bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Circulating T Follicular Helper Cells Induced via IL-12/21 in Patients With Acute on Chronic Hepatitis B Liver Failure
Authors: Du Bingying , Teng Jiaming , Yin Rongkun , Tian Yuanyuan , Jiang Tingwang , Du Yanan , Cai Wei 
Published: March 2021

ObjectivesT Follicular helper (Tfh) cells, recognized as a distinct CD4+ T cell subset, mediate the development of long-lived humoral immunity via B cell activation/differentiation. Tfh cells play an important role during hepatic viral infection, but its role in hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) remains to be explored.Materials and MethodsThe frequency of Tfh cells, serum pro-inflammatory cytokine (IL-12, IL-21, IL-17 and TNF) levels and IgG/M levels were investigated in HBV-ACLF (n = 36), serious chronic hepatitis B (n = 21), moderate chronic hepatitis B patients (n = 32) and healthy control (HC) subjects (n = 10).ResultsCirculating Tfh cells were significantly increased in HBV-ACLF patients compared to other groups, correlating well with MELD score. However, the frequency of Tfh cells decreased in ameliorated HBV-ACLF patients. Furthermore, serum IL-12 and IL-21 levels were higher in HBV-ACLF patients, compared to other groups. Naïve CD4+ T cells from HC subjects differentiate into Tfh cells following treatment with HBV-ACLF patients’ serum, a process that can be blocked by IL-12/21 neutralizing antibodies. Tfh cells induced by HBV-ACLF patient’s serum promoted the proliferation and IgG production of B cells in vitro. Moreover, circulating CD19+ B cells, serum and liver IgG/M levels were significantly higher in HBV-ACLF patients, compared to other groups.ConclusionsOur data demonstrated that there was a high frequency of Tfh cells and high levels of serum IL-12/21 in HBV-ACLF patients. Naïve CD4+ T cells differentiate into Tfh cells in the presence of HBV-ACLF patients’ serum rich in IL-12/21, which can be blocked by neutralizing IL-12/21 antibodies. These data may provide useful insights for both clinical and basic research in the treatment of HBV-ACLF.
Management and Prognosis of Interstitial Lung Disease With Lung Cancer (ILD-LC): A Real-World Cohort From Three Medical Centers in China
Authors: Xiaohong Xie , Liqiang Wang , Na Li , Xinqing Lin , Yinyin Qin , Ming Liu , Ming Ouyang , Qian Han , Qun Luo , Shiyue Li , Chunyan Li , Xiaoqian Wang , Shuanying Yang , Wei Huang , Mei Liu , Ping Wang , Chengzhi Zhou 
Published: March 2021

Background and ObjectiveInterstitial lung disease with lung cancer (ILD-LC) is rare and its management has not been fully described. This study aimed to investigate the management and prognosis of ILD-LC patients in China.MethodsThe present analysis is a retrospective real-world cohort study. Clinical data of ILD-LC patients were obtained from 3 hospitals in China. The overall survival (OS) of patients was analyzed. Univariate and multivariate regression analyses were performed.ResultsOne hundred eighty-four ILD-LC patients included were biased toward male (85.3%), smokers (75.5%), idiopathic pulmonary fibrosis (IPF) (58.2%) patients with comorbidities (67.9%) and ECOG-PS score of 1 (65.2%). Most patients were advanced peripheral non-small cell lung cancer. The initial anti-cancer regimen for ILD-LC is mainly chemotherapy, and patients with early-stage LC prefer surgery. In the anti-cancer cohort, the number of ILD-LC patients who underwent the 2nd and 3rd or more anti-cancer regimens were 78 (55.7%) and 32 (22.8%), respectively. In the non-anticancer cohort, the median OS was 3.5 months. In the early-stage cohort, the median OS was 14.2 months in the systematic therapy group; however, the median OS was not reached in the surgery group. In the advanced-stage cohort with systematic therapy, the median OS was 7.2 months. Interstitial pneumonia (IIP) and anti-angiogenesis were associated with OS in the univariate analysis, whereas anti-angiogenesis was an independent protective factor for advanced LC with ILD.ConclusionPatients with ILD-LC have very poor prognosis. Appropriate anti-tumor treatment can prolong the survival time of patients who can tolerate it. Targeted therapy and immunotherapy are alternative treatments for LC patients with mild ILD. For ILD patients with advanced LC, antiangiogenic regimens significantly improve the prognosis of the disease.
Gray Matter Atrophy in Amnestic Mild Cognitive Impairment: A Voxel-Based Meta-Analysis
Authors: Zhang Jinhuan , Liu Yongfeng , Lan Kai , Huang Xingxian , He Yuhai , Yang Fuxia , Li Jiaying , Hu Qingmao , Xu Jinping , Yu Haibo 
Published: March 2021

Background: Voxel-based morphometry (VBM) has been widely used to investigate structural alterations in amnesia mild cognitive impairment (aMCI). However, inconsistent results have hindered our understanding of the exact neuropathology related to aMCI.Objectives: Our aim was to systematically review the literature reporting VBM on aMCI to elucidate consistent gray matter alterations, their functional characterization, and corresponding co-activation patterns.Methods: The PubMed, Web of Science, and EMBASE databases were searched for VBM studies on aMCI published from inception up to June 2020. Peak coordinates were extracted from clusters that showed significant gray matter differences between aMCI patients and healthy controls (HC). Meta-analysis was performed using seed-based d mapping with the permutation of subject images (SDM-PSI), a newly improved meta-analytic method. Functional characterization and task-based co-activation patterns using the BrainMap database were performed on significant clusters to explore their functional roles. Finally, VBM was performed based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to further support the findings.Results: A total of 31 studies with 681 aMCI patients and 837 HC were included in this systematic review. The aMCI group showed significant gray matter atrophy in the left amygdala and right hippocampus, which was consistent with results from the ADNI dataset. Functional characterization revealed that these regions were mainly associated with emotion, cognition, and perception. Further, meta-regression analysis demonstrated that gray matter atrophy in the left inferior frontal gyrus and the left angular gyrus was significantly associated with cognitive impairment in the aMCI group.Conclusions: The findings of gray matter atrophy in the left amygdala and right hippocampus are highly consistent and robust, and not only offer a better understanding of the underlying neuropathology but also provide accurate potential biomarkers for aMCI.
Galvanic Vestibular Stimulation Produces Cross-Modal Improvements in Visual Thresholds
Authors: Voros Jamie L. , Sherman Sage O. , Rise Rachel , Kryuchkov Alexander , Stine Ponder , Anderson Allison P. , Clark Torin K. 
Published: March 2021

BackgroundStochastic resonance (SR) refers to a faint signal being enhanced with the addition of white noise. Previous studies have found that vestibular perceptual thresholds are lowered with noisy galvanic vestibular stimulation (i.e., “in-channel” SR). Auditory white noise has been shown to improve tactile and visual thresholds, suggesting “cross-modal” SR.ObjectiveWe investigated galvanic vestibular white noise (nGVS) (n = 9 subjects) to determine the cross-modal effects on visual and auditory thresholds.MethodsWe measured auditory and visual perceptual thresholds of human subjects across a swath of different nGVS levels in order to determine if some individual-subject determined best nGVS level elicited a reduction in thresholds as compared the no noise condition (sham).ResultsWe found improvement in visual thresholds (by an average of 18%, p = 0.014). Subjects with higher (worse) visual thresholds with no stimulation (sham) improved more than those with lower thresholds (p = 0.04). Auditory thresholds were unchanged by vestibular stimulation.ConclusionThese results are the first demonstration of cross-modal improvement with galvanic vestibular stimulation, indicating galvanic vestibular white noise can produce cross-modal improvements in some sensory channels, but not all.
Radiomics Analysis Based on Contrast-Enhanced MRI for Prediction of Therapeutic Response to Transarterial Chemoembolization in Hepatocellular Carcinoma
Authors: Zhao Ying , Wang Nan , Wu Jingjun , Zhang Qinhe , Lin Tao , Yao Yu , Chen Zhebin , Wang Man , Sheng Liuji , Liu Jinghong , Song Qingwei , Wang Feng , An Xiangbo , Guo Yan , Li Xin , Wu Tingfan , Liu Ai Lian 
Published: March 2021

PurposeTo investigate the role of contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics for pretherapeutic prediction of the response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).MethodsOne hundred and twenty-two HCC patients (objective response, n = 63; non-response, n = 59) who received CE-MRI examination before initial TACE were retrospectively recruited and randomly divided into a training cohort (n = 85) and a validation cohort (n = 37). All HCCs were manually segmented on arterial, venous and delayed phases of CE-MRI, and total 2367 radiomics features were extracted. Radiomics models were constructed based on each phase and their combination using logistic regression algorithm. A clinical-radiological model was built based on independent risk factors identified by univariate and multivariate logistic regression analyses. A combined model incorporating the radiomics score and selected clinical-radiological predictors was constructed, and the combined model was presented as a nomogram. Prediction models were evaluated by receiver operating characteristic curves, calibration curves, and decision curve analysis.ResultsAmong all radiomics models, the three-phase radiomics model exhibited better performance in the training cohort with an area under the curve (AUC) of 0.838 (95% confidence interval (CI), 0.753 - 0.922), which was verified in the validation cohort (AUC, 0.833; 95% CI, 0.691 - 0.975). The combined model that integrated the three-phase radiomics score and clinical-radiological risk factors (total bilirubin, tumor shape, and tumor encapsulation) showed excellent calibration and predictive capability in the training and validation cohorts with AUCs of 0.878 (95% CI, 0.806 - 0.950) and 0.833 (95% CI, 0.687 - 0.979), respectively, and showed better predictive ability (P = 0.003) compared with the clinical-radiological model (AUC, 0.744; 95% CI, 0.642 - 0.846) in the training cohort. A nomogram based on the combined model achieved good clinical utility in predicting the treatment efficacy of TACE.ConclusionCE-MRI radiomics analysis may serve as a promising and noninvasive tool to predict therapeutic response to TACE in HCC, which will facilitate the individualized follow-up and further therapeutic strategies guidance in HCC patients.
Association Between Digoxin Use and Cancer Incidence: A Propensity Score-Matched Cohort Study With Competing Risk Analysis
Authors: Tai Chi-Jung , Yang Yi-Hsin , Tseng Tzyy-Guey , Chang Fang-Rong , Wang Hui-Chun 
Published: March 2021

Background: Previous studies neglected death as a critical competing risk while estimating the cancer risk for digoxin users. Therefore, the current study aims to assess the effectiveness of digoxin on cancer prevention by competing risk analysis.Methods: We performed a population-based retrospective cohort study using the Taiwan National Health Insurance Research database between 1998 and 2010. After one-to-one propensity score-matching from 36,160 patients with defined criteria, we enrolled 758 patients both in digoxin and β-blocker group for further analysis.Results: The results showed that the digoxin group had higher all-cause mortality than the β-blocker group in the 4- year (10.4 vs. 4.9%) and 8 years (13.6 vs. 7.0%) follow-up. The subdistribution HR of cancer incidence in the digoxin group compared to the β-blocker group was 1.99 (95% confidence interval [CI]: 1.22–3.01) and 1.46 (95% CI: 1.01–2.15) in the 4 years and 8 years follow-up, respectively.Conclusions: The result of our study showed the usage of digoxin has no benefit in cancer prevention compared with β-blocker. The possibility of β-blocker as a new drug candidate for cancer prevention needs further clinical evaluation. The current study also emphasized the necessity of competing risk analysis applying to similar clinical researches.
Abacavir Increases Purinergic P2X7 Receptor Activation by ATP: Does a Pro-inflammatory Synergism Underlie Its Cardiovascular Toxicity?
Authors: Collado-Díaz Víctor , Martinez-Cuesta Maria Ángeles , Blanch-Ruiz Maria Amparo , Sánchez-López Ainhoa , García-Martínez Patricia , Peris José E , Usach Iris , Ivorra Maria Dolores , Lacetera Alessandra , Martín-Santamaría Sonsoles , Esplugues Juan V. , Alvarez Angeles 
Published: March 2021

The cardiovascular toxicity of Abacavir is related to its purinergic structure. Purinergic P2X7-receptors (P2X7R), characterized by activation by high concentrations of ATP and with high plasticity, seem implicated. We appraise the nature of the interplay between Abacavir and P2X7R in generating vascular inflammation. The effects of Abacavir on leukocyte-endothelium interactions were compared with those of its metabolite carbovir triphosphate (CBV-TP) or ATP in the presence of apyrase (ATP-ase) or A804598 (P2X7R-antagonist). CBV-TP and ATP levels were evaluated by HPLC, while binding of Abacavir, CBV-TP and ATP to P2X7R was assessed by radioligand and docking studies. Hypersensitivity studies explored a potential allosteric action of Abacavir. Clinical concentrations of Abacavir (20 µmol/L) induced leukocyte-endothelial cell interactions by specifically activating P2X7R, but the drug did not show affinity for the P2X7R ATP-binding site (site 1). CBV-TP levels were undetectable in Abacavir-treated cells, while those of ATP were unaltered. The effects of Abacavir were Apyrase-dependent, implying dependence on endogenous ATP. Exogenous ATP induced a profile of proinflammatory actions similar to Abacavir, but was not entirely P2X7R-dependent. Docking calculations suggested ATP-binding to sites 1 and 2, and Abacavir-binding only to allosteric site 2. A combination of concentrations of Abacavir (1 µmol/L) and ATP (0.1 µmol/L) that had no effect when administered separately induced leukocyte-endothelium interactions mediated by P2X7R and involving Connexin43 channels. Therefore, Abacavir acts as a positive allosteric modulator of P2X7R, turning low concentrations of endogenous ATP themselves incapable of stimulating P2X7R into a functional proinflammatory agonist of the receptor.
Treatment Outcomes of Extensively Drug-Resistant Tuberculosis in Pakistan: A Countrywide Retrospective Record Review
Authors: Abubakar Muhammad , Ahmad Nafees , Ghafoor Abdul , Latif Abdullah , Ahmad Izaz , Atif Muhammad , Saleem Fahad , Khan Shereen , Khan Amjad , Khan Amer Hayat 
Published: March 2021

Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan.Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value &lt;0.05 reflected a statistical significant association.Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80–45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients’ age of &gt;60 years (OR = 4.69, 95%CI:1.57–15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14–4.85) had statistically significant positive association with death, whereas baseline body weight &gt;40 kg (OR = 0.43, 95%CI:0.25–0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19–0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04–3.54) with LTFU.Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes.
Health, Work, and Family Strain – Psychosocial Experiences at the Early Stages of Long-Term Sickness Absence
Authors: Standal Martin I. , Foldal Vegard S. , Hagen Roger , Aasdahl Lene , Johnsen Roar , Fors Egil A. , Solbjør Marit 
Published: March 2021

BackgroundKnowledge about the psychosocial experiences of sick-listed workers in the first months of sick leave is sparse even though early interventions are recommended. The aim of this study was to explore psychosocial experiences of being on sick leave and thoughts about returning to work after 8–12 weeks of sickness absence.MethodsSixteen individuals at 9–13 weeks of sick leave participated in semi-structured individual interviews. Data was analyzed through Giorgi’s descriptive phenomenological method.ResultsThree themes emerged: (1) energy depleted, (2) losing normal life, (3) searching for a solution. A combination of health, work, and family challenges contributed to being drained of energy, which affected both work- and non-work roles. Being on sick leave led to a loss of social arenas and their identity as a contributing member of society. Participants required assistance to find solutions toward returning to work.ConclusionEven in this early stage of long-term sick leave, sick listed workers faced complex challenges in multiple domains. Continuing sick leave was experienced as necessary but may challenge personal identity and social life. Those not finding solutions may benefit from additional early follow-up that examine work-related, social and personal factors that influence return to work.
“Doing Things Together Is What It’s About”: An Interpretative Phenomenological Analysis of the Experience of Group Therapeutic Songwriting From the Perspectives of People With Dementia and Their Family Caregivers
Authors: Clark Imogen N. , Baker Felicity A. , Tamplin Jeanette , Lee Young-Eun C. , Cotton Alice , Stretton-Smith Phoebe A. 
Published: March 2021

BackgroundThe wellbeing of people living with dementia and their family caregivers may be impacted by stigma, changing roles, and limited access to meaningful opportunities as a dyad. Group therapeutic songwriting (TSW) and qualitative interviews have been utilized in music therapy research to promote the voices of people with dementia and family caregivers participating in separate songwriting groups but not together as dyads.ProceduresThis study aimed to explore how ten people with dementia/family caregiver dyads experienced a 6-week group TSW program. Dyads participated in homogenous TSW groups involving 2–4 dyads who were either living together in the community (2 spousal groups) or living separately because the person with dementia resided in a care home (1 family group, 1 spousal group). The TSW program, informed by personhood, couplehood, family centered and group process frameworks, involved creating original lyrics through song parody and song collage. Qualified Music Therapists facilitated sessions and interviewed each dyad separately. Interviews were analyzed using interpretative phenomenological analysis.FindingsFive recurrent group themes were developed, indicating group TSW: (1) was a positive shared experience, benefiting both members of the dyad and motivating further engagement with music; (2) stimulated mental processes and reignited participants’ interests and skills; (3) provided meaningful opportunities for reflection and connection with memories and life experiences; and (4) prompted interaction and collaboration, leading to social connections, empathic relationships and experiences of inclusion. Participants also highlighted how: (5) the facilitated process supported engagement, highlighting abilities and challenging doubts.ConclusionDyads identified group TSW as an opportunity to recognize strengths, voice ideas and opinions, share meaningful experiences, and do “more with music.” Participants valued TSW as a new, creative and stimulating experience that enabled connection with self and others and led to feelings of pride and achievement. Our findings further recognize how therapeutic intention and approach were reflected in participants’ engagement and responses regardless of dementia stage and type, dyad relationship, or musical background. This research may broaden perspectives and expand understanding about how people with dementia and their family caregivers access and engage in music therapy.
The Outcomes of Health Education Programme on Stress Level Among the Caregivers of Post Total Knee Replacement Surgery
Authors: Samsuddin Md. Fadlisham , Karim Jalina , Salim Azizul Akram 
Published: March 2021

Introduction: Stress level among the caregivers is often related to caregivers' lack of knowledge and skill to care for the patients. A health education program to the caregivers is one of the important elements in increasing the knowledge and skills in managing patients at home. The specific objectives of this study were to determine caregiver's stress level in managing post total knee replacement (TKR) patients pre and post of a health education program.Materials and Methods: A clinical intervention trial design was conducted in Hospital Universiti Sains Malaysia (HUSM) with a sample size of 32 caregivers. A validated Zarit Burden Interview (ZBI) questionnaire was used to measure the stress level pre and post of the health education program on the management of patients post-TKR surgery which was adopted from Fresno Surgical Hospital in California.Results: The findings showed that there was a significant difference between pre and post level of stress (p ≤ 0.001).Conclusion: This study revealed the positive outcome of the health education program. It reduced the stress level among the caregivers in caring for their relatives with post-TKR surgery.