bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community-based complex interventions to sustain independence in older people, stratified by frailty: a protocol for a systematic review and network meta-analysis
Authors: Crocker Thomas F , Clegg Andrew , Riley Richard D. , Lam Natalie , Bajpai Ram , Jordão Magda , Patetsini Eleftheria , Ramiz Ridha , Ensor Joie , Forster Anne , Gladman John R F 
Published: February 2021

IntroductionMaintaining independence is a primary goal of community health and care services for older people, but there is currently insufficient guidance about which services to implement. Therefore, we aim to synthesise evidence on the effectiveness of community-based complex interventions to sustain independence for older people, including the effect of frailty, and group interventions to identify the best configurations.Methods and analysisSystematic review and network meta-analysis (NMA). We will include randomised controlled trials (RCTs) and cluster RCTs of community-based complex interventions to sustain independence for older people living at home (mean age ≥65 years), compared with usual care or another complex intervention. We will search MEDLINE (1946 to September 2020), Embase (1947 to September 2020), CINAHL (1981 to September 2020), PsycINFO (1806 to September 2020), CENTRAL and clinical trial registries from inception to September 2020, without date/language restrictions, and scan included papers’ reference lists. Main outcomes were: living at home, activities of daily living (basic/instrumental), home-care services usage, hospitalisation, care home admission, costs and cost effectiveness. Additional outcomes were: health status, depression, loneliness, falls and mortality. Interventions will be coded, summarised and grouped. An NMA using a multivariate random-effects model for each outcome separately will determine the relative effects of different complex interventions. For each outcome, we will produce summary effect estimates for each pair of treatments in the network, with 95% CI, ranking plots and measures, and the borrowing of strength statistic. Inconsistency will be examined using a ‘design-by-treatment interaction’ model. We will assess risk of bias (Cochrane tool V.2) and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation for NMA approach.Ethics and disseminationThis research will use aggregated, anonymised, published data. Findings will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. They will be disseminated to policy-makers, commissioners and providers, and via conferences and scientific journals.PROSPERO registration numberCRD42019162195.
Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
Authors: Zhang Yan , Yang Hui , Zhao Jun , Wan Ping , Hu Ye , Lv Kun , Hu YiRen , Yang Xi , Ma Mingzhe 
Published: February 2021

BackgroundThe activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.MethodsMonocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.ResultsTAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.ConclusionsOur data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.
Seismicity Simulation and a Forecast Model Based on Monte Carlo Simulation Techniques and Performance of Distribution Models
Authors: Karaca Hakan 
Published: February 2021

In seismic hazard studies, simulation techniques are exploited relatively less compared to other statistical methods. The main purposes of their use were merely scientific: either to reduce uncertainty in seismic hazard or to test the consistency of a forecast. Its limited exploitation in the field does not mean that the method could not be exploited further. Given sufficient data and with the right models, a full-scale simulation is possible, which in fact becomes a forecast with future timing, location and magnitude of future events are simulated.Within this context, the main purpose of this study is to layout a method to create a full scale simulation with all the parameters namely the time, location and magnitude of an earthquake is simulated. For that purpose, in addition to the main parameters defining past seismic patterns, namely the temporal, spatial, magnitude distributions, the combined spatio-magnitude distribution is also modeled. As another improvement compared to the current procedures, occurrence date is assigned to the simulated event according to the inter-event time distribution, which enhances the simulation procedure. The eventual temporal distribution and the associated earthquake rates are checked with the original earthquake rate for its consistency. In the end, a simulation procedure, which can also be used as a forecast model is developed to improve the existing procedures further.
The 9 April 2013 Kaki earthquake (Mw 6.3) in SW Iran occurred along a blind backthrust in the Fars geological province of the Zagros Fold and Thrust Belt
Authors: Khalili Marzieh , Dilek Yildirim 
Published: February 2021

Abstract

The Zagros Fold and Thrust Belt (ZFTB) in southern Iran is a seismically active tectonic zone, where SW-vergent thrust faults and NW–SE- and NE–SW-oriented strike-slip fault systems accommodate crustal shortening, resulting from the active Arabia–Eurasia collision. The majority of earthquakes in Iran occur within the ZFTB, posing a major hazard for society. The 9 April 2013 Kaki Earthquake (Mw 6.3) in the southern part of the ZFTB took place along a fault that was previously unknown regarding its surface expression, geometry and kinematics. We have used surface–subsurface distributions and focal mechanism solutions of the Kaki Earthquake aftershocks to characterize the fault system responsible for the quake. Our results indicate that it was a NE-vergent thrust fault with a minor dextral component that slipped
c.
7–17 km at depth, causing the Kaki Earthquake. There were no surface ruptures, although some surface fissures developed in fluvial terraces during the main shock. We interpret this fault as a blind backthrust, which probably represents a reactivated Mesozoic basement fault emanating from the Zagros detachment surface. An upper shallow décollement zone within the Miocene Gachsaran Salt facilitated its upward propagation on the back-limb of an overturned syncline.
Intratumoral Plasmid IL12 Expands CD8+ T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti–PD-1 Therapy
Authors: Telli Melinda L. , Nagata Hiroshi , Wapnir Irene , Acharya Chaitanya R. , Zablotsky Kaitlin , Fox Bernard A. , Bifulco Carlo B. , Jensen Shawn M. , Ballesteros-Merino Carmen , Le Mai Hope , Pierce Robert H. , Browning Erica , Hermiz Reneta , Svenson Lauren , Bannavong Donna , Jaffe Kim , Sell Jendy , Foerter Kellie Malloy , Canton David A. , Twitty Christopher G. , Osada Takuya , Lyerly H. Kim , Crosby Erika J. 
Published: February 2021

AbstractPurpose:Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.Patients and Methods:Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.Results:Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.Conclusions:These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma
Authors: Armstrong Andrew J. , Nixon Andrew B. , Carmack Andrea , Yang Qian , Eisen Tim , Stadler Walter M. , Jones Robert J. , Garcia Jorge A. , Vaishampayan Ulka N. , Picus Joel , Hawkins Robert E. , Hainsworth John D. , Kollmannsberger Christian K. , Logan Theodore F. , Puzanov Igor , Pickering Lisa M. , Ryan Christopher W. , Protheroe Andrew , George Daniel J. , Halabi Susan 
Published: February 2021

AbstractPurpose:Biomarkers are needed in patients with non–clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib.Patients and Methods:ASPEN (NCT01108445) was an international, randomized, open-label phase II trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC with no prior systemic therapy. Patients were randomized to everolimus or sunitinib and treated until disease progression or unacceptable toxicity. The primary endpoint was radiographic progression-free survival (PFS) defined by RECIST 1.1. Plasma angiokines were collected at baseline, cycle 3, and progression and associated with PFS and overall survival (OS).Results:We enrolled 108 patients, 51 received sunitinib and 57 everolimus; of these, 99 patients had evaluable plasma for 23 angiokines. At the final data cutoff, 94 PFS and 64 mortality events had occurred. Angiokines that were independently adversely prognostic for OS were osteopontin (OPN), TIMP-1, thrombospondin-2 (TSP-2), hepatocyte growth factor (HGF), and VCAM-1, and these were also associated with poor-risk disease. Stromal derived factor 1 (SDF-1) was associated with improved survival. OPN was also significantly associated with worse PFS. No statistically significant angiokine-treatment outcome interactions were observed for sunitinib or everolimus. Angiopoeitin-2 (Ang-2), CD-73, HER-3, HGF, IL6, OPN, PIGF, PDGF-AA, PDGF-BB, SDF-1, TGF-b1-b2, TGFb-R3, TIMP-1, TSP-2, VCAM-1, VEGF, and VEGF-R1 levels increased with progression on everolimus, while CD-73, ICAM-1, IL6, OPN, PlGF, SDF-1, TGF-b2, TGFb-R3, TIMP-1, TSP-2, VEGF, VEGF-D, and VCAM-1 increased with progression on sunitinib.Conclusions:In patients with metastatic NC-RCC, we identified several poor prognosis angiokines and immunomodulatory chemokines during treatment with sunitinib or everolimus, particularly OPN.
Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Authors: Pullarkat Vinod A. , Lacayo Norman J. , Jabbour Elias , Rubnitz Jeffrey E. , Bajel Ashish , Laetsch Theodore W. , Leonard Jessica , Colace Susan I. , Khaw Seong Lin , Fleming Shaun A. , Mattison Ryan J. , Norris Robin , Opferman Joseph T. , Roberts Kathryn G. , Zhao Yaqi , Qu Chunxu , Badawi Mohamed , Schmidt Michelle , Tong Bo , Pesko John C. , Sun Yan , Ross Jeremy A. , Vishwamitra Deeksha , Rosenwinkel Lindsey , Kim Su Young , Jacobson Amanda , Mullighan Charles G. , Alexander Thomas B. , Stock Wendy 
Published: February 2021

Abstract

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients &lt;45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population.

Significance:
In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.
See related commentary by Larkin and Byrd, p. 1324.
This article is highlighted in the In This Issue feature, p. 1307
Deep Neural Networks Can Predict New-Onset Atrial Fibrillation From the 12-Lead ECG and Help Identify Those at Risk of Atrial Fibrillation–Related Stroke
Authors: Raghunath Sushravya , Pfeifer John M. , Ulloa-Cerna Alvaro E. , Nemani Arun , Carbonati Tanner , Jing Linyuan , vanMaanen David P. , Hartzel Dustin N. , Ruhl Jeffery A. , Lagerman Braxton F. , Rocha Daniel B. , Stoudt Nathan J. , Schneider Gargi , Johnson Kipp W. , Zimmerman Noah , Leader Joseph B. , Kirchner H. Lester , Griessenauer Christoph J. , Hafez Ashraf , Good Christopher W. , Fornwalt Brandon K. , Haggerty Christopher M. 
Published: February 2021

Background:
Atrial fibrillation (AF) is associated with substantial morbidity, especially when it goes undetected. If new-onset AF could be predicted, targeted screening could be used to find it early. We hypothesized that a deep neural network could predict new-onset AF from the resting 12-lead ECG and that this prediction may help identify those at risk of AF-related stroke.

Methods:
We used 1.6 M resting 12-lead digital ECG traces from 430 000 patients collected from 1984 to 2019. Deep neural networks were trained to predict new-onset AF (within 1 year) in patients without a history of AF. Performance was evaluated using areas under the receiver operating characteristic curve and precision-recall curve. We performed an incidence-free survival analysis for a period of 30 years following the ECG stratified by model predictions. To simulate real-world deployment, we trained a separate model using all ECGs before 2010 and evaluated model performance on a test set of ECGs from 2010 through 2014 that were linked to our stroke registry. We identified the patients at risk for AF-related stroke among those predicted to be high risk for AF by the model at different prediction thresholds.

Results:
The area under the receiver operating characteristic curve and area under the precision-recall curve were 0.85 and 0.22, respectively, for predicting new-onset AF within 1 year of an ECG. The hazard ratio for the predicted high- versus low-risk groups over a 30-year span was 7.2 (95% CI, 6.9–7.6). In a simulated deployment scenario, the model predicted new-onset AF at 1 year with a sensitivity of 69% and specificity of 81%. The number needed to screen to find 1 new case of AF was 9. This model predicted patients at high risk for new-onset AF in 62% of all patients who experienced an AF-related stroke within 3 years of the index ECG.

Conclusions:
Deep learning can predict new-onset AF from the 12-lead ECG in patients with no previous history of AF. This prediction may help identify patients at risk for AF-related strokes.
Clinical Characteristics and In-Hospital Outcomes of Varying Definitions of Minor Stroke
Authors: Xiong Yunyun , Gu Hongqiu , Zhao Xing-Quan , Yang Xin , Wang Chunjuan , Wang Yi-Long , Liu Li-Ping , Zhou Qi , Fisher Marc , Li Zixiao , Wang Yongjun 
Published: February 2021

Background and Purpose:
A variety of definitions for minor stroke have been proposed. We aimed to compare the clinical characteristics and outcomes of minor stroke defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 versus ≤3.

Methods:
We retrieved acute ischemic stroke patients with NIHSS score ≤5 in the CSCA study (China Stroke Center Alliance) between August 2015 and 2019. In-hospital clinical outcomes including all-cause mortality, stroke, and myocardial infarction were compared between the NIHSS score ≤5 and NIHSS score ≤3 groups using absolute standardized differences (ASD).

Results:
A total of 1 006 798 patients were registered in the CSCA program from 1476 hospitals, 472 352 patients had NIHSS score ≤5, of whom 356 314 patients had NIHSS score ≤3. The in-hospital composite events of death, myocardial infarction, or recurrent stroke were not significantly different between the NIHSS score ≤5 and NIHSS score ≤3 groups (5.6% [26 346/472 352] versus 5.2% [18 682/356 314]; ASD, 1.8). The in-hospital all-cause mortality (0.1% [443/472 352] versus 0.1% [255/356 314]; ASD, <0.01), recurrent ischemic stroke (5.3% [25 026/472 352] versus 5.0% [17 777/356 314]; ASD, 1.4), and hemorrhagic stroke (0.5% [2151/472 352] versus 0.4% [1475/356 314]; ASD, 1.5) were not significantly different between both the NIHSS score ≤5 and NIHSS score ≤3 groups.

Conclusions:
Our large-scale study identified that minor stroke using NIHSS scores ≤5 and ≤3 as the definition was comparable with each other regarding in-hospital all-cause mortality, recurrent stroke, and hemorrhagic stroke. This observation may be useful for future comparison studies and clinical trial design.
Penitence and Crusade in the Assumption Chapel of the Real Monasterio de Las Huelgas, Burgos
Authors: Streit Jessica Renee 
Published: February 2021

Abstract
This study aims to interpret the visual qualities of the Assumption Chapel, located in the Cistercian monastery of Santa Maria La Real de Las Huelgas, Burgos. Rejecting the “mudejar” paradigm often used to explain the chapel’s connections to Andalusi architecture, the article instead considers its relationships to a group of twelfth- and thirteenth-century domed churches in Iberia and the French Pyrenees, as well as to Las Huelgas’s adjacent, late-Romanesque cloister. In so doing, it situates the Assumption Chapel in a broader context of monuments related to penitence and crusade in the Holy Land and Iberia. It also considers the chapel’s form and function in the light of Las Huelgas’s ritual topography. Most broadly, this study shows how seemingly incongruent visual languages—in this case Romanesque and Andalusi—can comprise a coherent program of imagery.
Legal Intervention in Planning Regulations: Cooper v Wandsworth in a West African Context.
Authors: Mensah Kwadwo B. 
Published: February 2021

One of the most important problems facing many West African cities in recent times is rapid and seemingly uncontrollable urbanization. The enormous pressure which these developments have had on public systems in general - sanitation, sewage, housing, health care and transport, has forced many cities to think of innovative ways of handling these crisis. Planning departments with substantial expertise in urban problems, are being set up or are being re-organized to meet these new challenges. The powers that planning departments have, and their impact on the lives of ordinary citizens cannot be over-estimated. To prevent abuse of power and to make them responsive to the needs of citizens, several methods are used to control them. Judicial review of administrative actions is the legal method used to control many public bodies in English speaking West African countries.
In this article, I shall argue that in spite of its strengths, there is a general tendency to use judicial review to protect common law values like individual proprietary rights against the claims of state institutions. In West Africa, because of the weakness of public institutions, the intervention of the law, while protecting important private rights may hamper administrative effectiveness. Anticipating the use of the leading English case, Cooper v Wandsworth2 in reviewing planning decisions in West Africa, I shall conclude that such a position may not only diminish administrative effectiveness, but it may also diminish property rights.
Les Sous-Regions Rurales de la Province Orientale Dans la Dynamique de L’histoire Recente du Zaire: De 1960 à 1985 (Cas Du Bas-Uélé)
Authors: Dieudonné Mily Denda-Sakala 
Published: February 2021

The Rural Sub-Regions of the East-Province in the Recent Historical Dynamics of Zaïre: from 1960 to 1985 (The Case of the Bas-Uélé)
This study takes the Sub-Region of the Bas-Ulélé as an example of the recent history of the rural areas in Zaire. It gives a description from an insider’s point of view based on local research, results in a testimony relating the complete deterioration of rural potentialities in Zaire.
The article describes how in the first years after independence, the rich natural resources and the colonial infrastructure brought prosperous development. From 1964 to 1966, however, the Simba-rebellion ravaged the area, destroying a great deal of the infrastructure and caused large-scale massacres among the local population.
After the crushing of the rebellion, the subsequent revival was quickly halted by constant bureaucratic hindrances and interference from Mobutu’s MPR. “Zairisation” led to farther deterioration of the economic infrastructure.
From 1980 on, the Sub-Region was neglected more and more by the central government and even by its elected representatives. Finally, the liberalising of gold-prospecting withdrew farmers, schoolchildren and teachers form their normal activities leading only to more misery in the area.
Definition de L’adjectif en Langues Bantu
Authors: Baka Jean 
Published: February 2021

Definition of the Adjective in Bantu Languages
In Bantu, as in other language groups, the definition of the adjective depends on the type of criteria that one uses. Some authors make use of morphological criteria, some of syntactic criteria and others of semantic criteria. From this variety of criteria there follows a diversity of definitions. One can reach, nevertheless, a more appropriate definition, by having recourse to the whole set of possible criteria but giving primacy to the syntactic ones. Such definition allows us – on the one hand – to bypass the dichotomy between nouns and pronouns which is founded on a purely morphological criterion « the form of the prefix » and – on the other hand – to restrict the meaning of the word 'adjective' to a purely semantic notion.