bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Biological Characteristics at the Peak of Cell Death in Different Hereditary Retinal Degeneration Mutants
Authors: Wei Chunling , Li Yan , Feng Xiaoxiao , Hu Zhulin , Paquet-Durand François , Jiao Kangwei 
Published: October 2021

Purpose: The present work investigated changes in the gene expression, molecular mechanisms, and pathogenesis of inherited retinal degeneration (RD) in three different disease models, to identify predictive biomarkers for their varied phenotypes and to provide a better scientific basis for their diagnosis, treatment, and prevention.Methods: Differentially expressed genes (DEGs) between retinal tissue from RD mouse models obtained during the photoreceptor cell death peak period (Pde6brd1 at post-natal (PN) day 13, Pde6brd10 at PN23, Prphrd2 at PN29) and retinal tissue from C3H wild-type mice were identified using Illumina high-throughput RNA-sequencing. Co-expression gene modules were identified using a combination of GO and KEGG enrichment analyses and gene co-expression network analysis. CircRNA-miRNA-mRNA network interactions were studied by genome-wide circRNA screening.Results:Pde6brd1, Pde6brd10, and Prphrd2 mice had 1,926, 3,096, and 375 DEGs, respectively. Genes related to ion channels, stress, inflammatory processes, tumor necrosis factor (TNF) production, and microglial cell activation were up-regulated, while genes related to endoplasmic reticulum regulation, metabolism, and homeostasis were down-regulated. Differential expression of transcription factors and non-coding RNAs generally implicated in other human diseases was detected (e.g., glaucoma, diabetic retinopathy, and inherited retinal degeneration). CircRNA-miRNA-mRNA network analysis indicated that these factors may be involved in photoreceptor cell death. Moreover, excessive cGMP accumulation causes photoreceptor cell death, and cGMP-related genes were generally affected by different pathogenic gene mutations.Conclusion: We screened genes and pathways related to photoreceptor cell death. Additionally, up-stream regulatory factors, such as transcription factors and non-coding RNA and their interaction networks were analyzed. Furthermore, RNAs involved in RD were functionally annotated. Overall, this study lays a foundation for future studies on photoreceptor cell death mechanisms.
Comprehensive of N1-Methyladenosine Modifications Patterns and Immunological Characteristics in Ovarian Cancer
Authors: Liu Jinhui , Chen Can , Wang Yichun , Qian Cheng , Wei Junting , Xing Yan , Bai Jianling 
Published: October 2021

Backgroundrecently, many researches have concentrated on the relevance between N1-methyladenosine (m1A) methylation modifications and tumor progression and prognosis. However, it remains unknown whether m1A modification has an effect in the prognosis of ovarian cancer (OC) and its immune infiltration.MethodsBased on 10 m1A modulators, we comprehensively assessed m1A modification patterns in 474 OC patients and linked them to TME immune infiltration characteristics. m1Ascore computed with principal component analysis algorithm was applied to quantify m1A modification pattern in OC patients. m1A regulators protein and mRNA expression were respectively obtained by HPA website and RT-PCR in clinical OC and normal samples.ResultsWe finally identified three different m1A modification patterns. The immune infiltration features of these m1A modification patterns correspond to three tumor immune phenotypes, including immune-desert, immune-inflamed and immune-excluded phenotypes. The results demonstrate individual tumor m1A modification patterns can predict patient survival, stage and grade. The m1Ascore was calculated to quantify individual OC patient’s m1A modification pattern. A high m1Ascore is usually accompanied by a better survival advantage and a lower mutational load. Research on m1Ascore in the treatment of OC patients showed that patients with high m1Ascore showed marked therapeutic benefits and clinical outcomes in terms of chemotherapy and immunotherapy. Lastly, we obtained four small molecule drugs that may potentially ameliorate prognosis.ConclusionThis research demonstrates that m1A methylation modification makes an essential function in the prognosis of OC and in shaping the immune microenvironment. Comprehensive evaluation of m1A modifications improves our knowledge of immune infiltration profile and provides a more efficient individualized immunotherapy strategy for OC patients.
Clinical Features and Risk Factors for Active Tuberculosis in Takayasu Arteritis: A Single-Center Case-Control Study
Authors: Zhou Jiawei , Ji Ruoyu , Zhu Rui , Zhou Jingya , Li Jing , Tian Xinping , Chen Yuexin , Zheng Yuehong 
Published: October 2021

BackgroundsTakayasu arteritis (TAK) is a chronic, granulomatous vasculitis correlated with tuberculosis (TB). The two diseases share similar pathological characteristics and clinical manifestations which increase the difficulty to diagnose. Active tuberculosis (ATB) has implications for treatment strategies in TAK patients. Therefore, the investigation of clinical features and potential risk factors of ATB in TAK patients is vital.MethodsThe study reviewed hospitalized patients diagnosed with TAK in our hospital from 2008, to 2021. TAK patients with ATB were enrolled as the case group. The control group was randomly selected in a 3:1 ratio. The clinical characteristics of TAK patients with and without ATB were compared. Multivariate logistic regression analysis was performed to determine risk factors for ATB in TAK patients.ResultsWe reviewed 1,789 patients and ultimately identified 30 (1.7%) ATB cases. TAK patients with ATB were more prone to develop symptoms including fever (p=0.001), fatigue (p=0.003), cough (p=0.037), expectoration (p&lt;0.001), weight loss (p=0.003), and night sweating (p&lt;0.001). Increased level of hypersensitive C reactive protein (hsCRP, p=0.001), decreased level of albumin (p=0.031), and higher positive rate of T-SPOT.TB test (p&lt;0.001) were observed in the case group. Multivariate logistic regression analysis revealed that hsCRP &gt;8 mg/L (OR 9.108; 95% CI, 1.096–75.711; p=0.041) and positive T-SPOT.TB result (OR 68.669; 95% CI, 7.291–646.738; p&lt;0.001) were risk factors for ATB in TAK patients. The proportion of patients undergoing subsequent surgery for Takayasu arteritis was lower in patients with ATB (p&lt;0.001).ConclusionOur study suggested that the diagnosis of ATB should be considered when TAK patients experienced symptoms including fever, fatigue, weight loss, etc. hsCRP &gt;8 mg/L and positive T-SPOT.TB result were identified as independent risk factors for ATB in TAK patients.
Is Immune Therapy Plus Chemotherapy More Effective Than Immune Therapy Alone for Unresectable Recurrent Nasopharyngeal Carcinoma?
Authors: Zhou Xin , Niu XiaoShuang , Liu PeiYao , Ou Dan , Zhu Yi , Wang XiaoShen 
Published: October 2021

ObjectiveTo evaluate whether the combination of immune checkpoint inhibitor (ICI) with chemotherapy is more effective than ICI alone in the treatment of recurrent, locoregionally advanced, unresectable nasopharyngeal carcinoma (RAU-NPC), which has progressed after second line chemotherapy.Methods and materialsPatients with RAU-NPC that progressed after second chemotherapy were prescribed ICI once every 3 weeks, either alone or combined with chemotherapy at the discretion of treating physicians, until confirmed disease progression, unacceptable toxicity, or voluntary withdrawal. The primary endpoint was the objective response rate (ORR). The secondary endpoints included safety, duration of response (DOR), and progression-free survival (PFS).ResultsFrom June 2016 to July 2021, 28 patients were enrolled in this study.21 patients received ICI plus chemotherapy, and 7 patients received ICI alone. Altogether, there were 7 (25%) complete response (CR) and 12 (42.8%) partial response (PR), respectively. Stable disease (SD) and progressive disease (PD) were defined in 4 (14.3%) and 5 (17.8%) cases, respectively. The ORR was 19 out of 28 (67.8%). The disease control rate (DCR) was 23 out of 28 (82.1%).Two patients (28.6%) in the ICI alone group and five (23.8%) in the combination group achieved CR (P=0.801). 2 patient (28.6%) in the ICI alone group and 10 (47.6%) in the combination group achieved PR (P=0.378). With a median follow-up of 16 months (2-61 months), five patients terminated ICI due to disease progression, one patient was lost to follow-up, and the remaining 22 patients continued with ICI. Neither the median PFS nor the median DOR was reached. All observed adverse events were defined as ≤ Grade 2.ConclusionICI alone or combined with chemotherapy demonstrated promising antitumor activity in RAU-NPC patients that progressed after second line chemotherapy, with a low toxicity profile. Compared with ICI alone, chemotherapy plus ICI did not improve CR or PR in our study.
Comparison of Hysterosalpingography With Laparoscopy in the Diagnosis of Tubal Factor of Female Infertility
Authors: Tan Jifan , Deng Min , Xia Meng , Lai Muhua , Pan Wenwei , Li Yubin 
Published: October 2021

Background:Laparoscopy is considered to be the gold standard in the evaluation of causes leading to infertility. Hysterosalpingography (HSG) permits indirect visualization of the cervical canal, uterine cavity, and tube patency, which is helpful for evaluating the causes of infertility.Objective:This study aimed to detect tubal abnormalities in infertile women by HSG or laparoscopy and determine the value of HSG in diagnosing fallopian tube status.Methods:The study group consisted of 1,276 patients. HSG was performed as a preliminary test for the evaluation of fallopian tube status. Women were subjected to laparoscopic examination on evidence of HSG abnormalities.Results:The negative predictive value of HSG for detecting patency or occlusion for the right/left tube was 92.08 and 95.44%, respectively. The kappa values for the consistent diagnosis in the right/left tube were 0.470 and 0.574, respectively. In cases of low patency of the right/left tube, there was a greater than a 40% chance for the tube to be patent, and the remaining high probability was pelvic adhesion. The positive predictive value of HSG for detecting patency or occlusion for both tubes was 87.2%. The kappa value was 0.898 [95% CI (0.838, 0.937),p&lt; 0.001], which meant that the diagnostic accuracy of HSG for both tube patency/occlusion was explicit. The kappa value for the diagnosis of hydrosalpinx (especially for bilateral tube hydrosalpinx) was 0.838 [95% CI (0.754, 0.922),p&lt; 0.001], and the diagnostic accuracy for HSG was 79.8, 67.9, and 72.4%, respectively.Conclusion:The current study concluded that HSG is a good diagnostic modality to detect tube abnormalities in infertile patients. HSG and laparoscopy are complementary to each other and whenever the patient is undertaken for diagnosis of infertility. Cost-effective HSG had good predictive value in identifying tubal factor infertility.
Characterization of the Oral Microbiome Among Children With Type 1 Diabetes Compared With Healthy Children
Authors: Moskovitz Moti , Nassar Mira , Moriel Nadav , Cher Avital , Faibis Sarit , Ram Diana , Zangen David , Yassour Moran , Steinberg Doron 
Published: October 2021

Aim: Current microbiome profiling of type 1 diabetes mellitus (T1D) patients is mostly limited to gut microbiome. We characterized the oral microbiome associated with T1D in children after the onset of the disease and explored its relationship with oral physiological factors and dental status.Methods: This cohort study comprised 37 children aged 5–15 years with T1D and 29 healthy children matched in age and gender. Unstimulated whole saliva was collected from diabetic and non-diabetic children, in the morning after brushing their teeth and a fasting period of at least 1 h before sampling. 16S rRNA gene-based analysis was performed by Powersoil Pro kit by Qiagen and Phusion High-Fidelity PCR Master Mix. Oral physiological and dental parameters studied included decayed, missing, and filled teeth index, salivary flow rate, and salivary pH, glucose, calcium, phosphate, and urea levels.Results: Of the identified 105 different genera and 211 different species, the most abundant genera were Streptococcus, Prevotella, Veillonella, Haemophilus, and Neisseria. Streptococcus was more abundant in T1D children. The diabetes group had 22 taxa at the genus level and 33 taxa at the species level that were not present in the control group and the control group exhibited 6 taxa at the genus level and 9 taxa at the species level that did not exist in the diabetes group. In addition, Catonella, Fusobacterium, and Mogibacterium differed between healthy and T1D subjects. Eight species and eight subspecies were significantly more abundant among healthy children than in T1D children. Porphyromonas and Mogibacterium genera were significantly correlated with salivary parameters. We found similarities between taxa revealed in the present study and those found in gut microbiome in type 1 diabetes mellitus according to gutMDisorder database.Conclusions: Salivary microbiome analysis revealed unique microbial taxa that differed between T1D children and healthy subjects. Several genera found in the saliva of T1D children were associated with gut microbiome in T1D individuals.
Characteristics and Outcomes of Intravenous Thrombolysis in Mild Ischemic Stroke Patients
Authors: Tang Huan , Yan Shenqiang , Wu Chenglong , Zhang Yanxing 
Published: October 2021

Objective: This study assessed the characteristics of intravenous thrombolysis (IVT) with respect to early neurological deterioration (END) and functional outcome in mild ischemic stroke patients.Methods: Data were obtained from acute mild ischemic stroke patients (defined as having a National Institute of Health Stroke Score (NIHSS) ≤ 5) treated with IVT in our hospital from July 2017 to December 2020. END was defined as the NIHSS increased ≥1 over the baseline at 24 h after IVT. A modified Rankin scale (mRS) ≤ 1 at 3 months was considered as a favorable outcome, and an mRS ≥2 at 3 months was an unfavorable outcome.Results: Two hundred thirty-three acute mild ischemic stroke patients (all patients underwent MRI and DWI restriction) with IVT were included in this study. Thirty-one patients experienced END, and 57 patients experienced an unfavorable outcome at 3 months. With multivariate analysis, END was associated with an elevated baseline systolic blood pressure (SBP) (OR = 1.324, 95% CI, 1.053–1.664, p = 0.016) and coronary heart disease (OR = 4.933, 95% CI, 1.249–19.482, p = 0.023). An unfavorable outcome at 3 months after IVT was independently associated with a baseline elevated SBP (OR = 1.213, 95% CI, 1.005–1.465, p = 0.045), baseline NIHSS (OR = 1.515, 95% CI, 1.186–1.935, p = 0.001), prior hyperlipemia (OR = 3.065, 95% CI, 1.107–8.482, p = 0.031), cardioembolic stroke (OR = 0.323, 95% CI, 0.120–0.871, p = 0.025), and END at 24 h (OR = 4.531, 95% CI, 1.950–10.533, p &lt; 0.001) in mild ischemic stroke patients.Conclusion: In mild ischemic stroke patients with IVT, an elevated baseline SBP and coronary heart disease were associated with END. The elevated baseline SBP, baseline NIHSS, a history of prior hyperlipemia, cardioembolic stroke, and END at 24 h after IVT were useful in predicting an unfavorable outcome at 3 months.
Pediatric Gastrointestinal Endoscopy: Diagnostic Yield and Appropriateness of Referral Based on Clinical Presentation: A Pilot Study
Authors: Fachler Tahel , Shteyer Eyal , Orlanski Meyer Esther , Shemasna Ibrahim , Lev Tzion Raffi , Rachman Yelena , Bergwerk Ari , Turner Dan , Ledder Oren 
Published: October 2021

Objectives: There is a lack of evidence-based consensus for the utility of gastrointestinal endoscopy (GIE) in an array of frequently occurring symptoms in children. We aimed to assess the diagnostic yield of endoscopy in an effort to aid clinical decision making.Methods: Retrospective analysis included patients ≤18 years who underwent GIE during one calendar year at Shaare Zedek Medical Center. We excluded children referred for predefined obvious indications for GIE, planned follow-up procedures, and therapeutic endoscopy. Clinician-assigned indication for endoscopy as well as endoscopic and histologic findings were recorded. Diagnostic yield of GIE was determined according to referral indication.Results: There were 794 endoscopies performed of which 329 were included in the analysis (mean age 9.3 ± 5.0 years, 51% female). No significant complications of GIE were recorded. Six major referral indications were identified among which abdominal pain was the most frequent 88/329 (26%) of whom 32/88 (36%) had a significant diagnostic finding. Among the other major indications, diagnostic findings were found in 36/85 (43%) children with primary indication of chronic diarrhea, 14/33 (42%) failure to thrive, 15/32 (46%) short stature, 30/56 (54%) iron deficiency, and 20/48 (42%) weight loss.Conclusions: Pediatric GIE is a safe procedure with diverse clinical indications. The diagnostic yield of endoscopy is variable, depending on the referral indication. These data can assist formulating judicious referral practices.
Adverse Effects Associated With Currently Commonly Used Antifungal Agents: A Network Meta-Analysis and Systematic Review
Authors: Yang Yan-Li , Xiang Zi-Jian , Yang Jing-Hua , Wang Wen-Jie , Xu Zhi-Chun , Xiang Ruo-Lan 
Published: October 2021

Background: Invasive fungal infections (IFI) is an important contributing factor in morbidity and mortality of immunocompromised and critically ill patients. Although the therapeutic effects of these drugs on IFI have been well documented, the long-term use of antifungal agents has raised concerns about drug tolerability and treatment-related toxicity risks.Methods: We searched articles published before June 30, 2020 in four electronic databases: Web of Science, Cochrane Library, embase and PubMed.Results: 66 trials were determined to meet our inclusion criteria, providing data on 18,230 participants. We sorted out 23 AEs by system organ classes and six laboratory AEs, 13 of these were used to construct 13 network meta-analyses. Compared with LAmB, anidulafungin, caspofungin, micafungin, fluconazole, and posaconazole had a significantly low incidence of discontinuation of therapy due to AEs (OR = 0.24 (0.09,0.65), 0.24 (0.13,0.43), 0.32 (0.19,0.52), 0.38 (0.23,0.62) and 0.35 (0.17,0.69), respectively).Conclusion: We found that echinocandins are the most tolerated antifungal agents with high safety. The AEs of triazole drugs are mainly concentrated on the increase in liver enzymes, nervous system disorders, especially visual disorders, gastrointestinal disorders, and cardiac diseases. LAmB is the least tolerated and has the most abundant AEs.
Curcuma longa Hepatotoxicity: A Baseless Accusation. Cases Assessed for Causality Using RUCAM Method
Authors: Stati Gianmarco , Rossi Francesco , Sancilio Silvia , Basile Mariangela , Di Pietro Roberta 
Published: October 2021

Curcuma longa is a perennial herb that belongs to the Zingiberaceae family. To date, literature includes more than 11.000 scientific articles describing all its beneficial properties. In the last 3 decades various surveys by the U.S. Food and Drug Administration (FDA) concluded that curcumin, the most active ingredient of the drug, is a “generally safe” compound with strong anti-oxidant effects. Curcuma longa was introduced in the daily diet by ayurvedic teachers due to its beneficial effects on health. Nonetheless, recently several reports, from the various global surveillance systems on the safety of plant products, pointed out cases of hepatotoxicity linked to consumption of food supplements containing powdered extract and preparations of Curcuma longa. The latest trend is the use of Curcuma longa as a weight-loss product in combination with piperine, which is used to increase its very low systemic bioavailability. Indeed, only 20 mg piperine, one of the alkaloids found in black pepper (Piper nigrum), assumed at the same time with 2 g curcumin increased 20-fold serum curcumin bioavailability. This combination of natural products is now present in several weight loss supplements containing Curcuma longa. The enhanced drug bioavailability caused by piperine is due to its potent inhibition of drug metabolism, being able to inhibit human P-glycoprotein and CYP3A4, while it interferes with UDP-glucose dehydrogenase and glucuronidation activities in liver. While only few cases of hepatotoxicity, assessed using Roussel Uclaf Causality Assessment Method (RUCAM) method, from prolonged intake of piperine and curcumin have been reported, it would be reasonable to speculate that the suspected toxicity of Curcuma longa could be due to the concomitant presence of piperine itself. Hence, not only there is the need of more basic research to understand the etiopathology of curcumin-related hepatotoxicity and of the combination curcumin-piperine, but human trials will be necessary to settle this dispute.
Effect of the cPKCγ-Ng Signaling System on Rapid Eye Movement Sleep Deprivation-Induced Learning and Memory Impairment in Rats
Authors: Xu Shu , Zhang Yanbo , Xu Zhiqing , Song Luping 
Published: October 2021

Objective: Rapid eye movement sleep deprivation (REM-SD) can cause a decline in learning and memory and lead to changes in behavior. Therefore, REM sleep plays a key role in processes that govern learning and memory. However, the mechanism underlying REM-SD-induced learning and memory impairment is unclear and the underlying molecular signaling still needs to be identified. In the present study, we investigated the role of the cPKCγ-Ng signaling pathway in REM-SD-induced learning and memory impairment.Method: Sixty male rats were divided into Control, REM-SD, REM-SD+cPKCγ activator PMA, REM-SD+cPKCγ inhibitor H-7, and sleep revival (SR) groups. The Morris water maze was used to assess spatial learning and memory. Western blot analysis was used to detect cPKCγ total protein expression and membrane translocation levels, and Ng total protein expression and phosphorylation levels.Results: The REM-SD group performed worse on the Morris water maze test than the control group. Western blot analysis showed that cPKCγ membrane translocation and Ng phosphorylation levels were significantly lower in the REM-SD group. SR following REM-SD restored learning and memory ability, cPKCγ transmembrane translocation, and Ng phosphorylation levels, but not to levels observed before REM-SD. PMA and H-7 significantly improved/disrupted task ability as well as cPKCγ transmembrane translocation and Ng phosphorylation levels in REM-SD rats.Conclusion: The REM-SD induced learning and memory impairment in rats and may be associated with the cPKCγ-Ng signaling pathway. Specifically, activation of the cPKCγ-Ng signaling pathway may protect against REM-SD.