bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sevoflurane Aggravates the Progress of Alzheimer’s Disease Through NLRP3/Caspase-1/Gasdermin D Pathway
Authors: Tian Di , Xing Yanmei , Gao Wenli , Zhang Hongyan , Song Yifeng , Tian Ya , Dai Zhongliang 
Published: January 2022

Background: Alzheimer’s disease (AD) is the most common form of dementia worldwide. Previous studies have reported that sevoflurane, a frequently used anesthetic, can induce cognitive impairment in preclinical and clinical settings. However, the mechanism underlying the development of this neurotoxicity is currently unclear.Methods: Seven-month-old APP/PS1 mice were placed in an anesthesia induction box containing 3% sevoflurane in 100% O2 for 6 h, while BV2 cells were cultured with 4% sevoflurane for 6 h. Pyroptosis and tau protein expression in excised hippocampus tissues and cells were measured using Western blotting and immunofluorescence assay. Caspase-1 and NLRP3 were knocked out in BV2 microglia using CRISPR/Cas9 technology to determine whether they mediate the effects induced by sevoflurane.Results: Sevoflurane directly activated caspase-1 to induce pyroptosis in the mouse model of AD via NLRP3 and AIM2 activation. In addition, sevoflurane mediated cleavage of gasdermin D (GSDMD) but not gasdermin E (GSDME), promoted the biosynthesis of downstream interleukin-1β and interleukin-18, and increased β-amyloid (Aβ) deposition and tau phosphorylation. The nontoxic caspase-1 small-molecule inhibitor VX-765 significantly inhibited this activation process in microglia, while NLRP3 deletion suppressed sevoflurane-induced caspase-1 cleavage and subsequently pyroptosis, as well as tau pathology. Furthermore, silencing caspase-1 alleviated the sevoflurane-induced release of IL-1β and IL-18 and inhibited tau-related enzymes in microglia.Conclusion: This study is the first to report that clinical doses of sevoflurane aggravate the progression of AD via the NLRP3/caspase-1/GSDMD axis. Collectively, our findings elucidate the crucial mechanisms of NLRP3/caspase-1 in pyroptosis and tau pathogenesis induced by sevoflurane and suggest that VX-765 could represent a novel therapeutic intervention for treating AD.
The Alkali-Tolerant Bacterium of Bacillus thuringiensis EM-A1 Can Effectively Perform Heterotrophic Nitrification and Aerobic Denitrification
Authors: Wang Tingjiang , Chen Mengping , Liang Xiwen , Chen Fali , He Tengxia , Li Zhu 
Published: January 2022

Removal of nitrogen from hydroxylamine could effectively improve the wastewater treatment efficiency. In this work, Bacillus thuringiensis EM-A1 was obtained from a biogas digester with hydroxylamine as the only nitrogen source. Hydroxylamine (100%) and total nitrogen (71.86%) were efficiently removed under the following conditions: 30°C, sucrose as carbon source, carbon to nitrogen ratio 40, rotation speed 150 rpm, pH 9.58, and inoculant concentration of 0.58×108 colony-forming units. Ammonium was completely consumed by strain EM-A1, and 8.32 ± 0.08 mg/L of nitrate was produced during the ammonium removal process. During aerobic denitrification, the removal efficiencies of NO2−-N and NO3−-N by strain EM-A1 were 100 and 76.67%, respectively. There were about 29.34 ± 0.18%, 26.71 ± 0.36%, and 23.72 ± 0.88% initial total nitrogen lost as nitrogenous gas when NH4+, NO3−, and NO2− were separately used as the sole nitrogen source. The specific activities of ammonia monooxygenase, hydroxylamine oxidoreductase, nitrate reductase, and nitrite oxidoreductase were successfully detected as 0.37, 0.88, 0.45, and 0.70 U/mg protein, respectively. These results indicated that B. thuringiensis EM-A1 is a promising candidate for bioremediation of inorganic nitrogen from wastewater.
Clinical Characteristics and Genetic Analysis of a Family With Birt-Hogg-Dubé Syndrome and Congenital Contractural Arachnodactyly
Authors: Qiu Jiayong , Lou Yao , Zhu Yingwei , Wang Min , Peng Huifang , Hao Yingying , Jiang Hongwei , Mao Yimin 
Published: January 2022

Background: Birt-Hogg-Dubé (BHD) syndrome and congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome are clinically rare autosomal dominant genetic diseases. In this study, we describe an extremely rare family with BHD syndrome and CCA.Objective: To investigate the clinical and genetic characteristics of a family with BHD syndrome and CCA.Methods: We describe the clinical characteristics, family history, and clinical manifestations of the patient’s family members. The patient underwent a blood test, computed tomography (CT) of the chest, color Doppler ultrasound of the abdomen and heart, and digital radiography of the hands. Whole exome sequencing was performed on his family members.Results: Two years ago, the male proband developed chest tightness and shortness of breath that was accompanied by an irritating cough as well as repeated (four times) spontaneous pneumothorax. The chest CT indicated spontaneous pneumothorax on the right side and cyst and bullae in both lungs. He had no kidney tumors or skin lesions. His son had a history of pulmonary bullae and experienced spontaneous pneumothorax twice. The proband, his mother, and his son were all born with a hand deformity. The sequencing results demonstrated that both the proband and his son had heterozygous variations of the folliculin (FLCN) gene c.1015C &gt; T (p. Gln339Ter) and fibrillin-2 (FBN2) gene c.3485G &gt; A (p. Cys1162Tyr), which are associated with BHD syndrome and CCA, respectively.Conclusion: For patients with chest tightness, shortness of breath, recurrent spontaneous pneumothorax, and congenital hand deformity without inducement, genetic testing should be carried out as soon as possible to make a clear diagnosis, which can then guide treatment and genetic counseling.
Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2
Authors: Markewitz Robert , Juhl David , Pauli Daniela , Görg Siegfried , Junker Ralf , Rupp Jan , Engel Sarah , Steinhagen Katja , Herbst Victor , Zapf Dorinja , Krüger Christina , Brockmann Christian , Leypoldt Frank , Dargvainiene Justina , Schomburg Benjamin , Sharifzadeh Shahpour , Nejad Lukas Salek , Wandinger Klaus-Peter , Ziemann Malte 
Published: January 2022

BackgroundHeterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses.MethodsWe performed assays for anti-S1 IgG and IgA, anti-NCP IgG and a surrogate neutralization assay on serum samples collected from 57 participants on the day of the second vaccination as well as the following seven days.ResultsAll examined vaccination regimens induced detectable antibody responses within the examined time frame. Both heterologous regimens induced responses earlier and with a higher amplitude than homologous ChAdOx1 nCoV-19. Between the heterologous regimens, amplitudes were somewhat higher for ChAdOx1 nCoV-19 + mRNA-1273. There was no difference in latency between the IgG and IgA responses. Increases in the surrogate neutralization assay were the first changes to be detectable for all regimens and the only significant change seen for homologous ChAdOx1 nCoV-19.DiscussionBoth examined heterologous vaccination regimens are superior in immunogenicity, including the latency of the response, to homologous ChAdOx1 nCoV-19. While the IgA response has a shorter latency than the IgG response after the first dose, no such difference was found after the second dose, implying that both responses are driven by separate plasma cell populations. Early and steep increases in surrogate neutralization levels suggest that this might be a more sensitive marker for antibody responses after vaccination against SARS-CoV-2 than absolute levels of anti-S1 IgG.
Adherence to the Mediterranean Diet and Its Association With Sleep Quality and Chronotype Among Youth: A Cross-Sectional Study
Authors: Naja Farah , Hasan Hayder , Khadem Safiya Hassan , Buanq Maryam Ahmed , Al-Mulla Haya Khalid , Aljassmi Aysha Khalifa , Faris MoezAlIslam Ezzat 
Published: January 2022

BackgroundEvidence indicates that many university students have poor adherence to a healthy diet accompanied by unhealthy lifestyle behaviors. Chrono-nutrition is an emerging field of research that examines the pattern of optimum daily activity in relation to the human's dietary patterns, and their reflections of variable health indicators such as sleep quality. However, there is a scarcity of research that examines the relationship between adherence to the healthy eating pattern, like the Mediterranean diet (MD), with sleep quality and chronotype among university students.MethodsA cross-sectional study was conducted, and convenience sampling was used. Participants were assessed for adherence to the MD using the Mediterranean Diet Quality Index (KIDMED), for sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and for chronotype using the Morningness-Eveningness questionnaire (MEQ).ResultsThe study included 503 university students, most of them (81.5%) were females. Only 15.1 and 16.9% reported morningness chronotype and good sleep quality, respectively. About half of the students showed medium and high adherence to the KIMED. In-depth analysis revealed that students with good adherence to the MD were more likely to have a good sleep quality (OR = 0.35; 95%CI: 0.21–0.59; P &lt; 0.001) even after adjustment for age and sex (OR = 0.36; 95%CI: 0.21–0.62; P &lt; 0.001). The regression analysis also showed that those with good adherence to the MD had a significant association with better subjective sleep quality, less sleep latency, sleep disturbance, and daytime dysfunction even after adjustment for age and sex. Those with morningness chronotype had about a six-fold higher chance to have good adherence to the MD (OR = 5.67; 95%CI: 2.86–11.26; P &lt; 0.001, respectively).ConclusionsGood adherence to the healthy diet presented in the MD among university students is associated with morningness chronotype and with improved overall sleep quality and sleep components. Long-term, controlled intervention research works are warranted for more elaboration on the impact of chronotype and dietary habits on sleep quality and other important aspects such as mental health and academic achievement.
Establishing a Predictive Nomogram for Cervical Lymph Node Metastasis in Patients With Papillary Thyroid Carcinoma
Authors: Hu Qiao , Zhang Wang-Jian , Liang Li , Li Ling-Ling , Yin Wu , Su Quan-Li , Lin Fei-Fei 
Published: January 2022

ObjectivesThe purpose of this study was to establish a nomogram for predicting cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC).Materials and MethodsA total of 418 patients with papillary thyroid carcinoma undergoing total thyroidectomy with cervical lymph node dissection were enrolled in the retrospective study from January 2016 to September 2019. Univariate and multivariate Logistic regression analysis were performed to screen the clinicopathologic, laboratory and ultrasound (US) parameters influencing cervical lymph nodes metastasis and develop the predicting model.ResultsCLNM was proved in 34.4% (144/418) of patients. In the multivariate regression analysis, Male, Age &lt; 45 years, Tumor size &gt; 20mm, multifocality, ambiguous boundary, extracapsular invasion and US-suggested lymph nodes metastasis were independent risk factors of CLNM (p &lt; 0.05). Prediction nomogram showed an excellent discriminative ability, with a C-index of 0.940 (95% confidence interval [CI], 0.888-0.991), and a good calibration.ConclusionThe established nomogram showed a good prediction of CLNM in patients with PTC. It is conveniently used and should be considered in the determination of surgical procedures.
Primary Thyroid NUT Carcinoma With High PD-L1 Expression and Novel Massive IGKV Gene Fusions: A Case Report With Treatment Implications and Literature Review
Authors: Zhou Juan , Duan Miao , Jiao Qiong , Chen Chunyan , Xing Aiyan , Su Peng , Tang Juan , Zhang Hui , Liu Zhiyan 
Published: January 2022

BackgroundNuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a NUT gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma.MethodUltrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence in situ hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC.ResultsWe describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the NUT gene on chromosome 15q14. The NGS results revealed a BRD4-NUT gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of NUTM1 occurred in the exon region, and the mutation site was 15q14. Moreover, BRD4 single-nucleotide variation (SNV) occurs in the 3′ UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery.ConclusionThyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of IGKV gene fusions in addition to the BRD4-NUT fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.
Predictive Effect of Systemic Immune-Inflammation Index Combined With Prognostic Nutrition Index Score on Efficacy and Prognosis of Neoadjuvant Intraperitoneal and Systemic Paclitaxel Combined With Apatinib Conversion Therapy in Gastric Cancer Patients With Positive Peritoneal Lavage Cytology: A Prospective Study
Authors: Ding Ping’an , Yang Peigang , Sun Chenyu , Tian Yuan , Guo Honghai , Liu Yang , Li Yong , Zhao Qun 
Published: January 2022

BackgroundGastric cancer with only peritoneal lavage cytology (GC-CY1) is a special type of gastric cancer, which is defined as stage IV. The pre-treatment systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) are representative blood indexes of systemic inflammatory response and nutritional status. However, the clinical significance of combined detection of these two indexes is still unclear. This study aims to evaluate the clinical value of the new score system by combining SII and PNI (SII-PNI score) as a predictor of efficacy and prognosis after neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel combined with Apatinib conversion therapy for GC-CY1 patients.MethodsWe registered a prospective clinical study involving 36 GC-CY1 patients from April 2018 to August 2019 (NCT03718624). All patients underwent re-laparoscopic exploration after treatment. According to free cancer cells (FCCs) status, these patients were divided into FCCs group and non-FCCs group. The SII-PNI score ranged from 0 to 2 as follows: score of 2, high SII (≥512.1) and low PNI (≤52.9); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI.ResultsAll patients underwent re-laparoscopic exploration after 3 cycles of NIPS paclitaxel and Apatinib conversion therapy. Among them, 28 cases (77.78%) were in non-FCCs group, and 8 cases (22.22%) were in FCCs group. The SII-PNI score of non-FCCs patients was significantly lower than that of FCCs patients (p=0.041). The prognosis of patients with high SII-PNI score was significantly worse than that of patients with low SII-PNI score (p&lt;0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting overall survival and progression-free survival (p=0.001, 0.002).ConclusionPretreatment SII-PNI score is an important predictor for the efficacy of GC-CY1 patients after NIPS paclitaxel combined with Apatinib conversion therapy, which can help to identify high-risk groups and predict prognosis.
Treatment Interruptions During Stereotactic Body Radiotherapy for Prostate Cancer
Authors: Pepin Abigail N. , Zwart Alan , Danner Malika , Ayoob Marylin , Yung Thomas , Collins Brian T. , Kumar Deepak , Suy Simeng , Aghdam Nima , Collins Sean P. 
Published: January 2022

BackgroundDuring the course of radiation treatment for prostate cancer, patients may have unintentional interruptions in their treatment course due to a wide variety of factors. Stereotactic body radiation therapy (SBRT) decreases the number of treatments compared to conventionally fractionated radiation; hence, it has the potential to decrease treatment delays and non-completion. This study sought to determine the incidence of treatment delay and characterize the etiology and length in a large cohort of men treated with SBRT for their prostate cancer.MethodsOne thousand three hundred and thirty-six patients treated with SBRT from 2008 to 2021 at the Georgetown University Hospital for prostate cancer were included in this retrospective study. A treatment delay was defined as a patient requiring longer than 14 days to complete 5 fractions of SBRT. Non-completion was defined as patients treated with less than 5 fractions. In the patients who experienced delays, chart review was performed to characterize the length and etiology of each delay. Multivariate analysis was performed via binary logistic regression modeling on PSPP.ResultsAll individuals in the cohort eventually completed the planned 5-fraction regimen. Thirty-three patients experienced a treatment delay. Median length of time to complete treatment was 11 days (range 5–155 days). In patients who experienced a delay, nearly half (45.5%) experienced only a one-day delay. The most common reason for a delay was a technical issue (48.5%), including the machine maintenance, fiducial misalignment, or inadequate pretreatment bowel preparation. Other reasons included unplanned breaks due to acute side effects (21.2%), logistical issues (18.2%), non-treatment related health issues (9.1%), and inclement weather (3.0%). There were no significant sociodemographic, oncologic, or treatment variables that predicted treatment interruption on multivariate analysis.ConclusionsThe incidence of treatment interruptions in patients undergoing SBRT for their prostate cancer was low. Most treatment delays were short.
Physiologically Based Pharmacokinetic Modeling in Pregnant Women Suggests Minor Decrease in Maternal Exposure to Olanzapine
Authors: Zheng Liang , Yang Hongyi , Dallmann André , Jiang Xuehua , Wang Ling , Hu Wei 
Published: January 2022

Pregnancy is accompanied by significant physiological changes that might affect the in vivo drug disposition. Olanzapine is prescribed to pregnant women with schizophrenia, while its pharmacokinetics during pregnancy remains unclear. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model of olanzapine in the pregnant population. With the contributions of each clearance pathway determined beforehand, a full PBPK model was developed and validated in the non-pregnant population. This model was then extrapolated to predict steady-state pharmacokinetics in the three trimesters of pregnancy by introducing gestation-related alterations. The model adequately simulated the reported time-concentration curves. The geometric mean fold error of Cmax and AUC was 1.14 and 1.09, respectively. The model predicted that under 10 mg daily dose, the systematic exposure of olanzapine had minor changes (less than 28%) throughout pregnancy. We proposed that the reduction in cytochrome P4501A2 activity is counteracted by the induction of other enzymes, especially glucuronyltransferase1A4. In conclusion, the PBPK model simulations suggest that, at least at the tested stages of pregnancy, dose adjustment of olanzapine can hardly be recommended for pregnant women if effective treatment was achieved before the onset of pregnancy and if fetal toxicity can be ruled out.
Social Media for Health Campaign and Solidarity Among Chinese Fandom Publics During the COVID-19 Pandemic
Authors: Jiang Qiaolei , Liu Shiyu , Hu Yue , Xu Jing 
Published: January 2022

Background:As a highly contagious disease, the COVID-19 pandemic has become a serious health threat and psychological burden for the global communities. From the conceptual perspective of affordances, this research examined the role of social media for health campaign and psychological support during the global crisis.Methods:Data from both social media and a nationwide survey were collected and analyzed. Face mask-related posts on Sina Weibo from January 1, 2020, to June 30, 2020, were retrieved and studied. Face mask wearing as a well-established preventive measure was identified and examined from hashtag topics. A nationwide survey with a randomized experiment embedded was conducted to further investigate the mobilizing dynamics.Results:During the escalation phase in the first half of 2020, the hashtag topic “#national mask campaign#,” initiated by a celebrity, topped the ranking of mask-related topics on Weibo. The findings indicated that prevention activities, solidarity expression, and names of celebrity idols were frequently discussed. With celebrity idols as opinion leaders, millions of fandom publics actively participated in this hashtag health campaign. Results of the nationwide survey show the popularity of fan identity, and the experiment results demonstrate the strong mobilizing power of celebrity idol and fandom community in civic engagement and participation among young Chinese.Conclusions:The research demonstrates how the affordances of social media, such as liking, commenting, reposting, and hashtagging can be influential in promoting health behaviors and expressing solidarity. Implications for public health professionals and policymakers to raise awareness and understanding about health campaignsviasocial media are discussed.