late-onset neurological deficits (LONDs) in patients with kyphosis or kyphoscoliosis.

Summary of Background Data.

Patients with kyphosis or kyphoscoliosis might suffer from LONDs, and surgical correction may improve neurological function. Nevertheless, there exists a significant gap in the identification of predictive factors for LONDs in these patients.

Methods.

A consecutive series of 244 patients with kyphosis or kyphoscoliosis who underwent corrective surgery between April 2010 and June 2024 were included in our study. Relevant measurements, including the Cobb angle, deformity angular ratio (DAR), and level of the apex were assessed and calculated using X-ray imaging. Spinal cord morphology at the apex of the major curve was evaluated using preoperative axial T2-weighted magnetic resonance imaging (MRI) to categorize patients into three types based on the spinal cord shape classification system (SCSCS). To identify independent risk factors associated with LONDs, we employed univariate analysis followed by backward stepwise multivariate logistic regression analysis. A nomogram was established based on the identified independent risk factors to predict the likelihood of LONDs in patients with kyphosis or kyphoscoliosis.

Results.

The mean age of the 244 patients was 46.4±17.8 years, with an observed incidence of LONDs at 57.8%. The backward stepwise multivariate logistic regression analysis indicated that age, etiological diagnosis and SCSCS were independent predictors of LONDs. Utilizing these independent risk factors, we constructed a nomogram model to estimate the probability of LONDs. The concordance index (C-index) of the model was 0.912 (95% CI, 0.876–0.947), indicating a satisfactory level of accuracy in predicting the likelihood of LONDs.

Conclusion.

The predictive factors for LONDs include age, etiological diagnosis and SCSCS. We developed a nomogram model to predict LONDs, which could be useful for patient counseling and facilitating treatment-related decision-making.
Regenerative Skincare Technologies Derived From Human Fibroblasts: Growth Factors and Exosomes for Transformative Outcomes
Authors: Cheng Tsing , Naughton Gail K. , Makino Elizabeth T. , Kadoya Kuniko , Maitra Prithwiraj
Published: October 2024

BACKGROUND

Since the early 2000s, human fibroblast conditioned media (HFCM) has been used in topical growth factor skincare to support skin regeneration and skin rejuvenation. Human fibroblast conditioned media contains the fibroblast secretome including growth factors as well as exosomes. The potential benefits of topically applied exosomes are gaining interest in the medical aesthetic field.

OBJECTIVE

This article aims to summarize the preclinical and clinical data available on regenerative HFCM-based topical skincare with a focus on studies investigating products applied to improve overall facial skin rejuvenation and/or after in-office cosmetic procedures. In addition, available data on fibroblast-derived exosomes will be covered.

METHODS

A focused literature review was conducted to provide an overview of evidence on HFCM-based topical skincare.

RESULTS

Human fibroblast conditioned media–based skincare significantly reduces signs of skin aging including photodamage, coarse lines and wrinkles, and sagging. After in-office cosmetic procedures, HFCM-based skincare can stimulate skin recovery and reduce downtime as well as provide skin quality benefits to enhance overall treatment outcomes. Application of purified exosomes from HFCM also demonstrated significant improvements in multiple skin aging parameters.

CONCLUSION

Human fibroblast conditioned media combines naturally secreted fibroblast-derived growth factors and exosomes that stimulate skin regeneration and rejuvenation as evidenced by a variety of assays and assessments including in vitro preclinical studies, clinical investigator grading, instrumentation measurements, biopsy analyses, and patient-reported outcomes.
A Forecast of the HIV Clinician Workforce Need in the United States: Results of a Quantitative National Survey
Authors: Norberg Andrea , Nelson John , Lin Haiqun , Lazo Elizabeth , Stanislaus Dominic , Chu Carolyn , Bolduc Philip
Published: October 2024

There is a decreasing HIV care workforce in the United States, whereas the need for HIV care and prevention continues to increase. To better understand this issue, a quantitative, anonymous, one-time, self-administered survey was conducted. The survey was completed by 1,004 prescribing clinicians currently providing HIV-related health care. Clinicians of younger age and Black race, advanced practice registered nurses, and family medicine physicians were more likely to report continuing with the same number of patients or increasing the number of patients in their HIV practice in the next 5 years. The need for more prescribing HIV care clinicians is paramount because 17.8% reported plans to stop HIV clinical care wholly or to decrease the number of people living with HIV in their practice over the next 5 years. The most common reasons for leaving include retirement, administrative burden, and burnout.
Return to Sport After Conservative Management of Midshaft Clavicle Fractures in Professional Jockeys
Authors: Fahy Stephen , Ó Doinn Tiarnán , Pugh Jennifer , Kenny Patrick
Published: October 2024

Objective:

This study explores the functional recovery and rates return to play (RTP) of professional jockeys following midshaft clavicle fractures, which have been managed conservatively. The high incidence of these fractures in horse racing underscores the importance of evaluating nonsurgical recovery paths for effective RTP.

Design:

We used a retrospective cohort study to assess treatment outcomes.

Setting:

The research is set in the professional horse racing scene of Ireland.

Participants:

Sixteen professional Irish jockeys with conservatively managed midshaft clavicular fractures were examined. Jockeys who underwent surgery or were inactive at injury time were excluded.

Interventions:

The study involved no direct interventions.

Main Outcome Measures:

Recovery was assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score and Patient-Reported Outcome Measures, alongside racing records to track RTP.

Results:

The all-male cohort had an average age of 27 years. Results showed an average 67.1-day absence from racing, with 94% returning to preinjury competition levels. Complications were minimal, and patient outcomes were positive, as indicated by a mean QuickDASH score of 2.58, suggesting minimal residual disability.

Conclusions:

Findings highlight the success of conservative management for midshaft clavicle fractures in professional jockeys, enabling them to return to prior competitive levels with few complications and excellent functional recovery.
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.
Adenomatoid Tumor Mimicking Peritoneal Carcinomatosis: A Case Report
Authors: Jo Uiree
Published: October 2024

An adenomatoid tumor (AT) is a benign lesion, which is commonly located in the genital tract of both sexes. We present a case of a 66-yr-old woman with the unusual characteristics of an AT mimicking peritoneal carcinomatosis. The tumor was detected incidentally by ultrasound examination, and an ensuing imaging study raised suspicion of ovarian cancer with peritoneal carcinomatosis. From the pathologic diagnosis of frozen specimens, clear cell carcinoma was noted and the patient subsequently underwent cytoreductive surgery. An 8.5-cm-sized mass was observed on the uterine serosa, extending into the myometrium. In addition, multi-cystic nodular lesions were identified in the omentum, appendiceal and small bowel serosa, and the peritoneum. After histologic and extensive immunohistochemical examinations, the final diagnosis was AT. Recognition of the diverse presentations of AT is crucial for accurate diagnosis and appropriate treatment, as these tumors can involve multiple sites and mimic peritoneal carcinomatosis, potentially leading to a misdiagnosis of malignancy.
Lamin A and Emerin Protein Expression Remains Consistently Low and Nuclear Size is Unchanged in Normal Endometrium, Precancerous Lesions, and Endometrioid Carcinoma
Authors: Nishijima Yoshimi , Inoue Naoki , Iwase Akira , Ikota Hayato , Kobayashi Sayaka , Yokoo Hideaki , Saio Masanao
Published: October 2024

Nuclear laminar or inner nuclear membrane proteins, including lamin A, B1, and B2 and emerin, are involved in maintaining nuclear morphology. However, their expression patterns vary among tumors and remain incompletely understood. Endometrioid carcinoma (EC) exhibits mild nuclear atypia, although the underlying reasons have not been thoroughly explored. In this study, we quantitatively analyzed emerin and lamin A, B1, and B2 expression levels in normal endometrium (NE), precancerous lesions, and EC using computer-assisted image analysis to assess the proteins’ roles in nuclear morphologic change during tumorigenesis. From NE to EC, nuclear size remained unchanged, and lamin A and emerin were consistently expressed at low levels, whereas lamin B1 and B2 expression gradually decreased. Given the association between lamin A and emerin as well as their roles in nuclear morphology, these results indicate that their consistent low expression may underlie the preservation of nuclear size and shape in EC relative to NE. Conversely, lamin B1 and B2 are implicated in tumor progression rather than nuclear morphology maintenance. As lamin A and emerin are expressed in many organs and tumors, the consistently low expression of these proteins from NE to EC highlights a notable feature of the endometrium and endometrial carcinogenesis.
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

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

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

Genome-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

Prescribed 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

Per- 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

Exogenous 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.
GPCRVS - AI-driven decision support system for GPCR virtual screening
Authors: Latek Dorota , Prajapati Khushil , Dragan Paulina , Merski Matthew , Osial Przemyslaw
Published: October 2024

Summary: G protein-coupled receptors (GPCRs) constitute the largest and most frequently used family of molecular drug targets. The simplicity of GPCR drug design results from their common seven-transmembrane helix topology and well-understood signaling pathways. GPCRs are extremely sensitive to slight changes in the chemical structure of compounds, which allows for the reliable design of highly selective and specific drugs. Only recently has the number of GPCR structures, both in their active and inactive conformations together with their active ligands, become sufficient to comprehensively apply machine learning in decision support systems to predict compound activity for drug design. Here, we describe GPCRVS, an efficient machine learning web service for the online assessment of compound activity against several GPCR targets, including peptide and protein-binding GPCRs, the most difficult for virtual screening tasks. As a decision support system, GPCRVS evaluates compounds in terms of their activity range, the pharmacological effect they exert on the receptor, and the binding modes they could possibly demonstrate for certain types of GPCR receptors. GPCRVS can be applied to compounds ranging from small molecules to short peptides uploaded as common chemical format files. The activity class assignment and the binding affinity prediction are provided in a reference to similar predictions precomputed for already known active ligands of each GPCR target. This multiclass classification in GPCRVS, handling often incomplete and fuzzy biological data, was validated on ChEMBL-retrieved data sets for secretin-like and chemokine GPCR receptors. Availability and Implementation: GPCRVS is freely available at: https://gpcrvs.chem.uw.edu.pl .
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

Current 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.

Importance

Allergic 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

CetZs 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.

Significance

This 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

Comorbidities 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

Background

The 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.

Method

This 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.

Results

Women 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.

Conclusion

Excessive 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.
Phosphate amendment drives bloom of RNA viruses after soil wet-up
Authors: Sieradzki Ella T. , Allen G. Michael , Kimbrel Jeffrey A. , Nicol Graeme W. , Hazard Christina , Nuccio Erin , Blazewicz Steven J. , Pett-Ridge Jennifer , Trubl Gareth
Published: October 2024

Soil rewetting after a dry period results in a surge of activity and succession in both microbial and DNA virus communities. Less is known about the response of RNA viruses to soil rewetting—while they are highly diverse and widely distributed in soil, they remain understudied. We hypothesized that RNA viruses would show temporal succession following rewetting and that phosphate amendment would influence their trajectory, as viral proliferation may cause phosphorus limitation. Using 39 time-resolved metatranscriptomes and amplicon data, 2,190 RNA viral populations were identified across five phyla, with 37% of these predicted to infect bacteria (26%) or fungi (11%). Only 1.2% of viral populations had annotated capsid genes, suggesting most persist via intracellular replication without a free virion phase. Phosphate amendment altered RNA viral community composition within the first week and amended vs. unamended communities remained distinguishable for up to three weeks. While the overall host community remained stable, certain bacterial populations showed reduced abundance in phosphate-amended soils, likely due to increased viral lysis, as RNA bacteriophages, particularlyLeviviricetes, proliferated significantly. Notably, 60% of the viruses with increased abundance under phosphate amendment belonged to basalLenarviricotaclades rather than well-known groups likeLeviviricetes. We estimate RNA bacteriophage infections may affect 107–109bacteria per gram of soil, aligning with the total bacterial population (107–1010g−1soil), suggesting that RNA phages significantly influence bacterial communities post-wet-up, with phosphorus availability modulating this effect.

Highlights

Soil wet-up influences RNA virus dynamics for over a week

The majority of hosts predicted for RNA viruses were bacteria and fungi

Phosphate amendment preferentially supportsLenarviricotaover other RNA viruses

60% of vOTUs that responded to phosphate were from unknown bacteriophage clades

Most soil bacteria are predicted to be infected by RNA bacteriophages within a week
Spatiotemporal transcriptomic analyses reveal molecular gradient patterning during development and the tonotopic organization along the cochlear axis
Authors: Yan Mengzhen , Zhang Penghui , Wang Yafan , Wang Haojie , Li Junhong , Guo Xiang , Zeng Xiangyao , Feng Zhili , Gao Yushan , Deng Fei , Zhu Bicheng , Deng Di , Ma Lu , Feng Yong , Wu Hua-Jun , Zhao Yu , Li Jun
Published: October 2024

Disruption of cochlear architecture and development can lead to malfunction, resulting in hearing defects. However, the spatial molecular profiles critical for hearing function remain poorly understood due to the structural complexity of the cochlea. In this study, we performed comprehensive spatiotemporal transcriptomic analyses on the developing and adult cochlea, identifying numerous genes with gradient expression patterns in hair cells (HCs) and spiral ganglion neurons (SGNs) across the apical-to-basal axis. The gradient geneMyo7a, a well-known HC marker, established a decreasing gradient in outer hair cells (OHCs) from the apical to basal regions in adulthood. In contrast, the other class of gradient genes exhibited an opposing expression pattern toMyo7aalong the cochlear axis in adulthood, such asCalb2in HCs andNefhin SGNs, which potentially corresponds to the cochlear tuning properties for sensing gradient frequency sounds. Importantly, our analyses provided compelling evidences for the existence of distinct spatial subtypes of OHCs. The spatial analyses revealed regional heterogeneity in cell communication intensity between HCs and SGNs, with the weakest intensity at the apex, potentially aligning this region for detection of low-frequency sound. This study systematically characterized the fine spatial organizations in HCs, SGNs, and their regionalized cell-communications within the cochlea, offering insights into the morphological and molecular foundations underlying cochlear tonotopic organization and frequency discrimination.
Site-specific quantification of thein vivoUFMylome reveals myosin modification in ALS
Authors: Blazev Ronnie , Zee Barry M. , Peckham Hayley , Ng Yaan-Kit , Lewis Christopher T. A. , Zhang Chengxin , McNamara James W. , Goodman Craig A. , Gregorevic Paul , Ochala Julien , Steyn Frederik J. , Ngo Shyuan T. , Stokes Matthew P. , Parker Benjamin L.
Published: October 2024

UFMylation is a ubiquitin-like protein post-translational modification of Ubiquitin Fold Modifier 1 (UFM1) applied to substrate proteins. The UFMylation system is important for normal development and plays a critical role in a variety of cellular processes including regulating telomere length, stress responses and protein quality control. Here, we describe the development of an antibody-based enrichment approach to immunoprecipitatein vivoremnant UFMylated peptides and identification by liquid chromatography and tandem mass spectrometry (LC-MS/MS). We used this approach to identify >200 UFMylation sites from various mouse tissues revealing extensive modification in skeletal muscle. Furthermore, we show that UFMylation is increased in skeletal muscle biopsies from people living with Amyotrophic Lateral Sclerosis (plwALS). Quantification of UFMylation sites in these participant biopsies with multiplexed isotopic labeling and LC-MS/MS reveal prominent increases in myosin UFMylation. Finally,in silicomodelling suggest UFMylation of myosin directly adjacent to the ATP-binding site may regulate stability and/or function. Our data suggest that although UFMylation is not as widespread as ubiquitylation, itsin vivostatus is more complex than previously thought.
Investigation on the stabilities of doubly heavy tetraquark states
Authors: Park Woosung , Noh Sungsik
Published: October 2024

In our recent work [S. Noh and W. Park, Nonrelativistic quark model analysis of Tcc, ], the mass and binding energy of Tcc are found to be 3873 MeV and −2  MeV, respectively, which align with the observations reported at LHCb [R. Aaij (LHCb Collaboration), Observation of an exotic narrow doubly charmed tetraquark, ]. Based on our latest quark model approach, we extend our search for other potentially stable configurations of doubly heavy tetraquarks using our nonrelativistic quark model described in Noh and Park, [Nonrelativistic quark model analysis of Tcc, ]. Our numerical calculations indicate that the u¯s¯cb configuration is deeply bound. However, the u¯d¯cb configuration with the isospin symmetry in the light quark sector is relatively less bound. In this study, we emphasize a compulsory aspect for requiring a complete set of three-dimensional harmonic oscillator bases through the discussion of the u¯s¯cb configuration and investigate the essential differences between the u¯s¯cb and u¯d¯cb configurations.

Published by the American Physical Society
2024
Axion and dark fermion electromagnetic form factors in superfluid
He4
Authors: Chao Wei , Sun Si-Chun , Wang Xin , Xie Chen-Hui
Published: October 2024

Condensed matter materials have shown great potential in searching for light dark matter (DM) via detecting the phonon or magnon signals induced by the scattering of DM off the materials. In this paper, we study the possibility of detecting electromagnetic form factors of fermionic DM and axionlike particles (ALPs) using superfluid He4. The phonon induced by a sub-GeV fermionic DM scattering off the superfluid can be described using the effective field theory with the interaction between DM and the bulk He4. Signals arising from the electromagnetic form factors of light DM in the presence of an external electric field are calculated. Projected constraints on the charge radius, anapole moment, and magnetic moment of the DM are derived with 1  kg·yr exposure. The phonon signal induced by the scattering of ALPs off the superfluid is also calculated, which can put competitive and the first direct detection bounds on ALP-photon-dark photon couplings in the projected experiments.

Published by the American Physical Society
2024
Greening by enhancing self-efficacy: a viewpoint on employee-inclusive Octalysis framework
Authors: Haque Shamima , Panda Debadrita
Published: October 2024

Purpose

The purpose of this study is to investigate how gamification can be utilized to promote Employee Green Behavior (EGB) within organizations thereby enhancing corporate sustainability. The research aims to propose a structured gamification framework that can effectively motivate and engage employees in sustainability initiatives.

Design/methodology/approach

The viewpoint reviews existing literature on gamification, and its impact on EGB. The authors propose a conceptual model that highlights critical components for Octalysis framework and map this against various player types for various phases of a gamified system.

Findings

The Octalysis framework, with its eight core drives, is found to be an effective tool for fostering EGB by leveraging both intrinsic and extrinsic motivations. The viewpoint demonstrates that categorizing employees into distinct player types and tailoring gamification strategies accordingly can overcome motivational barriers and encourage sustained engagement in green practices.

Originality/value

This study introduces a novel approach to corporate sustainability by integrating gamification into EGB initiatives. This innovative approach enhances the understanding of EGB and provides practical insights for implementing effective gamification strategies in corporate sustainability efforts.
Intangible cultural heritage transmission: empowering generations through Emirati handicrafts at Turath center
Authors: Kottangal Achuthy , Purohit Deepika
Published: October 2024

Purpose

In order to preserve and honor authentic Bedouin Emirati heritage history, the Turath Centre for Traditional Handicrafts, which operates under the supervision of the Art authority of Dubai culture, which is essential. The center aims and its strategy for cultural preservation, then the effects of its operations on community development are all explored in this article.

Design/methodology/approach

The goals and strategies employed by the Turath Centre to promote traditional Emirati crafts are analyzed in this study using the qualitative methodology that blends historical analysis and ethnographical research. It also examines the effects of the center's training programs and workshops. This study reveals the methods the Turath Centre uses to disseminate cultural heritage through a thorough analysis of the supporting documentation and on-site observations.

Findings

According to the research, the Turath Center effectively instructs community people in a variety of craft areas, such as traditional weaving, silversmith work, and burqa sewing and intangible facets of Emirati history though Al Talli and Al Sadu Weave. This study highlights the value of the Turath Centre's contribution to community development and preservation of Emirati heritage though younger generations.

Research limitations/implications

Although this study offers insightful information, there are certain limitations. Specifically, more research is required to evaluate the efforts of the Turath Center's adaptability and impact over time.

Practical implications

The results highlighted the consideration to these educational programs and their capacity to foster heritage industries, increase cultural tourism, and promote Emirati culture internationally.

Social implications

By enhancing Bedouin heritage culture and encouraging pride and identity among community members, the Turath Center's activities support unity in society.

Originality/value

This research offers valuable insights into the Turath Centre's role in preserving Bedouin Emirati heritage and fostering community development, the center symbolizes Dubai's aim for cultural growth and makes a significant contribution to cultural preservation.