bluuebunny/crossref_metadata_2025_split huggingface dataset:
GCM2 p.Tyr394Ser variant in Ashkenazi Israeli patients with suspected familial isolated hyperparathyroidism
Authors: Szalat Auryan , Shpitzen Shoshana , Pollack Rena , Mazeh Haggi , Durst Ronen , Meiner Vardiella 
Published: December 2023

ContextA germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the GCM2 [(NM_ 004752.4) c.1181A&gt; C; p.Tyr394Ser; rs142287570] variant was reported in PHPT Ashkenazi Jews (AJ).ObjectiveTo evaluate the presence of the GCM2 p.Tyr394Ser variant in Israeli patients addressed for genetic evaluation to characterize their phenotype and clinical management.MethodPatients with PHPT who underwent addressed for genetic screening for suspected familial hypocalciuric hypercalcemia (FHH), a family history of isolated hyperparathyroidism (FIHP), or failed parathyroidectomy with persistent PHPT were recruited. Those with normal initial selected gene sequencing or hyperparathyroid genetic panel completed the GCM2 p.Tyr394Ser variant sequencing. The prevalence of this variant was evaluated using our local genomic database.ResultsA total of 42 single individuals from unrelated kindreds were evaluated. A disease-causing mutation was found in 11 (26.1%) patients: 10 were diagnosed with FHH (eight CASR and two AP2S1 mutations), and one patient had a CKN2B mutation. In 28 of the remaining patients, the GCM2 p.Tyr394Ser variant was positive in three (10.7%), and all were AJ. Within AJ (15/28, 53.5%), the rate of the p.Tyr394Ser variant was 3/15 (20%), and of those, two had a history of familial isolated hyperparathyroidism. Multi-glandular parathyroid adenoma/hyperplasia was also observed in two of these patients. No clinical or laboratory findings could discriminate patients with the GCM2 p.Tyr394Ser variant from those with FHH. Cinacalcet normalized the calcium levels in one patient. The prevalence of the GCM2 p.Tyr394Ser variant in 15,407 tests in our local genomic database was 0.98%.ConclusionIn contrast to previous observations, the GCM2 p.Tyr394Ser variant-associated phenotype may be mild in AJ with FIHP, sometimes mimicking FHH. Because surgery may be curative, surgeons should be aware of the possibility of multiple gland diseases in these patients. The clinical spectrum and clinical utility of screening for this variant warrant further investigation.
KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells
Authors: Du Ying , Ye Hui , Lin Mei , Cao Lili 
Published: December 2023

ObjectiveTo explore the role of Krüppel-like factor 14 (KLF14) and its underlying mechanism(s) of action in cell-cycle regulation in cervical cancer.MethodsLentiviral infection was used to construct KLF14, KLF14 zinc-finger structural mutations, and empty vector controls in SiHa and HeLa cervical cancer cells. The effect of KLF14 on cervical cancer cell cycle was detected by flow cytometry. The effect of KLF14 on the expression of cyclin-dependent kinase 2 (CDK2), cyclin A2 (CCNA2), and MAPK signalling pathway-related molecules was detected by fluorescence quantitative RT-PCR (qRT-PCR) and western blot. Cervical cancer cells were treated with JNK-pathway inhibitors/agonists before we assessed changes in the cell cycle and the expression of the CDK2, CCNA2, and p-JNK/JNK. Subcutaneous xenograft studies to explore the effects of KLF14 on cervical cancer cell proliferation in vivo, and western blotting was implemented to measure the expression of CCNA2, CDK2, and the activation levels of the MAPK-signaling pathway proteins in tumours.ResultsThe proportion of cells in the S phase was increased in the KLF14-overexpressing group compared with the control group (P&lt;0.001); CDK2, CCNA2, and p-JNK/JNK expression levels were elevated in the KLF14-overexpressing group relative to the control group (all P&lt;0.05). When JNK-pathway activation was inhibited/promoted, the proportion of cells in the S phase was reduced/increased (P&lt;0.05) and CDK2 and CCNA2 expression levels were reduced/decreased, respectively (all P&lt;0.05). Vivo experiments revealed that KLF14 inhibited cervical cancer cell proliferation (P&lt;0.01) and that p-JNK/JNK, CDK2, and CCNA2 expression levels were augmented in tumours in the overexpression group (P&lt;0.01).ConclusionKLF14 induced S-phase arrest in cervical cancer cells and inhibited the proliferation of cervical cancer cells in vivo; the induction of S-phase arrest was related to its zinc-finger structure. KLF14 also activated the JNK pathway to induce S-phase arrest and promote the expression of CDK2 and CCNA2. In summary, KLF14 activates the JNK-signaling pathway to induce S-phase arrest in cervical cancer cells
Immunologic barriers in liver transplantation: a single-cell analysis of the role of mesenchymal stem cells
Authors: Li Haitao , Yu Saihua , Liu Haiyan , Chen Lihong , Liu Hongzhi , Liu Xingwen , Shen Conglong 
Published: December 2023

BackgroundThis study aimed to analyze the biomarkers that may reliably indicate rejection or tolerance and the mechanism that underlie the induction and maintenance of liver transplantation (LT) tolerance related to immunosuppressant or mesenchymal stem cells (MSCs).MethodsLT models of Lewis-Lewis and F344-Lewis rats were established. Lewis-Lewis rats model served as a control (Syn). F344-Lewis rats were treated with immunosuppressant alone (Allo+IS) or in combination with MSCs (Allo+IS+MSCs). Intrahepatic cell composition particularly immune cells was compared between the groups by single-cell sequencing. Analysis of subclusters, KEGG pathway analysis, and pseudotime trajectory analysis were performed to explore the potential immunoregulatory mechanisms of immunosuppressant alone or combined with MSCs.ResultsImmunosuppressants alone or combined with MSCs increases the liver tolerance, to a certain extent. Single-cell sequencing identified intrahepatic cell composition signature, including cell subpopulations of B cells, cholangiocytes, endothelial cells, erythrocytes, hepatic stellate cells, hepatocytes, mononuclear phagocytes, neutrophils, T cells, and plasmacytoid dendritic cells. Immunosuppressant particularly its combination with MSCs altered the landscape of intrahepatic cells in transplanted livers, as well as gene expression patterns in immune cells. MSCs may be included in the differentiation of T cells, classical monocytes, and non-classical monocytes.ConclusionThese findings provided novel insights for better understanding the heterogeneity and biological functions of intrahepatic immune cells after LT treated by IS alone or in combination with MSCs. The identified markers of immune cells may serve as the immunotherapeutic targets for MSC treatment of liver transplant rejection.
Factors contributing to emotional distress when caring for children with imperforate anus: a multisite cross-sectional study in China
Authors: Lv Meng , Feng-Fang Ya , Wang Yi , Zhen-Xu Hong 
Published: December 2023

BackgroundImperforate anus (IA) has a life-long impact on patients and their families. The caregivers of children with IA (CoCIA) might experience distress, which could be detrimental to them physically and mentally. However, there are limitations in the related studies. This study aimed to investigate the prevalence of IA and the associated factors contributing to the distress experienced by CoCIA.MethodsA cross-sectional study was conducted in three tertiary children's hospitals from November 2018 to February 2019. Distress was assessed using the Chinese version of the Kessler Psychological Distress Scale, and possible determinants were assessed by the Caregiver Reaction Assessment, the Parent Stigma Scale, the Parent Perception of Uncertainty Scale, and the Social Support Scale. Demographic and clinical information was also collected. Multiple regression analysis was performed to explore the association between variables.ResultsOut of 229 CoCIA, 52.9% reported experiencing a high level of distress or above. The data analysis revealed that health problems associated with caregiving, stigma, uncertainty, social support, and children who underwent anal reconstruction surgery 1 year before or earlier could significantly predicate caregivers' distress, and these factors could explain 50.1% of the variance.ConclusionsThe majority of the caregivers of children with IA experience high levels of distress, particularly when their children undergo anal reconstruction surgery 1 year before or earlier. Additionally, health problems related to caregiving, stigma, uncertainty, and low social support could significantly predicate caregivers' distress. It is important for clinical staff to be aware of the prevalent situation of caregivers' distress and to make targeted interventions focused on addressing modifiable factors that should be carried out in family-based care.
Gender gap–Gender-specific development in the field of obstetrics and gynecology in Germany in the last 20 years
Authors: Hertling Stefan , Kaiser Mario , Schleußner Ekkehard , Loos Franziska Maria , Eckhardt Niklas , Graul Isabel 
Published: December 2023

BackgroundGender Gap refers to differences between men and women in terms of access to medical education, career development, and leadership positions in medical practice and research. Although women now make up most medical school graduates in many countries, they are often underrepresented in higher positions.ObjectiveThe aim of this study is therefore to analyze the gender-specific development in the field of Obstetrics and Gynecology in Germany over the past 20 years and to survey the current status quo.Materials and methodsAn narrative review was carried out on the development of female graduates of human medicine, the proportion of women in contract medical care and clinical care, as well as the gender-specific evaluation of obtaining a gynecological/obstetric additional qualification. habilitation figures in the field of Obstetrics and Gynecology were evaluated about gender distribution. All data were received from federal institutes.ResultsA total of 46.7% (n = 95,234) of all inpatient doctors were female. A total of 46.7% (n = 95,234) of the physicians in hospitals were female. A total of 46% (1,832/3,958) were the portion of females as assistant physicians, 39.8% (n = 45.551) as specialists, 35.3% (n = 18789) as senior physicians, 25.1% (n = 2394) as first senior physicians and 25% (n = 10) as chief physicians in hospital. A total of 64.6% (n = 3958) of the physicians in Obstetrics and Gynecology were female. A total of 46% (1,832/3,958) were the portion of females as assistant physicians, 64.6% (n = 3958) as specialists, 65.0% (n = 1919) as senior physicians, 26.4% (n = 207) first senior physicians and 25% (n = 10) as chief physicians in Obstetrics and Gynecology.DiscussionThe problem with the gender gap in medicine, does not seem to be access to teaching or starting a residency. But in the functions with increasing responsibility and management functions, e.g., as senior physicians, women are already rarely seen. In Obstetrics and Gynecology, too, there is a shortage of women in leading positions, despite the relatively high numbers, for example as senior physicians. Factors like maternity and establishing a family are points mentioned therefore, but also stereotypes seem to be considerable facts.ConclusionHowever, it is important to recognize the need for more women in higher positions in medicine and actively work to encourage more women to choose a career in medicine.
A bidirectional Mendelian randomization study investigating the causal role between gut microbiota and insomnia
Authors: Yang Jie , Su Tengfei , Zhang Yating , Jia Menghan , Yin Xiang , Lang Yue , Cui Li 
Published: December 2023

BackgroundIt has emerged that disturbances of the gut microbiota (GM) are linked to insomnia. However, the causality of the observed associations remains uncertain.MethodsWe conducted a two-sample Mendelian randomization analysis based on genome-wide association study data to explore the possible causal link between GM and insomnia. The GM data were from the MiBioGen consortium, while the summary statistics of insomnia were obtained from the FinnGen consortium R9 release data. Cochran’s Q statistics were used to analyze instrumental variable heterogeneity.ResultsAccording to the inverse variance weighted estimates, the family Ruminococcaceae (odds ratio = 1.494, 95% confidence interval:1.004–2.223, p = 0.047) and the genus Lachnospiraceae (odds ratio = 1.726, 95% confidence interval: 1.191–2.501, p = 0.004) play a role in insomnia risk. In contrast, the genus Flavonifractor (odds ratio = 0.596, 95% confidence interval: 0.374–0.952, p = 0.030) and the genus Olsenella (odds ratio = 0.808, 95% confidence interval: 0.666–0.980, p = 0.031) tended to protect against insomnia. According to the reverse MR analysis, insomnia can also alter GM composition. Instrumental variables were neither heterogeneous nor horizontal pleiotropic.ConclusionIn conclusion, our Mendelian randomization study provides evidence of a causal relationship between GM and insomnia. The identified GM may be promising gut biomarkers and new therapeutic targets for insomnia. This investigation also provides a foundation for future studies examining the influence of GM on sleep disorders beyond insomnia, with potential implications for redefining the mechanisms governing sleep regulation.
Percutaneous uniportal full-endoscopic surgery for treating symptomatic lumbar facet joint cysts under local anesthesia combined with monitored anesthesia care: a preliminary report of eight cases with at least 1 year follow-up
Authors: Tan Haining , Yu Lingjia , Li Xiang , Yang Yong , Zhu Bin 
Published: December 2023

BackgroundLumbar facet joint cysts (FJCs) are a relatively rare clinical pathology that can result in radiculopathy or neurogenic claudication. Various treatments such as percutaneous aspiration and surgery have been reported to have good clinical outcomes. However, few clinical studies have aimed to treat symptomatic lumbar FJCs by using uniportal full-endoscopic (UFE) surgery. This study aimed to investigate the preliminary clinical outcomes of UFE surgery for the treatment of lumbar FJCs under local anesthesia combined with monitored anesthesia care (MAC).MethodsEight patients (five males and three females) with symptomatic lumbar FJCs who underwent UFE surgery under local and MAC anesthesia were enrolled in this study between January 2018 and April 2022. The clinical characteristics, radiological features, operative information, visual analog scale (VAS) score, Oswestry disability index (ODI), and overall outcome rating based on the modified MacNab criteria were retrospectively analyzed.ResultsOf the eight patients, four underwent a transforaminal approach and four underwent an interlaminar approach. Postoperatively, the mean VAS score for leg pain decreased from 6.1 before surgery to 0.6 after surgery, and the ODI decreased from 74.5% to 14.7%. All patients were followed up for more than 1 year, and the good-to-excellent rate based on the modified MacNab criteria remained 100% at the last follow-up. No complications occurred during the follow-up period.ConclusionLumbar FJCs can cause severe radiating leg pain and/or neurogenic claudication due to the dural sac compression and nerve roots. As an alternative treatment, UFE decompression under local and MAC anesthesia may provide effective clinical outcomes for symptomatic lumbar FJCs.
Abnormalities of cerebral blood flow and the regional brain function in Parkinson’s disease: a systematic review and multimodal neuroimaging meta-analysis
Authors: Xie Hao , Yang Yang , Sun Qian , Li Ze-Yang , Ni Min-Hua , Chen Zhu-Hong , Li Si-Ning , Dai Pan , Cui Yan-Yan , Cao Xin-Yu , Jiang Nan , Du Li-Juan , Yu Ying , Yan Lin-Feng , Cui Guang-Bin 
Published: December 2023

BackgroundParkinson’s disease (PD) is a neurodegenerative disease with high incidence rate. Resting state functional magnetic resonance imaging (rs-fMRI), as a widely used method for studying neurodegenerative diseases, has not yet been combined with two important indicators, amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF), for standardized analysis of PD.MethodsIn this study, we used seed-based d-mapping and permutation of subject images (SDM-PSI) software to investigate the changes in ALFF and CBF of PD patients. After obtaining the regions of PD with changes in ALFF or CBF, we conducted a multimodal analysis to identify brain regions where ALFF and CBF changed together or could not synchronize.ResultsThe final study included 31 eligible trials with 37 data sets. The main analysis results showed that the ALFF of the left striatum and left anterior thalamic projection decreased in PD patients, while the CBF of the right superior frontal gyrus decreased. However, the results of multimodal analysis suggested that there were no statistically significant brain regions. In addition, the decrease of ALFF in the left striatum and the decrease of CBF in the right superior frontal gyrus was correlated with the decrease in clinical cognitive scores.ConclusionPD patients had a series of spontaneous brain activity abnormalities, mainly involving brain regions related to the striatum-thalamic-cortex circuit, and related to the clinical manifestations of PD. Among them, the left striatum and right superior frontal gyrus are more closely related to cognition.Systematic review registrationhttps://www.crd.york.ac.uk/ PROSPERO (CRD42023390914).
Primary squamous cell carcinoma of the pancreas: an update on a rare neoplasm from the SEER database
Authors: Ford Jacob A. , Bhatt Arjun , Kim Rachel C. , Larkins Michael , Burke Aidan M. 
Published: December 2023

IntroductionPancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy.MethodsPatients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality.ResultsOf 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p &lt; 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p&lt;0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy.ConclusionPancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients‘ ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.
Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO
Authors: Trumet Leah , Ries Jutta , Ivenz Niclas , Sobl Philip , Wehrhan Falk , Lutz Rainer , Kesting Marco , Weber Manuel 
Published: December 2023

BackgroundThe options of (neo-)adjuvant immunotherapy in addition to surgery in the treatment of oral squamous cell carcinoma (OSCC) are steadily increasing, but patients do not always respond to therapy as intended. The objectives of this study were to investigate the systemic perioperative course of the biomarkers CD45RO, TGF-β, and IL-8 in non-tumor-related minor and tumor-related major maxillofacial surgery and to perform association analyses with demographic and histomorphologic parameters. A deeper understanding of surgery-related changes in various of different immune biomarkers could help to better understand the immunologic consequences of surgery which could influence immunotherapeutic protocols.MethodsPeripheral whole blood from 38 patients was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) at five different timepoints before and after maxillofacial surgery to detect changes in mRNA expression of the biomarkers TGF-β, IL-8 and CD45RO. All patients underwent general anesthesia to undergo either resection and free flap reconstruction for OSCC or minor maxillofacial surgery (controls). Statistical analysis was done using Mann-Whitney-U test, Wilcoxon test, and Spearman’s correlation.ResultsCompared to the preoperative expression, there was a significant postoperative downregulation of CD45RO, TGF-β and IL-8 until the 4th postoperative day (p ≤ 0.003) in OSCC patients. For TGF-β and IL-8, the reduction in expression was significant (p ≤ 0.004) compared to controls. By postoperative day 10, all analyzed parameters converged to baseline levels. Only CD45RO still showed a significant downregulation (p=0.024). Spearman analysis revealed a significant correlation between increased duration of surgery and perioperative reduction in peripheral blood expression of CD45RO, TGF-β and IL-8 (p ≤ 0.004). Perioperative changes in TGF-β and PD-L1 expression were shown to be not correlated. Preoperative TGF-β expression was significantly lower in patients with lymph node metastases (p=0.014).ConclusionWith regard to the analyzed parameters, major oncologic head-and-neck surgery does not seem to have long-lasting systemic immunologic effects. Reduced CD45RO might be an expression of transient systemic immunosuppression in response to major surgery. The association of duration of surgery with expression changes of immunologic markers supports efforts to keep the duration of surgery as short as possible. As perioperative TGF-β and PD-L1 expression changes are not associated, these results support further investigation of a combined perioperative anti-PD-1 and anti-TGF-β immunotherapy.