bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough
Authors: Li Wanzhen , Zhang Tongyangzi , Gu Wenhua , Shi Wenbo , Wang Shengyuan , Zhu Yiqing , Shi Cuiqin , Yu Li , Xu Xianghuai 
Published: January 2024

Background: Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC. Objectives: This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC. Design: For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results. Methods: The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP. Results: Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), −4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 ( p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, −19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, −8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources. Conclusions: The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting. Trial registration: This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).
Evolocumab use in clinical practice in Switzerland: final data of the observational HEYMANS cohort study
Authors: Sudano Isabella , Krähenbühl Stephan , Mach François , Anstett Anne , Dhalwani Nafeesa , Bridges Ian , Sibartie Mahendra , Ray Kausik K. 
Published: January 2024

Aims: The HEYMANS study observed patients receiving evolocumab as part of routine clinical hyperlipidemia management. It was designed to capture data on clinical parameters relevant to health authorities and physicians. Methods: This was a European multi-country observational cohort serial chart review study; data on the Swiss cohort are reported here. Patients were prescribed evolocumab as per the Swiss reimbursement criteria in force at the time and were invited chronologically. The study consisted of a 6-month period prior to initiation of evolocumab, a 12-month core observation period (entered by 75 patients, completed by 74 patients), and an 18-month extended observation period (entered by 40 patients, completed by 34 patients). The primary objective was to describe the clinical characteristics of patients receiving evolocumab. Secondary objectives included to describe lipid levels, evolocumab use, and patterns of use of other lipid-lowering therapies (LLT, that is, statins and/or ezetimibe) over time. The study was conducted in the Swiss cohort between May 2017 and June 2021. Results: Patients who received evolocumab in Swiss routine practice mostly were in secondary prevention (93%) and had a history of statin intolerance (85%) with 53% receiving no background LLT. One-third had familial hypercholesterolemia. Patients initiated evolocumab at a median low-density lipoprotein cholesterol (LDL-C) of 3.6 mmol/L, which decreased by 54% within 3 months to 1.6 mmol/L and was stable thereafter. Overall, 61% achieved the LDL-C goal of <1.4 mmol/L with more patients attaining this goal when they received evolocumab with a statin and/or ezetimibe (84%) compared to 41% when receiving evolocumab alone. An LDL-C reduction of ⩾50% was achieved by 85% of patients. Persistence with evolocumab at 12 months was 85%. Conclusion: In Swiss clinical practice, evolocumab was mainly prescribed to patients with very high cardiovascular risk, who had very high LDL-C levels. Most patients continued to use evolocumab throughout the study period. In these patients, LDL-C was reduced by >50% within 3 months and LDL-C reductions were maintained over time. Guideline-recommended LDL-C goals for this very high-risk cohort were more frequently attained in patients receiving a combination of statin and/or ezetimibe and evolocumab. Trial registration: ClinicalTrials.gov Identifier: NCT02770131.
Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis
Authors: Palaiodimou Lina , Katsanos Aristeidis H. , Turc Guillaume , Romoli Michele , Theodorou Aikaterini , Lemmens Robin , Sacco Simona , Velonakis Georgios , Vlachopoulos Charalambos , Tsivgoulis Georgios 
Published: January 2024

Background: Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. Objectives: We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. Design: A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Data sources and methods: Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Results: Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01–1.36; I2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94–1.17; I2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92–1.40; I2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70–4.00; I2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90–1.29; I2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81–1.49; I2 = 0%) were similar between the groups. Conclusion: Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. Trial registration: PROSPERO registration ID: CRD42023448707.
Educational interventions for promoting sexual and reproductive health in school counselors: a three-arm, randomized control trial comparing lecturing, buzz group and role-play
Authors: Alavi-Arjas Fatemeh , Firouzabadi Maryam , Farnam Farnaz , Balvardi Mohadeseh , Taheri Mahdiye , Riazi Hedyeh , Pourramezani Naimeh , Keshavarz Zohreh 
Published: January 2024

Background and objective: School-based sexual and reproductive health (SRH) education is often reported as being inadequate and/or inconsistent. This study aimed to investigate the educational interventions for promoting SRH in school counselors and compare the results in three groups: lecturing, buzz group and role-play. Materials and methods: An intervention quasi-experimental design was employed to evaluate the usefulness of educating SRH topics by using interactive teaching methods for 120 school counselors. Changes in the participants’ knowledge, attitudes and self-efficacy toward SRH education were evaluated by each group using a pretest and a posttest. Results: The results of this study revealed that 75% of counselors deemed SRH training vital and felt that the best SRH educators are health care providers and the reason might be their lack of educational skills. They also stated that the most significant barriers to education in schools include concerns about parental feedback and lack of appropriate abilities. Conclusion: The present study showed that the use of all three methods (lecturing, buzz groups and role-play) in SRH training improves the level of knowledge, attitude and self-efficacy; although role-play could have been more effective than lecturing in improving counselors’ knowledge.
High CTLA-4 transcriptomic expression correlates with high expression of other checkpoints and with immunotherapy outcome
Authors: Krishnamurthy Nithya , Nishizaki Daisuke , Lippman Scott M. , Miyashita Hirotaka , Nesline Mary K. , Pabla Sarabjot , Conroy Jeffrey M. , DePietro Paul , Kato Shumei , Kurzrock Razelle 
Published: January 2024

Background: CTLA-4 impedes the immune system’s antitumor response. There are two Food and Drug Administration-approved anti-CTLA-4 agents – ipilimumab and tremelimumab – both used together with anti-PD-1/PD-L1 agents. Objective: To assess the prognostic implications and immunologic correlates of high CTLA-4 in tumors of patients on immunotherapy and those on non-immunotherapy treatments. Design/methods: We evaluated RNA expression levels in a clinical-grade laboratory and clinical correlates of CTLA-4 and other immune checkpoints in 514 tumors, including 489 patients with advanced/metastatic cancers and full outcome annotation. A reference population (735 tumors; 35 histologies) was used to normalize and rank transcript abundance (0–100 percentile) to internal housekeeping gene profiles. Results: The most common tumor types were colorectal (140/514, 27%), pancreatic (55/514, 11%), breast (49/514, 10%), and ovarian cancers (43/514, 8%). Overall, 87 of 514 tumors (16.9%) had high CTLA-4 transcript expression (⩾75th percentile rank). Cancers with the largest proportion of high CTLA-4 transcripts were cervical cancer (80% of patients), small intestine cancer (33.3%), and melanoma (33.3%). High CTLA-4 RNA independently/significantly correlated with high PD-1, PD- L2, and LAG3 RNA levels (and with high PD-L1 in univariate analysis). High CTLA-4 RNA expression was not correlated with survival from the time of metastatic disease [ N = 272 patients who never received immune checkpoint inhibitors (ICIs)]. However, in 217 patients treated with ICIs (mostly anti-PD-1/anti-PD- L1), progression-free survival (PFS) and overall survival (OS) were significantly longer among patients with high versus non-high CTLA-4 expression [hazard ratio, 95% confidence interval: 0.6 (0.4–0.9) p = 0.008; and 0.5 (0.3–0.8) p = 0.002, respectively]; results were unchanged when 18 patients who received anti-CTLA-4 were omitted. Patients whose tumors had high CTLA-4 and high PD-L1 did best; those with high PD-L1 but non-high CTLA-4 and/or other expression patterns had poorer outcomes for PFS ( p = 0.004) and OS ( p = 0.009) after immunotherapy. Conclusion: High CTLA-4, especially when combined with high PD-L1 transcript expression, was a significant positive predictive biomarker for better outcomes (PFS and OS) in patients on immunotherapy.
Combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer: a real-world cohort study and meta-analysis
Authors: Hong XinYi , Qiu ShanHu , Ding Bo , Xu Hao , Shen Yang 
Published: January 2024

Background: Anlotinib is a novel oral small-molecule receptor tyrosine kinase inhibitor. However, the efficacy and safety of its combined use with chemotherapy remain unclear in patients with advanced ovarian cancer. Objectives: To assess the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with advanced ovarian cancer. Design: A multi-center retrospective real-world analysis and a meta-analysis. Data sources and methods: We enrolled patients with advanced ovarian cancer who received a combination therapy of Anlotinib and chemotherapy from 15 medical centers. We also searched electronic databases for studies assessing the efficacy and safety of the combined use of Anlotinib with chemotherapy in patients with ovarian cancer. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), and median progression-free survival (mPFS). Results: A total of 71 patients, who were predominantly recurrent cases, were included in the real-world study. The ORR and DCR of the included patients were 40.8% and 76.1%, respectively; and their mPFS was 4.6 months. The log-rank test showed that previous antiangiogenic therapy was related to a longer mPFS (p < 0.05). Five studies in total were eligible for meta-analysis. The random-effects meta-analysis model showed that the ORR, DCR, and mPFS were 33.8% [95% confidence interval (CI) 22.7–44.8% from four studies], 90.6% (95% CI 73.6–99.9% from five studies), and 6.6 months (95% CI 4.9–8.4 months from five studies). The most common adverse events were hand-foot syndrome and hypertension. Conclusion: The combined use of Anlotinib with chemotherapy showed potential in treating patients with advanced ovarian cancer, with a tolerable safety profile.
The Actin Cytoskeleton as a Regulator of Proteoglycan 4
Authors: Gonzalez-Nolde Sofia , Schweiger Cameron J. , Davis Elizabeth E.R. , Manzoni Thomas J. , Hussein Samer M.I. , Schmidt Tannin A. , Cone Stephanie G. , Jay Gregory D. , Parreno Justin 
Published: January 2024

Objective The superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies. Materials and methods A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed. Results PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling. Conclusion Actin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.
Functional outcome improvement from 3 to 12 months after intracerebral hemorrhage
Authors: Morotti Andrea , Nawabi Jawed , Pilotto Andrea , Toffali Maddalena , Busto Giorgio , Mazzacane Federico , Cavallini Anna , Laudisi Michele , Gentile Luana , Viola Maria Maddalena , Schlunk Frieder , Bartolini Diletta , Paciaroni Maurizio , Magoni Mauro , Bassi Chiara , Simonetti Luigi , Fainardi Enrico , Casetta Ilaria , Zini Andrea , Padovani Alessandro 
Published: January 2024

Introduction: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH. Materials and Methods: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression. Results: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96–1.00, p = 0.017 and OR 0.45, 95% CI 0.25–0.81, p = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07–2.61, p = 0.023). Patients with mild-moderate disability at 3 months (mRS 2–3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68–20.86, p < 0.001). Discussion and Conclusion: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice.
Coping in patients with hematologic malignancies undergoing hematopoietic cell transplantation
Authors: Newcomb Richard , Amonoo Hermioni L. , Nelson Ashley M. , Choe Joanna , Holmbeck Katherine , Nabily Anisa , Lee Stephanie J. , LeBlanc Thomas W. , El-Jawahri Areej 
Published: January 2024

Abstract
Patients undergoing hematopoietic cell transplantation (HCT) must cope with physical and psychological symptoms. Yet, studies examining pre-HCT coping are limited. We aimed to characterize pre-HCT coping, evaluate the association of coping with baseline quality of life (QOL) and psychological distress, and identify sociodemographic factors associated with pre-HCT coping. We conducted a cross-sectional analysis of baseline data from a multisite randomized supportive care intervention trial among patients with hematologic malignancies undergoing allogeneic or autologous HCT. We assessed patient-reported QOL, psychological distress, and coping within 72 hours of admission for HCT. We used the median split method to dichotomize coping and multivariate regression analyses to characterize the association of coping with psychological distress and QOL. Of patients awaiting HCT (n = 360; mean age, 55.4 years; 49.7% autologous), 43.5% were high users of approach-oriented coping, whereas 31.3% were high users of avoidant coping. Patients reported high use of emotional support (60.9%), acceptance (51.2%), self-blame (33%), and denial (31.3%). Older age (≥65 years) was associated with less frequent use of avoidant coping (odds ratio, 0.5; P = .01). Approach-oriented coping was associated with better pre-HCT QOL (Beta(B) = 6.7; P = .001), and lower depression (B = −1.1; P = .001) and anxiety (B = −0.9; P = .02) symptoms. Avoidant coping was associated with worse pre-HCT QOL (B = −13.3; P &lt; .001) and symptoms of depression (B = 1.9; P &lt; .001), anxiety (B = 3.1; P &lt; .001), and posttraumatic stress disorder (B = 8.1; P &lt; .001). Pre-HCT coping is strongly associated with psychological distress and QOL. These data support the need for interventions to address coping during HCT hospitalization. This clinical trial was registered at www.clinicaltrials.gov as #NCT03641378.
Reprogramming of pyrimidine nucleotide metabolism supports vigorous cell proliferation of normal and malignant T cells
Authors: Watanabe Tatsuro , Yamamoto Yuta , Kurahashi Yuki , Kawasoe Kazunori , Kidoguchi Keisuke , Ureshino Hiroshi , Kamachi Kazuharu , Yoshida-Sakai Nao , Fukuda-Kurahashi Yuki , Nakamura Hideaki , Okada Seiji , Sueoka Eisaburo , Kimura Shinya 
Published: January 2024

Abstract
Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human T-cell lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL cells through regulation of uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes the monophosphorylation of cytidine/uridine and their analogues during pyrimidine biosynthesis and drug metabolism. We found that UCK2 was overexpressed aberrantly in HTLV-1–infected T cells but not in normal T cells. T-cell activation via T-cell receptor (TCR) signaling induced expression of UCK2 in normal T cells. Somatic alterations and epigenetic modifications in ATL cells activate TCR signaling. Therefore, we believe that expression of UCK2 in HTLV-1–infected cells is induced by dysregulated TCR signaling. Recently, we established azacitidine-resistant (AZA-R) cells showing absent expression of UCK2. AZA-R cells proliferated normally in vitro, whereas UCK2 knockdown inhibited ATL cell growth. Although uridine and cytidine accumulated in AZA-R cells, possibly because of dysfunction of pyrimidine salvage biosynthesis induced by loss of UCK2 expression, the amount of UTP and CTP was almost the same as in parental cells. Furthermore, AZA-R cells were more susceptible to an inhibitor of dihydroorotic acid dehydrogenase, which performs the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, and more resistant to dipyridamole, an inhibitor of pyrimidine salvage biosynthesis, suggesting that AZA-R cells adapt to UCK2 loss by increasing de novo pyrimidine nucleotide biosynthesis. Taken together, the data suggest that fine-tuning pyrimidine biosynthesis supports vigorous cell proliferation of both normal T cells and ATL cells.