bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome
Authors: Zhang Qian , Yang Shuya , Chen Xin , Wang Hongdan , Li Keyan , Zhang Chaonan , Liao Shixiu , Qin Litao , Hou Qiaofang 
Published: September 2023

Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype.Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband.Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G&gt;C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband’s kidney tissue.Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.
TAGAP expression influences CD4+ T cell differentiation, immune infiltration, and cytotoxicity in LUAD through the STAT pathway: implications for immunotherapy
Authors: Xu Zhanyu , Zheng Tiaozhan , Zheng Zhiwen , Jiang Wei , Huang Liuliu , Deng Kun , Yuan Liqiang , Qin Fanglu , Sun Yu , Qin Junqi , Li Shikang 
Published: September 2023

BackgroundT-cell Activation GTPase Activating Protein (TAGAP) plays a role in immune cell regulation. This study aimed to investigate TAGAP’s expression and its potential impact on CD4+ T cell function and prognosis in lung adenocarcinoma (LUAD).MethodsWe analyzed TAGAP expression and its correlation with immune infiltration and clinical data in LUAD patients using multiple datasets, including The Cancer Genome Atlas (TCGA-LUAD), Gene Expression Omnibus (GEO), and scRNA-seq datasets. In vitro and in vivo experiments were conducted to explore the role of TAGAP in CD4+ T cell function, chemotaxis, and cytotoxicity.ResultsTAGAP expression was significantly lower in LUAD tissues compared to normal tissues, and high TAGAP expression correlated with better prognosis in LUAD patients. TAGAP was positively correlated with immune/stromal/ESTIMATE scores and immune cell infiltration in LUAD. Single-cell RNA sequencing revealed that TAGAP was primarily distributed in CD4+/CD8+ T cells. In vitro experiments showed that TAGAP overexpression enhanced CD4+ T cell cytotoxicity, proliferation, and chemotaxis. Gene Set Enrichment Analysis (GSEA) indicated that TAGAP was enriched in the JAK-STAT signaling pathway. In vivo experiments in a xenograft tumor model demonstrated that TAGAP overexpression suppressed tumor growth and promoted CD4+ T cell cytotoxicity.ConclusionsTAGAP influences CD4+ T cell differentiation and function in LUAD through the STAT pathway, promoting immune infiltration and cytotoxicity. This study provides a scientific basis for developing novel LUAD immunotherapy strategies and exploring new therapeutic targets.
Cytotoxic innate intraepithelial lymphocytes control early stages of Cryptosporidium infection
Authors: Hariss Fatima , Delbeke Marie , Guyot Karine , Zarnitzky Pauline , Ezzedine Mohamad , Certad Gabriela , Meresse Bertrand 
Published: September 2023

BackgroundIntraepithelial lymphocytes (IELs) are the first immune cells to contact and fight intestinal pathogens such as Cryptosporidium, a widespread parasite which infects the gut epithelium. IFN-γ producing CD4+ T IELs provide an efficient and a long-term protection against cryptosporidiosis while intraepithelial type 1 innate lymphoid cells limits pathogen spreading during early stages of infection in immunodeficient individuals. Yet, the role of T-cell like innate IELs, the most frequent subset of innate lymphocytes in the gut, remains unknown.MethodsTo better define functions of innate IELs in cryptosporidiosis, we developed a co-culture model with innate IELs isolated from Rag2-/- mice and 3D intestinal organoids infected with C. parvum using microinjection.ResultsThanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IELs secrete IFN-γ in response to C. parvum, the cytokine was not sufficient to inhibit parasite proliferation at early stages of the infection. The rapid protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis of the Cryptosporidium-infected organoids revealed that epithelial cells down regulated Serpinb9b, a granzyme inhibitor, which may increase their sensitivity to cytolytic attack by innate IELs.ConclusionBased on these data we conclude that innate IELs, most likely T-cell-like innate IELs, provide a rapid protection against C. parvum infection through a perforin/granzymes-dependent mechanism. C. parvum infection. The infection may also increase the sensitivity of intestinal epithelial cells to the innate IEL-mediated cytotoxic attack by decreasing the expression of Serpin genes.
Study of efficacy and antibody duration to fourth-dose booster of Ad5-nCoV or inactivated SARS-CoV-2 vaccine in Chinese adults: a prospective cohort study
Authors: Xu Nani , Xu Yu , Dai Rongrong , Zheng Lin , Qin Pan , Wan Peng , Yang Yejing , Jiang Jianmin , Zhang Hangjie , Hu Xiaowei , Lv Huakun 
Published: September 2023

IntroductionChina experienced a record surge of coronavirus disease 2019 cases in December 2022, during the pandemic.MethodsWe conducted a randomized, parallel-controlled prospective cohort study to evaluate efficacy and antibody duration after a fourth-dose booster with Ad5-nCoV or inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine.ResultsA total of 191 participants aged ≥18 years who had completed a three-dose regimen of the inactivated SARS-CoV-2 vaccine 6 months earlier were recruited to receive the intramuscular Ad5-nCoV booster or the inactivated SARS-CoV-2 vaccine. The Ad5-nCoV group had significantly higher antibody levels compared with the inactivated vaccine group at 6 months after the fourth vaccination dose. After the pandemic, the breakthrough infection rate for the Ad5-nCoV and the inactivated vaccine groups was 77.89% and 78.13%, respectively. Survival curve analysis (p = 0.872) and multivariable logistic regression analysis (p = 0.956) showed no statistically significant differences in breakthrough infection between the two groups.DiscussionCompared with a homologous fourth dose, a heterologous fourth dose of Ad5-nCoV elicited a higher immunogenic response in healthy adults who had been immunized with three doses of inactivated vaccine. Nevertheless, the efficacy of the two vaccine types was equivalent after the pandemic.
Comparison of the safety and efficacy of radiofrequency thermocoagulation with percutaneous balloon compression for treating trigeminal neuralgia: a systematic review and meta-analysis
Authors: Wu Zeyu , Zhao Yongming , Liu Jiang , Fan Yiyue , Yang Ying 
Published: September 2023

ObjectiveThis study aimed to systematically assess the efficacy and complications of radiofrequency thermocoagulation (RFT) and percutaneous balloon compression (PBC) for treating trigeminal neuralgia (TN).MethodsChinese and English studies on RFT and PBC in the treatment of TN were systematically searched using CNKI, Wanfang Data, VIP, PubMed, EMBASE, Cochrane Library, and until December 31, 2022. Further, the literature was strictly screened using specific inclusion and exclusion criteria. The RevMan 5.4 software was used for data processing and meta-analysis.ResultsOverall, 16 studies with 3,326 patients were included. The results of meta-analysis revealed that no significant difference was present between the two groups in terms of the rate of efficacy immediately after surgery, 1 month after surgery, and 3 months after surgery (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.35–1.54, p = 0.41; OR = 0.41, 95% CI 0.13–1.32, p = 0.13; OR = 0.40, 95% CI 0.10–1.60, p = 0.20); however, at 12 months after surgery, the difference was statistically significant (OR = 0.27, 95% CI 0.10–0.75, p = 0.01). Notably, there was no significant difference in the postoperative sleep quality index between the two groups immediately after surgery and 1 month after surgery (SMD = −0.01, 95% CI −2.47 to 2.44, p = 0.99; SMD = 0.14, 95% CI −3.95 to 4.22, p = 0.95). Further, statistically significant differences were observed between the two groups in the incidence of postoperative masticatory muscle strength decline and oral herpes (OR = 0.37; 95% CI 0.21–0.63, p = 0.0003; OR = 0.25, 95% CI 0.10–0.61, p = 0.003). In addition, a statistically significant difference was found in the recurrence rate at 1-year follow-up (OR = 2.23, 95% CI 1.03–4.81, p = 0.04); however, no statistically significant differences were found in the recurrence rate at the 2-year follow-up (OR = 1.95, 95% CI 0.33–11.59, p = 0.46).ConclusionIn the treatment of TN, both RFT and PBC can achieve good short-term efficacy, and no significant differences were noted between the outcomes of the two approaches. Compared with RFT, PBC may result in a lower pain score and recurrence rate in the medium and long terms, but it is a higher incidence of cold sores, and the decrease of masticatory muscle strength is more obvious.
Reassessment of oxidative stress in idiopathic sudden hearing loss and preliminary exploration of the effect of physiological concentration of melatonin on prognosis
Authors: Song Jianxiong , Ouyang Fang , Xiong Yuanping , Luo Qing , Jiang Hongqun , Fan Li , Zhang Zhiyuan 
Published: September 2023

Background and purposeThe pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unclear, and there is no targeted treatment. This research aimed to verify the role of oxidative stress in ISSNHL and explore whether melatonin has a protective effect on hearing.Materials and methodsA total of 43 patients with ISSNHL and 15 healthy controls were recruited to detect the level of melatonin, reactive oxygen species (ROS), and total antioxidant capacity (TAC) in the blood and compared before and after treatment. Multivariate logistic regression models were performed to assess the factors relevant to the occurrence and improvement of ISSNHL.ResultsThe patients with ISSNHL showed significantly higher ROS levels than controls (4.42 ± 4.40 vs. 2.30 ± 0.59; p = 0.031). The levels of basal melatonin were higher (1400.83 ± 784.89 vs. 1095.97 ± 689.08; p = 0.046) and ROS levels were lower (3.05 ± 1.81 vs. 5.62 ± 5.56; p = 0.042) in the effective group as compared with the ineffective group. Logistic regression analysis showed that melatonin (OR = 0.999, 95% CI 0.997–1.000, p = 0.049), ROS (OR = 1.154, 95% CI 1.025–2.236, p = 0.037), and vertigo (OR = 3.011, 95% CI 1.339–26.983, p = 0.019) were independent factors associated with hearing improvement. Besides, the level of melatonin (OR = 0.999, 95% CI 0.998–1.000, p = 0.023) and ROS (OR = 3.248, 95% CI 1.109–9.516, p = 0.032) were associated with the occurrence of ISSNHL.ConclusionOur findings may suggest oxidative stress involvement in ISSNHL etiopathogenesis. The level of melatonin and ROS, and vertigo appear to be predictive of the effectiveness of hearing improvement following ISSNHL treatment.
Right upper lobe segmentectomy and subsegmentectomy guided by classification pattern of peripheral segmental veins
Authors: Li Zhikai , Chen Shuangqing , Ren Dahu , Kong Yuhong , Xu Shun , Duan Guochen , Zhang Xiaopeng 
Published: September 2023

BackgroundStudies have analyzed the simplified branching pattern of peripheral segmental veins and developed a standardized approach for intersegmental vein identification in the right upper lobe (RUL). However, the identification approach of intersubsegmental veins has not been reported. This study aimed to supplement the identification approach of intersubsegmental veins and the classification pattern of peripheral segmental veins by using three-dimensional computed tomography bronchography and angiography (3D-CTBA).Materials and methodsA total of 600 patients with ground glass opacity (GGO) who had undergone 3D-CTBA preoperatively at Hebei General Hospital between September 2020 and September 2022 were used for the retrospective study. We reviewed the anatomical variations of RUL veins in these patients using 3D-CTBA images.ResultsAccording to the anatomical position, the peripheral segmental veins structures of RUL were classified into five categories: “Iab type of anterior with central vein” (256/600, 42.7%), “Ib type of anterior with central vein” (166/600, 27.7%), “Central vein type” (38/600, 6.3%), “Anterior vein type” (81/600, 13.5%), “Right top pulmonary vein type” (57/600, 9.5%). The approach for intersegmental vein and intersubsegmental veins identification was divided into five types: anterior approach, posterobronchial approach, central vein approach, V2t approach, and intermediate bronchus posterior surface approach.ConclusionsThe classification pattern of peripheral segmental veins should find wide application. Further, approaches identifying intersegmental veins and intersubsegmental veins may help thoracic surgeons perform safe and accurate RUL segmentectomy.
Clinical characteristic–assisted surgical benefit stratification for resection of primary tumor in patients with advanced primary malignant bone neoplasms: a population-based propensity score–matched analysis
Authors: Tong Yuexin , Jiang Liming , Cui Yuekai , Pi Yangwei , Gong Yan , Zhao Dongxu 
Published: September 2023

BackgroundPrimary tumor resection (PTR) is the standard treatment for patients with primary malignant bone neoplasms (PMBNs). However, it remains unclear whether patients with advanced PMBNs still benefit from PTR. This study aimed to develop a prediction model to estimate the beneficial probability of PTR for this population.MethodsThis study extracted data from patients diagnosed with advanced PMBNs, as recorded in the Surveillance, Epidemiology, and End Results (SEER) database, with the period from 2004 to 2015. The patient cohort was then bifurcated into two groups: those who underwent surgical procedures and the non-surgery group. Propensity score matching (PSM) was utilized to mitigate any confounding factors in the study. The survival rates of patients from both the surgical and non-surgery groups were evaluated using Kaplan–Meier (K-M) curves analysis. Moreover, the study used this method to assess the capacity of the nomogram to distinguish patients likely to derive benefits from surgical intervention. The study was grounded in the hypothesis that patients who underwent PTR and survived beyond the median overall survival (OS) time would potentially benefit from the surgery. Subsequently, logistic regression analysis was performed to ascertain significant predictors, facilitating the development of a nomogram. This nomogram was subjected to both internal and external validation using receiver operating characteristic curves, area under the curve analysis, calibration plots, and decision curve analysis.ResultsThe SEER database provided a total of 839 eligible patients for the study, among which 536 (63.9%) underwent PTR. Following a 2:1 PSM analysis, patients were classified into two groups: 364 patients in the surgery group and 182 patients in the non-surgery group. Both K-M curves and multivariate Cox regression analysis revealed that patients who received PTR had a longer survival duration, observed both before and after PSM. Crucial factors such as age, M stage, and tumor size were identified to be significantly correlated with surgical benefits in patients with advanced PMBNs. Subsequently, a nomogram was developed that uses these independent predictors. The validation of this predictive model confirmed its high accuracy and excellent discrimination ability of the nomogram to distinguish patients who would most likely benefit from surgical intervention.ConclusionIn this study, we devised a user-friendly nomogram to forecast the likehood of surgical benefits for patients diagnosed with advanced PMBNs. This tool facilitates the identification of the most suitable candidates for PTR, thus promoting more discerning and effective use of surgical intervention in this patient population.
The relationship between musicianship and pain. Is chronic pain and its management a problem for student musicians only?
Authors: Korte Michaela , Cerci Deniz , Wehry Roman , Timmers Renee , Williamson Victoria J. 
Published: September 2023

IntroductionThe neuro-biological side of chronic pain research has presented reliable evidence of distinct cortical and spinal alteration compared to healthy individuals. Furthermore, research suggests that musicians are especially vulnerable to pain, and recent neurological investigations into musicians' brain plasticity support this hypothesis. However, chronic pain is not acute pain plus time, but a separate condition, and little is known about musicians' chronic pain-related emotions and behaviors. This knowledge, however, is a crucial step in understanding how chronic pain is processed by musicians.MethodsThis study investigated pain catastrophizing as a critical pain-related behavior and emotional concept alongside six complementary variables: anxiety, depression, depersonalisation, burnout, coping strategies and professional identity.Results103 under- and postgraduate students from various higher education institutions participated in an online survey. Students were allocated into three groups according to their main study subject and type of institution: music college musicians, university musicians and university non-musicians. A tree model confirmed the current chronic pain multifactorial model, suggesting a combination of several variables before catastrophizing pain. Group testing, however, showed that university non-musicians' pain catastrophizing was significantly worse especially when compared to music college musicians. Music college musicians and university musicians were less prone to maladaptive pain processes, despite perceiving pain for significantly longer.DiscussionThis novel finding indicates that chronic pain does not inevitably lead to dysfunctional pain processing for musicians and should be reflected accordingly to optimize pain-control. The biopsychosocio model of chronic pain provides a robust framework for future research in this population.
Prenatal MRI diagnosis and outcomes of abdominal or sacrococcygeal teratomas and parasitic fetuses
Authors: Li Xu , Lin Hui hui , Hu Ke fei , Peng Yun 
Published: September 2023

ObjectiveTo investigate the MRI findings of fetal abdominal or sacrococcygeal teratomas and parasitic fetuses and analyze the outcomes on the basis of follow-up assessments.MethodsThe MRI data of 60 cases of abdominal or sacrococcygeal masses were examined. The outcomes were followed up and compared with the prenatal MRI diagnoses.ResultsThe 60 cases included 52 cases of sacrococcygeal teratomas and eight cases of abdominal lesions. The common types of sacrococcygeal teratomas were type I (21/52, 40.4%) and type II (20/52, 38.5%); type III sacrococcygeal teratomas were rarer (8/52, 15.4%), while type IV tumors (3/52, 5.7%) were frequently complicated with hydronephrosis. Other complications included polyhydramnios in 22 cases, placental edema in six cases, and fetal hydronephrosis in three cases (all type IV). Seven of the eight parasitic fetuses were located in the abdominal cavity, and one was located in the sacrococcygeal region. Postnatal surgery was performed in 51 cases (51/60), including 44 with teratomas and seven with parasitic fetuses. In one case with hydronephrosis, peritoneal effusion, and subcutaneous edema, treatment was discontinued after birth (1/60). Fetal induction of labor was observed in eight cases (8/60). Prenatal ultrasound yielded incorrect or ambiguous diagnoses in 11 cases, while 51 cases showed a favorable course after surgery.ConclusionsMRI shows high accuracy in the diagnosis of fetal sacrococcygeal teratomas and parasitic fetuses. The prognosis in these cases is generally good. However, type IV sacrococcygeal teratomas are prone to fetal hydronephrosis and misdiagnosis and show a poorer prognosis.
Natural product-inspired synthesis of coumarin–chalcone hybrids as potential anti-breast cancer agents
Authors: Alhakamy Nabil A. , Saquib Mohammad , Sanobar  , Khan Mohammad Faheem , Ansari Waseem Ahmad , Arif Deema O. , Irfan Mohammad , Khan Mohammad Imran , Hussain Mohd Kamil 
Published: September 2023

Twelve novel neo-tanshinlactone–chalcone hybrid molecules were constructed through a versatile methodology involving the Horner–Wadsworth–Emmons (HWE) olefination of 4-formyl-2H-benzo [h]chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, viz. MCF-7 (ER + ve), MDA-MB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate in vitro anti-cancer activity in a range of 6.8–19.2 µM (IC50). Compounds 30 (IC50 = 6.8 µM and MCF-7; IC50 = 8.5 µM and MDA-MB-231) and 31 (IC50 = 14.4 µM and MCF-7; IC50 = 15.7 µM and MDA-MB-231) exhibited the best activity with compound 30 showing more potent activity than the standard drug tamoxifen. Compound 30 demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds 30 and 31 met Lipinski’s rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood–brain barrier crossing. Based on the aforementioned results, compound 30 has been identified as a potential anti-breast cancer lead molecule.