bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connexin 43 contributes to perioperative neurocognitive disorder by attenuating perineuronal net of hippocampus in aged mice
Authors: Zhang Qian , Zhang Yuxin , Cong Peilin , Wu Qianqian , Wan Hanxi , Huang Xinwei , Li Xinyang , Li Zhouxiang , Li Jingxuan , Wu Huanghui , Tian Li , Xiong Lize 
Published: October 2024

Abstract

Background
Perioperative neurocognitive disorder (PND) is a prevalent form of cognitive impairment in elderly patients following anesthesia and surgery. The underlying mechanisms of PND are closely related to perineuronal nets (PNNs). PNNs, which are complexes of extracellular matrix primarily surrounding neurons in the hippocampus, play a critical role in neurocognitive function. Connexin 43 (Cx43) contributes to cognitive function by modulating the components of PNNs. This study was designed to investigate the specific regulatory mechanisms of Cx43 on PNNs and its pivotal role in the development of PND.
Methods
Eighteen-month-old wild-type and Gja1fl/fl C57BL/6 mice were subjected to abdominal surgery under 1.4% isoflurane anesthesia. Cognitive functions, particularly learning and memory, were evaluated via the Y-maze test, Barnes maze (BM) and contextual fear conditioning test (CFT). The mRNA and protein expression levels of Cx43 were assessed by using quantitative reverse transcription polymerase chain reaction (qRT-PCR), fluorescent in situ hybridization (FISH), western blotting and flow cytometry. The quantity of PNNs was measured by Wisteria floribunda agglutinin (WFA) and Aggrecan staining.
Results
Aged mice subjected to anesthesia and surgery exhibited deficits in hippocampus-dependent cognitive functions, which were accompanied by increased Cx43 mRNA and protein expression. Conditional knockout (cKO) of Cx43 in astrocytes alleviated cognitive deficits and promoted the number of PNNs and dendritic spines in the hippocampus by targeting Dmp1. Knockdown of Dmp1 attenuated the beneficial effects of Cx43 cKO on cognitive deficits induced by anesthesia and surgery.
Conclusion
Our findings indicate that anesthesia and surgery induce an increase in Cx43 expression, which inhibits the formation of PNNs and dendritic spines in hippocampus by suppressing Dmp1 transcription, leading to cognitive deficits in aged mice. These results offer new mechanistic insights into the pathogenesis of PND and identify potential targets for therapeutic intervention.
Higher bone mineral density at six years of age in very preterm born infants fed human milk compared to formula - follow-up of an RCT
Authors: Toftlund Line H , Beck-Nielsen Signe Sparre , Agertoft Lone , Halken Susanne , Zachariassen Gitte 
Published: October 2024

Abstract

Purpose
In very preterm born infants’ nutritional intake is important to reduce the risk of severe metabolic bone disease including the risk of a lower bone mineral density (BMD). The aim of this study was to evaluate bone mineral content (BMC) and BMD (equals BMC per bone area (BA)) at six years of age in very preterm born infants fed different diets post discharge.
Methods
A prospective follow-up study of 281 children born very preterm (gestational age ≤32+0 weeks) and enrolled in a multicentre RCT on post discharge nutrition. Infants fed human milk (HM) were randomised to unfortified HM (UHM) or fortified human milk (FHM) from hospital discharge to four months corrected age. Those not fed HM received a preterm formula (PF). At six years of age, BMD and BMC were assessed by dual-energy X-ray absorptiometry (DXA) scan (Lunar Prodigy) and adjusted for sex, age, and anthropometrics.
Results
A number of 192 very preterm born children (59 fed UHM, 67 FHM and 66 PF) had a DXA scan performed at 6 (5.8 - 8.3) years of age. No significant difference was found comparing UHM and FHM according to height, weight, BA, BMC, and BMD at six years of age. A multiple regression analysis showed significantly improved BMD in breastfed children compared to PF fed children.
Conclusions
Fortified compared to non-fortified human milk post discharge did not improve BMD significantly at 6 years of age in very preterm born infants. Breastfed children demonstrated higher BMD than formula fed children.
A cross-sectional study of the Evaluation of Iodine Deficiency among Pregnant Women Attending Antenatal Clinic at a Community Health Centre
Authors: Antwi-Baffour Samuel , Mensah Benjamin Tetteh , Appiah Nana Yaa Asiedua , Armah Dorinda Naa Okailey , Annison Lawrence 
Published: October 2024

Abstract

Background
Iodine deficiency is a critical global health issue, especially among pregnant women. Iodine is essential for producing thyroid hormones, which are vital for metabolic regulation and the development of the nervous system, bones, and muscles during pregnancy and early childhood. Pregnancy increases the maternal thyroid gland's iodine requirement, and severe deficiency can cause hypothyroidism in both mother and fetus. This can lead to preterm birth, low birth weight, miscarriage, and impaired cognitive development in children.
Methods
This cross-sectional study aimed to evaluate the dietary habits and iodine levels among pregnant women was conducted from January to December 2021. It included 158 pregnant women who provided informed consent. Data were collected using a pretested questionnaire on sociodemographic characteristics and dietary intake, alongside urine samples for urinary iodine concentration (UIC) analysis.
Results
Participants had a mean age of 29.37 years and an average household size of 3.552. Dietary analysis through a modified food frequency questionnaire (FFQ) showed infrequent consumption of iodine-rich foods. Urine samples analyzed using the Sandell-Kolthoff reaction revealed a mean UIC of 200.24 µmol/L, with 50.6% of participants having levels below the recommended threshold for pregnant women.
Conclusions
The study revealed high prevalence of iodine deficiency among the participants, highlighting the need for improved public health interventions to boost iodine intake during pregnancy. The findings stress the urgent need for better dietary education and supplementation programs to ensure adequate iodine levels among pregnant women, particularly in Sub-Saharan Africa, to mitigate the adverse effects of iodine deficiency.
Histopathological growth patterns of liver metastases - a retrospective, consecutive, single- center, pilot study and literature review of non-colorectal carcinoma metastasis studies
Authors: Baráth Bence , Pósfai Boglárka , Abbasi Parsa , Zombori Tamás , Lantos Tamás , Sejben Anita 
Published: October 2024

Abstract

Objective
Histopathological growth patterns (HGPs) in liver metastases have been identified to have prognostic value; however, they currently do not influence therapeutic decisions, and the literature mainly focuses on colorectal adenocarcinoma metastases. Hitherto, they have only been examined in a consecutive setting in 5 studies.
Methods
Patients between 2011 and 2016 were included with the ICD code C7870. General clinicopathological data were obtained from medical charts. Histological slides of the metastases were evaluated by two pathologists with consensus. Statistical analyses were carried out by using the Kruskal-Wallis (continuous variables) and Fisher’s exact test (categorical variables). The Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS), and time-to-progression (TTP) curves, and the logrank test was applied to compare survival curves. All statistical tests were two-sided and p-values less than 0.05 were considered statistically significant.
Results
Altogether 41 patients were included in our study. The majority were diagnosed with secondary colorectal adenocarcinoma (n = 32). Replacement pattern proved to be the most common (n = 22), followed by desmoplastic (n = 15), and pushing (n = 4). There was no significant association found between HGPs and stage (p = 0.105), secondary tumour focality (p = 0.898), largest diameter primary (p = 0.316) and secondary carcinoma (p = 0.441), completeness of resection (p = 0.492), and the presence of venous spread (p = 1). There were no significant results found between HGPs and PFS (p = 0.417), OS (p = 0.297), and TTP (p = 0.267).
Conclusions
Further studies regarding the prognostic utility of HGPs have to be carried out in the future. Our results reflect that HGPs may not be valuable in a consecutive setting.
Novel Use of Siltuximab in a Patient with Somatic UBA1 Mutated VEXAS Syndrome
Authors: Cáceres-Nazario Beatriz , Rivenbark Joshua , Saha Manish K. , Mathews Stephanie , Rubinstein Samuel M. 
Published: October 2024

Abstract

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an increasingly recognized disorder that occurs due to somatic mutations of a ubiquitin-activating enzyme encoded by ubiquitin-like modifier activating enzyme 1 gene, UBA1. Clinical findings associated with VEXAS syndrome include recurrent fevers, polychondritis, periorbital edema, pleural effusions, myocarditis and/or pericarditis, hepatosplenomegaly, myelodysplastic syndrome, cytopenias, inflammatory arthritis, neutrophilic dermatosis, and deep venous thrombosis. Novel renal manifestations like interstitial nephritis are infrequent, and to our knowledge, acute renal failure due to C3 glomerulonephritis (C3GN) has not yet been reported. Overwhelming systemic inflammation can result in morbid end-organ damage and death. While there is no formal guideline or established protocol for its management, treatment of VEXAS syndrome with tocilizumab, an interleukin-6 (IL-6)-directed therapy, has been described in the literature. Here, we report a case of a 71-year-old male patient presenting with C3GN as an initial manifestation of VEXAS syndrome and explore the rationale for our approach to treatment with IL-6 blockade. Our patient was initially treated with two inpatient doses of tocilizumab with successful transition to siltuximab in the outpatient setting. He continues to benefit from ongoing siltuximab treatment for more than one year to date without any safety issues or relapse of VEXAS syndrome.
Efficacy of Adipose Stromal Cells-Enriched High- Density Fat Graft Combined with BTX-A for Raynaud’s Phenomenon: A Prospective Cohort Study
Authors: Deng Chengliang , Liu Xin , Wei Miaomiao , Wu Bihua , Zhang Tianhua , Xiao Shune , Min Peiru , Zhang Yixin 
Published: October 2024

Abstract

Background: Conventional treatments for Raynaud’s phenomenon (RP) often show limited effectiveness due to their inability to address both vascular and inflammatory aspects. This study evaluates the combination of high-density fat grafting (HDFG) with botulinum toxin A (BTX-A) for treating RP.
Methods: Eleven patients with 20 affected hands diagnosed with RP were recruited and randomly assigned to receive either HDFG combined with BTX-A (intervention group, n=11) or HDFG alone (control group, n=9). Efficacy was assessed using Visual Analog Scale (VAS) pain scores and McCabe Cold Sensitivity Scores, along with finger ulcer healing time and infrared thermal imaging to evaluate blood perfusion improvements.
Results: The HDFG-BTX group showed significant improvements in hand symptoms. VAS pain scores decreased from a pre-treatment mean of 5.33 to 0.84 post-treatment (mean reduction of 4.49, p=0.018), indicating effective pain relief. McCabe scores improved from 272.73 to 75.00 (mean reduction of 197.73, p=0.001), demonstrating reduced cold sensitivity. Ulcer healing time was shorter in the HDFG-BTX group (14.25 days) compared to HDFG alone (25.6 days, p<0.001), highlighting faster recovery. Infrared imaging indicated significant enhancements in blood perfusion.
Conclusion: HDFG combined with BTX-A is a reliable and beneficial intervention for RP, leading to high patient satisfaction.
Non-invasive intracranial pressure monitoring in management of slit ventricle syndrome - Case report
Authors: Fagundes Walter , Cruz Paulo Vitor da , Valentim Wander , Frigieri Gustavo , Mir Wajid Majeed 
Published: October 2024

Abstract

Slit ventricle syndrome (SVS) is condition of severe headaches, usually intermittent, suffered by patients after ventricular shunting for hydrocephalus with normal or smaller ventricle size, although in some cases the correct diagnosis and management can be a significant challenge. This case report aims to highlight the application of non-invasive ICP monitoring (nICP) technology in the diagnose and management of SVS providing insights into its benefits and limitations. A 6-year-old boy with a known history of autism spectrum disorder had undergone a VPS for a communicating hydrocephalus. Post operative, patient was asymptomatic with magnetic resonance images (MRI) showing small ventricle size. However, the patient started to develop recurrent symptoms of headache, nausea, and vomiting, a fresh MRI was ordered which demonstrated findings consistent with the previous MRI. We therefore decided to evaluate ICP and compliance by non-invasive monitoring using brain4care technology. Noninvasive monitoring was suggestive of low ICP and hyperdrainage, leading to the adjustment of the shunt valve from a medium to high pressure device, which normalized ICP waves and ICP as well ventricles size and the patient became asymptomatic. Therefore, we propose that noninvasive ICP monitoring may be a helpful tool to better classify the SVS type and guide the appropriated management.
Genetic Screening of ATP7B Gene in Iranian Wilson Disease Patients: A diverse landscape of pathogenic variants
Authors: Hashemi Seyyed-Saleh , Jafari Seyed Ali , Gholoobi Aida , Hamzehloei Tayebeh 
Published: October 2024

Abstract

Background/Objective:
Wilson's disease (WD) is an autosomal recessive condition caused by mutations in the ATP7B gene, leading to the copper accumulation in various organs. Data on the ATP7B mutation spectrum in Iran and the Middle East is insufficient. This study aims to screen the ATP7B gene in unrelated Iranian families (n = 23) from northeastern Iran.
Methods
DNA was extracted from peripheral blood, and variant screening was performed using direct sequencing of the entire ATP7B gene coding region. The full 3D structure of the defective proteins was determined using the I-TASSER software.
Results
The overall frequency of causative variant detection was 84.7% (39/46). Among the 23 patients with WD, we identified 13 different causative variants: eight missense, two nonsense, one splicing, one deletion, and one deletion/insertion changes. Two of which were novel: c.3431delTinsAGA (p.Phe1144Ter) and c.1156G > A (p.Gly386Arg). The c.2807T > A (p.Leu936Ter) variant at exon 12 was the most prevalent in our study, with an allelic frequency of 17.39%, followed by c.3188C > T (p.Ala1063Val) at exon 14, exhibiting an allelic frequency of 13.04%. Exons 12, 13, and 14 were identified as mutation hot spots, with detection rate of 50% (23/46). Ten out of the 13 variants identified in our study were reported for the first time in Iran (this report).
Conclusion
We reported two novel variants that broaden the known spectrum of mutations associated with the ATP7B gene. The variants identified in this study can facilitate carrier screening and presymptomatic detection and can be used in prenatal genetic diagnosis in affected families.
Dietary habits and minerals intake in patients with grass pollen allergy
Authors: Rogacka Natalia , Jagielska Joanna , Grygiel-Górniak Bogna 
Published: October 2024

Abstract

Specific dietary components (e.g., fatty acids and micronutrients) are crucial in food allergy; however, their exact role in the diet in grass pollen allergy needs to be better established. Since specific macro- and microminerals (trace elements) can stimulate the immune system, this study aimed to estimate the dietary habits and mineral intake in patients with allergic diseases. Anthropometric, biochemical, serological, and nutritional habits analyses were done in patients with grass pollen allergy and compared to the healthy control group. Daily food rations (DFR) were improperly balanced, and high intake of protein and fat and low carbohydrate were observed in both groups. Saturated fatty acids (SFA), phosphorus, and copper were supplied in high amounts, while mono- and polyunsaturated fatty acids, magnesium, and zinc were within the reference range and comparable in both analyzed groups. Insufficient calcium intake resulted in a low Ca:P ratio. A similar analysis showed higher macronutrients, SFA, sodium, magnesium, and copper intake and lower calcium and phosphorus consumption in allergic patients than in the control group. Total IgE positively correlated with platelet level and negatively with zinc intake. The diet of patients with grass pollen allergy needs to be better balanced regarding macronutrients and selected elements. Correcting and controlling the number of nutrients that increase the risk of immune system dysregulation in such patients (particularly reducing excessive SFA intake and increasing insufficient calcium intake) is advisable.
The efficacy of second-line nivolumab versus tyrosine kinase inhibitors for renal cell carcinoma with bone metastases: A multi-institutional retrospective study
Authors: Yamamichi Gaku , Kato Taigo , Yoshimura Akihiro , Tani Masaru , Horibe Yuki , Liu Yutong , Sassi Nesrine , Okuda Yohei , Oka Toshiki , Uemura Toshihiro , Yamamoto Akinaru , Ishizuya Yu , Hayashi Takuji , Yamamoto Yoshiyuki , Hatano Koji , Kawashima Atsunari , Takao Tetsuya , Nishimura Kensaku , Takada Shingo , Tsujihata Masao , Nonomura Norio 
Published: October 2024

Abstract

Immune checkpoint inhibitor combination therapy has been standardized for first-line treatment for metastatic renal cell carcinoma (mRCC), leading to the changes in second-line treatment options such as nivolumab or tyrosine kinase inhibitors (TKIs). However, there have been few reports comparing the efficacy of these drugs in mRCC patients, especially with bone metastases (BM), which are associated with a poor prognosis. Therefore, we aimed to compare the efficacy of nivolumab and TKIs as second-line treatments for 87 mRCC patients with BM and the microenvironments of the primary tumor and BM lesions. Multivariate analysis revealed poor risk according to the IMDC classification (p < 0.01) and high serum ALP value (p = 0.031) as worse prognostic factors, while there was no significant difference of overall survival between patients with nivolumab and TKIs. However, the objective response rate at BM lesions was significantly higher with TKIs than with nivolumab (p = 0.014). Immunohistochemistry analysis also revealed that VEGFR2 expression was significantly higher at BM lesions compared to that in primary tumors, showing the potential benefit of TKIs over nivolumab in mRCC patients with BM. In conclusion, TKIs could be the promising second-line treatment for mRCC with metastasis limited to the bone.
Prediction and Unsupervised Clustering of Fertility Intention Among Migrant Workers Based on Machine Learning: A Cross- sectional Survey from China
Authors: Guo Xinghong , Chen Yiyang , Fang Chaoyang , Liu Jingru , Yan Shuming , Fei Fengyi , Xinya Cheng , Wu Jian , Ye Beizhu 
Published: October 2024

Abstract

Background
Although China has implemented multiple policies to encourage childbirth, the results have been underwhelming. Migrant workers account for a considerable proportion of China’s population, most of whom are of childbearing age. However, few articles focus on their fertility intentions.
Method
From August 3 to August 29, 2023, we conducted a cross-sectional survey in Henan Province, China, which included 18806 participants. Machine learning was used to construct a predictive model for the fertility intention of migrant workers, and unsupervised clustering was used to explore subgroup classification.
Result
Out of 18806 participants, only 1057 had fertility intention. We constructed a predictive model for fertility intention based on XGBoost, with an AUC of 0.83. Age, number of children, and marital status are the most important characteristics that affect the fertility intention of migrant workers. Subsequently, unsupervised clustering was conducted on participants without fertility intentions, and it was found that they could be divided into three categories of population. The first group of people is the youngest and mostly unmarried without pregnancy, the second group has the lowest monthly income and self-perceived economic level, and the third group is the oldest and has the highest proportion of women. Regardless of the group, economic and age factors are the main reasons for participants not having a family plan in the near future.
Conclusion
The fertility intention of the migrant workers is at an extremely low level. Improving childcare-related benefits and family support services to reduce the economic and time costs of childcare is an effective measure to reverse fertility intentions.
Identification of a risk allele at SLC41A3 and a protective allele HLA-DPB1*02:01 associated with sarcopenia in Japanese
Authors: Furutani Motoki , Kimura Tetsuaki , Fukunaga Koya , Suganuma Mutsumi , Takemura Marie , Matsui Yasumoto , Satakae Shosuke , Nakano Yukiko , Mushiroda Taisei , Niida Shumpei , Ozaki Kouichi , Hosoyama Tohru , Shigemizu Daichi 
Published: October 2024

Abstract

Background Age-related alterations in muscle tissue morphology and function, as well as chronic pro-inflammatory conditions, contribute to the development of sarcopenia. To elucidate the multidimensional pathogenesis of sarcopenia, we performed a comprehensive genetic analysis, including common variants, rare variants and human leukemia antigen (HLA).
Methods A total of 129 older adults were analyzed using WGS, including 67 sarcopenia patients and 62 normal controls. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus. Whole-genome sequence (WGS) data and associated clinical data were obtained from the National Center for Geriatrics and Gerontology Biobank in Japan. We performed logistic regression adjusted for age, sex, and body mass index for common variant (minor allele frequency [MAF] ≧ 1%), rare variant (MAF < 1%) and HLA analyses. For the functional analysis, we performed RNA interference using human myoblasts and estimated gene expressions (MYOG, MYMK, MYMG) by quantitative PCR.
Results Rare variant analysis identified five rare coding variants of genes—SLC41A3, SYNRG, CLUAP1, CCHCR1, and ALDH2—expressed in skeletal muscle (P < 5×10-5). Of these, a deleterious frameshift deletion in SLC41A3 was associated with the pathogenesis of sarcopenia (P = 0.0012, odds ratio [OR] = 11.52, 95% confidence interval [CI] = 2.62 to 50.69). This deletion significantly reduced expression of myogenin (MYOG), a factor involved in myoblast differentiation. (P = 0.0094), but did not affect the fusion of myogenic cells. We also discovered a new protective allele, HLA-DPB1*02:01 associated with sarcopenia (OR = 0.17, 95% CI = 0.06 to 0.51, P = 0.0015), which has a high occurrence rate in the Northeast Asian population.
Conclusion Rare variant analysis identified a deleterious frameshift deletion in SLC41A3 as a risk factor for sarcopenia. Our findings suggest that the suppression of MYOG could play a role in myogenesis or muscle maintenance, although this mutation did not impact the terminal differentiation of human myoblasts. Additionally, HLA analysis revealed that HLA-DPB1*02:01 has a protective effect, especially in Northeast Asian populations. Our study enhances the understanding of the etiology of sarcopenia and provides new insights into the mechanisms of its pathogenesis.