bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study
Authors: Hsieh Hui-Hsia , Wu Tien-Yuan , Chen Chi-Hua , Kuo Yu-Hung , Hour Mann-Jen 
Published: June 2023

Background: Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy. Objective: In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). Design: We conducted a retrospective analysis. Methods: In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively. Result : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001). Conclusion: Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.
Retrospective characterization of nodal marginal zone lymphoma
Authors: Stuver Robert , Drill Esther , Qualls David , Okwali Michelle , Lee Batlevi Connie , Caron Philip C. , Dogan Ahmet , Epstein-Peterson Zachary D. , Falchi Lorenzo , Hamlin Paul A. , Horwitz Steven M. , Imber Brandon S. , Intlekofer Andrew M. , Johnson William T. , Khan Niloufer , Kumar Anita , Lahoud Oscar B. , Lue Jennifer Kimberly , Matasar Matthew J. , Moskowitz Alison J. , Noy Ariela , Owens Colette N. , Palomba M. Lia , Schöder Heiko , Vardhana Santosha A. , Yahalom Joachim , Zelenetz Andrew D. , Salles Gilles , Straus David J. 
Published: June 2023

Abstract
Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin B-cell lymphoma that has historically been difficult to define, though is now formally recognized by the World Health Organization Classification. To better characterize the clinical outcomes of patients with NMZL, we reviewed a sequential cohort of 187 patients with NMZL to describe baseline characteristics, survival outcomes, and time-to-event data. Initial management strategies were classified into five categories: observation, radiation, anti-CD20 monoclonal antibody therapy, chemoimmunotherapy, or other. Baseline Follicular Lymphoma International Prognostic Index scores were calculated to evaluate prognosis. A total of 187 patients were analyzed. The five-year overall survival was 91% (95% confidence interval [CI], 87-95), with a median follow-up time of 71 months (range, 8-253) among survivors. A total of 139 patients received active treatment at any point, with a median follow-up time of 56 months (range, 13-253) among survivors who were never treated. The probability of remaining untreated at five years was 25% (95% CI, 19-33). For those initially observed, the median time to active treatment was 72 months (95% CI, 49-not reached). For those who received at least one active treatment, the cumulative incidence of receiving a second active treatment at 60 months was 37%. Transformation to large B-cell lymphoma was rare, with a cumulative incidence of 15% at 10 years. In summary, our series is a large cohort of uniformly diagnosed NMZL with detailed analyses of survival and time to event analyses. We showed that NMZL commonly presents as an indolent lymphoma for which initial observation is often a reasonable strategy.
A modified CALGB 10403 in adolescents and young adults with acute lymphoblastic leukemia in Central America
Authors: Rangel-Patiño Juan , Lee-Tsai Yu Ling , Urbalejo-Ceniceros Victor Itaí , Luna-Perez Maria Elena Monserrat , Espinosa-Bautista Karla Adriana , Amador Lauro Fabian , Cabrera-García Álvaro , Balderas-Delgado Carolina , Inclan-Alarcon Sergio I , Neme-Yunes Yvette , Sanchez-Albarrán Jose Manuel , Apodaca Elia Ixel , Meillon-García Luis , Stock Wendy , Demichelis-Gómez Roberta 
Published: June 2023

Abstract
Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults. Historically, this patient group has been treated using adult-based regimens, which entails a high rate of treatment-related mortality and a poor overall survival (OS). The use of the CALGB 10403, a pediatric-inspired regimen, has been proven effective in this patient subgroup. Nonetheless, low- and middle-income countries (LMICs) may present limited access to standard care treatments implemented elsewhere, warranting the need for further research to improve outcomes among vulnerable populations. In this study, we present the outcomes in terms of safety and effectiveness of using a modified CALGB 10403 regimen to reflect drug and resource availability in LMICs. Modifications included the use of Escherichia coli asparaginase,6-mercaptopurine instead of thioguanine and the use of rituximab among patients with CD20+. A total of 95 patients with a median age of 23 (range, 14-49) years treated with this modified scheme were prospectively assessed at 5 centers in Mexico and 1 in Guatemala. Among these, 87.8% achieved a complete response after induction. During follow-up, 28.3% of patients relapsed. Two-year OS rate was 72.1%. Factors associated with worse OS included hyperleukocytosis (hazard ratio [HR], 4.28; 95% confidence interval [CI], 1.81-10.10) and postinduction minimal residual disease (HR, 4.67; 95% CI, 1.75-12.44). Most patients presented hepatotoxicity (51.6% and 53.7% during induction and consolidation, respectively), and the treatment-related mortality was 9.5%. Overall, results highlight that implementing a modified CALGB 10403 regimen in Central America is feasible, and it is associated with improvements in clinical outcomes and a manageable safety profile.
Cardiac events after standard of care idecabtagene vicleucel for relapsed and refractory multiple myeloma
Authors: Lee Dae Hyun , Kumar Abhishek , Mohammed Turab , Peres Lauren C. , Alsina Melissa , Bachmeier Christina , Blue Brandon J. , Brayer Jason , Chandrasekhar Sanjay , Grajales Cruz Ariel , De Avila Gabe , Elmariah Hany , Faramand Rawan , Freeman Ciara , Jain Michael , Khadka Sushmita , Khimani Farhad , Liu Hien , Nishihori Taiga , Oswald Laura B. , Castaneda Puglianini Omar A. , Shain Kenneth H. , Smith Eric , Baz Rachid C. , Locke Frederick L. , Oliveira Guilherme H. , Alomar Mohammed , Hansen Doris K. 
Published: June 2023

Abstract
Idecabtagene vicleucel (ide-cel) is a type of B-cell maturation antigen (BCMA)–targeting chimeric antigen receptor T-cell (CAR-T) approved for the treatment of relapsed and refractory multiple myeloma (RRMM). Currently, the incidence of cardiac events associated with ide-cel remains unclear. This was a retrospective single-center observational study of patients treated with ide-cel for RRMM. We included all consecutive patients who received standard-of-care ide-cel treatment at least 1-month follow-up. Baseline clinical risk factors, safety profile, and responses were examined based on the development of a cardiac event. A total of 78 patients were treated with ide-cel, and 11 patients (14.1%) developed cardiac events: heart failure (5.1%), atrial fibrillation (10.3%), nonsustained ventricular tachycardia (3.8%), and cardiovascular death (1.3%). Only 11 of the 78 patients had repeat echocardiogram. Baseline risk factors associated with the development of cardiac events included being female sex and having poor performance status, λ light-chain disease, and advanced Revised International Staging System stage. Baseline cardiac characteristics were not associated with cardiac events. During index hospitalization after CAR-T, higher-grade (≥grade 2) cytokine release syndrome (CRS) and immune cell–associated neurologic syndrome were associated with cardiac events. In multivariable analyses, the hazard ratio for the association of the presence of cardiac events with overall survival (OS) was 2.66 and progression-free survival (PFS) was 1.98. Ide-cel CAR-T for RRMM was associated with similar cardiac events as other types of CAR-T. Worse baseline performance status and higher-grade CRS and neurotoxicity were associated with cardiac events after BCMA-directed CAR-T-cell therapy. Our results suggest that the presence of cardiac events may confer worse PFS or OS; although because of the small sample size, the power to detect an association was limited.
Revisiting dose-finding of monoclonal antibodies in migraine
Authors: Al-Hassany Linda , Karsan Nazia , Lampl Christian , Goadsby Peter J. , MaassenVanDenBrink Antoinette 
Published: June 2023

AbstractMigraine is a debilitating disorder, and while the introduction of monoclonal antibodies (mAbs) has led to efficacious and tolerable responses, a substantial number of patients are so-called “non-responders”. We introduce reasons for this insufficient response, including insufficient blockade of Calcitonin Gene-Related Peptide (CGRP) or its receptor. We present a clinical case, i.e. a female migraine patient who mistakenly administered supratherapeutic (three-fold higher) doses of erenumab leading to more efficacious clinical responses without any side-effects. This example illustrates that the initial dosages might have been too low, resulting in a remaining undesired increased effect of CGRP. While a capsaicin forearm model has repeatedly been used to evaluate the pharmacokinetic-pharmacodynamic relationship of mAbs, we provide directions to revisit or reconsider dose-finding and dose-ranging of these drugs. These directions include (i) refinement and application of a capsaicin forehead model (instead of a forearm model) to study trigeminovascular activity and improve dosing, and (ii) reconsideration of trial populations. Indeed, the dose-finding studies were mainly performed in relatively young and normal-weight males, while most phase III/IV trials are marked by a high female-to-male ratio, mainly consisting of overweight to obese females. Considering these aspects in future trials could optimize healthcare for a larger proportion of migraine patients.
Hormone replacement therapy in women and risk of carpal tunnel syndrome: a systematic review and metaanalysis
Authors: Manosroi Worapaka , Atthakomol Pichitchai , Phinyo Phichayut , Danpanichkul Pojsakorn 
Published: June 2023

Abstract
Background
Carpal tunnel syndrome (CTS) is the most common entrapment mononeuropathy. Menopausal status and/or estrogen level may play a role in CTS. The evidence regarding the association between hormone replacement therapy (HRT) in postmenopausal women and CTS is still conflicting. This meta-analysis aimed to investigate the association between carpal tunnel syndrome (CTS) and women using hormone replacement therapy (HRT).

Methods
A search was conducted in the PubMed/Medline, Scopus, Embase, and Cochrane databases, from their inception through July 2022. Studies which reported on the association between any type of HRT use and the risk of developing CTS in postmenopausal women compared to a control group were included. Studies which did not include a control group were excluded. Of the 1573 articles extracted from database searches, seven studies involving 270,764 women were included of which 10,746 had CTS. The association between CTS and HRT use was evaluated using the pooled odds ratio (OR) with a 95% confidence interval (CI) under random-effects modelling. Risk of bias in each study was assessed using the Newcastle–Ottawa Scale (NOS) and version 2 of the Cochrane tool for assessing risk of bias in randomized trials (RoB 2).

Results
HRT use showed no statistically significant association with a higher risk of CTS with pooled odds ratio (OR) 1.49, 95% confidence interval (CI) 0.99–2.23, and p = 0.06, although high heterogeneity among the studies was observed (I2 97.0%, Q-test p-value < 0.001). Subgroup analysis of groups in non-randomized controlled studies showed a significantly increased risk of CTS, while groups in randomized controlled studies showed a decreased risk of CTS (pooled OR 1.87, 95% CI 1.24–2.83 versus pooled OR 0.79, 95% CI 0.69–0.92, respectively) with the p-value of group difference < 0.001. The risk of bias in most of the included studies was estimated to be low.

Conclusions
This meta-analysis supports the safety of using HRT in postmenopausal women with potential risk factors for CTS.

Level of evidence
I, Prognosis.
Registration: INPLASY (202280018).
Genetic architecture of acute hyperthermia resistance in juvenile rainbow trout (Oncorhynchus mykiss) and genetic correlations with production traits
Authors: Lagarde Henri , Lallias Delphine , Patrice Pierre , Dehaullon Audrey , Prchal Martin , François Yoannah , D’Ambrosio Jonathan , Segret Emilien , Acin-Perez Ana , Cachelou Frederic , Haffray Pierrick , Dupont-Nivet Mathilde , Phocas Florence 
Published: June 2023

Abstract
Background
Selective breeding is a promising solution to reduce the vulnerability of fish farms to heat waves, which are predicted to increase in intensity and frequency. However, limited information about the genetic architecture of acute hyperthermia resistance in fish is available. Two batches of sibs from a rainbow trout commercial line were produced: the first (N = 1382) was phenotyped for acute hyperthermia resistance at nine months of age and the second (N = 1506) was phenotyped for main production traits (growth, body length, muscle fat content and carcass yield) at 20 months of age. Fish were genotyped on a 57 K single nucleotide polymorphism (SNP) array and their genotypes were imputed to high-density based on the parent’s genotypes from a 665 K SNP array.

Results
The heritability estimate of resistance to acute hyperthermia was 0.29 ± 0.05, confirming the potential of selective breeding for this trait. Since genetic correlations of acute hyperthermia resistance with the main production traits near harvest age were all close to zero, selecting for acute hyperthermia resistance should not impact the main production traits, and vice-versa. A genome-wide association study revealed that resistance to acute hyperthermia is a highly polygenic trait, with six quantitative trait loci (QTL) detected, but explaining less than 5% of the genetic variance. Two of these QTL, including the most significant one, may explain differences in acute hyperthermia resistance across INRAE isogenic lines of rainbow trout. Differences in mean acute hyperthermia resistance phenotypes between homozygotes at the most significant SNP was 69% of the phenotypic standard deviation, showing promising potential for marker-assisted selection. We identified 89 candidate genes within the QTL regions, among which the most convincing functional candidates are dnajc7, hsp70b, nkiras2, cdk12, phb, fkbp10, ddx5, cygb1, enpp7, pdhx and acly.

Conclusions
This study provides valuable insight into the genetic architecture of acute hyperthermia resistance in juvenile rainbow trout. We show that the selection potential for this trait is substantial and selection for this trait should not be too detrimental to improvement of other traits of interest. Identified functional candidate genes provide new knowledge on the physiological mechanisms involved in acute hyperthermia resistance, such as protein chaperoning, oxidative stress response, homeostasis maintenance and cell survival.
Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China
Authors: Jing Cao , Wei Tang , Ning Wang , Fang Zheng , Gang Xiao , Xingzhi Wang , Guoqiang Zhou , Min Wang 
Published: June 2023

Abstract
Background
Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China.

Methods
A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL.

Results
A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3–93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2–84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons.

Conclusions
Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.
Clonal diversity of Staphylococcus aureus isolates in clinical specimens from selected health facilities in Ethiopia
Authors: Ibrahim Rajiha Abubeker. , Mekuria Zelalem , Wang Shu-Hua , Mediavilla Jose R. , Kreiswirth Barry , Seyoum Eyasu T. , Mariam Solomon H. , Gebreyes Wondwossen A. , Kefale Tesfa Addis , Guma Geremew Tasew , Berhe Nega 
Published: June 2023

AbstractStaphylococcus aureus is among the top three causative agents of nosocomial infection in Ethiopia. The majority of studies in Ethiopia have focused on the epidemiology of S. aureus in hospital settings, with limited molecular genotyping results. Molecular characterization of S. aureus is essential for identification of strains, and contributes to the control and prevention of S. aureus infection. The aim of the current study was to determine the molecular epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates recovered from clinical specimens in Ethiopia. A total of 161 MSSA and 9 MRSA isolates were characterized using pulsed-field gel electrophoresis (PFGE) and staphylococcal protein A (spa) typing. Based on the PFGE analysis, MSSA isolates were grouped into eight pulso-types groups (from A to I), while MRSA isolates clustered into three (A, B and C) pulso-types with more than 80% similarity. The spa typing analysis showed diversity of S. aureus with 56 distinct spa types. Spa type t355 was most prevalent (56/170, 32.9%), while eleven new spa types were detected including t20038, t20039, and t20042. The identified spa types were clustered into 15 spa-clonal complexes (spa-CCs) using BURP analysis; novel/unknown spa types were further subjected to MLST analysis. The majority of isolates belonged to spa-CC 152 (62/170, 36.4%), followed by spa-CC 121 (19/170, 11.2%), and spa-CC 005 (18 /170, 10.6%). Of the nine MRSA isolates, 2 (22.2%) were spa-CC 239 with staphylococcal cassette chromosome (SCC)mec III. These findings highlight the diversity of S. aureus strains in Ethiopia, as well as the presence of potentially epidemic strains circulating in the country necessitating further characterization of S. aureus for antimicrobial resistance detection and infection prevention purposes.
Feasible intervention combinations for achieving a safe exit of the Zero-COVID policy in China and its determinants: an individual-based model study
Authors: Cheng Qu , Hao Xingjie , Wu Degang , Wang Qi , Spear Robert C. , Wei Sheng 
Published: June 2023

Abstract
Background
Although several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how the thresholds change with the assumed key epidemiological parameters and population characteristics.

Methods
We developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons).

Results
We identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations.

Conclusions
The analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China’s cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration.