bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment
Authors: Petrosyan Edgar , Fares Jawad , Fernandez Luis G. , Yeeravalli Ragini , Dmello Crismita , Duffy Joseph T. , Zhang Peng , Lee-Chang Catalina , Miska Jason , Ahmed Atique U. , Sonabend Adam M. , Balyasnikova Irina V. , Heimberger Amy B. , Lesniak Maciej S. 
Published: January 2023

Abstract
Immunotherapy has emerged as a powerful strategy for halting cancer progression. However, primary malignancies affecting the brain have been exempt to this success. Indeed, brain tumors continue to portend severe morbidity and remain a globally lethal disease. Extensive efforts have been directed at understanding how tumor cells survive and propagate within the unique microenvironment of the central nervous system (CNS). Cancer genetic aberrations and metabolic abnormalities provoke a state of persistent endoplasmic reticulum (ER) stress that in turn promotes tumor growth, invasion, therapeutic resistance, and the dynamic reprogramming of the infiltrating immune cells. Consequently, targeting ER stress is a potential therapeutic approach. In this work, we provide an overview of how ER stress response is advantageous to brain tumor development, discuss the significance of ER stress in governing antitumor immunity, and put forth therapeutic strategies of regulating ER stress to augment the effect of immunotherapy for primary CNS tumors.
Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma
Authors: Danlos François-Xavier , Texier Matthieu , Job Bastien , Mouraud Severine , Cassard Lydie , Baldini Capucine , Varga Andrea , Yurchenko Andrey A. , Rabeau Audrey , Champiat Stéphane , Letourneur Diane , Bredel Delphine , Susini Sandrine , Blum Yuna , Parpaleix Aurelien , Parlavecchio Cedric , Tselikas Lambros , Fahrner Jean-Eudes , Goubet Anne-Gaelle , Rouanne Mathieu , Rafie Saloomeh , Abbassi Alae , Kasraoui Ines , Breckler Marie , Farhane Siham , Ammari Samy , Laghouati Salim , Gazzah Anas , Lacroix Ludovic , Besse Benjamin , Droin Nathalie , Deloger Marc , Cotteret Sophie , Adam Julien , Zitvogel Laurence , Nikolaev Sergey I. , Chaput Nathalie , Massard Christophe , Soria Jean-Charles , Gomez-Roca Carlos , Zalcman Gerard , Planchard David , Marabelle Aurelien 
Published: January 2023

AbstractCancer immunotherapy combinations have recently been shown to improve the overall survival of advanced mesotheliomas, especially for patients responding to those treatments. We aimed to characterize the biological correlates of malignant pleural mesotheliomas’ primary resistance to immunotherapy and antiangiogenics by testing the combination of pembrolizumab, an anti–PD-1 antibody, and nintedanib, a pan-antiangiogenic tyrosine kinase inhibitor, in the multicenter PEMBIB trial (NCT02856425). Thirty patients with advanced malignant pleural mesothelioma were treated and explored. Unexpectedly, we found that refractory patients were actively recruiting CD3+CD8+ cytotoxic T cells in their tumors through CXCL9 tumor release upon treatment. However, these patients displayed high levels of somatic copy-number alterations in their tumors that correlated with high blood and tumor levels of IL6 and CXCL8. Those proinflammatory cytokines resulted in higher tumor secretion of VEGF and tumor enrichment in regulatory T cells. Advanced mesothelioma should further benefit from stratified combination therapies adapted to their tumor biology.Significance:Sequential explorations of fresh tumor biopsies demonstrated that mesothelioma resistance to anti–PD-1 + antiangiogenics is not due to a lack of tumor T-cell infiltration but rather due to adaptive immunosuppressive pathways by tumors, involving molecules (e.g., IL6, CXCL8, VEGF, and CTLA4) that are amenable to targeted therapies.This article is highlighted in the In This Issue feature, p. 799
Frequency distribution of the initial number of Bursaphelenchus xylophilus carried by adult Monochamus carolinensis in Illinois, with reference to that by M. alternatus in Japan
Authors: Togashi Katsumi , Appleby James E. , Oloumi-Sadeghi Hassan , Malek Richard B. 
Published: January 2023

Summary
The pine wood nematode (PWN), Bursaphelenchus xylophilus, is the causative agent of pine wilt disease and is transmitted primarily by cerambycid adults of the genus Monochamus. It is believed to have been introduced into Japan from North America in the 1900s and confirmed to have invaded western Europe in 1999. The nematode has been devastating pine forests in invaded areas because the native pine species are susceptible. This study examined the number of PWN carried by individual M. carolinensis adults (initial PWN load) immediately after emerging from dead Pinus sylvestris and P. strobus trees in Illinois, USA. The data were compared with the initial PWN load on M. alternatus adults emerging from dead P. thunbergii trees in Japan ca 80 years after the PWN invasion. When the zero-inflated negative binomial model was fitted to the initial PWN loads it provided three results. First, the PWN exhibited clumped distributions among vectors in the PWN-M. carolinensis-P. sylvestris or P. strobus system in Illinois and the PWN-M. alternatus-P. thunbergii system in Japan. Second, there was no difference in the frequency distribution of the initial PWN load between the three disease systems. Third, the initial PWN load increased as the overwintering PWN density in wood or the adult body mass increased, whereas it decreased as the emergence date of vectors increased. Consequently, the frequency distribution of initial PWN load exhibited no evolutionary change in Japan and the initial PWN load was considered to be determined by environmental factors and conditions.
A Global–Regional-Unified Atmospheric Dynamical Core on the Yin–Yang Grid
Authors: Chen Siyuan , Zhao Yifan , Peng Xindong , Li Xiaohan 
Published: January 2023

Abstract
A global–regional-unified nonhydrostatic dynamical core was constructed on the Yin–Yang grid using a semi-implicit semi-Lagrangian solver. Arbitrary coordinate rotation was possible for both global and limited-area models with a multilevel nesting capability. Significant flexibility is available when configuring the model’s horizontal mesh using coordinate rotation. The performance of the dynamical core was assessed using a series of numerical tests in Cartesian and spherical coordinates. The results illustrate the reasonable ability of the piecewise rational method to manage sharp gradient advection and the capability of the dry dynamical core to simulate fine structures in target systems in the Cartesian and spherical configurations. An average convergence rate of 2.43 was confirmed for the dry dynamical core in the balanced flow test. The nested grid improved the fine structure simulation of the baroclinic wave development without affecting wave propagation. The propagating speed of the vortex remained unchanged in the nested grid in the colliding modons test, although the vorticity amplitude decayed more slowly than that in the coarse grid. Proper development of topographic waves was achieved for both large- and small-scale mountains with a clear damping effect in association with the off-center semi-implicit average. A deepened trough in the nesting region, in comparison with that in the parent grid, was simulated in a topographic Rossby wave test. The implementation of coordinate rotation and grid nesting improved the numerical performance when managing atmospheric dynamical problems at relatively low cost.
MiR-155-5p-SOCS1/JAK1/STAT1 participates in hepatic lymphangiogenesis in liver fibrosis and cirrhosis by regulating M1 macrophage polarization
Authors: Bi Jian , Liu Jia , Chen Xiuli , Shi Na , Wu Hao , Tang Haiying , Mao Jingwei 
Published: January 2023

Background The role and underlying mechanism of liver macrophages and their derived miR-155-5p in hepatic lymphangiogenesis in liver fibrosis remain unclear. Here, we investigated the mechanism by which macrophages and miR-155-5p were involved in lymphangiogenesis during liver fibrosis and cirrhosis. Methods In vivo, hepatic lymphatic vessel expansion was evaluated; the liver macrophage subsets, proportion of peripherally-derived macrophages and expressions of CCL25, MCP-1, VAP-1 and MAdCAM-1 were documented; and miR-155-5p in the peripheral blood and liver was detected. In vitro, macrophages with miR-155-5p overexpression and inhibition were used to clarify the effect of miR-155-5p on regulation of macrophage polarization and the possible signalling pathway. Results Hepatic lymphangiogenesis was observed in mice with liver fibrosis and cirrhosis challenged with carbon tetrachloride (CCl4). In the liver, the number of M1 macrophages was associated with lymphangiogenesis and the degree of fibrosis. The liver recruitment of peripherally-derived macrophages occurred during liver fibrosis. The levels of miR-155-5p in the liver and peripheral blood gradually increased with aggravation of liver fibrosis. In vitro, SOCS1, a target of miR-155-5p, regulated macrophage polarization into the M1 phenotype through the JAK1/STAT1 pathway. Conclusion MiR-155-5p-SOCS1/JAK1/STAT1 pathway participates in hepatic lymphangiogenesis in mice with liver fibrosis and cirrhosis induced by CCl4 by regulating the polarization of macrophages into the M1 phenotype.
Venous Thromboembolism in Japanese Patients with Gynecologic Cancer
Authors: Suzuki Takahito , Tsurimoto Shota , Tada Takayasu , Yamamura Ryo , Katoh Hiromasa , Noji Yoshihiro , Yamaguchi Masato , Fujino Susumu 
Published: January 2023

Objective Gynecologic cancer, including cervical, endometrial, and ovarian cancer, comprises the fifth leading type of cancer and is an important malignant disease in women. Previous studies in Western countries have reported respective prevalence rates for venous thromboembolism (VTE) of 3.3%–18.7%, 0.8%–8.1%, and 7.2%–20.9%. In this study, we aimed to identify the characteristics associated with VTE in Japanese patients. Methods We carried out a retrospective cohort study to compare the clinicopathological characteristics of patients with each gynecologic cancer with and without concomitant VTE. Patients: Patients with cervical, endometrial, or ovarian cancer treated at Fukui Prefectural Hospital, Japan, from April 2010 to March 2020. Results Among 699 patients with gynecologic cancer, 50 developed VTE within 5 years after their cancer diagnosis, including 16/357 patients with cervical cancer (5.6%), 12/185 with endometrial cancer (6.8%), and 22/157 with ovarian cancer (14.6%). The 1-year mortality rate after symptomatic VTE onset was 47.8%. The VTE group included significantly more older patients and more patients with advanced cancer or poor performance status compared with the non-VTE group. There was no significant difference in the rate of surgical treatment. Symptomatic, but not asymptomatic VTE, was associated with shorter survival. Conclusion Several baseline characteristics differed between patients with and without VTE. The incidences of VTE and some risk factors were similar in Japanese patients with gynecologic cancers compared with patients in other countries. Patients with VTE had some factors that worsened their prognosis, with patients with gynecologic cancer and symptomatic VTE having an especially poor prognosis.
Family violence content in baccalaureate and master's level social work programs
Authors: Renner Lynette M. , Driessen Molly C. 
Published: January 2023

Summary Scholars continue to call for social work students to be better prepared in the areas of family violence. In this study, we gathered information on the inclusion of intimate partner violence (IPV), child maltreatment, and elder abuse content in accredited baccalaureate and master's level social work programs across the United States. A survey invitation was sent to 538 baccalaureate and 306 master's level social work program directors in the summer of 2020. The final sample consisted of program directors representing 177 baccalaureate and 79 master's level social work programs. Survey data were analyzed using descriptive statistics. Findings Data revealed that 12.43% of baccalaureate social work programs had a course on elder abuse, 25.42% had a course specific to IPV, and 60.45% had a course focused on child maltreatment; however, few programs required these courses. Master's program directors reported that 6.33% of their programs had a course on elder abuse, 34.18% on IPV, and 46.84% on child maltreatment; yet only three programs required a course on child maltreatment and none required courses on IPV or elder abuse. Applications Social workers will likely work with client systems who experience family violence and it is critical that social work programs look for ways to improve the quantity and quality of family violence content into their curricula. It is also important for state licensing boards to require content on family violence at the initial and renewal stages. These educational efforts will enhance the knowledge and abilities of the social work workforce.
Acute severe asthma and its predictors of mortality in rural Southwestern Nigeria: a-five year retrospective observational study
Authors: Ibrahim Azeez Oyemomi , Aremu Shuaib Kayode , Afolabi Babatunde Adeola , Ajani Gbadebo Oladimeji , Kolawole Fasanmi Tolulope , Oguntoye OlufunmilayoAdenike 
Published: January 2023

Objectives There is an observed paucity of data regarding the predictors of asthma mortality in Nigeria. This study aimed to ascertain the clinical presentations and predictors of acute severe asthma mortality in rural Southwestern Nigeria. Methods A retrospective observational study using a data form and a standardized questionnaire was used to review the 124 patients admitted at Emergency Department between January 2015 and December 2019. The data were analyzed using SPSS Version 22.0. The results were presented in descriptive and tabular formats. Binary logistic regression analysis was used to determine the predictors of asthma mortality and a p-value <.05 was considered statistically significant. Results A total of 124 patients were studied. The acute severe asthma mortality was 4.8% and its predictors were older age (Crude odds Ratio (COR), 14.857; 95% CI: 2.489–88.696, p < .001), Tobacco smoking (COR, 6.741; 95% CI: 1.170–38.826, p = .016), more than three co-morbidities (COR, 2.750; 95% CI: 1.147–26.454, p = 0.012), diabetes mellitus (COR, 13.750; 95% CI: 2.380–79.433, p < .001), Human Immunodeficiency virus (COR, 117.000; 95% CI: 9.257–1479.756, p < .001), ≥2 days before presentation (COR, 7.440; 95% CI: 1.288–42.980, p = .039), and Short-acting-B2-agonists overuse (COR, 7.041; 95% CI: 1.005–62.165, p = .044). Conclusion The mortality rate was 4.8% and its predictors were older age patients, tobacco smoking, multiple co-morbidities, diabetes mellitus, HIV, SP02 <90%, delay presentation, and Short-acting-B2-agonists over use, The study showed that there is high prevalence of asthma mortality in rural Southwestern Nigeria. The findings may be used to plan for asthma preventions and control programs in rural settings, and may also provide an impetus for prospective research on these outcomes.
Clinical trial design and analysis for comparing three treatments with intra-individual right- and left-hand data
Authors: Machida Ryunosuke , Sakamaki Kentaro , Kuchiba Aya 
Published: January 2023

Background: Chemotherapy-induced peripheral neuropathy can occur in the right and left hand. Studies on prevention treatments for chemotherapy-induced peripheral neuropathy have largely adopted either self-controlled designs or parallel designs to compare two preventive treatments. When three treatment options (two experimental treatments and a control treatment) are available, both designs can be extended. However, no clinical trials have adopted a self-controlled design to compare three prevention treatments for chemotherapy-induced peripheral neuropathy. The incomplete block crossover design for more than two treatments can be extended to compare three treatments in the self-controlled design. In simple extension, some of the participants receive two experimental treatments in both hands; however, it may be difficult to administer different experimental treatments in both hands for practical reasons, such as a concern for the different types of unexpected adverse events. This study proposes a design and analysis method appropriate for the situation where only one experimental treatment is provided to each participant. Methods: We assume clinical trials to compare each of the two experimental treatments ( E1 and E2) with the control treatment ( C) and between two experimental treatments only when both experimental treatments are superior to the control treatment. We propose a self-controlled design, which equally randomizes to four arms to adjust for the dominant hand effect: Arm 1: E1 for right hand, C for left hand; Arm 2: C for right hand, E1 for left hand; Arm 3: E2 for right hand, C for left hand; and Arm 4: C for right hand, E2 for left hand. We compare operating characteristics of the proposed design with the three-arm parallel design in which the same treatment is performed in both hands by participants. We also assess three proposed analysis methods for comparisons between experimental treatments in the self-controlled design under several conditions of correlations between right and left hands using simulation studies. Results: The simulation studies showed that the proposed design was more powerful than the three-arm parallel design when correlation was 0.3 or higher. For comparisons between experimental treatments, the methods based on the regression model, including the outcome of hands with C as a covariate, had the highest power under modest to high correlation among the analysis methods in the self-controlled design. Conclusion: The proposed design can improve the power for comparing between two experimental treatments and the control treatment. Our design is useful in situations where it is undesirable for participants to receive different experimental treatments in both hands for practical reasons.
Adapting an Objective Structured Clinical Examination (OSCE) on Conducting Difficult Conversations Between Nephrology Fellows and Patients to a Virtual Platform: A Research Letter
Authors: Watson Maura A. , Howle Anna M. , Lenz Oliver , Scalese Ross J. , King Joshua D. , Bolanos Jonathan A. , Yuan Christina M. 
Published: January 2023

Background: We previously described a nephrology-specific “Breaking Bad News” Objective Structured Clinical Examination (OSCE) assessing nephrology fellow communication and counseling skills in 3 scenarios: kidney replacement therapy (KRT) in kidney failure, urgent KRT in acute kidney injury (AKI), and kidney biopsy (KBx). Objective: The main objectives of this study is to adapt the OSCE to a virtual platform, simulating nephrology patient telemedicine encounters involving difficult conversations, and to assess fellow and faculty satisfaction with the virtual format. Design: Description of a formative telemedicine simulation for nephrology fellows. Setting: Fully virtual simulation conducted by 2 academic medical simulation centers. Participants: Nephrology faculty and fellows at 3 urban/suburban training programs in the eastern United States. Measurements: Description of the virtual OSCE process. Fellow and faculty satisfaction overall and for each scenario. Faculty and fellow estimates of frequency of virtual patient encounters in the past year. Methods: The OSCE consisted of 3 scenarios: KRT in kidney failure, urgent KRT in AKI, and KBx. Objective Structured Clinical Examinations were administered in May 2021. Each scenario lasted 20 minutes. The AKI scenario was audio only. Fellows telephoned a simulated patient surrogate for urgent KRT consent. Kidney failure and KBx scenarios were video encounters. Faculty observed while muted/video off. Immediately after the OSCE, fellows and faculty were anonymously surveyed regarding their satisfaction with each scenario, the OSCE overall, and their estimate of outpatient encounters and inpatient KRT counseling done virtually in the preceding year. Results: Seventeen fellows completed the OSCE at 2 centers (3 programs). Sixteen (94%) completed the survey. Almost 94% rated the OSCE as a good/very good approximation of telemedicine encounters. Those satisfied/very satisfied with each scenario are as follow: 100% for AKI, 75% for kidney failure, and 75% for KBx. Two commented that they often did urgent KRT counseling by telephone. Fellows estimated a median 20% (interquartile range: 175, 50%) of counseling for acute inpatient KRT and a median 50% (IQR: 33.75, 70%) of outpatient encounters were virtual in the prior year. Two (regarding the kidney failure and KBx scenarios) indicated they would not have counseled similar outpatients virtually. Limitations: The 15-minute interactions may be too short to allow the encounter to be completed comfortably. A small number of programs and fellows participated, and programs were located in urban/suburban areas on the east coast of the United States. Conclusions: Overall, fellows felt that the OSCE was a good approximation of virtual encounters. The OSCE is an opportunity for fellows to practice telemedicine communication skills.
Experience and Attitudes Toward Telehealth in Student-Run Free Clinics (SRFC)
Authors: Luong Hanna N. , Shahin Ahmad , Porter Katherine R. , Chavez Augustine 
Published: January 2023

Introduction/Objectives: Telehealth services expanded during the coronavirus disease 2019 (COVID-19) pandemic. Student-run free clinics (SRFC) deliver important health care services to underserved populations, who may face barriers to telehealth use. This study characterizes telehealth usage, experiences, and attitudes among individuals working in SRFCs. Methods: In November 2021, a survey adapted from the COVID-19 Healthcare Coalition Telehealth Impact Physician Survey was sent to all registrants who identified themselves as students at the 2020 Society of Student-Run Free Clinics Annual Conference. Results: Thirty-eight individuals of 576 registrants (7%) representing 21 of 88 (24%) SRFCs completed the survey. Twenty-one (58%) individuals reported using telehealth in their clinic. Those that did not cited lack of infrastructure as a barrier (eg, broadband, Internet challenges, technology investments), were more likely to serve homeless (P  = .01), and less likely to serve non-English speaking populations (P  = .02). There were increases in telehealth and decreases in in-person visits after March 11, 2020 though changes did not reach statistical significance. At least 15 (68%) wanted to continue chronic disease management, preventative care, and mental/behavioral health via telehealth after COVID-19. Most felt that telehealth was easy to use and improved the health, safety, and timeliness of care of patients, but not work satisfaction or access to care. Difficulty accessing physical devices, Internet, and data was the most-cited barrier to maintaining and accessing telehealth. Conclusions: Nearly all participants cited significant benefits and barriers to telehealth that impacted perceived access to care and sustainability. SRFCs’ experiences may be modulated by their underserved populations and role in student education. Addressing barriers, particularly patient- and clinic-level technology challenges, could work to improve inequities in telehealth uptake.