bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis B Virus Screening Before Cancer Chemotherapy in Taiwan: A Nationwide Population-Based Study
Authors: Sun Wei-Chih , Tang Pei-Ling , Chen Wen-Chi , Tsay Feng-Woei , Wang Huay-Min , Tsai Tzung-Jiun , Kao Sung-Shuo , Cheng Jin-Shiung , Tsai Wei-Lun 
Published: July 2021

Background: Reactivation of the hepatitis B virus (HBV) during cancer chemotherapy is a severe and sometimes fatal complication. In 2009, the National Health Insurance (NHI) in Taiwan recommended and reimbursed screening for HBV infection and prophylactic antiviral therapy before cancer chemotherapy. In this study, we determined the HBV screening rate in patients with cancer undergoing chemotherapy in Taiwan.Methods: We retrospectively collected data from the National Health Insurance Research Database on patients who received systemic chemotherapy for solid or hematologic cancers from January 2000 through December 2012. We defined HBV screening based on testing for serum HBsAg within 2 years of the first chemotherapy commencement. We calculated overall and annual HBV screening rates in all patients and subgroups of age, gender, cancer type, hospital level, physician's department, and implementation of NHI reimbursement for HBV screening before cancer chemotherapy.Results: We enrolled 379,639 patients. The overall HBV screening rate was 45.9%. The screening rates were higher in males, those with hematological cancer, those at non-medical centers and medical departments. The HBV screening rates before (2000–2008) and after the implementation of NHI reimbursement (2009–2012) were 38.1 and 57.5%, respectively (p &lt; 0.0001). The most common practice pattern of HBV screening was only HBsAg (64.6%) followed by HBsAg/HBsAb (22.1%), and HBsAg/HBcAb/HBsAb (0.7%) (p &lt; 0.0001). The annual HBV screening rate increased from 31.5 to 66.3% (p &lt; 0.0001). The screening rates of solid and hematological cancers significantly increased by year; however, the trend was greater in solid cancer than in hematological cancer (35.9 and 26.2%, p &lt; 0.0001).Conclusions: The HBV screening rate before cancer chemotherapy was fair but increased over time. These figures improved after implementing a government-based strategy; however, a mandatory hospital-based strategy might improve awareness of HBV screening and starting prophylactic antiviral therapy before cancer chemotherapy.
Regional Differences in Epidemiological and Clinical Characteristics, Treatment, and Clinical Outcomes of COVID-19 in Wuhan and Remote Areas of Hubei Province
Authors: Ren Honggang , Guo Xingyi , Palazón-Bru Antonio , Yang Pengcheng , Huo Nan , Wang Runsheng , Sun Yu , Hu Qinyong , Yang Hua , Xu Guogang 
Published: July 2021

Background: The Coronavirus disease 2019 (COVID-19) pandemic has been a major threat to global health. Regional differences in epidemiological and clinical characteristics, treatment and outcomes of patients have not yet been investigated. This study was conducted to investigate these differences amongCOVID-19 patients in Hubei Province, China.Methods: This retrospective cross-sectional study analyzed data on 289 COVID-19 patients from designated hospitals in three regions:Urban (Wuhan Union West Hospital), Suburban areas of Wuhan (Hannan Hospital) and Enshi city, between February 8 and 20, 2020. The final date of follow-up was December 14th, 2020. The outcomes were case fatality rate and epidemiological and clinical data.Results: Urban Wuhan experienced a significantly higher case fatality rate (21.5%) than suburban Wuhan (5.23%) and rural area of Enshi (3.51%). Urban Wuhan had a higher proportion of patients on mechanical ventilation (24.05%) than suburban Wuhan (0%) and rural Enshi (3.57%). Treatment with glucocorticoids was equivalent in urban and suburban Wuhan (46.84 and 45.75%, respectively) and higher than Enshi (25.00%). Urban Wuhan had a higher proportion of patients with abnormal tests including liver function and serum electrolytes and a higher rate of pneumonia (p &lt; 0.01 for all). Urban Wuhan also had a higher incidence of respiratory failure, heart disease, liver disease and shock, compared with the other two regions (all p &lt; 0.05).Conclusions: Our findings revealed that there are regional differences in COVID-19. These findings provide novel insights into the distribution of appropriate resources for the prevention, control and treatment of COVID-19 for the global community.
Regional Difference in Myelination in Monocarboxylate Transporter 8 Deficiency: Case Reports and Literature Review of Cases in Japan
Authors: Iwayama Hideyuki , Tanaka Tatsushi , Aoyama Kohei , Moroto Masaharu , Adachi Shinsuke , Fujisawa Yasuko , Matsuura Hiroki , Takano Kyoko , Mizuno Haruo , Okumura Akihisa 
Published: July 2021

Background: Monocarboxylate transporter 8 (MCT8) is a thyroid hormone transmembrane transporter protein. MCT8 deficiency induces severe X-linked psychomotor retardation. Previous reports have documented delayed myelination in the central white matter (WM) in these patients; however, the regional pattern of myelination has not been fully elucidated. Here, we describe the regional evaluation of myelination in four patients with MCT8 deficiency. We also reviewed the myelination status of previously reported Japanese patients with MCT8 deficiency based on magnetic resonance imaging (MRI).Case Reports: Four patients were genetically diagnosed with MCT8 deficiency at the age of 4–9 months. In infancy, MRI signal of myelination was observed mainly in the cerebellar WM, posterior limb of internal capsule, and the optic radiation. There was progression of myelination with increase in age.Discussion: We identified 36 patients with MCT8 deficiency from 25 families reported from Japan. The available MRI images were obtained at the age of &lt;2 years in 13 patients, between 2 and 4 years in six patients, between 4 and 6 years in three patients, and at ≥6 years in eight patients. Cerebellar WM, posterior limb of internal capsule, and optic radiation showed MRI signal of myelination by the age of 2 years, followed by centrum semiovale and corpus callosum by the age of 4 years. Most regions except for deep anterior WM showed MRI signal of myelination at the age of 6 years.Conclusion: The sequential pattern of myelination in patients with MCT8 deficiency was largely similar to that in normal children; however, delayed myelination of the deep anterior WM was a remarkable finding. Further studies are required to characterize the imaging features of patients with MCT8 deficiency.
The Efficacy and Safety of Acupuncture for Prophylaxis of Vestibular Migraine: A Study Protocol for a Randomized Controlled Trial
Authors: Hu Tianye , Hu Hantong , Chen Feng , Jiang Bin , Shen Fengfei , Su Yingying , Yang Mengyi , Hu Jin 
Published: July 2021

Introduction:With a high incidence rate and low diagnosis rate, vestibular migraine (VM) can seriously affect the quality of life of patients, but it remains difficult to manage by current treatment options. Acupuncture may be a potential treatment option for VM prophylaxis, but the currently available evidence is still uncertain. Therefore, this trial aims to evaluate the efficacy and safety of acupuncture for VM prophylaxis.Methods:This is a 28-week parallel, randomized, controlled clinical trial including 4 weeks of baseline, 8 weeks of treatment, and 16 weeks of follow-up. A total of 72 participants will be randomly assigned to two groups. The participants will receive acupuncture in the experimental group, while the participants in the control group will be treated with venlafaxine. The primary outcome measures are change in vertigo/migraine days and vertigo/migraine attacks, vertigo severity, and migraine intensity per 4 weeks from baseline. The secondary outcome measures are change in doses of rescue medication, anxiety level, depression level, and quality of life per 4 weeks from baseline. Adverse events will be recorded for safety evaluation.Discussion:This study will investigate the efficacy and safety of acupuncture for VM prophylaxis. The results will contribute to determining whether acupuncture can serve as an optional treatment strategy for treating VM.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0464088.
Intrinsic Network Brain Dysfunction Correlates With Temporal Complexity in Generalized Anxiety Disorder and Panic Disorder
Authors: Xu Li , Xu Huazhen , Ding Huachen , Li Jinyang , Wang Chun 
Published: July 2021

Background: Generalized anxiety disorder (GAD) and panic disorder (PD) are the two severe subtypes of anxiety disorders (ADs), which are similar in clinical manifestation, pathogenesis, and treatment. Earlier studies have taken a whole-brain perspective on GAD and PD in the assumption that intrinsic fluctuations are static throughout the entire scan. However, it has recently been suggested that the dynamic alternations in functional connectivity (FC) may reflect the changes in macroscopic neural activity patterns underlying the critical aspects of cognition and behavior, and thus may act as biomarkers of disease.Methods: In this study, the resting-state functional MRI (fMRI) data were collected from 26 patients with GAD, 22 patients with PD, and 26 healthy controls (HCs). We investigated dynamic functional connectivity (DFC) by using the group spatial independent component analysis, a sliding window approach, and the k-means clustering methods. For group comparisons, the temporal properties of DFC states were analyzed statistically.Results: The dynamic analysis demonstrated two discrete connectivity “States” across the entire group, namely, a more segregated State I and a strongly integrated State II. Compared with HCs, patients with both GAD and PD spent more time in the weakly within-network State I, while performing fewer transitions and dwelling shorter in the integrated State II. Additionally, the analysis of DFC strength showed that connections associated with ADs were identified including the regions that belonged to default mode (DM), executive control (EC), and salience (SA) networks, especially the connections between SA and DM networks. However, no significant difference was found between the GAD and PD groups in temporal features and connection strength.Conclusions: More common but less specific alterations were detected in the GAD and PD groups, which implied that they might have similar state-dependent neurophysiological mechanisms and, in addition, could hopefully help us better understand their abnormal affective and cognitive performances in the clinic.
Investigation of the Relationship Between Subjective Symptoms of Visual Fatigue and Visual Functions
Authors: Zheng Fuhao , Hou Fang , Chen Ruru , Mei Jianhui , Huang Pingping , Chen Bingzhen , Wang Yuwen 
Published: July 2021

PurposeTo investigate whether the severity of symptoms of visual fatigue might be associated with clinical visual measures and basic visual functions, such as accommodation, vergence, and contrast sensitivity.MethodsIn this study, 104 students were recruited (25 males, 79 females, Age 23.4 ± 2.5) for this study. Those with high myopia, strabismus, anisometropia, eye disease or history of ophthalmological surgery were excluded. The included subjects completed a questionnaire that assesses the severity of visual fatigue. Then, binocular accommodative facility, vergence facility and contrast sensitivity using a quick contrast sensitivity function approach were measured in a random sequence. Next, the correlations between each symptom of visual fatigue in the questionnaire and accommodative facility, vergence facility and contrast sensitivity were examined.ResultsFactor analysis indicated that visual fatigue, as captured by the scores of a subset of the questionnaire items, could be strongly related to binocular accommodative facility and binocular contrast sensitivity, but not to vergence facility. We also found that binocular accommodative facility and contrast sensitivity at high spatial frequencies are related.ConclusionOur findings suggest that visual fatigue is related to the ability of human observers to encode visual details through their binocular vision.
Targeting Thymidylate Synthase Enhances the Chemosensitivity of Triple-Negative Breast Cancer Towards 5-FU-Based Combinatorial Therapy
Authors: Haritha Nair Hariprasad , Nawab Akbar , Vijayakurup Vinod , Anto Nikhil Ponnoor , Liju Vijayasteltar B. , Alex Vijai V. , Amrutha Areekkara Nisthul , Aiswarya Sreekumar U. , Swetha Mundanattu , Vinod Balachandran S. , Sundaram Sankar , Guijarro Maria V. , Herlevich Thomas , Krishna Archana , Nestory Nesteena K. , Bava Smitha V. , Sadasivan Chittalakkottu , Zajac-Kaye Maria , Anto Ruby John 
Published: July 2021

BackgroundThe ongoing treatment modalities for breast cancer (BC) primarily rely on the expression status of ER, PR and HER-2 receptors in BC tissues. Our strategy of chemosensitization provides new insights to counter chemoresistance, a major obstacle that limits the benefits of chemotherapy of mammary cancers.MethodsBy utilizing a murine breast cancer model employing NSG mice bearing orthotopic triple-negative breast cancer (TNBC) xenografts, we have evaluated the ability of phytochemical curcumin in chemosensitizing BC to 5-Fluorouracil (5-FU) chemotherapy and the differential modulations of cellular events in response to this strategy, independent of their receptor status.ResultsA significant synergistic antitumor potential was observed in the murine model with a sub-optimal dose treatment of 5-FU plus curcumin, as evaluated by a reduction in the tumor-related parameters. We authenticated the pivotal role of thymidylate synthase (TS) in regulating the 5-FU–curcumin synergism using the TNBC pre-clinical model. Our study also confirmed the pharmacological safety of this chemotherapeutic plus phytoactive combination using acute and chronic toxicity studies in Swiss albino mice. Subsequently, the molecular docking analysis of curcumin binding to TS demonstrated the affinity of curcumin towards the cofactor-binding site of TS, rather than the substrate-binding site, where 5-FU binds. Our concomitant in vivo and in silico evidence substantiates the superior therapeutic index of this combination.ConclusionThis is the first-ever pre-clinical study portraying TS as the critical target of combinatorial therapy for mammary carcinomas and therefore we recommend its clinical validation, especially in TNBC patients, who currently have limited therapeutic options.
Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan
Authors: Yu Kenneth H. , Hendifar Andrew E. , Alese Olatunji B. , Draper Amber , Abdelrahim Maen , Burns Ethan , Khan Gazala , Cockrum Paul , Bhak Rachel H. , Nguyen Catherine , DerSarkissian Maral , Duh Mei Sheng , Bahary Nathan 
Published: July 2021

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score &lt;2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively.ConclusionsPatients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.
Postoperative Radiotherapy for Patients With Resectable Stage III-N2 Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Lei Tianyu , Li Jing , Zhong Hao , Zhang Huibo , Jin Yan , Wu Jie , Li Lan , Xu Bin , Song Qibin , Hu Qinyong 
Published: July 2021

PurposeFor resectable cases of stage III-N2 non-small cell lung cancer (NSCLC), the best treatment after surgery is still uncertain. The effect of postoperative radiotherapy (PORT) is controversial. Thus, we performed this updated meta-analysis to reassess the data of PORT in stage III-N2 NSCLC patients, to figure out whether these patients can benefit from PORT.MethodsWe conducted searches of the published literature in EMBASE, PubMed, and the Cochrane Library for relevant randomized control trials (RCTs) comparing PORT group with the non-PORT group in NSCLC patients at stage III-N2. These studies allowed the prior chemotherapy in the treatment. We extracted the data from these articles and used the hazard ratios (HRs) and their 95% confidence intervals (CIs) as summary statistics for estimating the effect of PORT on overall survival (OS), disease-free survival (DFS), local-regional recurrence-free survival (LRFS).ResultThe analyses of seven randomized controlled trials (1,318 participants) show no benefit of PORT on survival (HR, 0.87; 95% CI, 0.71 to 1.07; p = 0.18) but a significantly different effect of PORT on DFS (HR, 0.83; 95% CI, 0.71 to 0.97; p = 0.02) and LRFS (HR, 0.64; 95% CI, 0.50 to 0.81; p = 0.0003). There is not enough evidence of a difference in the effect on survival by the utility of chemotherapy along with PORT though subgroup analysis of no chemotherapy group, concurrent chemoradiotherapy and sequential chemoradiotherapy group. Even in trials with 3D-CRT radiation technique, the pooled analysis shows no benefit of PORT on survival in patients with stage III-N2 NSCLC (data is not shown).ConclusionOur findings illustrate that in the postoperative treatment for patients with stage III-N2 NSCLC, PORT contributes to a significantly increased DFS and LR and may not associate with an improved OS, indicating a cautious selection.
Down-Regulation of Toll-Like Receptor 5 (TLR5) Increased VEGFR Expression in Triple Negative Breast Cancer (TNBC) Based on Radionuclide Imaging
Authors: Jiang Wen , Han Yeming , Liang Ting , Zhang Chao , Gao Feng , Hou Guihua 
Published: July 2021

In this study, GFP-tagged TNBC 4T1 cells with down-regulated TLR5 expression (TLR5− 4T1) and normal TLR5 expression (TLR5+ 4T1) were constructed, respectively. RT-PCR and Western blot studies showed that down-regulation of TLR5 obviously increased the expression of VEGFR in 4T1 cells. Highly stable radio-probes 125I-anti-TLR5 mAb/125I-VEGF/125I-IgG were obtained with labeling rates over 85% and radiochemical purities above 90%. Among these three probes, 125I−anti−TLR5 mAb and 125I-VEGF were used for specifically imaging TNBC, while 125I-IgG was used for comparison. Whole-body phosphorus autoradiography showed clear imaging at 48 h after injection of 125I-anti-TLR5 mAb and 125I-VEGF also provided clear imaging at 24 h. Biodistribution study demonstrated a higher tumor uptake of 125I-anti-TLR5 mAb in TLR5+ group compared with that in TLR5− group (P &lt; 0.05), whereas tumor uptake of 125I-VEGF in TLR5+ group was lower than that in the TLR5− group (P &lt; 0.05). Immunohistochemical staining suggested that the expression of TLR5 was lower, whereas the expression of VEGFR, CD31, and MVD (microvessel density) was higher in TLR5− tumor-bearing mice. In summary, the down-regulation of TLR5 in TNBC promoted the VEGFR expression and angiogenesis, resulting in the proliferation of TNBC cells. TLR5/VEGF might be a better indicator for monitoring the development of TNBC.
Poloxamer 188 Attenuates Ischemia-Reperfusion-Induced Lung Injury by Maintaining Cell Membrane Integrity and Inhibiting Multiple Signaling Pathways
Authors: Tang Shih-En , Liao Wen-I , Pao Hsin-Ping , Hsu Chin-Wang , Wu Shu-Yu , Huang Kun-Lun , Chu Shi-Jye 
Published: July 2021

Background: Poloxamer 188 (P188) possesses anti-inflammatory properties and can help to maintain plasma membrane function. P188 has been reported to exert beneficial effects in the treatment of various disorders. However, the effects of P188 in ischemia/reperfusion (IR)-induced acute lung injury have not been examined.Methods: We investigated the ability of P188 to attenuate IR-induced acute lung injury in rats and hypoxia/reoxygenation (HR) injury in murine epithelial cells. Isolated perfused rat lungs were exposed to 40 min ischemia followed by 60 min reperfusion to induce IR injury.Results: IR led to lung edema, increased pulmonary arterial pressure, promoted lung tissue inflammation and oxidative stress, and upregulated the levels of TNF-α, IL-6 and CINC-1, and increased Lactic dehydrogenase (LDH) activity in bronchoalveolar lavage fluid. IR also downregulated the levels of inhibitor of κB (IκB-α), upregulated nuclear factor (NF)-κB (NF-κB), and promoted apoptosis in lung tissues. P188 significantly suppressed all these effects. In vitro, P188 also exerted a similar effect in murine lung epithelial cells exposed to HR. Furthermore, P188 reduced the number of propidium iodide-positive cells, maintained cell membrane integrity, and enhanced cell membrane repair following HR.Conclusion: We conclude that P188 protects against lung IR injury by suppressing multiple signaling pathways and maintaining cell membrane integrity.
Decreased Serum Brain-Derived Neurotrophic Factor Concentrations 72 Hours Following Marathon Running
Authors: Roeh Astrid , Holdenrieder Stefan , Schoenfeld Julia , Haeckert Jan , Halle Martin , Falkai Peter , Scherr Johannes , Hasan Alkomiet 
Published: July 2021

Background: Physical exercise has been linked to beneficial effects on brain plasticity. One potential key mechanism for this relationship is an exercise-induced increase of brain-derived neurotrophic factor (BDNF). However, the kinetics of BDNF in athletes during training phase, extreme exercise competition, and recovery period have not been investigated so far.Methods: We assessed serum BDNF concentrations in 51 marathon runners (23% female, mean age 43 years) in a longitudinal study design over a period of 6 months. Assessments were conducted during the training period before the marathon and after the marathon race during short-term (24 to 72 h) and long-term (3 months) follow-ups. Potential confounders (fitness level, sex, and platelet count) were included in subsequent linear-model analyses.Results: Linear mixed-model analyses revealed a main effect of time for BDNF concentrations over the study period (F(4,89.389) = 4.296, p = 0.003). Values decreased significantly with the lowest values at 72 h after the marathon compared to baseline (p = 0.025), a finding that was more pronounced in the larger male cohort.Conclusion: Prolonged exercise induces a significant decrease in serum BDNF concentration 72 h post-exercise. We assume that this observation is mainly driven by regenerative mechanisms and a higher muscular utilization.