bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type II alveolar epithelial cell aryl hydrocarbon receptor protects against allergic airway inflammation through controlling cell autophagy
Authors: Wang Ji , Zhao Yilin , Zhang Xin , Tu Wei , Wan Rongjun , Shen Yingchun , Zhang Yan , Trivedi Ruchik , Gao Peisong 
Published: July 2022

RationaleAryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, has been considered as an important regulator for immune diseases. We have previously shown that AhR protects against allergic airway inflammation. The underlying mechanism, however, remains undetermined.ObjectivesWe sought to determine whether AhR specifically in type II alveolar epithelial cells (AT2) modulates allergic airway inflammation and its underlying mechanisms.MethodsThe role of AhR in AT2 cells in airway inflammation was investigated in a mouse model of asthma with AhR conditional knockout mice in AT2 cells (Sftpc-Cre;AhRf/f). The effect of AhR on allergen-induced autophagy was examined by both in vivo and in vitro analyses. The involvement of autophagy in airway inflammation was analyzed by using autophagy inhibitor chloroquine. The AhR-regulated gene profiling in AT2 cells was also investigated by RNA sequencing (RNA-seq) analysis.ResultsSftpc-Cre;AhRf/f mice showed exacerbation of allergen-induced airway hyperresponsiveness and airway inflammation with elevated Th2 cytokines in bronchoalveolar lavage fluid (BALF). Notably, an increased allergen-induced autophagy was observed in the lung tissues of Sftpc-Cre;AhRf/f mice when compared with wild-type mice. Further analyses suggested a functional axis of AhR-TGF-β1 that is critical in driving allergic airway inflammation through regulating allergen-induced cellular autophagy. Furthermore, inhibition of autophagy with autophagy inhibitor chloroquine significantly suppressed cockroach allergen–induced airway inflammation, Th2 cytokines in BALFs, and expression of autophagy-related genes LC3 and Atg5 in the lung tissues. In addition, RNA-seq analysis suggests that autophagy is one of the major pathways and that CALCOCO2/NDP52 and S1009 are major autophagy-associated genes in AT2 cells that may contribute to the AhR-mediated cockroach allergen–induced airway inflammation and, subsequently, allergic asthma.ConclusionThese results suggest that AhR in AT2 cells functions as a protective mechanism against allergic airway inflammation through controlling cell autophagy.
Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV)
Authors: Pi Linhua , Lin Jian , Zheng Ying , Wang Zhen , Zhou Zhiguang 
Published: July 2022

BackgroundSubacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis.Case presentationWe report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement.ConclusionsInactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.
Effects of remote ischemic conditioning on sleep complaints in Parkinson's disease–rationale, design, and protocol for a randomized controlled study
Authors: Ji Qiling , Wang Xuemei , Zhao Wenbo , Wills Melissa , Yun Ho Jun , Tong Yanna , Cai Lipeng , Geng Xiaokun , Ding Yuchuan 
Published: July 2022

ObjectiveSleep disturbances are common non-motor symptoms of Parkinson's disease. The symptoms affect the quality of patients' life by impeding normal sleep cycles and causing excessive daytime sleepiness. Remote Ischemic Conditioning (RIC) is a therapy often used for ischemic stroke patients to minimize infarct size and maximize post-stroke neurological function. Animal experiments have shown that RIC plays a protective role for retinal ganglion cells and other critical areas of the brain of Parkinson's disease. However, whether RIC improves excessive daytime sleepiness (EDS) for patients with Parkinson's disease remains to be determined.MethodsThis is a single-center, double-blind, and randomized controlled trial, which includes patients with Parkinson's disease with EDS. All recruited patients will be randomly assigned either to the RIC or the control group (i.e., sham-RIC) with 20 patients in each group. Both groups receive RIC or sham-RIC treatment once a day for 28 days within 24 h of enrollment. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Questionnaire39 (PDQ39) score scales, and adverse events, such as inability to tolerate the treatment leading to suspension of the study or objective signs of tissue or neurovascular injury caused by RIC and/or sham-RIC are evaluated at 7, 14, 28, and 90 days after enrollment.ResultsThe primary goal of this study is to assess the feasibility of the treatments in patients with Parkinson's disease by measuring serious RIC-related adverse events and any reduced incidence of adverse events during the trial and to study potential efficacy, improvement of patients' excessive daytime sleepiness, quality of life-based on ESS, PSQI, PDSS-2, and PDQ39 scores. The secondary goal is to confirm the safety of the treatments.ConclusionThis study is a prospective randomized controlled trial to determine the safety, feasibility, and potential efficacy of RIC for patients with Parkinson's disease associated with EDS.
An MRI-based pelvimetry nomogram for predicting surgical difficulty of transabdominal resection in patients with middle and low rectal cancer
Authors: Yuan Yuan , Tong Dafeng , Liu Minglu , Lu Haidi , Shen Fu , Shi Xiaohui 
Published: July 2022

ObjectiveThe current work aimed to develop a nomogram comprised of MRI-based pelvimetry and clinical factors for predicting the difficulty of rectal surgery for middle and low rectal cancer (RC).MethodsConsecutive mid to low RC cases who underwent transabdominal resection between June 2020 and August 2021 were retrospectively enrolled. Univariable and multivariable logistic regression analyses were carried out for identifying factors (clinical factors and MRI-based pelvimetry parameters) independently associated with the difficulty level of rectal surgery. A nomogram model was established with the selected parameters for predicting the probability of high surgical difficulty. The predictive ability of the nomogram model was assessed by the receiver operating characteristic (ROC) curve and decision curve analysis (DCA).ResultsA total of 122 cases were included. BMI (OR = 1.269, p = 0.006), pelvic inlet (OR = 1.057, p = 0.024) and intertuberous distance (OR = 0.938, p = 0.001) independently predicted surgical difficulty level in multivariate logistic regression analysis. The nomogram model combining these predictors had an area under the ROC curve (AUC) of 0.801 (95% CI: 0.719–0.868) for the prediction of a high level of surgical difficulty. The DCA suggested that using the nomogram to predict surgical difficulty provided a clinical benefit.ConclusionsThe nomogram model is feasible for predicting the difficulty level of rectal surgery, utilizing MRI-based pelvimetry parameters and clinical factors in mid to low RC cases.
The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer
Authors: Meng Silu , Liu Yuhuan , Wang Xiaoyan , Wu Xue , Xie Wan , Kang Xiaoyan , Liu Xiaoyu , Guo Lili , Wang Changyu 
Published: July 2022

ObjectiveTo evaluate the prognostic value and explore the biological significance of gap junction protein beta 2 (GJB2 or Cx26) in cervical cancer (CC).MethodsWe first compared GJB2 expression between CC and normal tissues using public databases and immunohistochemistry (IHC). Based on The Cancer Genome Atlas data (TCGA cohort, n = 304) and tissue microarray samples (OBC cohort, n = 111), we explored the prognostic value of GJB2 for CC patients using bioinformatics analysis and IHC scoring. To explore the biological significance of GJB2, Gene set enrichment analysis (GSEA) and Gene Ontology (GO) were performed. The impact of GJB2 on the immune microenvironment was analyzed by CIBERSORTx and ESTIMATE algorithms. We finally investigated the relationship between GJB2 and drug sensitivity based on the Genomics of Drug Sensitivity in Cancer (GDSC).ResultsThe expression of GJB2 was significantly increased in CC over normal tissues. Both the TCGA and OBC cohort found that patients with high GJB2 expression had shorter overall survival (OS) time, and high GJB2 expression was the independent risk factor for prognosis (TCGA: HR, 2.566; 95% CI, 1.066–6.180; p = 0.036; OBC: HR, 2.198; 95% CI, 1.019–4.741; p = 0.045). GJB2 was correlated with patient clinical factors such as tumor size and differentiation grade. The p53 signaling pathway and toll-like receptor pathway may be regulated by GJB2. The abundance of various immune cells was significantly different between the low and high GJB2 expression groups. The ImmuneScore was significantly increased in the high GJB2 expression group. In addition, the expression level of GJB2 was positively correlated with the natural log of the half-maximal inhibitory concentration (LN_IC50) value of cisplatin/paclitaxel (Spearman r = 0.238/0.153, p &lt; 0.001).ConclusionGJB2 can serve as a potential prognostic marker of poor survival and a therapeutic target in CC. Moreover, GJB2 may affect the immune microenvironment and is correlated with chemoresistance.
Case Report: Sustained complete remission on combination therapy with olaparib and pembrolizumab in BRCA2-mutated and PD-L1-positive metastatic cholangiocarcinoma after platinum derivate
Authors: Zhou Taotao , Mahn Robert , Möhring Christian , Sadeghlar Farsaneh , Meyer Carsten , Toma Marieta , Kreppel Barbara , Essler Markus , Glowka Tim , Matthaei Hanno , Kalff Jörg C. , Strassburg Christian P. , Gonzalez-Carmona Maria A. 
Published: July 2022

Cholangiocarcinoma (CCA) still has a poor prognosis and remains a major therapeutic challenge. When curative resection is not possible, palliative systemic chemotherapy with gemcitabine and platinum derivate as first line followed by a 5-FU doublet combination as second line is the standard therapy. Recently, targeted therapy and immunotherapy have rapidly emerged as personalized therapeutic approaches requiring previous tumor sequencing and molecular profiling. BRCA mutations are well-characterized targets for poly (ADP-ribose) polymerase inhibitors (PARPi). However, BRCA gene mutations in CCA are rare and few data of PARPi in the treatment of CCA are available. Immunotherapy with programmed death receptor-1 (PD-1) has been shown to be effective in combination with chemotherapy or in PD-L1-positive CCA. However, data from immunotherapy combined with targeted therapy, including PARPi, are lacking. In this report, we present the case of a male patient with PD-L1-positive and BRCA2-mutated metastatic intrahepatic cholangiocarcinoma, who was treated with a combined therapy with PARP (PARPi), olaparib, and a PD-1 antibody, pembrolizumab, as second-line therapy after gemcitabine/platinum derivate failure. Combined therapy was able to induce a long-lasting complete remission for over 15 months. The combined therapy was feasible and well tolerated. Only mild anemia and immune-related thyroiditis were observed, which were easily manageable and did not result in discontinuation of olaparib and pembrolizumab.ConclusionThe presented case showed substantial clinical activity of a combination with olaparib/pembrolizumab in advanced BRCA2-mutated CCA. Thus, identifying targetable molecular signatures and combinations of targeted therapies with immunotherapy reveals a promising strategy to effectively treat patients with cholangiocarcinoma and should be considered after failure of standard chemotherapy.
A mobile health + health coaching application for the management of chronic non-cancer pain in older adults: Results from a pilot randomized controlled study
Authors: Kaul Usha , Scher Clara , Henderson Charles R. , Kim Patricia , Dyhrberg Mette , Rudin Vanessa , Lytle Millie , Bundy Nicole , Reid M. Carrington 
Published: July 2022

IntroductionThe rapid growth of mobile health (mHealth) devices holds substantial potential for improving care and care outcomes in aging adults with chronic non-cancer pain (CNCP), however, research evaluating these devices in older adults remains limited.ObjectiveTo ascertain the feasibility and preliminary efficacy of an mHealth intervention (Mymee) that combines symptom, diet, and behavior tracking via a smartphone application with data analytics to detect associations between symptoms and lifestyle factors along with weekly health coaching sessions to mitigate CNCP in adults 55 years of age and older.MethodsParticipants (N = 31) in this pilot study were recruited from one primary care practice in New York City and randomized to an intervention [app + up to 12 health coaching sessions (scheduled approximately once weekly) + usual care] or a control (app + usual care) arm. Feasibility measures included recruitment (proportion of eligible persons who enrolled) and retention rates (proportion of subjects completing a follow-up assessment) as well as adherence with the weekly coaching sessions and logging daily data on the app. Efficacy outcomes (e.g., pain intensity, self-efficacy, disability, anxiety) were assessed at baseline and follow-up (~16 weeks after baseline). Descriptive statistics were obtained and general linear mixed models used for primary analyses.ResultsParticipants had a mean (standard deviation) age of 67.32 (9.17) and were mostly female (61%). Feasibility outcomes were mixed as evidenced by recruitment and retention rates of 74% and 65%, respectively. The mean number of weekly coaching sessions attended by intervention participants was 6.05 (SD = 5.35), while the average number of days logging data on the app was 44.82 (34.02). We found a consistent trend in favor of the intervention, where pain intensity, affect, and quality of life measures improved considerably more among intervention (vs. control) participants. Finally, the proportion of participants with GAD-7 scores at follow up decreased by 0.35 to 0, whereas controls did not change, a significant effect in favor of the intervention (p = 0.02).ConclusionsThis study supports the need for future research that seeks to enhance feasibility outcomes and confirm the efficacy of the Mymee intervention among aging adults with CNCP.
Efficacy and safety of 12 immunosuppressive agents for idiopathic membranous nephropathy in adults: A pairwise and network meta-analysis
Authors: Liu Jiarong , Li Xiang , Huang Tianlun , Xu Gaosi 
Published: July 2022

Background: Immunosuppressants have been applied in the remedy of idiopathic membranous nephropathy (IMN) extensively. Nevertheless, the efficacy and safety of immunosuppressants do not have final conclusion. Thus, a pairwise and network meta-analysis (NMA) was carried out to seek the most recommended therapeutic schedule for patients with IMN.Methods: Randomized controlled trials (RCTs) including cyclophosphamide (CTX), mycophenolate mofetil (MMF), tacrolimus-combined mycophenolate mofetil (TAC + MMF), cyclosporine (CsA), tacrolimus (TAC), leflunomide (LEF), chlorambucil (CH), azathioprine (AZA), adrenocorticotropic hormone (ACTH), non-immunosuppressive therapies (CON), steroids (STE), mizoribine (MZB), and rituximab (RIT) for patients with IMN were checked. Risk ratios (RRs) and standard mean difference (SMD) were reckoned to assess dichotomous variable quantities and continuous variable quantities, respectively. Total remission (TR) and 24-h urine total protein (24-h UTP) were compared using pairwise and NMA. Then interventions were ranked on the basis of the surface under the cumulative ranking curve (SUCRA).Results: Our study finally included 51 RCTs and 12 different immunosuppressants. Compared with the CON group, most regimens demonstrated better therapeutic effect in TR, with RR of 2.1 (95% CI) (1.5–2.9) for TAC, 1.9 (1.3–2.8) for RIT, 2.5 (1.2–5.2) for TAC + MMF, 1.9 (1.4–2.7) for CH, 1.8 (1.4–2.4) for CTX, 2.2 (1.0–4.7) for ACTH, 1.6 (1.2–2.1) for CsA, 1.6 (1.0–2.5) for LEF, and 1.6 (1.1–2.2) for MMF. In terms of 24-h UTP, TAC (SMD, −2.3 (95% CI −3.5 to −1.1)), CTX (SMD, −1.7 (95% CI −2.8 to −0.59)), RIT (SMD, −1.8 (95% CI −3.5 to −0.11)), CH (SMD, −2.4 (95% CI −4.3 to −0.49)), AZA (SMD, −−4.2 (95% CI −7.7 to −0.68)), and CsA (SMD, −1.7 (95% CI −3 to −0.49)) were significantly superior than the CON group. As for adverse effects (AEs), infections, nausea, emesia, myelosuppression, and glucose intolerance were the collective adverse events for most immunosuppressants.Conclusion: This study indicates that TAC + MMF performed the best in terms of TR, and TAC shows the best effectiveness on 24-h UTP compared with other regimens. On the contrary, there seems to be little advantage on STE alone, LEF, AZA, and MZB in treating patients with IMN compared with CON.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021287013]
Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons
Authors: Alsanie Walaa F. , Abdelrahman Sherin , Alhomrani Majid , Gaber Ahmed , Habeeballah Hamza , Alkhatabi Heba A. , Felimban Raed I. , Hauser Charlotte A. E. , Tayeb Hossam H. , Alamri Abdulhakeem S. , Raafat Bassem M. , Anwar Sirajudheen , Alswat Khaled A. , Althobaiti Yusuf S. , Asiri Yousif A. 
Published: July 2022

Background: Gabapentin is widely prescribed as an off-label drug for the treatment of various diseases, including drug and alcohol addiction. Approximately 83–95% of the usage of gabapentin is off-label, accounting for more than 90% of its sales in the market, which indicates an alarming situation of drug abuse. Such misuse of gabapentin has serious negative consequences. The safety of the use of gabapentin in pregnant women has always been a serious issue, as gabapentin can cross placental barriers. The impact of gabapentin on brain development in the fetus is not sufficiently investigated, which poses difficulties in clinical decisions regarding prescriptions.Methods: The consequences effect of prenatal gabapentin exposure on the development of ventral midbrain dopaminergic neurons were investigated using three-dimensional neuronal cell cultures. Time-mated Swiss mice were used to isolate embryos. The ventral third of the midbrain was removed and used to enrich the dopaminergic population in 3D cell cultures that were subsequently exposed to gabapentin. The effects of gabapentin on the viability, ATP release, morphogenesis and genes expression of ventral midbrain dopaminergic neurons were investigated.Results: Gabapentin treatment at the therapeutic level interfered with the neurogenesis and morphogenesis of vmDA neurons in the fetal brain by causing changes in morphology and alterations in the expression of key developmental genes, such as Nurr1, Chl1, En1, Bdnf, Drd2, and Pitx3. The TH + total neurite length and dominant neurite length were significantly altered. We also found that gabapentin could halt the metabolic state of these neuronal cells by blocking the generation of ATP.Conclusion: Our findings clearly indicate that gabapentin hampers the morphogenesis and development of dopaminergic neurons. This implies that the use of gabapentin could lead to serious complications in child-bearing women. Therefore, caution must be exercised in clinical decisions regarding the prescription of gabapentin in pregnant women.
Brucea javanica Oil Emulsion Promotes Autophagy in Ovarian Cancer Cells Through the miR-8485/LAMTOR3/mTOR/ATG13 Signaling Axis
Authors: Wang Yihan , Chen Bocen , Xiao Man , Wang Xiaoli , Peng Yunhua 
Published: July 2022

Background: Ovarian cancer is a common malignant tumor of the female reproductive tract, with the highest mortality rate. At present, no effective approaches to improve the survival rate exist. B. javanica Oil Emulsion (BJOE), an extract from B. javanica (L.) Merr. [Simaroubaceae], exhibits antitumor effects and can increase the sensitivity of radiotherapy and chemotherapy in many types of cancers. MiR-8485, a discovered miRNA, has been shown to be involved in the occurrence and development of tumors. The purpose of this study was to investigate the effect of BJOE on the regulation of mammalian rapamycin target protein (mTOR) autophagy signal pathway and related autophagy factors on ovarian cancer cells through miR-8485.Methods: The main chemical constituents of BJOE were determined by UHPLC-MS/MS. Detection of miR-8485 expression in ovarian cancer cells treated with BJOE by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK8 experiment and flow cytometry were used to observe the effects of BJOE and overexpression of miR-8485 on cell proliferation and apoptosis. Then, monodansylcadaverine (MDC) fluorescence staining was used to observe the changes of autophagy vesicles before and after the effect of BJOE and overexpressed miR-8485 on cancer cells. Next, the binding sites between miR8485 and mammalian rapamycin target protein activator 3 (LAMTOR3) were detected by double luciferase reporter assay. Furthermore, qRT-PCR and Western blot experiments were used to explore the changes of autophagy-related factors LAMTOR3, mTOR and autophagy-related 13 (ATG13), and microtubule associated protein 1 light chain 3 beta (LC3-Ⅱ) after BJOE and overexpression of miR-8485, in addition to autophagy inhibitor (3-MA) for rescue experiment verification.Results: The qRT-PCR results showed that the expression of miR-8485 increased after BJOE treatment in the SKOV3 cell. The CCK8 assay and flow cytometry analysis revealed that both BJOE and miR-8485 overexpression inhibited the proliferation and promoted the apoptosis of the SKOV3 cell. MDC fluorescence staining showed that BJOE and miR-8485 overexpression led to a significant increase in autophagy vesicles in the SKOV3 cell. Double luciferase reporter assay confirmed the existence of binding sites between miR8485 and LAMTOR3. The results of qRT-PCR and Western blot showed that BJOE and overexpressed miR-8485 downregulated the expression of LAMTOR3 and mTOR and up-regulated the expression of ATG13 and LC3-Ⅱ.Conclusion: 1) MiR-8485 may be the key factor of BJOE in promoting autophagy and apoptosis and inhibiting cell proliferation of ovarian cancer cells; 2) BJOE may play an antitumor role by regulating LAMTOR3/mTOR/ATG13 signaling axis through miR-8485 to promote autophagy in ovarian cancer cells.