bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-operative management after chemoradiotherapy plus consolidation or sandwich (induction with bevacizumab and consolidation) chemotherapy in patients with locally advanced rectal cancer: a multicentre, randomised phase II trial (NOMINATE trial)
Authors: Akiyoshi Takashi , Shinozaki Eiji , Taguchi Senzo , Chino Akiko , Hiratsuka Makiko , Tominaga Tetsuro , Nonaka Takashi , Toda Shigeo , Matoba Shuichiro , Matsui Shimpei , Okabayashi Koji , Mukai Toshiki , Hiyoshi Yukiharu , Yamaguchi Tomohiro , Nagasaki Toshiya , Yamaguchi Kensei , Ueno Masashi , Kuroyanagi Hiroya , Fukunaga Yosuke , Ishizuka Naoki , Konishi Tsuyoshi 
Published: March 2022

IntroductionTotal mesorectal excision (TME) and postoperative adjuvant chemotherapy following neoadjuvant chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer (LARC). However, neoadjuvant CRT has no recognised impact on reducing distant recurrence, and patients suffer from a long-lasting impairment in quality of life (QOL) associated with TME. Total neoadjuvant therapy (TNT) is an alternative approach that could reduce distant metastases and increase the proportion of patients who could safely undergo non-operative management (NOM). This study is designed to compare two TNT regimens in the context of NOM for selecting a more optimal regimen for patients with LARC.Methods and analysisNOMINATE trial is a prospective, multicentre, randomised phase II selection design study. Patients must have clinical stage II or III (T3-T4Nany) LARC with distal location (≤5 cm from the anal verge or for those who are candidates for abdominoperineal resection or intersphincteric resection). Patients will be randomised to either arm A consisting of CRT (50.4 Gy with capecitabine) followed by consolidation chemotherapy (six cycles of CapeOx), or arm B consisting of induction chemotherapy (three cycles of CapeOx plus bevacizumab) followed by CRT and consolidation chemotherapy (three cycles of CapeOx). In the case of clinical complete response (cCR) or near cCR, patients will progress to NOM. Response assessment involves a combination of digital rectal examination, endoscopy and MRI. The primary endpoint is the proportion of patients achieving pathological CR or cCR≥2 years, defined as the absence of local regrowth within 2 years after the start of NOM among eligible patients. Secondary endpoints include the cCR rate, near cCR rate, rate of NOM, overall survival, distant metastasis-free survival, locoregional failure-free survival, time to disease-related treatment failure, TME-free survival, permanent stoma-free survival, safety of the treatment, completion rate of the treatment and QOL. Allowing for a drop-out rate of 10%, 66 patients (33 per arm) from five institutions will be accrued.Ethics and disseminationThe study protocol was approved by Wakayama Medical University Certified Review Board in December 2020. Trial results will be published in peer-reviewed international journals and on the jRCT website.Trial registration numberjRCTs051200121
Confounding adjustment methods in longitudinal observational data with a time-varying treatment: a mapping review
Authors: Wijn Stan R W , Rovers Maroeska M , Hannink Gerjon 
Published: March 2022

ObjectivesTo adjust for confounding in observational data, researchers use propensity score matching (PSM), but more advanced methods might be required when dealing with longitudinal data and time-varying treatments as PSM might not include possible changes that occurred over time. This study aims to explore which confounding adjustment methods have been used in longitudinal observational data to estimate a treatment effect and identify potential inappropriate use of PSM.DesignMapping review.Data sourcesWe searched PubMed, from inception up to January 2021, for studies in which a treatment was evaluated using longitudinal observational data.Eligibility criteriaMethodological, non-medical and cost-effectiveness papers were excluded, as were non-English studies and studies that did not study a treatment effect.Data extraction and synthesisStudies were categorised based on time of treatment: at baseline (interventions performed at start of follow-up) or time-varying (interventions received asynchronously during follow-up) and sorted based on publication year, time of treatment and confounding adjustment method. Cumulative time series plots were used to investigate the use of different methods over time. No risk-of-bias assessment was performed as it was not applicable.ResultsIn total, 764 studies were included that met the eligibility criteria. PSM (165/201, 82%) and inverse probability weighting (IPW; 154/502, 31%) were most common for studies with a treatment at baseline (n=201) and time-varying treatment (n=502), respectively. Of the 502 studies with a time-varying treatment, 123 (25%) used PSM with baseline covariates, which might be inappropriate. In the past 5 years, the proportion of studies with a time-varying treatment that used PSM over IPW increased.ConclusionsPSM is the most frequently used method to correct for confounding in longitudinal observational data. In studies with a time-varying treatment, PSM was potentially inappropriately used in 25% of studies. Confounding adjustment methods designed to deal with a time-varying treatment and time-varying confounding are available, but were only used in 45% of the studies with a time-varying treatment.
A case-control, multicentre study of consecutive patients with COVID-19 and acute (myo)pericarditis: incidence, risk factors, clinical characteristics and outcomes
Authors: Mirò Òscar , Sabaté Manel , Jiménez Sònia , Mebazaa Alexandre , Martínez-Nadal Gemma , Piñera Pascual , Burillo-Putze Guillermo , Martín Alfonso , Martín-Sánchez Francisco Javier , Jacob Javier , Alquézar-Arbé Aitor , García-Lamberechts Eric Jorge , Llorens Pere , González del Castillo Juan 
Published: March 2022

ObjectiveTo estimate incidence, risk factors, clinical characteristics and outcomes of acute (myo)pericarditis (AMP) in patients with COVID-19.MethodsCase-control, retrospective review, consecutive case inclusion performed in 62 Spanish EDs. All COVID-19 patients with AMP (cases) were compared in clinical characteristics and outcomes with COVID-19 without AMP (control group A) and non-COVID patients with AMP (control group B). We estimated unadjusted standardised incidence (SI, not adjusted by population’s age/sex) of AMP in COVID-19 and non-COVID populations (per 100 000/year).ResultsWe identified 67 AMP in COVID-19 patients (SI=56.5, OR with respect to non-COVID patients=4.43, 95% CI=3.98 to 4.94). Remarkably, COVID-19 cases presented with chest pain less frequently than non-COVID patients and had less typical ECG changes, higher NT-proBNP (N-terminal prohormone of brain natriuretic peptide), more left and right ventricular dysfunction in echocardiography and more need of inotropic/vasopressor drugs. Admission to intensive care was higher than control group A (OR=3.22, 95% CI=1.43 to 7.23), and in-hospital mortality was higher than control group B (OR=7.75, 95% CI=2.77 to 21.7).ConclusionAMP is unusual as a form of COVID-19 presentation (about 1‰ cases), but SI is more than fourfold higher than non-COVID population, and it is less symptomatic, more severe and has higher in-hospital mortality; therefore, rapid recognition, echocardiographic assessment of myopericardial inflammation/dysfunction and treatment with vasoactive drugs when needed are recommended in AMP in patients with COVID-19.
Torus orbit closures in flag varieties and retractions on Weyl groups
Authors: Lee Eunjeong , Masuda Mikiya , Park Seonjeong 
Published: March 2022

A finite Coxeter group W has a natural metric d and if [Formula: see text] is a subset of W, then for each [Formula: see text], there is [Formula: see text] such that [Formula: see text]. Such q is not unique in general but if [Formula: see text] is a Coxeter matroid, then it is unique, and we define a retraction [Formula: see text] so that [Formula: see text]. The T-fixed point set [Formula: see text] of a T-orbit closure Y in a flag variety G/B is a Coxeter matroid, where G is a semi-simple algebraic group, B is a Borel subgroup, and T is a maximal torus of G contained in B. We define a retraction [Formula: see text] geometrically, where W is the Weyl group of [Formula: see text], and show that [Formula: see text]. We introduce another retraction [Formula: see text] algebraically for an arbitrary subset [Formula: see text] of W when W is a Weyl group of classical Lie type, and show that [Formula: see text] when [Formula: see text] is a Coxeter matroid.
Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance
Authors: Elhamamsy Amr R. , Metge Brandon J. , Alsheikh Heba A. , Shevde Lalita A. , Samant Rajeev S. 
Published: March 2022

Abstract
Ribosomes are a complex ensemble of rRNA and ribosomal proteins that function as mRNA translation machines. Ribosome biogenesis is a multistep process that begins in the nucleolus and concludes in the cytoplasm. The process is tightly controlled by multiple checkpoint and surveillance pathways. Perturbations in these checkpoints and pathways can lead to hyperactivation of ribosome biogenesis. Emerging evidence suggests that cancer cells harbor a specialized class of ribosomes (onco-ribosomes) that facilitates the oncogenic translation program, modulates cellular functions, and promotes metabolic rewiring. Mutations in ribosomal proteins, rRNA processing, and ribosome assembly factors result in ribosomopathies that are associated with an increased risk of developing malignancies. Recent studies have linked mutations in ribosomal proteins and aberrant ribosomes with poor prognosis, highlighting ribosome-targeted therapy as a promising approach for treating patients with cancer. Here, we summarize various aspects of dysregulation of ribosome biogenesis and the impact of resultant onco-ribosomes on malignant tumor behavior, therapeutic resistance, and clinical outcome. Ribosome biogenesis is a promising therapeutic target, and understanding the important determinants of this process will allow for improved and perhaps selective therapeutic strategies to target ribosome biosynthesis.
Molecular Characterization ofKRASWild-type Tumors in Patients with Pancreatic Adenocarcinoma
Authors: Philip Philip A. , Azar Ibrahim , Xiu Joanne , Hall Michael J. , Hendifar Andrew Eugene , Lou Emil , Hwang Jimmy J. , Gong Jun , Feldman Rebecca , Ellis Michelle , Stafford Phil , Spetzler David , Khushman Moh'd M. , Sohal Davendra , Lockhart A. Craig , Weinberg Benjamin A. , El-Deiry Wafik S. , Marshall John , Shields Anthony F. , Korn W. Michael 
Published: March 2022

AbstractPurpose:KRAS mutation (MT) is a major oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). A small subset of PDACs harbor KRAS wild-type (WT). We aim to characterize the molecular profiles of KRAS WT PDAC to uncover new pathogenic drivers and offer targeted treatments.Experimental Design:Tumor tissue obtained from surgical or biopsy material was subjected to next-generation DNA/RNA sequencing, microsatellite instability (MSI) and mismatch repair status determination.Results:Of the 2,483 patients (male 53.7%, median age 66 years) studied, 266 tumors (10.7%) were KRAS WT. The most frequently mutated gene in KRAS WT PDAC was TP53 (44.5%), followed by BRAF (13.0%). Multiple mutations within the DNA-damage repair (BRCA2, ATM, BAP1, RAD50, FANCE, PALB2), chromatin remodeling (ARID1A, PBRM1, ARID2, KMT2D, KMT2C, SMARCA4, SETD2), and cell-cycle control pathways (CDKN2A, CCND1, CCNE1) were detected frequently. There was no statistically significant difference in PD-L1 expression between KRAS WT (15.8%) and MT (17%) tumors. However, KRAS WT PDAC were more likely to be MSI-high (4.7% vs. 0.7%; P &lt; 0.05), tumor mutational burden–high (4.5% vs. 1%; P &lt; 0.05), and exhibit increased infiltration of CD8+ T cells, natural killer cells, and myeloid dendritic cells. KRAS WT PDACs exhibited gene fusions of BRAF (6.6%), FGFR2 (5.2%), ALK (2.6%), RET (1.3%), and NRG1 (1.3%), as well as amplification of FGF3 (3%), ERBB2 (2.2%), FGFR3 (1.8%), NTRK (1.8%), and MET (1.3%). Real-world evidence reveals a survival advantage of KRAS WT patients in overall cohorts as well as in patients treated with gemcitabine/nab-paclitaxel or 5-FU/oxaliplatin.Conclusions:KRAS WT PDAC represents 10.7% of PDAC and is enriched with targetable alterations, including immuno-oncologic markers. Identification of KRAS WT patients in clinical practice may expand therapeutic options in a clinically meaningful manner.
Development and Validation of a Clinical Predictive Model for Identifying Hypertrophic Cardiomyopathy Patients at Risk for Atrial Fibrillation: The HCM-AF Score
Authors: Carrick Richard T. , Maron Martin S. , Adler Arnon , Wessler Benjamin , Hoss Sara , Chan Raymond H. , Sridharan Aadhavi , Huang Dou , Cooper Craig , Drummond Jennifer , Rakowski Harry , Maron Barry J. , Rowin Ethan J. 
Published: March 2022

Background:
Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), associated with impaired quality of life, risk for embolic stroke, and unpredictable onset. We sought to create a predictive model to identify risk for AF development in HCM.

Methods:
A cohort of 1900 patients with HCM followed for newly diagnosed AF in the Tufts HCM center was used for model development. A cohort of 387 patients from Toronto General Hospital was used for external validation. Data in the development cohort generated the HCM-AF score, a point score to predict AF probability at 2 and 5 years: left atrial dimension (+2 points per 6 mm increase), age at clinical evaluation (+3 points per 10-year increase), age at initial HCM diagnosis (−2 points per 10-year increase), and heart failure symptoms (+3 points if symptomatic).

Results:

The HCM-AF score stratifies risk as low (<1.0%/y; score ≤17), intermediate (1.0-2.0%/y; score 18 to 21), and high risk (>2.0%/y; score ≥22) for AF development for individual patients. Concordance of the HCM-AF score was 0.70 in the development cohort and 0.68 in the external validation cohort. In the development cohort, 17.2% of high-risk patients developed AF (rate 3.4%/y), while only 3.3% of low-risk patients developed AF (rate 0.7%/y) at 5 years (
P
<0.001). Similarly, in the external validation cohort, 13.3% of high-risk patients developed AF (rate 2.7%/y), whereas only 1.1% of low-risk patients developed AF (rate 0.2%/y). The HCM-AF score provided greater predictive power for future AF risk than left atrial dimension alone (concordance of 0.58) and outperformed other non–HCM risk models.

Conclusions:
The HCM-AF score is a novel externally validated predictive tool to identify AF risk in HCM. This score can reliably stratify patients with HCM to risk of newly diagnosed AF and offers the opportunity to inform expectations regarding future clinical course.
One-Year Outcomes and Factors Associated With Mortality Following Acute Myocardial Infarction in Northern Tanzania
Authors: Hertz Julian T. , Sakita Francis M. , Kweka Godfrey L. , Tarimo Tumsifu G. , Goli Sumana , Prattipati Sainikitha , Bettger Janet P. , Thielman Nathan M. , Bloomfield Gerald S. 
Published: March 2022

Background:
Little is known about long-term outcomes and uptake of secondary preventative therapies following acute myocardial infarction (AMI) in sub-Saharan Africa.

Methods:
Consecutive patients presenting with AMI (as defined by the Fourth Universal Definition of AMI Criteria) to a northern Tanzanian referral hospital were enrolled in this prospective observational study. Follow-up surveys assessing mortality, medication use, and rehospitalization were administered at 3, 6, 9, and 12 months following initial presentation, by telephone or in person. Multivariate logistic regression was performed to identify baseline clinical and sociodemographic factors associated with one-year mortality.

Results:

Of 152 enrolled patients with AMI, 5 were lost to one-year follow-up (96.7% retention rate). Mortality rates were 34.9% (53 of 152 participants) during the initial hospitalization, 48.7% (73 of 150 patients) at 3 months, 52.7% (78 of 148 patients) at 6 months, 55.4% (82 of 148 patients) at 9 months, and 59.9% (88 of 147 patients) at one year. Of 59 patients surviving to one-year follow-up, 43 (72.9%) reported persistent anginal symptoms, 5 (8.5%) were taking an antiplatelet, 8 (13.6%) were taking an antihypertensive, 30 (50.8%) had been rehospitalized, and 7 (11.9%) had ever undergone cardiac catheterization. On multivariate analysis, one-year mortality was associated with lack of secondary education (odds ratio, 0.26 [95% CI, 0.11–0.58];
P
=0.001), lower body mass index (odds ratio, 0.90 [95% CI, 0.82–0.98];
P
=0.015), and higher initial troponin (odds ratio, 1.30 [95% CI, 1.05–1.80];
P
=0.052).

Conclusions:
In northern Tanzania, AMI is associated with high all-cause one-year mortality and use of evidence-based secondary preventative therapies among AMI survivors is low. Interventions are needed to improve AMI care and outcomes.
Early Childhood Growth and Risk of Adult Cerebrovascular Disease: The NFBC1966
Authors: Kivelä Milja , Paananen Markus , Kajantie Eero , Ojaniemi Marja , Nedelec Rozenn , Rusanen Harri , Miettunen Jouko , Rissanen Ina 
Published: March 2022

Background:
Low birth weight is associated with an increased risk of adulthood cerebrovascular disease (CVD). Not much is known about effects of early childhood growth. We studied whether the risk of adult CVD is associated with growth or nutritional factors during early childhood.

Methods:
Within the Northern Finland Birth Cohort 1966, 11 991 persons were followed from birth to 52 years of age. CVD diagnoses were extracted from national hospital and death registers with diagnostic coding based on the World Health Organization recommendations. Cox proportional hazard models were used to estimate associations of childhood growth variables, growth trajectories (by Latent Class Growth Modeling), and nutritional factors with adult CVD, for example, ischemic and hemorrhagic strokes. The analyses were adjusted for childhood socioeconomic status and birth weight.

Results:
A total of 453 (3.8%) CVDs were recorded during follow-up. Among females, groups with low early childhood weight and height had an increased risk for adulthood ischemic CVDs, with an adjusted hazard ratio of 1.97 (95% CI, 1.21–3.20) and 2.05 (CI, 1.11–3.81), respectively. In addition, females with body mass index over 1 SD at body mass index rebound had an increased risk for ischemic CVDs (adjusted hazard ratio, 1.90 [CI, 1.19–3.04]) compared with females with body mass index −1 to +1 SD. These associations were not found among males.

Conclusions:
The findings suggest that timing of weight gain during childhood is of significance for development of CVD risk among females.
Caught in the ACTS: Defining Abstract Cognitive Task Sequences as an Independent Process
Authors: Desrochers Theresa M. , Ahuja Aarit , Maechler Marvin R. , Shires Jorja , Yusif Rodriguez Nadira , Berryhill Marian E. 
Published: March 2022

Abstract
Cognitive neuroscience currently conflates the study of serial responses (e.g., delay match to sample/nonsample, n-back) with the study of sequential operations. In this essay, our goal is to define and disentangle the latter, termed abstract cognitive task sequences (ACTS). Existing literatures address tasks requiring serial events, including procedural learning of implicit motor responses, statistical learning of predictive relationships, and judgments of attributes. These findings do not describe the behavior and underlying mechanism required to succeed at remembering to evaluate color, then shape; or to multiply, then add. A new literature is needed to characterize these sorts of second-order cognitive demands of studying a sequence of operations. Our second goal is to characterize gaps in knowledge related to ACTS that merit further investigation. In the following sections, we define more precisely what we mean by ACTS and suggest research questions that further investigation would be positioned to address.
Tactics and Pathologies of Party Primaries: A Test for Democratic Consolidation in Tanzania
Authors: Babeiya Edwin 
Published: March 2022

Abstract
Since 1995, political parties in Tanzania have been engaging in electoral processes by fielding candidates for elective posts, mobilizing voters and representing constituencies in decision-making bodies. These processes have obliged political parties to nominate candidates to contest for various seats. The manner in which political parties obtain their candidates varies. In that process, it is only the major parties that conduct competitive intraparty nominations. Using several benchmarks such as membership restrictions, selection methods, ethical conduct, conflict management, support mobilization and voices of ordinary members, this paper reveals several democratic deficits. Some of these include; marginalization of special groups and ordinary members, limited/lack of internal party democracy, presence of dysfunctional party structures, preponderance of unethical practices particularly corruption and lack of effective accountability mechanisms. Primaries in Tanzania are thus far from being an encouraging indicator of democratic consolidation. They are mostly a challenge and a distress to democratic consolidation. Primaries are still far from being platforms for party members and/or public scrutiny and authorization of prospective candidates. Despite popular participation in these primaries, nomination outcomes get determined by political parties’ top leadership. This is the experience for the ruling party and the opposition. Political parties in Tanzania have an obligation of echoing appeals for democratization within their internal structures.
When the Silent Past Gets a Troubling Voice
Authors: Elsherif Nermin 
Published: March 2022

Abstract
This article traces the contemporary (re)interpretations of a 14 minutes of American newsreel footage depicting 1928 Cairo as it circulated through popular Facebook communities dedicated to the nostalgic discourse of Egypt’s ‘good old days’ or ‘al-zaman al-gamīl,’ perceived as an era of morality and proper Egyptianness. Among the several orientalist scenes captured on the footage was a character improvisation perceived to be ‘profane’ by the proponents of this ideal imaginary of the past. Considering online and offline ethnography and discourse analysis of online commentaries, this article examines how nationalism, conspiracy theories, identity politics and post-revolutionary frustrations are discussed through the circulation of representations of the nation’s past. By tracing the pre-and post-digital life of this footage, it presents a case study on how cultural texts acquire meanings as they migrate from one medium to another and how online publics are formed around the (re)circulation and (re)interpretation of these texts.
Protecting Women from Violence in Turkey: The Contentious Decision to Withdrawing from Istanbul Convention
Authors: Apaydin Deniz Tekin 
Published: March 2022

Abstract
The Turkish President formally announced the decision to withdraw from the Council of Europe Convention on Preventing and Combating Violence against Women and Domestic Violence (the Istanbul Convention) on 20 March 2021. This announcement drew serious intra-national and international reaction. Despite the critiques and protests, the denunciation of the treaty became legally effective by 01 July 2021. This study aims to shed some light on this development mainly from an international law and constitutional law perspective. In this regard, first, the denunciation from an international treaty in general and the Convention in particular will be given from an international law point of view. Next, the national legal outlook will be presented mainly from a constitutional standpoint. Here particular emphasis will be on the new government system in effect since 2018, and the presidential decrees and presidential decisions as important tools of this system. Finally, the study will demonstrate the current situation and project future possibilities.