bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of HTLV-1 seroconversion between pregnancies in Nagasaki, Japan, 2011–2018
Authors: Komatsu Nahoko , Iwanaga Masako , Hasegawa Yuri , Miura Shoko , Fuchi Naoki , Moriuchi Hiroyuki , Yanagihara Katsunori , Miura Kiyonori 
Published: November 2022

BackgroundHuman T-cell leukemia virus type-1 (HTLV-1) is transmitted vertically from an infected mother to her child via breastfeeding during infancy or horizontally via sexual contact. However, little information is available on the HTLV-1 seroconversion rate in pregnant mothers and the impact of new HTLV-1 infection on mothers and babies during the perinatal period.MethodsFrom the database of a prefecture-wide antenatal adult T-cell leukemia prevention program in Nagasaki, Japan, we extracted data on 57,323 pregnant women who were screened for anti-HTLV-1 antibody during 2011–2018. Data on the 16,863 subjects whose HTLV-1 proviral load (PVL) was measured more than twice were included in our analyses.ResultsIn total, 133 (0.79%) pregnant women were HTLV-1-positive during their first pregnancy and nine (0.05%) seroconverted before or during subsequent pregnancies (between pregnancies). The median PVL (per 100 peripheral blood mononuclear cells) was significantly lower in the seroconverted mothers (0.10%) than in the initially seropositive mothers (0.15%). A repeated measures correlation analysis for the individual PVLs of the HTLV-1-positive pregnant women showed that PVL increased with parity number (rrm = 0.25) with no perinatal problems.ConclusionThe HTLV-1 seroconversion rate between pregnancies was 0.05%, and their HTLV-1 PVL increased annually but no perinatal problems were noted.
Microbial communities in the liver and brain are informative for postmortem submersion interval estimation in the late phase of decomposition: A study in mouse cadavers recovered from freshwater
Authors: Wang Linlin , Zhang Fuyuan , Zeng Kuo , Dong Wenwen , Yuan Huiya , Wang Ziwei , Liu Jin , Pan Jiaqing , Zhao Rui , Guan Dawei 
Published: November 2022

IntroductionBodies recovered from water, especially in the late phase of decomposition, pose difficulties to the investigating authorities. Various methods have been proposed for postmortem submersion interval (PMSI) estimation and drowning identification, but some limitations remain. Many recent studies have proved the value of microbiota succession in viscera for postmortem interval estimation. Nevertheless, the visceral microbiota succession and its application for PMSI estimation and drowning identification require further investigation.MethodsIn the current study, mouse drowning and CO2 asphyxia models were developed, and cadavers were immersed in freshwater for 0 to 14 days. Microbial communities in the liver and brain were characterized via 16S rDNA high-throughput sequencing.ResultsOnly livers and brains collected from 5 to 14 days postmortem were qualified for sequencing. There was significant variation between microbiota from liver and brain. Differences in microbiota between the cadavers of mice that had drowned and those only subjected to postmortem submersion decreased over the PMSI. Significant successions in microbial communities were observed among the different subgroups within the late phase of the PMSI in livers and brains. Eighteen taxa in the liver which were mainly related to Clostridium_sensu_stricto and Aeromonas, and 26 taxa in the brain which were mainly belonged to Clostridium_sensu_stricto, Acetobacteroides, and Limnochorda, were selected as potential biomarkers for PMSI estimation based on a random forest algorithm. The PMSI estimation models established yielded accurate prediction results with mean absolute errors ± the standard error of 1.282 ± 0.189 d for the liver and 0.989 ± 0.237 d for the brain.ConclusionsThe present study provides novel information on visceral postmortem microbiota succession in corpses submerged in freshwater which sheds new light on PMSI estimation based on the liver and brain in forensic practice.
Non-invasive brain stimulation therapy on neurological symptoms in patients with multiple sclerosis: A network meta analysis
Authors: Zhang Xiaoyun , Huai Yaping , Wei Zhiqiang , Yang Weiwei , Xie Qizhi , Yi Li 
Published: November 2022

ObjectiveThe aim of the study was to evaluate non-invasive brain stimulation (NIBS) [including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES)] on neurological symptoms in patients with multiple sclerosis (PwMS).MethodWe searched PubMed, Embase, Cochrane Library, Web of Science and Ovid MEDLINE until February 2022. And we evaluated the included studies for methodological quality by the Cochrane bias risk assessment tool and assessed the studies' certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. We performed network meta analysis (NMA) by using Stata 15 and ranked the results of the NMA by using the surface under the cumulative ranking curve (SUCRA) ranking chart.ResultTwenty seven clinical trials were finally included (N = 596, 66.4% women). For the immediate effects, rTMS over M1 yielded the most optimal scheme for fatigue reduction among all the interventions compared to the sham stimulation groups [MD = −0.85, 95% CI (−1.57, −0.14)] (SUCRA = 82.6%). iTBS over M1 yielded the most signifcant reduced pain level than the sham groups did [MD = −1.26, 95% CI (−2.40, −0.11)] (SUCRA = 98.4%). tDCS over F3 was the best protocol of NIBS to improve quality of life (QOL) [MD = 1.41, 95% CI = (0.45,2.36)] (SUCRA = 76.7%), and iTBS over M1 may significantly reduce spasticity compared to sham stimulation [MD = −1.20, 95% CI = (−1.99, −0.41)] (SUCRA = 90.3%). Furthermore, rTMS, tRNS, and tDCS on certain areas may improve PwMS accuracy, response time, manual dexterity, pain relief and QOL, but does not show statistically significant differences. The evidence assessed using GRADE is very low.ConclusionBased on the NMA and SUCRA ranking, we can conclude that symptoms including fatigue, pain, spasticity, and QOL can be improved by following NIBS protocol after treatment. Nonetheless, most of the included studies lack a good methodology, and more high-quality randomized clinical trials are needed.
Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis
Authors: Shao Yingzhe , Du Juan , Song Yajun , Li Yanfei , Jing Lijun , Gong Zhe , Duan Ranran , Yao Yaobing , Jia Yanjie , Jiao Shujie 
Published: November 2022

PurposeWe aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity.MethodsWe retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis.ResultsCompared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p &lt; 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 109/L, p &lt; 0.001), and neutrophil count (median 6.14 vs. 3.1 × 109/L, p &lt; 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p &lt; 0.001), blood WBC count (median 9.70 vs. 7.70 × 109/L, p &lt; 0.001), neutrophil count (median 7.50 vs. 4.80 × 109/L, p &lt; 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 109/L, p &lt; 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018–6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64–0.80, p &lt; 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705).ConclusionSerum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.
Association between the C-reactive protein to albumin ratio and adverse clinical prognosis in patients with young stroke
Authors: Du Yang , Zhang Jia , Li Ning , Guo Jiahuan , Liu Xinmin , Bian Liheng , Zhao Xingquan , Liu Yanfang 
Published: November 2022

BackgroundThe inflammatory response plays an important role in ischemic stroke, and the incidence of stroke in young adults has increased rapidly in recent years. The C-reactive protein-to-albumin ratio (CAR) is a new index that reflects the overall inflammatory status of patients with major diseases; however, no studies have reported the relationship between CAR and young stroke.MethodsThe participants' baseline characteristics and laboratory examination results, including CAR, were obtained at admission. The modified Rankin Scale (mRS) scores at the 30-day and 90-day follow-ups were obtained from all patients. All the participants included in the study were classified into four groups according to CAR quartiles (Q1–Q4). Logistic regression was used to analyze the relationship between different CAR levels and adverse outcomes (mRS 3–6 and mRS 2–6). We also plotted receiver operating characteristic curves of CAR for adverse clinical outcomes and calculated the area under the curve and cutoff values.ResultsA total of 630 patients with young stroke were enrolled in the study. In the multivariate logistic regression model, at the 30-day follow-up, the Q3 and Q4 (significantly increased CAR) groups showed an elevated risk of mRS score of 2–6 (odds ratio [OR]: 2.94; 95% confidence interval [CI]: 1.40–6.16, p &lt; 0.01; OR: 4.01; 95% CI: 1.88–8.91, p &lt; 0.01). At the 90-day follow-up, the Q3 and Q4 groups still showed an elevated risk of an mRS score of 2–6 (Q3, OR: 2.76; 95% CI: 1.30–5.86, p &lt; 0.01; Q4, OR: 2.63; 95% CI: 1.22–5.65, p &lt; 0.01).ConclusionA significantly increased CAR was independently associated with an increased risk of adverse outcomes in young patients with stroke.
Association between pre-diagnostic dietary copper, zinc, and copper-to-zinc ratio and severity of ovarian cancer
Authors: Yin Jia-Li , Tao Tao , Wen Zhao-Yan , Wang Ran , Sun Ming-Hui , Gao Chang , Chang Yu-Jiao , Yan Shi , Qin Xue , Zhao Yu-Hong , Wang Lan , Gao Song 
Published: November 2022

BackgroundThe impact of dietary trace elements intake on ovarian cancer (OC) severity is unknown.ObjectiveWe firstly explore the relationship between dietary copper (Cu), zinc (Zn), and copper-to-zinc (Cu/Zn) ratio and severity of OC.MethodsThis cross-sectional study included 701 women from the OC follow-up study between 2015 and 2020. Dietary information was collected by a validated food frequency questionnaire (FFQ). The severity information of OC including age at diagnosis, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, and histopathologic grade was ascertained from medical records. Logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of aforementioned associations.ResultsAmong 701 participants, the number of patients age at diagnosis older than 50 were 443 (63.2%). The number of patients diagnosed as serous, III–IV stage, and poorly differentiation OC were 477 (68.05%), 336 (47.93%), and 597 (85.16%), respectively. In addition, compared with the lowest tertile intake, higher possibility of non-serous OC was associated with the pre-diagnosis dietary Cu (OR = 2.39, 95% CI = 1.28–4.47, p trend &lt; 0.05) and Cu/Zn ratio (OR = 2.06, 95% CI = 1.26–3.39, P trend &lt; 0.05) in the highest tertile intake. The risk of poorly differentiation OC at diagnosis was significant inversely related to dietary Cu intake (OR = 0.40, 95% CI = 0.18–0.88, P trend &lt; 0.05). Besides, the results of subgroup analyses were consistent with the main findings but not all of them showed statistical significance.ConclusionPre-diagnostic dietary Cu and Cu/Zn ratio were contributed to reducing the severity of OC at diagnosis, especially for the risk of serous OC and poorly differentiation OC.
Large-cell neuroendocrine carcinoma of the gynecologic tract: Prevalence, survival outcomes, and associated factors
Authors: Pang Li , Chen Jie , Chang Xiaohan 
Published: November 2022

BackgroundWe aimed to assess the clinical behavior of gynecologic large-cell neuroendocrine carcinoma (LCNEC) via a retrospective analysis of data from 469 patients.MethodsPatients diagnosed with gynecologic LCNEC from 1988 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox hazard regression analyses were performed to assess independent predictors of overall survival (OS) and cancer-specific survival (CSS). OS and CSS were also evaluated using the Kaplan–Meier method, and the effects of different treatment regimens on prognosis were compared according to disease stage.ResultsCervical, ovarian, and endometrial LCNEC were observed in 169, 219, and 79 patients, respectively. The 5-year OS rates for patients with cervical, ovarian, and endometrial LCNEC were 35.98%, 17.84%, and 23.21%, respectively, and the median duration of overall survival was 26, 11, and 11 months in each group. The 5-year CSS rates for the three groups were 45.23%, 19.23%, and 31.39%, respectively, and the median duration of CSS was 41, 12, and 11 months in each group. Multivariate analysis revealed that American Joint Committee on Cancer stage, lymph node metastasis, and chemotherapy were independent prognostic factors for OS and CSS in patients with cervical LCNEC. Lymph node metastasis, surgery, and chemotherapy were independent prognostic factors for OS and CSS in the ovarian group and for OS in the endometrial group. Lymph node metastasis and surgery were also independent prognostic factors for CSS in the endometrial group.ConclusionSurgery alone may help to improve overall survival and CSS in patients with early-stage cervical LCNEC. In contrast, surgery+chemotherapy and surgery+radiotherapy may help to improve survival in those with early-stage ovarian and endometrial LCNEC, respectively. Regardless of subtype, comprehensive treatment involving surgery, CTX, and RT should be considered to improve prognosis in patients with advanced-stage gynecologic LCNEC.
Central nervous system germ cell tumor, an archetypal AYA tumor and a model for pediatric and neuro-oncology collaboration, review from the EURACAN domain 10 group
Authors: Faure Conter Cecile , Calaminus Gabriele , Nicholson James , Idbaih Ahmed , Hoang Xuan Khê , Vasiljevic Alexandre , Morana Giovanni , Szathmari Alexandru , Ajithkumar Thankamma , Frappaz Didier 
Published: November 2022

Simple Summary: Adolescents and young adults (AYA) with cancer often fall through gaps between children’s and adults’ cancer services. They are consequently under-represented in clinical trials, and their survival is often inferior to that of children or adults with the same tumor type; in this paper, we use the example of central nervous system germ cell tumors (CNS-GCT), as a model of AYA tumor to illustrate this challenge. We describe how we have built bridges between pediatric and adult oncology, how this can apply to other types of brain tumors, and discuss ways to promote cancer care in the AYA population.Adolescents and young adults (AYA) with cancer are under-represented in clinical trials and have thus not benefited from the same improvement in outcomes as either younger or older patients. Central nervous system germ cell tumors (CNS-GCT) represent an ideal model of AYA tumor as their incidence peaks during adolescence and young adulthood. Since the early 90’s, SIOP (International Society of Pediatric Oncology) has launched two successive European trials: SIOP CNS-GCT96 (January 1996 to December 2005) and SIOP CNS-GCTII protocols (October 2011 to July 2018), for CNS-GCTs. With the removal of the upper age limit in the SIOP CNS-GCTII trial, and closer collaboration between pediatric and adult oncologists within AYA multidisciplinary tumor boards, the proportion of adults enrolled in France has dramatically increased over time. The current article will use the example of CNS-GCT to illustrate how to build a bridge between pediatric and adult oncology, how this can apply to other types of brain tumors, and how to promote cancer care in the AYA population.
Alagille syndrome due to a de novo NOTCH2 mutation presenting as prenatal oligohydramnios and congenital bilateral renal hypodysplasia: A case report
Authors: Xu Fengdan , Peng Qi , He Xiaoguang , Chen Xiaolan , Jiang Shuanglan , Lu Xiaomei , Li Ning 
Published: November 2022

IntroductionHere, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a de novo variant of the NOTCH2 gene.Case presentationA 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a de novo heterozygous splicing variant (c.5930-2A &gt; G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.ConclusionsOur case expands the spectrum of pathogenic variants of the NOTCH2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.
Using ear molding to correct auricular helix adhesion deformity
Authors: Chen Lili , Li Chenlong , He Aijuan , Chen Ying , Tong Hua , Fu Yaoyao , Zhang Tianyu 
Published: November 2022

ObjectivesThis study examined the effectiveness of Byrd's EarWell system for the treatment of auricular helix adhesion.MethodsThe newborns with helix adhesion were treated with ear molding. The photos of pinna were taken before, during, and after the treatment. The immediate and long-term outcomes, as well as the complications, were assessed by two independent plastic surgeons.Study designA retrospective study. Data on family history, neonatal weight, gestational age, delivery method, laterality, gender, age of initiating treatment, medical comorbidities, duration of treatment, and follow-up time were collected.Study site and periodFrom 2019 to 2021, infants treated with the EarWell System in the Eye and ENT Hospital of Fudan University were enrolled in this study.ResultsA total of 46 newborns (66 ears) with helix adhesion were included. The average onset time of treatment was 4.57 ± 3.63 weeks. The average duration of treatment was 7.40 ± 2.05 weeks. 97.0% ears’ (64/66) immediate results were excellent or good. During long-term follow-up, 95.5% ears achieved excellent or good outcomes. Age of initiation treatment significantly affected immediate (p = 0.001) and long-term (p = 0.004) outcomes.ConclusionsEarWell System was an effective method to correct auricular helix adhesion. Using this approach, patients with helix adhesion could avoid surgeries. Age of initiation treatment was the predictor of successful correction.
Pharmacophore-based virtual screening approaches to identify novel molecular candidates against EGFR through comprehensive computational approaches and in-vitro studies
Authors: Opo F A Dain Md , Moulay Mohammed , Zari Ali , Alqaderi Afnan , Alkarim Saleh , Zari Talal , Bhuiyan Mohiuddin Ahmed , Mahmoud Maged Mostafa , Aljoud Fadwa , Suhail Mohd , Edris Sherif , Ramadan Wafaa S. , Kamal Mohammad Amjad , Nemmiche Saïd , Ahammad Foysal 
Published: November 2022

Alterations to the EGFR (epidermal growth factor receptor) gene, which primarily occur in the axon 18–21 position, have been linked to a variety of cancers, including ovarian, breast, colon, and lung cancer. The use of TK inhibitors (gefitinib, erlotinib, lapatinib, and afatinib) and monoclonal antibodies (cetuximab, panitumumab, and matuzumab) in the treatment of advanced-stage cancer is very common. These drugs are becoming less effective in EGFR targeted cancer treatment and developing resistance to cancer cell eradication, which sometimes necessitates stopping treatment due to the side effects. One in silico study has been conducted to identify EGFR antagonists using other compounds, databases without providing the toxicity profile, comparative analyses, or morphological cell death pattern. The goal of our study was to identify potential lead compounds, and we identified seven compounds based on the docking score and four compounds that were chosen for our study, utilizing toxicity analysis. Molecular docking, virtual screening, dynamic simulation, and in-vitro screening indicated that these compounds’ effects were superior to those of already marketed medication (gefitinib). The four compounds obtained, ZINC96937394, ZINC14611940, ZINC103239230, and ZINC96933670, demonstrated improved binding affinity (−9.9 kcal/mol, −9.6 kcal/mol, −9.5 kcal/mol, and −9.2 kcal/mol, respectively), interaction stability, and a lower toxicity profile. In silico toxicity analysis showed that our compounds have a lower toxicity profile and a higher LD50 value. At the same time, a selected compound, i.e., ZINC103239230, was revealed to attach to a particular active site and bind more tightly to the protein, as well as show better in-vitro results when compared to our selected gefitinib medication. MTT assay, gene expression analysis (BAX, BCL-2, and β-catenin), apoptosis analysis, TEM, cell cycle assay, ELISA, and cell migration assays were conducted to perform the cell death analysis of lung cancer and breast cancer, compared to the marketed product. The MTT assay exhibited 80% cell death for 75 µM and 100µM; however, flow cytometry analysis with the IC50 value demonstrated that the selected compound induced higher apoptosis in MCF-7 (30.8%) than in A549.