bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five novel cis-regulatory deletions of SOX10 cause Waardenburg syndrome type II
Authors: Huang Yu , Geng Jia , Long Yang , Xiong Wenyu , Kang Lu , Chen Meilin , Tang Ting , Zhong Mingjun , Bu Fengxiao , Lu Yu , Cheng Jing , Yuan Huijun 
Published: June 2024

IntroductionWaardenburg syndrome (WS) is a genetic disorder characterized by hearing loss, hypopigmentation, and distinct facial features. Despite &gt; 60% molecular diagnosis rate for WS patients, pathogenic variants within coding regions are predominant, with few non-coding copy number variations (CNVs) reported.MethodsIn this study, we performed whole genome sequencing (WGS) on 59 undiagnosed WS patients and analyzed the CNVs within the promoter and enhancer regions of the SOX10 gene.ResultsWe identified five novel pathogenic deletions ranging from 448 bp to 70 kb upstream of SOX10. Two deletions were in the enhancer region, while three were in the promoter and 5'UTR region. These CNVs manifested as WS type II in eight patients from five unrelated families, demonstrating phenotypic heterogeneity. Furthermore, analysis of CNV1 within the enhancer region suggested a potential mechanism involving Alu-mediated non-allelic homologous recombination (NAHR).ConclusionOur findings extend the mutation spectrum of the SOX10 gene and elucidate the pathogenic role of CNVs in cis-regulatory elements, particularly variations in enhancer and promoter regions, thereby enhancing clinical gene detection and interpretation of non-coding regions.
Effect of near-infrared spectroscopy on postoperative delirium in cardiac surgery with cardiopulmonary bypass: a systematic review and meta-analysis
Authors: Sun Qian , Wu Weiguo 
Published: June 2024

BackgroundPostoperative delirium (POD) is a common anesthetic side effect in cardiac surgery. However, the role of oxygen saturation monitoring in reducing postoperative delirium has been controversial. Therefore, this meta-analysis aimed to analyze whether NIRS monitoring during cardiac surgery under cardiopulmonary bypass could reduce the incidence of postoperative delirium.MethodsPubMed, Web of Science, Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) databases were systematically searched using the related keywords for randomized-controlled trials (RCTs) published from their inception to March 16, 2024. This review was conducted by the Preferred Reporting Project and Meta-Analysis Statement (PRISMA) guidelines for systematic review. The primary outcome was postoperative delirium, and the second outcomes included the length of ICU stay, the incidence of kidney-related adverse outcomes, and the incidence of cardiac-related adverse outcomes.ResultsThe incidence of postoperative delirium could be reduced under the guidance of near-infrared spectroscopy monitoring (OR, 0.657; 95% CI, 0.447–0.965; P = 0.032; I2 = 0%). However, there were no significant differences in the length of ICU stay (SMD, 0.005 days; 95% CI, −0.135–0.146; P = 0.940; I2 = 39.3%), the incidence of kidney-related adverse outcomes (OR, 0.761; 95% CI, 0.386–1.500; P = 0.430; I2 = 0%), and the incidence of the cardiac-related adverse outcomes (OR, 1.165; 95% CI, 0.556–2.442; P = 0.686; I2 = 0%) between the two groups.ConclusionNear-infrared spectroscopy monitoring in cardiac surgery with cardiopulmonary bypass helps reduce postoperative delirium in patients.Systematic Review RegistrationPROSPERO, identifier, CRD42023482675
A study protocol for a non-randomised evaluation of a growth-based career construction psychosocial intervention for higher education students
Authors: Chim Kathleen , Lai JoJo T. C. 
Published: June 2024

BackgroundDespite promising emerging evidence on the protective properties and interrelationships of posttraumatic growth, career adaptability and psychological flexibility, no studies have reported interventions that promote these positive personal resources among higher education students. Nurturing these positive personal resources in future interventions is recommended to holistically address students’ developmental, academic and career-related challenges associated with major transitions. This paper describes (a) the rationale for and development of a tailored growth-based career construction psychosocial intervention, ‘Sailing through Life and My Career Path’ (SLCP) for higher education students; and (b) a mixed-method non-randomised pre-post study to evaluate the effectiveness of the proposed psychosocial intervention in achieving positive participant outcomes.Methods and analysisOver a 12-week period, higher education students will be recruited to take part in group and independent learning activities that are tailored to nurture positive personal resources to overcome challenges related to developmental, academic and career-related transitions. Quantitative data will be collected before and after the intervention and will be analysed using SPSS v26. Follow-up semi-structured interviews with participants (students), interventionists (group facilitators), and administrators will be conducted to explore perceptions of the intervention, to understand its process of change, and to determine its feasibility and acceptability in the higher education setting. All interviews will be transcribed and analysed using thematic analysis.DiscussionBy filling in a gap in existing intervention research and practice, the proposed study serves to generate new knowledge and insights by evaluating the effectiveness of a tailored psychosocial intervention that responds to the complex needs associated with major life transitions of higher education students.
The role of diet in diabetes gastroparesis treatment: a systematic review and meta-analysis
Authors: Lin Dezhi , Wang Hui , Ou Yangxu , Li Longlong , Zhang Qiang , Yan Jiayin , Peng Dezhong , Peng Sihan 
Published: June 2024

BackgroundDiabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis.MethodsThis systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software.ResultsA total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin.ConclusionsLimited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.
Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor
Authors: Brown Conner , Kariuki Wangeci , Zhong Haizhen A. , Kippes Audra , Sui Yipeng 
Published: June 2024

BackgroundCannabidiol (CBD), a non-psychoactive phytocannabinoid of cannabis, is therapeutically used as an analgesic, anti-convulsant, anti-inflammatory, and anti-psychotic drug. There is a growing concern about the adverse side effects posed by CBD usage. Pregnane X receptor (PXR) is a nuclear receptor activated by a variety of dietary steroids, pharmaceutical agents, and environmental chemicals. In addition to the role in xenobiotic metabolism, the atherogenic and dyslipidemic effects of PXR have been revealed in animal models. CBD has a low affinity for cannabinoid receptors, thus it is important to elucidate the molecular mechanisms by which CBD activates cellular signaling and to assess the possible adverse impacts of CBD on pro-atherosclerotic events in cardiovascular system, such as dyslipidemia.ObjectiveOur study aims to explore the cellular and molecular mechanisms by which exposure to CBD activates human PXR and increases the risk of dyslipidemia.MethodsBoth human hepatic and intestinal cells were used to test if CBD was a PXR agonist via cell-based transfection assay. The key residues within PXR’s ligand-binding pocket that CBD interacted with were investigated using computational docking study together with site-directed mutagenesis assay. The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner. Human intestinal cells were treated with CBD and/or RES to estimate the functions of CBD in cholesterol uptake.ResultsCBD was a selective agonist of PXR with higher activities on human PXR than rodents PXRs and promoted the dissociation of human PXR from nuclear co-repressors. The key amino acid residues Met246, Ser247, Phe251, Phe288, Trp299, and Tyr306 within PXR’s ligand binding pocket were identified to be necessary for the agonistic effects of CBD. Exposure to CBD increased the circulating total cholesterol levels in mice which was partially caused by the induced expression levels of the key intestinal PXR-regulated lipogenic genes. Mechanistically, CBD induced the gene expression of key intestinal cholesterol transporters, which led to the increased cholesterol uptake by intestinal cells.ConclusionCBD was identified as a selective PXR agonist. Exposure to CBD activated PXR signaling and increased the atherogenic cholesterol levels in plasma, which partially resulted from the ascended cholesterol uptake by intestinal cells. Our study provides potential evidence for the future risk assessment of CBD on cardiovascular disease, such as dyslipidemia.
Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report
Authors: Tamayo-Trujillo Rafael , Ibarra-Castillo Rita , Laso-Bayas José Luis , Guevara-Ramirez Patricia , Cadena-Ullauri Santiago , Paz-Cruz Elius , Ruiz-Pozo Viviana A. , Doménech Nieves , Ibarra-Rodríguez Adriana Alexandra , Zambrano Ana Karina 
Published: June 2024

IntroductionLong QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the KCNH2 gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds.Case presentationA 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the KCNH2 gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the AKAP9 p.(Arg1654GlyfsTer23) (rs779447911), and TTN p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion.ConclusionBased on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.
Quantifying spatial CXCL9 distribution with image analysis predicts improved prognosis of triple-negative breast cancer
Authors: Cao Xi , Song Yu , Wu Huanwen , Ren Xinyu , Sun Qiang , Liang Zhiyong 
Published: June 2024

Background: The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9 expression and prognosis in triple-negative breast cancer (TNBC) is unclear.Methods: We investigated CXCL9 mRNA expression, clinicopathological features, and prognosis in TNBC patients. We also used computational image analysis to quantify and assess the distribution of CXCL9 protein in the tumor core (TC) and invasive margin (IM).Results: CXCL9 mRNA expression was significantly higher in TNBC tumors compared to normal tissue (p &lt; 0.001) and was associated with smaller tumors (p = 0.022) and earlier stages (p = 0.033). High CXCL9 mRNA expression was correlated with improved overall survival (OS) in three independent cohorts (all p &lt; 0.05). In a separate analysis, low CXCL9 protein expression was associated with increased lymph node metastasis (p = 0.018 and p = 0.036). High CXCL9 protein expression in the TC, IM, or both was associated with prolonged OS (all p &lt; 0.001).Conclusion: High CXCL9 expression, at both the mRNA and protein levels, is associated with improved prognosis in TNBC patients. CXCL9 expression in the TC and/or IM may be an independent prognostic factor.
Exosome-shuttled miR-150–5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis
Authors: Zheng Ting , Li Sipeng , Zhang Teng , Fu Wei , Liu Shuchang , He Yuxin , Wang Xiao , Ma Tao 
Published: June 2024

RationaleSepsis is a life-threatening organ dysfunction and lack of effective measures in the current. Exosomes from mesenchymal stem cells (MSCs) reported to alleviate inflammation during sepsis, and the preconditioning of MSCs could enhance their paracrine potential. Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms.MethodsExosomes were isolated and characterized from the supernatants of MSCs. The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model. Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms.ResultsLPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo. In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation. miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150–5p in LPS-Exo compared to that in Exo, and exosomal miR-150–5p was transferred into recipient macrophages and mediated macrophage polarization. Further investigation demonstrated that miR-150–5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.ConclusionThe current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150–5p as a novel molecular target for regulating immune hyperactivation during sepsis.
Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study
Authors: Shi Yong-Bin , Dong Hong-Lin , Chang Wen-Kai , Zhao Yan , Jin Hai-Jiang , Li Jun-Kai , Yan Sheng 
Published: June 2024

BackgroundPrevious research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study.MethodsGenetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test.ResultsWe identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08–2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42–0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25–3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P&lt;0.05).ConclusionOur systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.
“When she goes out, she feels better:” co-designing a Green Activity Program with Hispanic/Latino people living with memory challenges and care partners
Authors: Lassell Rebecca K. F. , Tamayo Valeria , Pena Triana A. , Kishi Misa , Zwerling Jessica , Gitlin Laura N. , Brody Abraham A. 
Published: June 2024

PurposeUtilizing a participatory approach, we sought to co-design a 12-week Green Activity Program (GAP) with Hispanic/Latino individuals living with memory challenges and their care partners, local outdoor professionals, and healthcare providers.MethodsParticipants were recruited via convenience and snowball sampling in the Bronx, New York with Hispanic/Latino persons living with memory challenges and care partners, outdoor activity professionals, and interdisciplinary healthcare providers/dementia experts. Co-design occurred iteratively with 5 focus groups and 4 individual interviews lasting 30–90 min and focused on program and research design. Sessions were recorded and transcribed. Utilizing directed content analysis data was coded using a priori codes program design and research design.Results21 participants completed co-design activities: (n = 8 outdoor activity professionals, n = 6 Hispanic/Latino persons living with memory challenges and care partners, and n = 7 interdisciplinary healthcare providers/dementia experts). Participant preferences for program design were captured by subcodes session duration (30–90 min), frequency (4–8 sessions), and delivery modes (in-person and phone). Participants' preferred nature activities included group exercise and outdoor crafts [crocheting], outcomes of social participation, connectedness to nature, decreased loneliness, and stewardship were identified. Preferred language for recruiting and describing the program were “memory challenges,” “Hispanic/Latino,” and “wellbeing.” Referral pathways were identified including community-based organizations and primary care.ConclusionCo-design was a successful form of engagement for people living with memory challenges that enabled participants to help design key elements of the GAP and research design. Our processes, findings, and recommendations for tailoring co-design to engage Hispanic/Latino people living with memory challenges can inform the development of other programs for this population.
Disease-modifying therapies and hematological disorders: a systematic review of case reports and case series
Authors: Scavone Cristina , Liguori Valerio , Adungba Olusola Jephthah , Cesare Daniele Di Giulio , Sullo Maria Giuseppa , Andreone Vincenzo , Sportiello Liberata , Maniscalco Giorgia Teresa , Capuano Annalisa 
Published: June 2024

IntroductionDisease modifying therapies (DMTs) used to treat multiple sclerosis (MS) can be associated to the occurrence of hematological disorders. This systematic review aims to provide an overview of these events occurring in real-life conditions, by describing case reports and series published in the literature.MethodsA literature search of all publications up to January 5th 2024 on the Medline and Embase databases was carried out. The results were presented both in the text and in tables.ResultsSixty-seven case reports/series were included in this review, of which more than half related to alemtuzumab, natalizumab and ocrelizumab. The publication date of included studies ranged from 2006 to 2024. The majority of case reports and series described the occurrence of late-onset hematological disorders (events that occurred more than 30 days after the first DMT administration), mainly represented by case of neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia. All cases reported a favorable outcome, apart one case report that described a fatal case. Among included cases, 4 articles, all related to natalizumab, described the occurrence of myeloid disorders in 13 newborns from mother receiving the DMT.DiscussionConsidering the limitations identified in the majority of included studies, further ad hoc studies are strongly needed to better evaluate the hematological disorders of DMTs. Meantime, the strict monitoring of treated patients for the occurrence of these toxicities should be highly recommended.
Anterior thalamic nucleus local field potentials during focal temporal lobe epileptic seizures
Authors: Singh Jaysingh , Miller Jacob A. , Lucas Timothy , Yang Jimmy , Sollars Caleb , Eliashiv Dawn S. , Bartolomei Fabrice 
Published: June 2024

ObjectiveTo analyze the local field potentials (LFPs) in patients with focal drug-resistant epilepsy (DRE) from the anterior nucleus of the thalamus (ANT) during inter-ictal state and seizure state.MethodANT stereotactic EEG (SEEG) recordings were studied in four patients with focal temporal lobe epilepsy. SEEG data was classified as inter-ictal and ictal state and sub-categorized into electrographic (ESz), focal aware seizure (FAS), focal with impaired awareness (FIA), or focal to bilateral tonic-clonic seizure (FBTC). LFP was analyzed at 4 Hz, 8 Hz, 16 Hz, 32 Hz, high gamma (100 Hz), and ripples (200 Hz) using spectrogram analysis and a statistical comparison of normalized power spectral density (PSD) averaged during seizures versus pre-ictal baseline segments.ResultThe LFP recordings were analyzed for 162 seizures (127 ESz, 23 FAS, 6 FIA, and 6 FBTC). Based on time-frequency data (spectrogram), a broad band of activity, occurring between 2 and 6 Hz and centered at 4 Hz, and thin-band activity occurring specifically at 8 Hz on the frequency spectrogram were observed during the inter-ictal state. Statistically significant changes in LFP-PSD were seen for FAS, FIA, and FBTC. We observed a significant gain in LFP at the lower frequency band during FAS at 4 Hz, FIA, and FBTC at 4, 8, and 16 Hz while also observing increases at higher frequencies during FBTC at 100 and 200 Hz and a decrease during FAS seizures at 32 Hz. In contrast, no significant change in LFP power was seen for electrographic seizures.InterpretationOur observations from a limited dataset indicate that all clinical seizure types, but not electrographic seizures, caused a change in ANT-LFP based on the magnitude of the associated power spectral density (PSD). Future work will be needed to validate the use of ANT-LFP at these frequencies as accurate measurements of seizure occurrence and severity. This work represents a first step toward understanding ANT thalamic LFP patterns during focal seizures and developing adaptive DBS strategies.