bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early Tumor–Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer
Authors: Kim Ryul , An Minae , Lee Hyuk , Mehta Arnav , Heo You Jeong , Kim Kyoung-Mee , Lee Song-Yi , Moon Jeonghyeon , Kim Seung Tae , Min Byung-Hoon , Kim Tae Jun , Rha Sun Young , Kang Won Ki , Park Woong-Yang , Klempner Samuel J. , Lee Jeeyun 
Published: December 2021

Abstract

Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little is known about mediators of chemotherapy response. To move forward, an understanding of the effects of standard chemotherapy on the tumor–immune microenvironment (TME) is needed. Coupling whole-exome sequencing, bulk RNA and single-cell transcriptomics from paired pretreatment and on-treatment samples in treatment-naïve patients with HER2-positive and HER2-negative gastric cancer, we define features associated with response to platinum-based chemotherapy. Response was associated with on-treatment TME remodeling including natural killer (NK) cell recruitment, decreased tumor-associated macrophages, M1-macrophage repolarization, and increased effector T-cell infiltration. Among chemotherapy nonresponders, we observed low/absent PD-L1 expression or modulation, on-treatment increases in Wnt signaling, B-cell infiltration, and LAG3-expressing T cells coupled to an exodus of dendritic cells. We did not observe significant genomic changes in early on-treatment sampling. We provide a map of on-treatment TME modulation with standard chemotherapy and nominate candidate future approaches.

Significance:
Using paired pretreatment and on-treatment samples during standard first-line chemotherapy, we identify chemotherapy-induced NK-cell infiltration, macrophage repolarization, and increased antigen presentation among responders. Increased LAG3 expression and decreased dendritic cell abundance were seen in nonresponders, emphasizing remodeling of the TME during chemotherapy response and resistance.
This article is highlighted in the In This Issue feature, p. 873
Early Termination of Acute Stroke Randomized Controlled Trials Published Between 2013 and 2020: A Systematic Review
Authors: Strong Brent , Oostema J. Adam , Nikroo Nadia , Hussain Murtaza , Reeves Mathew J. 
Published: December 2021

Background:
Termination of a clinical trial before the maximum planned sample size is accrued can occur for multiple valid reasons but has implications for the interpretation of results. We undertook a systematic review of contemporary acute stroke trials to document the prevalence of and reasons for early termination.

Methods:
We searched MEDLINE for randomized controlled trials of acute stroke therapies published between 2013 and 2020 in 9 major clinical journals. Manuscripts describing the primary results of phase 2 and phase 3 trials of acute stroke care were included. Data on study characteristics and adherence to CONSORT reporting guidelines were abstracted and summarized using descriptive statistics. Where feasible, we compared treatment effect sizes between trials terminated early and those not terminated early.

Results:
Of 96 randomized controlled trials, 39 (41%) were terminated early, 84 (88%) had a data and safety monitoring board, and 57 (59%) reported a prespecified statistical stopping rule. Among the 39 trials terminated early, 10 were discontinued for benefit, 10 due to logistical issues, 8 for futility, 6 because of newly available evidence, 1 for harm, and 4 for other or a combination of reasons. The median percentage of the maximum planned sample size accrued among trials terminated early was 63% (range, 8%–89%). Only 55% of trials (53 of 96) reported whether interim efficacy analyses were conducted, as recommended by the CONSORT guidelines. When 10 endovascular therapy trials were compared according to early termination status, the effect sizes of trials terminated early for benefit were only modestly larger than those not terminated early.

Conclusions:
The high prevalence of early termination in combination with the wide variety of reasons underscores the necessity of meticulous trial planning and adherence to methodological and reporting guidelines for early termination.

Registration:

URL:
https://www.crd.york.ac.uk/prospero/
; Unique identifier: CRD42019128727.
Activated Protein C Strengthens Cardiac Tolerance to Ischemic Insults in Aging
Authors: Ren Di , Fedorova Julia , Davitt Kayla , Van Le Tran Ngoc , Griffin John H. , Liaw Patricia C. , Esmon Charles T. , Rezaie Alireza R. , Li Ji 
Published: December 2021

Background:
APC (activated protein C) is a plasma serine protease with anticoagulant and anti-inflammatory activities. EPCR (Endothelial protein C receptor) is associated with APC’s activity and mediates its downstream signaling events. APC exerts cardioprotective effects during ischemia and reperfusion (I/R). This study aims to characterize the role of the APC-EPCR axis in ischemic insults in aging.

Methods:

Young (3–4 months) and aged (24–26 months) wild-type C57BL/6J mice, as well as EPCR point mutation (EPCR

R84A/R84A

) knockin C57BL/6J mice incapable of interaction with APC and its wild type of littermate C57BL/6J mice, were subjected to I/R. Wild-type APC, signaling-selective APC-2Cys, or anticoagulant-selective APC-E170A were administrated before reperfusion.

Results:

The results demonstrated that cardiac I/R reduces APC activity, and the APC activity was impaired in the aged versus young hearts possibly attributable to the declined EPCR level with aging. Serum EPCR measurement showed that I/R triggered the shedding of membrane EPCR into circulation, while administration of APC attenuated the I/R-induced EPCR shedding in both young and aged hearts. Subsequent echocardiography showed that APC and APC-2Cys but not APC-E170A ameliorated cardiac dysfunction during I/R in both young and aged mice. Importantly, APC elevated the resistance of the aged heart to ischemic insults through stabilizing EPCR. However, all these cardioprotective effects of APC were blunted in the EPCR

R84A/R84A

mice versus its wild-type littermates. The ex vivo working heart and metabolomics results demonstrated that AMPK (AMP-activated protein kinase) mediates acute adaptive response while AKT (protein kinase B) is involved in chronic metabolic programming in the hearts with APC treatment.

Conclusions:
I/R stress causes shedding of the membrane EPCR in the heart, and administration of APC prevents I/R-induced cardiac EPCR shedding that is critical for limiting cardiac damage in aging.
The Vizier Ankhu and the Dual Vizierate in the Late Middle Kingdom
Authors: Ilin-Tomich Alexander 
Published: December 2021

Abstract
The conjecture that the vizier Ankhu’s centre of life lay in Thebes has been expressed by previous scholars. This paper reviews the available evidence, complemented by a new reading of stela Cairo CG 20102 and the accounts of the smaller manuscript of pBoulaq 18. Taken together, the data suggests that Ankhu, his father, and his sons, all holding the office of the vizier, had their seat in Thebes. Given that at least one other vizier stands chronologically between Ankhu and his father, the association of Ankhu’s family with Thebes supports the hypothesis of a dual vizierate in the late Middle Kingdom; a theory long proposed but deemed unconfirmed.
Pauline Hopkins’ Literary Egyptology
Authors: Davies Vanessa 
Published: December 2021

Abstract
Author Pauline Hopkins produced work in a variety of genres: short stories, novels, a musical, a primer of facts. Like other African Americans of the eighteenth and early nineteenth centuries, she engaged with the history of the Nile Valley before the discipline of Egyptology was firmly established in the sphere of higher education in the US. Her serialized novel Of One Blood, published in 1902 and 1903, draws on a variety of sources, such as the English historian George Rawlinson, to tell a fictionalized story set in the contemporary present of the Upper Nile and to address issues related to the ancient past of that region. Her main character, Reuel, embodies links across time—ancient and contemporary—and space—the United States and the Nile River Valley. Through him, she shows the power and relevance of ancient history to contemporary life.
Filipino Science Teachers’ Evaluation on Webinars’ Alignments to Universal Design for Learning and Their Relation to Self-Efficacy amidst the Challenges of the COVID-19 Pandemic
Authors: Leonardo Mary Dane F. , Cha Jeongho 
Published: December 2021

Abstract
The COVID-19 pandemic has led teachers in the Philippines to rely on technology to provide and support continued education for K-12 students. However, it is not only technology, but also the interactive online learning environments crafted by teachers that impact student science learning. To support teachers to cope with pandemic teaching, the government provided professional development in the form of teacher-training webinars. This study evaluated the webinars using Universal Design for Learning (UDL) principles to understand the impact these professional development sessions had on science teachers’ self-efficacy for delivering science instruction during the pandemic. The study found that webinars including UDL design elements improved science teachers’ self-efficacy for teaching science and there were no significant differences in teacher perceptions relative to gender or teaching experience. Implications for the use of UDL to design long-term professional development offerings beyond the pandemic are discussed.
景寧畲話古全濁聲母的今讀
Authors: 項 夢冰 
Published: December 2021

摘要
大部分畲族所使用的語言是一種接近客家話的漢語方言，習慣上叫做畲話。浙江景寧畲族自治縣的畲族所說的畲話，古全濁聲母今讀清塞音、清塞擦音時存在較多不送氣的情形，主要是由通語、閩語、吳語的不同影響造成的層次累積，在確定畲話的性質時應當排除這一部分字音。
A Comparison of the Two-Minute Walk Test (2MWT) and Comprehensive High-level Activity Mobility Predictor (CHAMP) in People with a Leg Prosthesis
Authors: Gailey Robert S. , Gaunaurd Ignacio , Morgan Sara J. , Kristal Anat , Balkman Geoffrey S. , Newton Eavey M , Palomo Jose J , Shay Kevin M , Salem Rana , Hafner Brian J. 
Published: December 2021

Objective To determine if the two-minute walk test (2MWT) could serve as an alternative measure of high-level mobility in lower limb prosthesis users when circumstances preclude administration of the Comprehensive High-level Activity Mobility Predictor (CHAMP). Design Cross-sectional study. Setting Indoor recreational athletic field and gymnasium Subjects Fifty-eight adult lower limb prosthesis users with unilateral or bilateral lower limb amputation who participate in recreational athletic activities. Intervention N/A Main Measures The 2MWT and CHAMP while using their preferred prosthesis(es) on an indoor artificial athletic field or hardwood gymnasium floor. Results Thirty-nine men and nineteen women with a median age of 38.3 years participated in the study. Most participants experienced amputation(s) due to trauma (62%) or tumor (10%) and were generally higher functioning (K4 (91.4%) and K3 (8.6%)). The median (range) score for the CHAMP was 23.0 points (1.5–33.5) and the mean ± standard deviation (range) 2MWT distance walked was 188.6 ± 33.9 m (100.2–254.3 m). The CHAMP demonstrated a strong positive relationship with 2MWT (r = 0.83, p < 0.001). The 2MWT distance predicted 70% of the variance in CHAMP score. Conclusions Although the 2MWT does not test multi-directional agility like the CHAMP, they were found to be highly correlated. If space is limited, the two-minute walk test can serve as an alternative measure for assessing high-level mobility capabilities in lower limb prosthesis users.
Preparation and properties of reduced graphene oxide-carbon nanotubes aerogel/cotton flexible composite fabric with electromagnetic shielding function
Authors: Wang Peng , Liu Shuqiang , Zhang Man , Pan Zheng-Ze , Wu Gaihong , Li Fu , Zhang Aiqin , Huimin Li 
Published: December 2021

The electromagnetic pollution has become a serious problem with the rapid development of electromagnetic industry. The present work prepared an electromagnetic interference (EMI) functional composite fabric. Reduced graphene oxide (rGO)-carbon nanotubes (CNTs) aerogel with three-dimensional (3-D) architecture were coated to the cotton fabric with the assistance of waterborne polyurethane (WPU). The structure of graphene aerogel was affected by the amount of CNTs. Small amount of CNTs is helpful to minish the pore size of aerogel and thus improve the EMI value. However, it has been shown that excess CNTs will destroy the 3-D architecture of graphene aerogel. Result shows that the EMI shielding effectiveness exceeded 35 dB when the weight ratio of rGO and CNTs was 7:3, and EMI value of the corresponding composite fabric samples reached 34 dB. Consequently, excellent EMI results were obtained by the unique 3-D rGO-CNTs aerogel in the case of a small nano-carbon material amount. The present work will be expected to make contributions to the practical application of rGO-CNTs aerogel.
Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis
Authors: Shih Ya Wen , Su Jui Yuan , Kung Yu Shan , Lin Yu Huei , To Anh Duong Thi , Ridwan Edi Sampurno , Tsai Hsiu Ting 
Published: December 2021

Background: Breast cancer is one of the most common cancers and a major cause of death in women worldwide. Chemotherapy is mainly used to treat and control the progression of breast cancer. Leukopenia is the most common side effect of chemotherapy which may decrease immune function and further lead to serious fatal infections. The purpose of this study was to evaluate the effect of acupuncture on regulating hematopoietic function in chemotherapy-induced leukopenia among patients with breast cancer. Methods: PubMed, Embase, Cochrane Library, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure (CNKI) databases were searched to August 2021 for papers to include in a systematic review and meta-analysis. A random-effects model was applied. The effect size was calculated by Hedges’ g. Heterogeneity was determined using Cochran’s Q test. Moderator analyses were performed to examine potential sources of heterogeneity. A trial sequential analysis (TSA) was conducted to determine whether the current sample size was sufficient. Results: Ten randomized controlled trials involving 650 participants were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leukopenia during chemotherapy. Levels of white blood cells (WBCs) were increased (Hedges’ g = 0.70, P < .001, I2 = 34%), neutrophil counts (Hedges’ g = 0.80, P < .001, I2 = 0%) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased. Conclusions: The current meta-analysis supports acupuncture possibly ameliorating chemotherapy-induced leukopenia, as WBC and neutrophil values significantly increased after acupuncture in patients undergoing chemotherapy. Additionally, regardless of the type of acupuncture, values of WBCs increased. These findings are actionable and support both the clinical use of acupuncture to relieve chemotherapy-induced leukopenia and further research regarding the use of acupuncture in patients experiencing immunosuppression when undergoing chemotherapy. Trial Registration: PROSPERO-CRD42020215759.
Acute kidney injury and it's outcome following maternal near miss event: A prospective observational study from a tertiary care hospital
Authors: Thakur Geetika , Singh Aruna , Jain Vanita , Sikka Pooja , Arora Aashima , Suri Vanita 
Published: December 2021

Purpose Haemorrhage, preeclampsia and sepsis are the leading causes of renal dysfunction in women with a maternal nearmiss(MNM) complication. The study aimed to assess the prevalence, pattern and follow up of these women. Methods This was a hospital based prospective observational study, conducted over one year. All women with a MNM leading to acute kidney injury (AKI) were analysed for fetomaternal outcomes and renal function at 1 year of followup. Results The incidence of MNM was 43.04 per 1000 livebirths. 18.2% women developed AKI. 51.1% women developed AKI in the puerperal period. Most common cause of AKI was haemorrhage seen in 38.3% women. The majority of women had s.creatinine between 2.1 to 5 mg/dl and 44.68% required dialysis. 80.8% women recovered fully when the treatment was initiated within 24 h. One patient underwent renal transplant. Conclusion Early diagnosis and treatment of AKI results in full recovery.
Determinants of Mortality Among Severely Malnourished Children in Northern Nigeria
Authors: Nass Shafique Sani , Nass Nafisa Sani , Iliyasu Zubairu , Suleiman Bello , Yahaya Shamsuddeen , Habibu Bala , Bindawa Murtala Isa , Sani Aminu , Suleiman Medinat , Gachi Adamu Suleiman 
Published: December 2021

Objectives Severe Acute Malnutrition is a significant cause of mortality in children under the age of 5 years in low-resource settings, including Northern Nigeria. The study aimed to determine the associations between selected risk factors and mortality outcomes in children admitted with SAM in a facility in Katsina State, Northern Nigeria. Methods A prospective observational cohort of 201 children aged 6 to 59 months who were admitted with severe acute malnutrition (SAM) in stabilization centers in Katsina State, Northern Nigeria between May 18, 2021, and July 20, 2021, (63 days) were assessed followed up. Outcomes were analyzed using Kaplan-Meir analysis to estimate time to death, and Cox proportional-hazard regression model was used to determine predictors of mortality. Results The log-rank test showed significant differences in the probability of death between categories of diarrheal status (log-rank statistic = 9.760, P = .021) and presence of existing disease (comorbidity) (log-rank statistic = 5.338, P = .021). The study identified that severely malnourished children admitted with comorbidities showed significant association with time to event (death) (AHR: 4.109, 95% CI: 1.51, 32.60). The estimated mean time until death was 57.9 days (±3.0) for children without comorbidities and 20.1 (±3.0) days for children with comorbidities. The median survival time was 18 days for children with comorbidities. Conclusion The presence of comorbidities was significantly associated with mortality. Severely malnourished children with comorbidities had 4 times higher mortality risk than severely malnourished children admitted without comorbidities. Clinicians and health workers should give due emphasis to the early detection and effective management of comorbidities in children with severe acute malnutrition.
Mifepristone Adverse Events Identified by Planned Parenthood in 2009 and 2010 Compared to Those in the FDA Adverse Event Reporting System and Those Obtained Through the Freedom of Information Act
Authors: Cirucci Christina A. , Aultman Kathi A. , Harrison Donna J. 
Published: December 2021

Background As part of the accelerated approval of mifepristone as an abortifacient in 2000, the Food and Drug Administration (FDA) required prescribers to report all serious adverse events (AEs) to the manufacturer who was required to report them to the FDA. This information is included in the FDA Adverse Event Reporting System (FAERS) and is available to the public online. The actual Adverse Event Reports (AERs) can be obtained through the Freedom of Information Act (FOIA). Methods We compared the number of specific AEs and total AERs for mifepristone abortions from January 1, 2009 to December 31, 2010 from 1. Planned Parenthood abortion data published by Cleland et al. 2. FAERS online dashboard, and 3. AERs provided through FOIA and analyzed by Aultman et al. Results Cleland identified 1530 Planned Parenthood mifepristone cases with specific AEs for 2009 and 2010. For this period, FAERS online dashboard includes a total (from all providers) of only 664, and the FDA released only 330 AERs through FOIA. Cleland identified 1158 ongoing pregnancies in 2009 and 2010. FAERs dashboard contains only 95, and only 39 were released via FOIA. Conclusions There are significant discrepancies in the total number of AERs and specific AEs for 2009 and 2010 mifepristone abortions reported in 1. Cleland's documentation of Planned Parenthood AEs, 2. FAERS dashboard, and 3. AERs provided through FOIA. These discrepancies render the FAERS inadequate to evaluate the safety of mifepristone abortions.
Multimorbidity in large Canadian urban centres: A multilevel analysis of pooled 2015–2018 cross-sectional cycles of the Canadian Community Health Survey
Authors: Wilk Piotr , Stranges Saverio , Bellocco Rino , Bohn Torsten , Samouda Hanen , Nicholson Kathryn , Makovski Tatjana T , Maltby Alana 
Published: December 2021

Background There is limited knowledge on how the prevalence of multimorbidity varies within and across major Canadian urban centres. The objective of this study was to investigate the between-neighbourhood variation in the prevalence of multimorbidity in Canada’s large urban centres, controlling for compositional effects associated with individual-level demographic and socioeconomic factors. Methods Cross-sectional data from the 2015–2018 cycles of the Canadian Community Health Survey (CCHS) were pooled at the microdata level. Respondents (20 years and older) residing in one of the 35 census metropolitan areas (CMAs) were included ( N = 100,803). Census tracts (CTs) were used as a measure of neighbourhood. To assess the between-neighbourhood differences in multimorbidity prevalence, we fitted three sequential random intercept logistic regression models. Results During the 2015–2018 period, 8.1% of residents of large urban centres had multimorbidity. The results from the unadjusted model indicate that 13.4% of the total individual variance in multimorbidity could be attributed to the between-neighbourhood differences. After adjustment for overall characteristics of the CMAs in which these neighbourhoods are located, as well as for individual-level demographic and socioeconomic factors related to compositional effects, 11.0% of the individual variance in multimorbidity could still be attributed to the between-neighbourhood differences. Conclusion There is significant and substantial geographic variation in multimorbidity prevalence across neighbourhoods in Canada’s large urban centres. Residing in some neighbourhoods could be associated with increased odds of having multimorbidity, even after accounting for overall characteristics of the CMAs in which these neighbourhoods are located, as well as individual-level factors.