bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four novel mutations identification in 17 beta-hydroxysteroid dehydrogenase-3 deficiency and our clinical experience: possible benefits of early treatment
Authors: Wang Yunpeng , Xu Yu , Zhang Huijiao , Yin Danyang , Pan Yiming , He Xiwen , Li Shuaiting , Cheng Zhi , Zhu Gaohui , Zhao Ting , Huang Huizhe , Zhu Min 
Published: February 2024

IntroductionIndividuals with 17-beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency face a multitude of challenges, primarily concerning genital appearance, potential malignancy risks, and fertility issues. This study reports our findings from an investigation involving five individuals affected by 17β-HSD3 deficiency, ranging in age from pre-adolescence to adolescence. Notably, we identified four previously unreported mutations in these subjects.MethodsOur study included a comprehensive evaluation to determine the potential occurrence of testicular tumors. The methods involved clinical examinations, genetic testing, hormone profiling, and patient history assessments. We closely monitored the progress of the study subjects throughout their treatment.ResultsThe results of this evaluation conclusively ruled out the presence of testicular tumors among our study subjects. Moreover, four of these individuals successfully underwent gender transition. Furthermore, we observed significant improvements in genital appearance following testosterone treatment, particularly among patients in the younger age groups who received appropriate treatment interventions.DiscussionThese findings underscore the critical importance of early intervention in addressing concerns related to genital appearance, based on our extensive clinical experience and assessments. In summary, our study provides insights into the clinical aspects of 17β-HSD3 deficiency, emphasizing the vital significance of early intervention in addressing genital appearance concerns. This recommendation is supported by our comprehensive clinical assessments and experience.
What are the environmental factors that affect respiratory viral pathogen transmission and outcomes? A scoping review of the published literature
Authors: Spencer Elizabeth , Brassey Jon , Pluddemann Annette 
Published: February 2024

IntroductionRespiratory viral pathogens are a major cause of morbidity and mortality, and there is a need to understand how to prevent their transmission.MethodsWe performed a scoping review to assess the amount and scope of published research literature on environmental factors, including meteorological factors and pollution, that affect the transmission of respiratory viral pathogens. We used Joanna Briggs Institute methodology for conducting a scoping review. We searched the electronic databases: MEDLINE, Register of Controlled Trials (Cochrane CENTRAL), TRIP database, WHO Covid-19 Database, Global Index Medicus, LitCovid, medRxiv, and Google Scholar. We included studies on environmental exposures and transmission of respiratory viruses (including but not restricted to: influenza, respiratory syncytial virus (RSV), human coronaviruses, viral pneumonia).ResultsThe searches identified 880 studies for screening; after screening we included 481 studies, including 395 primary studies and 86 reviews. Data were extracted by one reviewer (ES) and independently checked by a second reviewer for accuracy (AP). All primary studies were observational, mostly using an ecological design; 2/395 primary studies were prospective cohorts. Among the primary studies, 241/395 were on SARS-CoV-2/COVID-19; 95 focussed on influenza; the remaining 59 reported on RSV, other coronaviruses, and other respiratory viruses. Exposures were most commonly temperature (306 primary studies) and humidity (201 primary studies); other commonly reported exposures were air pollution, wind speed, precipitation, season, and UV radiation. It was frequently reported, but not consistently, that temperature, humidity and air pollution were positively correlated with COVID-19 cases/deaths; for influenza, season/seasonality was commonly reported to be associated with cases/deaths.DiscussionThe majority of studies reported on SARS-CoV-2/COVID-19 and were of ecological design. Few prospective cohort studies have been done for any respiratory virus and environmental exposures. Understanding the role of environmental factors on transmission is limited by the lack of prospective cohort studies to inform decision making.Systematic Review Registrationhttps://osf.io/ntdjx/, identifier: 10.17605/OSF.IO/NTDJX.
CXCR5+TIM-3-PD-1+ stem-like cytotoxic CD8+ T cells: elevated in chronic rhinosinusitis and associated with disease severity
Authors: Liu Zhichen , Zhao Zixuan , Xie Huanxia , Lu Ning , Liu Jisheng , Jiao Qingqing 
Published: February 2024

BackgroundChronic rhinosinusitis (CRS) is a chronic inflammatory disease with an autoimmune background. Altered expression levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3), C-X-C chemokine receptor type 5 (CXCR5), and programmed cell death protein 1 (PD-1) are implicated in the progression of inflammatory and autoimmune diseases. Moreover, CXCR5+TIM-3-PD-1+ stem-like cytotoxic T cells function as memory stem cells during chronic disease processes and retain cytotoxicity-related gene networks.ObjectivesTo explore the expressions of CXCR5, TIM-3, and PD-1 on T cells and their correlation with clinical parameters in CRS.MethodsFlow cytometry was used to assess the expressions and co-expressions of CXCR5, TIM-3, and PD-1 on T cells in the tissues of the paranasal sinus and peripheral blood of patients with CRS as well as healthy controls. Immunofluorescence was used to assess the co-localization of TIM-3, CXCR5, and PD-1 with T cells. The disease severity of our patients with CRS was evaluated using the Lund-Mackay score. A complete blood count was also performed for the patients with CRS.ResultsExpression levels of CXCR5 and PD-1 on T cells were significantly increased in the nasal tissues of patients with CRS. Compared with those in healthy controls, patients with CRS had high percentages of CXCR5+TIM-3-PD-1+ CD8+ and CD4+ T cells in nasal tissues, while no significant difference was observed in peripheral blood levels. Patients with CRS had a higher density of nasal CXCR5+TIM-3-PD-1+ T cells than that in healthy controls. CXCR5+TIM-3-PD-1+ CD8+ T cell levels in the nasal polyps of patients with CRS were negatively correlated with the patients’ Lund-Mackay scores. The levels of CXCR5+TIM-3-PD-1+ T cells in nasal tissues were also negatively associated with disease duration and positively associated with the chronic inflammatory state of CRS.ConclusionsThe level of CXCR5+TIM-3-PD-1+ stem cell-like T cells, especially CXCR5+TIM-3-PD-1+ CD8+ T cells, is increased in CRS. Therefore, inducing CXCR5+TIM-3-PD-1+ T cell exhaustion may be an effective immunotherapy for CRS.
Somatostatin-SSTR3-GSK3 modulates human T-cell responses by inhibiting OXPHOS
Authors: Zhang Bo , Feng Huiru , Lin Hui , Li Rui 
Published: February 2024

IntroductionSomatostatin (SST) is a peptide hormone primarily synthesized in the digestive and nervous systems. While its impact on the endocrine system is well-established, accumulating evidence suggests a crucial role for SST and its analogues in modulating immune responses. Despite this, the precise mechanism through which SST regulates T cells has remained largely unknown.MethodsTo elucidate the impact of SST on human T cells, we conducted a series of experiments involving cell culture assays, molecular analyses, and metabolic profiling. Human T cells were treated with SST, and various parameters including proliferation, cytokine production, and metabolic activities were assessed. Additionally, we employed pharmacological inhibitors and genetic manipulations to dissect the signaling pathways mediating SST's effects on T cells.ResultsWe showed that SST diminishes T-cell proliferation by influencing IL-2 production and T-cell mitochondrial respiration, while having no discernible impact on TCR-induced glycolysis. Our findings also identified that the regulatory influence of SST on T-cell responses and metabolism is contingent on its receptor, SSTR3. Moreover, we demonstrated that SST governs T-cell responses and metabolism by acting through the T-cell metabolic checkpoint GSK3.DiscussionOur study provides novel insights into the immunoregulatory function of SST in human T cells, highlighting the complex interplay between hormonal signaling and immune regulation. Understanding the molecular mechanisms underlying SST's effects on T cells may offer therapeutic opportunities for manipulating immune responses in various pathological conditions.
The effects of atmospheric nitrogen deposition in coral-algal phase shifts on remote coral reefs
Authors: Fu Yichen , Chen Xiaoyan , Liu Yuchen , Li Yuxiao , Yu Kefu 
Published: February 2024

Remote seawater has been considered a potential refuge for corals in the face of anthropogenic disturbances. However, these remote areas may receive increased atmospheric N deposition, and the ecological consequences remain unclear. This field survey revealed coral-algal phase shifts in the mid-north of the South China Sea. These shifts were observed in 44%, 13.6%, and 26.5% of the sampled reef sites at depths of 1-4 m, 5-8 m, and 10-15 m, respectively. Over 50% of sections in the deeper depths hosted fewer corals compared to shallower areas, coinciding with a higher abundance of macroalgae in the deeper layers. Furthermore, based on long-term observation of atmospheric N flux, laboratory experiments were conducted to explore the cause of coral declines. The results indicate that N supply efficiently promoted macroalgae growth. The saturation of N absorption by macroalgae occurred within 2 weeks, leading to nutrient accumulation in seawater, especially nitrate, which had a direct impact on corals. While moderate N fluxes appeared to mitigate coral bleaching, high N fluxes, even with a balanced P supply or medium level of nutrients with an imbalanced N/P ratio, can both increase the susceptibility of corals to heat bleaching. This study explains the coral-algal phase shift in remote and relatively deep seawater and improves understanding of the cause-and-effect relationship between atmospheric N deposition and coral reef decline.
Case report: Dihydropyridine receptor (CACNA1S) congenital myopathy, a novel phenotype with early onset periodic paralysis
Authors: Aburahma Samah K. , Rousan Liqa A. , Shboul Mohammad , Biella Fabio , Lucchiari Sabrina , Comi Giacomo Pietro , Meola Giovanni , Pagliarani Serena 
Published: February 2024

IntroductionCACNA1S related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the CACNA1S gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness.Clinical descriptionBoth sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A&gt;G in CACNA1S. Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation.ConclusionThis novel phenotype supports the notion that there are age related differences in the clinical expression of CACNA1S gene mutations. This expands our understanding of mutations located in regions of the CACNA1S outside the highly conserved S4 segment, where most mutations thus far have been identified.
Embodied metacognition as strengthened functional connection between neural correlates of metacognition and dance in dancers: exploring creativity implications
Authors: Yang Ching-Ju , Yu Hsin-Yen , Hong Tzu-Yi , Cheng Li-Kai , Li Wei-Chi , Yeh Tzu-Chen , Chen Li-Fen , Hsieh Jen-Chuen 
Published: February 2024

IntroductionDance education fosters embodied metacognition, enhancing student’s creativity. This study examines the crucial role of functional connectivity (FC) between the neural correlates of metacognition (NCM) and dance (NCD) as the neurological foundation for dancers’ embodied metacognition. The investigation also explores whether these consolidated FCs inform the general creativity in dancers.MethodsThe research involved 29 dancers and 28 non-dancer controls. The study examined resting-state connections of the NCM through seed-based FC analysis. Correlation analyses were employed to investigate the connections between the targeted NCM-NCD FCs, initiated from the a priori NCM seed, and general creativity.ResultsDancers demonstrated heightened FC between NCM and NCD compared to non-dancer controls. The targeted regions included the putamen, globus pallidus, posterior cerebellum, and anterior insula of NCD. The dancers exhibited higher originality scores. In dancers, the enhanced FC showed a negative correlation with originality and a positive correlation with flexibility. Conversely, the controls exhibited no significant correlations.DiscussionExtended dance training enhances the NCM-NCD connection signifying embodied metacognition. This interconnectedness may serve as the neural predisposition for fostering general creativity performance in dancers. Dancers with heightened levels of originality could leverage the relatively weaker NCM-NCD FCs to facilitate better integration and coordination of creative cognitive processes. Our findings suggest that the consolidated functional connections as sculpted by domain-specific training may inform general creativity.
Absence of GATA3/FOXA1 co-expression predicts poor prognosis in upper tract urothelial carcinoma
Authors: Wang Yue , Wang Yunfan , He Huiying , Xiong Yan 
Published: February 2024

ObjectiveGATA binding protein 3 (GATA3) and forkhead box A1 (FOXA1) have been individually implicated in the progression of upper tract urothelial carcinoma (UTUC). This study aims to evaluate the prognostic value of GATA3/FOXA1 co-expression in UTUC patients.MethodsWe collected 108 UTUC pathological tissue samples with complete follow-up data and 24 normal control urothelial tissues. We created a 132-site microarray and performed immunohistochemistry (IHC) to measure GATA3 and FOXA1 expression levels. Kaplan-Meier survival and Cox regression analyses were conducted to assess UTUC prognosis.ResultsGATA3 expression was positively correlated with FOXA1 (P=0.031). Absence of GATA3/FOXA1 co-expression (GATA3-/FOXA1-) was associated with tumor extensive necrosis (P=0.001) after Bonferroni correction for multiple comparisons. GATA3-/FOXA1- was associated with shorter Disease-Free Survival (DFS) (P=0.001) and Cancer-Specific Survival (CSS) (P&lt;0.001) than other combination groups. Multivariate analyses identified extensive necrosis as an independent prognostic factor for CSS (P=0.030).ConclusionsOur study revealed a positive correlation between GATA3 and FOXA1 expression in UTUC. GATA3-/FOXA1- is linked to tumor extensive necrosis and poor prognosis in UTUC and may serve as a potential biomarker for UTUC patients.
Platinum-based neoadjuvant chemotherapy upregulates STING/IFN pathway expression and promotes TILs infiltration in NSCLC
Authors: Gao Huan , Zhang Xiaoni , Ren Mengdi , Jiang Aimin , Liu Na , Wang Jingjing , Zheng Xiaoqiang , Liang Xuan , Ruan Zhiping , Tian Tao , Fu Xiao , Yao Yu 
Published: February 2024

ObjectivesTo evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival.Materials and methodsA total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed.ResultsNACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS.ConclusionNACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.
Norovirus in children under 2 years of age: an epidemiological study in Panama during the COVID-19 pandemic
Authors: DeAntonio Rodrigo , Hess-Holtz Morgan , Abrego Leyda , Capitan-Barrios Zeuz , Donoso Leyla Hernandez , De León Tirza , Sáez Llorens Xavier , Moreno Brechla , Weil John Gerard 
Published: February 2024

IntroductionNorovirus infection is a common cause of acute gastroenteritis (AGE). Surveillance activities are important to aid investigation into effective norovirus control strategies, including vaccination. Here, we report ancillary findings related to the incidence, prevalence, and etiology of AGE caused by norovirus in Panama after adjustment of study methodology to comply with national coronavirus disease 2019 (COVID-19) mandates.MethodsIn January 2020, children aged &lt;2 years began enrolling into an epidemiological study in Panama to estimate the burden of norovirus in preparation for evaluating upcoming prevention strategies. This included an observational, longitudinal, community-based AGE surveillance study and a hospital-based AGE surveillance study. For the longitudinal study, healthy children aged 5–18 months were enrolled from January 6 through March 23, 2020, with a follow-up of approximately 6 months. The last participant was contacted on September 23, 2020. For the hospital-based study, starting on January 21, 2020, children aged &lt;2 years who were admitted to the Hospital del Niño Dr. José Renán Esquivel in Panama City due to AGE were evaluated. The last sample was collected on September 29, 2020. Collected stool samples were tested for norovirus as well as astrovirus, sapovirus, and various enteropathogens. Unfortunately, this study was disrupted by the subsequent implementation of disease transmission control procedures for the COVID-19 pandemic, and the study methodology was revised to comply with COVID-19 mandates.ResultsIn the longitudinal surveillance cohort [N = 400 (Chiriquí, n = 239; Panama, n = 161)], a total of 185 AGE episodes were documented (Chiriquí, n = 85; Panama, n = 100) resulting in an overall AGE incidence of 11.6 (95% CI: 9.99–13.4) episodes per 100 child-months. The norovirus-related AGE incidence was 0.3 (95% CI: 0.10–0.73) episodes per 100 child-months (5/185 AGE episodes) and the prevalence of norovirus was 4.6% (13/282 stool samples collected). In the hospital-based surveillance cohort, at least one pathogen was detected in 50% of samples (44/88 stool samples collected) and norovirus prevalence was 6.8% (6/88 stool samples collected).DiscussionThis report demonstrates how the occurrence of the COVID-19 pandemic hindered the conduct of clinical trials. However, this also created unique research opportunities to investigate the potential impact of pandemic control measures on the etiology of infectious diarrheal disease.
Optic nerve sheath diameter and its association with brain swelling in pediatric cerebral malaria: a retrospective study
Authors: Raees Madiha Q. , Gushu Montfort Benard , Taylor Terrie E. , Seydel Karl B. , Wynkoop Hunter J. , O’Brien Nicole F. 
Published: February 2024

IntroductionMortality in pediatric cerebral malaria (CM) in low- and middle-income countries (LMICs) is associated with brain swelling on magnetic resonance imaging (MRI); however, MRI is unavailable in most LMICs. Optic nerve sheath diameter (ONSD) measurement is an inexpensive method of detecting increased intracranial pressure compared with the invasive opening pressure (OP). Our primary objective was to determine if increased ONSD correlated with brain swelling on MRI in pediatric CM. Our secondary objective was to determine if increased ONSD correlated with increased OP and/or poor neurological outcome in pediatric CM. We hypothesized that increased ONSD would correlate with brain swelling on MRI and increased OP and that ONSD would be higher in survivors with sequelae and non-survivors.MethodsWe performed a retrospective chart review of children aged 0–12 years in Blantyre, Malawi, from 2013 to 2022 with CM as defined by the World Health Organization. Brain swelling on admission MRI was characterized by brain volume scores (BVS); severe swelling was scored as 7–8, mild-to-moderate as 4–6, normal as 3. The admission ONSD was measured via ultrasound; it was defined as abnormal if it was &gt;4.5 mm in children &gt;1 year and &gt;4 mm in children &lt;1 year. Favorable outcome was defined as a normal neurological exam on discharge in survivors. The primary and secondary objectives were evaluated using Spearman's correlation; and the demographics were compared using chi-square and the Kruskal–Wallis test (Stata, College Station, TX, USA).ResultsMedian age of the 207-patients cohort was 50 months [interquartile range (IQR) 35–75]; 49% (n = 102) were female. Of those, 73% (n = 152) had a favorable outcome, and 14% (n = 30) died. Twenty-nine (14%) had a normal BVS, 134 (65%) had mild-to-moderate swelling, and 44 (21%) had severe swelling. ONSD was elevated in 86% (n = 178) of patients, while 12% of patients had increased OP. There was a weakly positive correlation between BVS and ONSD (r = 0.14, p = 0.05). The median ONSD was not significantly different compared by discharge outcome (p = 0.11) or by BVS (p = 0.18).ConclusionONSD was not a reliable tool to correlate with BVS, neurological outcome, or OP in children with CM. Future studies to identify alternative methods of early identification of CM patients at highest risk for morbidity and mortality are urgently needed.