bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis
Authors: Min Wang , Qin Lingfeng , Zhang Haifeng , López-Giráldez Francesc , Jiang Ning , Kim Yeaji , Mohan Varsha K. , Su Minhong , Murray Katie N. , Grutzendler Jaime , Zhou Jenny Huanjiao 
Published: July 2024

BACKGROUND:
Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear.

METHODS:

Brain EC-specific CCM3-deficient (
Pdcd10
BECKO
) mice were generated by crossing
Pdcd10

fl/fl

mice with
Mfsd2a
-CreER
T2
mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches.

RESULTS:

Single-cell RNA-sequencing analyses from P10
Pdcd1
0
BECKO
mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier–associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6
Pdcd1
0
BECKO
brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the
Pdcd10
BECKO
model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in
Pdcd10
BECKO
mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins.

CONCLUSIONS:
CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss–induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.
Molecular taxonomy of myelodysplastic syndromes and its clinical implications
Authors: Bernard Elsa , Hasserjian Robert P. , Greenberg Peter L. , Arango Ossa Juan E. , Creignou Maria , Tuechler Heinz , Gutierrez-Abril Jesus , Domenico Dylan , Medina-Martinez Juan S. , Levine Max , Liosis Konstantinos , Farnoud Noushin , Sirenko Maria , Jädersten Martin , Germing Ulrich , Sanz Guillermo , van de Loosdrecht Arjan A. , Nannya Yasuhito , Kosmider Olivier , Follo Matilde Y. , Thol Felicitas , Zamora Lurdes , Pinheiro Ronald F. , Pellagatti Andrea , Elias Harold K. , Haase Detlef , Ganster Christina , Ades Lionel , Tobiasson Magnus , Palomo Laura , Della Porta Matteo Giovanni , Fenaux Pierre , Belickova Monika , Savona Michael R. , Klimek Virginia M. , Santos Fabio P. S. , Boultwood Jacqueline , Kotsianidis Ioannis , Santini Valeria , Solé Francesc , Platzbecker Uwe , Heuser Michael , Valent Peter , Finelli Carlo , Voso Maria Teresa , Shih Lee-Yung , Fontenay Michaela , Jansen Joop H. , Cervera José , Gattermann Norbert , Ebert Benjamin L. , Bejar Rafael , Malcovati Luca , Ogawa Seishi , Cazzola Mario , Hellström-Lindberg Eva , Papaemmanuil Elli 
Published: July 2024

Abstract
Myelodysplastic syndromes (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. Although genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations, and copy-neutral loss of heterozygosity were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91%, 43%, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and loss of heterozygosity at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow (BM) blast percentage across groups ranged from 1.5% to 10%, and the median overall survival ranged from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of BM blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and might inform future classification schemas and translational therapeutic research.
Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses
Authors: Wang Benlin , Qiu Yifeng , Xie Ming , Huang Pengcheng , Yu Yao , Sun Qi , Shangguan Wentai , Li Weijia , Zhu Zhangrui , Xue Jingwen , Feng Zhengyuan , Zhu Yuexuan , Yang Qishen , Wu Peng 
Published: July 2024

Abstract
Objective
Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.

Methods
We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.

Results
The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of
both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.

Conclusion
P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.
Biofilm-producing ability of methicillin-resistant Staphylococcus aureus clinically isolated in China
Authors: Yu Jingyi , Han Weihua , Xu Yanlei , Shen Li , Zhao Huilin , Zhang Jiao , Xiao Yanghua , Guo Yinjuan , Yu Fangyou 
Published: July 2024

Abstract
Background
Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections.

Results
Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types.

Conclusions
MRSA strains with biofilm production capability warrant increased vigilance.
Accuracy of oscillometric noninvasive blood pressure at the ankle in the lateral position during general anesthesia
Authors: Farag Ahmed , Mostafa Maha , Hasanin Ahmed , Sobh Lamis , Raafat Heba , Obayah Gihan , Youssef Maha 
Published: July 2024

Abstract
Background
This study aimed to evaluate the accuracy of ankle blood pressure measurements in relation to invasive blood pressure in the lateral position.

Methods
This prospective observational study included adult patients scheduled for elective non-cardiac surgery under general anesthesia in the lateral position. Paired radial artery invasive and ankle noninvasive blood pressure readings were recorded in the lateral position using GE Carescape B650 monitor. The primary outcome was the ability of ankle mean arterial pressure (MAP) to detect hypotension (MAP < 70 mmHg) using area under the receiver operating characteristic curve (AUC) analysis. The secondary outcomes were the ability of ankle systolic blood pressure (SBP) to detect hypertension (SBP > 140 mmHg) as well as bias (invasive measurement – noninvasive measurement), and agreement between the two methods using the Bland-Altman analysis.

Results
We analyzed 415 paired readings from 30 patients. The AUC (95% confidence interval [CI]) of ankle MAP for detecting hypotension was 0.88 (0.83–0.93). An ankle MAP of ≤ 86 mmHg had negative and positive predictive values (95% CI) of 99 (97–100)% and 21 (15–29)%, respectively, for detecting hypotension. The AUC (95% CI) of ankle SBP to detect hypertension was 0.83 (0.79–0.86) with negative and positive predictive values (95% CI) of 95 (92–97)% and 36 (26–46)%, respectively, at a cutoff value of > 144 mmHg. The mean bias between the two methods was − 12 ± 17, 3 ± 12, and − 1 ± 11 mmHg for the SBP, diastolic blood pressure, and MAP, respectively.

Conclusion
In patients under general anesthesia in the lateral position, ankle blood pressure measurements are not interchangeable with the corresponding invasive measurements. However, an ankle MAP > 86 mmHg can exclude hypotension with 99% accuracy, and an ankle SBP < 144 mmHg can exclude hypertension with 95% accuracy.
Multimorbidity and associated informal care receiving characteristics for US older adults: a latent class analysis
Authors: Liu Ruotong , Nagel Corey L. , Chen Siting , Newsom Jason T. , Allore Heather G. , Quiñones Ana R. 
Published: July 2024

Abstract
Background
Older adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes.

Methods
Data are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership.

Results
A four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05–1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05–2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29–3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19–0.77).

Conclusions
Results highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care.
Association of selected adipokines with vitamin D deficiency in children with inflammatory bowel disease
Authors: Geryk Milos , Kucerova Veronika , Velganova-Veghova Maria , Foltenova Hana , Bouchalova Katerina , Karasek David , Radvansky Martin , Karaskova Eva 
Published: July 2024

Abstract
Background
Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency.

Methods
The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants.

Results
Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines.

Conclusions
Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
The impact of regional disparities on the availability of meningococcal vaccines in the US
Authors: Schley Katharina , Jodar Eva , Presa Jessica V. , Willis Sarah J. , Prener Christopher G. 
Published: July 2024

Abstract
Background
In the United States (US), three types of vaccines are available to prevent invasive meningococcal disease (IMD), a severe and potentially fatal infection: quadrivalent conjugate vaccines against serogroups A, C, W, Y (MenACWY), and monovalent vaccines against serogroup B (MenB) as well as a newly licensed pentavalent vaccine (MenABCWY) protecting against serogroup A, B, C, W, and Y. The CDC’s Advisory Committee on Immunization Practices (ACIP) routinely recommends MenACWY vaccine for all 11- to 12-year-olds with a booster dose at 16 years. MenB vaccination is recommended based on shared clinical decision-making (SCDM) for 16- to 23-year-olds. Recently, the pentavalent meningococcal vaccine (MenABCWY) was recommended by the ACIP. Meningococcal vaccine uptake is suboptimal across the country, particularly among individuals with lower socioeconomic status (SES), despite these recommendations. The objective of the spatial analyses was to assess the relationship between stocking of MenACWY and MenB vaccines, area-level SES, and state-level policies.

Methods
The number of MenACWY and MenB doses stocked by vaccinators was obtained from IQVIA and the CDC’s Vaccine for Children (VFC) program and compiled into a county-level dataset from 2016 to 2019. SES, as measured using the CDC’s Social Vulnerability Index (SVI), state-level school recommendations, and universal purchasing programs were among the main county-level covariates included to control for factors likely influencing stocking. Data were stratified by public and private market. Bayesian spatial regression models were developed to quantify the variations in rates of stocking and the relative rates of stocking of both vaccines.

Results
After accounting for county-level characteristics, lower SES counties tended to have fewer doses of MenB relative to MenACWY on both public and private markets. Lower SES counties tended to have more supply of public vs. private doses. Universal purchasing programs had a strong effect on the markets for both vaccines shifting nearly all doses to the public market. School vaccination strategy was key for improving stocking rates.

Conclusions
Overall, the results show that MenACWY has greater stock relative to MenB across the US. This difference is exacerbated in vulnerable areas without school entry requirements for vaccination and results in inequity of vaccine availability. Beyond state-level policy and SES differences, SCDM recommendations may be a contributing factor, although this was not directly assessed by our model.
Knowledge of Alzheimer’s disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis
Authors: Sun Ya-Jun , Song Jie , Li Xu-Ping , Wang Xiao-Hui , Wu Yi-Xuan , Huang Jia-Ju , Wang Shi-Bin , Teng Yong-Yong 
Published: July 2024

Abstract
Background
This study aimed to assess the public knowledge regarding Alzheimer’s Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors.

Methods
A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer’s Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics.

Results
The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the “Symptoms” and “Caregiving” subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009–1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467–2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117–1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297–2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323–2.478) were more likely to have higher levels of awareness about Alzheimer’s disease.

Conclusions
Adults in Zhuhai show a limited knowledge of AD, particularly in the ‘Symptoms’ and ‘Caregiving’ subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.
Total hip arthroplasty with porous tantalum trabecular metal pads in patients with Crowe IV developmental dysplasia of the hip: a midterm followup study
Authors: Yang Cheng , Li Donghai , Sun Shuo , Yang Zhouyuan , Kang Pengde 
Published: July 2024

Abstract
Purpose
Crowe IV developmental dysplasia of the hip (DDH) is a catastrophic hip disease. Moreover, obtaining ideal clinical efficacy in conventional total hip arthroplasty (THA) is often difficult. In this study, we aimed to assess the mid-term clinical results of THA with porous tantalum trabecular metal (TM) pads for acetabular reconstruction in the treatment of Crowe IV DDH.

Methods
A cohort of 28 patients (32 hips) diagnosed with Crowe type IV DDH who underwent acetabular reconstruction during THA using TM pads with scheduled follow-up between 2011 and 2018, were included in this study. Eight cases were men and 24 were women, with a mean age of 48.4 years (range, 36–72 years) and a mean follow-up was 74.3 months (range, 42–132 months). All patients underwent acetabular reconstruction using TM pads and total hip replacement with subtrochanteric osteotomy.

Results
At the final follow-up, 28 hips (87.5%) demonstrated mild or no postoperative limping. The Harris Hip Score improved from 58.4 ± 10.6 preoperatively to 85.6 ± 8.9. The mean pain, stiffness, and function scores on the Western Ontario and McMaster University Osteoarthritis index were 86.5 ± 10.2, 87.3 ± 12.4 and 85.4 ± 11.6 respectively. The mean score of patient satisfaction was 90.4 ± 7.6. Additionally, the SF-12 physical summary score was 41.8 ± 5.6 and the SF-12 mental summary score was 51.6 ± 5.4. TM construct survivorship due to all-cause failure was 90.6% at 5 years with 3 hips at risk, 87.5% at 10 years with 4 hips at risk. The survivorship due to failure from aseptic loosening was 96.9% at 5 years with 1hips at risk and 93.75% at 10 years with 2 hips at risk.

Conclusion
This study demonstrated satisfactory mid-term clinical and radiological results with the application of TM pads for acetabular reconstruction combined with THA in patients with Crowe IV DDH.

Trial registration number
ChiCTR1800014526, Date: 18/01/2018.