bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II open‐label multicenter study to assess the antitumor activity of afatinib in lung cancer patients with activating epidermal growth factor receptor mutation from circulating tumor DNA: Liquid‐Lung‐A
Authors: Park Cheol‐Kyu , Lee Sung‐Yong , Lee Jae Cheol , Choi Chang‐Min , Lee Shin Yup , Jang Tae‐Won , Oh In‐Jae , Kim Young‐Chul 
Published: December 2020

AbstractBackgroundMutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment‐naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA.MethodsThe primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity).ResultsTherapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention‐to‐treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no significant difference in ORR between Groups A and B (80% and 67% RE, respectively). Median progression‐free survival (PFS) was 12.0 months, and no significant difference was observed according to the final afatinib dose, type of EGFRm, and Group A versus B. After progression, T790M mutation was found in 40% (6/15) of patients, and osimertinib was used as a second‐line treatment.ConclusionsAfatinib showed similar ORR and PFS in patients with lung cancer harboring EGFRm in their ctDNA regardless of tumor EGFRm results.Key pointsSignificant findings of the studyAfatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first‐line treatment of EGFR‐mutated non‐small cell lung cancer based on tumor genotyping.What this study addsOur findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real‐world setting.
Re‐Assessing Elite‐Public Gaps in Political Behavior
Authors: Kertzer Joshua D. 
Published: December 2020

AbstractPolitical scientists often criticize psychological approaches to the study of politics on the grounds that many psychological theories were developed on convenience samples of college students or members of the mass public, whereas many of the most important decisions in politics are made by elites, who are presumed to differ systematically from ordinary citizens. This paper proposes an overarching framework for thinking about differences between elites and masses, presenting the results of a meta‐analysis of 162 paired treatments from paired experiments on political elites and mass publics, as well as an analysis of 12 waves of historical elite and mass public opinion data on foreign policy issues over a 43 year period. It finds political scientists both overstate the magnitude of elite‐public gaps in decision‐making, and misunderstand the determinants of elite‐public gaps in political attitudes, many of which are due to basic compositional differences rather than to elites' domain‐specific expertise.
Mitochondrial quality surveillance as a therapeutic target in myocardial infarction
Authors: Zhu Hang , Toan Sam , Mui David , Zhou Hao 
Published: December 2020

AbstractMyocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. As mitochondrial dysfunction critically contributes to the pathogenesis of MI, intensive research is focused on the development of therapeutic strategies targeting mitochondrial homeostasis. Mitochondria possess a quality control system which maintains and restores their structure and function by regulating mitochondrial fission, fusion, biogenesis, degradation and death. In response to slight damage such as transient hypoxia or mild oxidative stress, mitochondrial metabolism shifts from oxidative phosphorylation to glycolysis, in order to reduce oxygen consumption and maintain ATP output. Mitochondrial dynamics are also activated to modify mitochondrial shape and structure, in order to meet cardiomyocyte energy requirements through augmenting or reducing mitochondrial mass. When damaged mitochondria cannot be repaired, poorly structured mitochondria will be degraded through mitophagy, a process which is often accompanied by mitochondrial biogenesis. Once the insult is severe enough to induce lethal damage in the mitochondria and the cell, mitochondrial death pathway activation is an inevitable consequence, and the cardiomyocyte apoptosis or necrosis program will be initiated to remove damaged cells. Mitochondrial quality surveillance is a hierarchical system preserving mitochondrial function and defending cardiomyocytes against stress. A failure of this system has been regarded as one of the potential pathologies underlying MI. In this review, we discuss the recent findings focusing on the role of mitochondrial quality surveillance in MI, and highlight the available therapeutic approaches targeting mitochondrial quality surveillance during MI.
Mesangial cells regulate the single nephron GFR and preserve the integrity of the glomerular filtration barrier: An intravital multiphoton microscopy study
Authors: Ziegler Vera , Fremter Katharina , Helmchen Julia , Witzgall Ralph , Castrop Hayo 
Published: December 2020

AbstractAimThe intraglomerular mesangial cells are located between the glomerular capillaries. Here we hypothesized that mesangial cells regulate the single nephron glomerular filtration rate (snGFR) and that mesangial cells support the integrity of the glomerular filtration barrier.MethodsWe assessed the function of mesangial cells in vivo by multiphoton microscopy. Mesangial cells were depleted in Munich Wistar Froemter rats using the Thy1.1 antibody model.ResultsThe Thy1.1 antibody caused the cell‐specific loss of 82 ± 3% of mesangial cells. After mesangial cell depletion, the baseline snGFR was reduced to 12.0 ± 1.2 vs 32.4 ± 3.2 nL/min in controls. In control rats, the snGFR decreased after angiotensin II infusion by 61 ± 3% (P = .004), whereas it remained unchanged in Thy1.1‐treated rats. The changes in the snGFR after angiotensin II infusion in control rats were accompanied by the marked rotation of the capillary loops within Bowman's space. This phenomenon was absent in anti‐Thy1.1‐treated rats. The glomerular sieving coefficient (GSCA) for albumin, used as a measure of the integrity of the glomerular filtration barrier, was low in control rats (0.00061 ± 0.00004) and increased after angiotensin II infusion (0.00121 ± 0.00015). In Thy1.1‐treated rats, the GSC was elevated (0.0032 ± 0.00059) and did not change in response to angiotensin II. Electron microscopy revealed the increased thickness of the glomerular basement membrane after mesangial cell depletion.ConclusionOur data suggest that mesangial cells actively contribute to the regulation of the snGFR. Furthermore, mesangial cells are crucially involved in maintaining the integrity of the glomerular filtration barrier, in part by modulating the thickness of the glomerular basement membrane.
Factors associated with the preventive healthcare service use among older adults in Korea: Focusing on age variation
Authors: Park Jane , Kahng Sang Kyoung 
Published: December 2020

AbstractThe importance of preventive health examinations for older adults has been well emphasized due to an increase in chronic diseases associated with age. In this study, we estimated the preventive health examination participation rate and its associated factors among the elderly with specific focuses on the moderating effects between age and socioeconomic status. We used data drawn from the first to sixth waves (4164 people) of the Korean Longitudinal Study of Aging for the elderly aged 65 and over. A generalized linear model was used to address research questions. The results showed that the participation rate decreased as older adults age. The interaction between age and education was also significant, indicating that older adults with higher education were more likely to use a preventive health examination compared to those with lower education. There were no significant interaction effects between income and age. Based on the findings, implications for theory and practice were discussed with specific focuses on age‐specific approaches in preventive healthcare services for older adults.
Rural resilience: The role of birth centers in the United States
Authors: Jolles Diana , Stapleton Susan , Wright Jennifer , Alliman Jill , Bauer Kate , Townsend Carla , Hoehn‐Velasco Lauren 
Published: December 2020

AbstractPurposeTo explore the role of the birth center model of care in rural health and maternity care delivery in the United States.MethodsAll childbearing families enrolled in care at an American Association of Birth Centers Perinatal Data RegistryTM user sites between 2012 and 2020 are included in this descriptive analysis.FindingsBetween 2012 and 2020, 88 574 childbearing families enrolled in care with 82 American Association of Birth Centers Perinatal Data RegistryTM user sites. Quality outcomes exceeded national benchmarks across all geographic regions in both rural and urban settings. A stable and predictable rate of transfer to a higher level of care was demonstrated across geographic regions, with over half of the population remaining appropriate for birth center level of care throughout the perinatal episode of care. Controlling for socio demographic and medical risk factors, outcomes were as favorable for clients in rural areas compared with urban and suburban communities.ConclusionsRural populations cared for within the birth center model of care experienced high‐quality outcomes.Health Policy ImplicationsA major focus of the United States maternity care reform should be the expansion of access to birth center models of care, especially in underserved areas such as rural communities.
The hallmarks of myotonic dystrophy type 1 muscle dysfunction
Authors: Ozimski Lauren L. , Sabater‐Arcis Maria , Bargiela Ariadna , Artero Ruben 
Published: December 2020

ABSTRACTMyotonic dystrophy type 1 (DM1) is the most prevalent form of muscular dystrophy in adults and yet there are currently no treatment options. Although this disease causes multisystemic symptoms, it is mainly characterised by myopathy or diseased muscles, which includes muscle weakness, atrophy, and myotonia, severely affecting the lives of patients worldwide. On a molecular level, DM1 is caused by an expansion of CTG repeats in the 3′ untranslated region (3′UTR) of the DM1 Protein Kinase (DMPK) gene which become pathogenic when transcribed into RNA forming ribonuclear foci comprised of auto complementary CUG hairpin structures that can bind proteins. This leads to the sequestration of the muscleblind‐like (MBNL) family of proteins, depleting them, and the abnormal stabilisation of CUGBP Elav‐like family member 1 (CELF1), enhancing it. Traditionally, DM1 research has focused on this RNA toxicity and how it alters MBNL and CELF1 functions as key splicing regulators. However, other proteins are affected by the toxic DMPK RNA and there is strong evidence that supports various signalling cascades playing an important role in DM1 pathogenesis. Specifically, the impairment of protein kinase B (AKT) signalling in DM1 increases autophagy, apoptosis, and ubiquitin–proteasome activity, which may also be affected in DM1 by AMP‐activated protein kinase (AMPK) downregulation. AKT also regulates CELF1 directly, by affecting its subcellular localisation, and indirectly as it inhibits glycogen synthase kinase 3 beta (GSK3β), which stabilises the repressive form of CELF1 in DM1. Another kinase that contributes to CELF1 mis‐regulation, in this case by hyperphosphorylation, is protein kinase C (PKC). Additionally, it has been demonstrated that fibroblast growth factor‐inducible 14 (Fn14) is induced in DM1 and is associated with downstream signalling through the nuclear factor κB (NFκB) pathways, associating inflammation with this disease. Furthermore, MBNL1 and CELF1 play a role in cytoplasmic processes involved in DM1 myopathy, altering proteostasis and sarcomere structure. Finally, there are many other elements that could contribute to the muscular phenotype in DM1 such as alterations to satellite cells, non‐coding RNA metabolism, calcium dysregulation, and repeat‐associated non‐ATG (RAN) translation. This review aims to organise the currently dispersed knowledge on the different pathways affected in DM1 and discusses the unexplored connections that could potentially help in providing new therapeutic targets in DM1 research.
Admission avoidance in tonsillitis and peritonsillar abscess: A prospective national audit during the initial peak of the COVID‐19 pandemic
Authors:   INTEGRATE (The UK ENT Trainee Research Network)
Published: December 2020

AbstractObjectivesTo report changes in practice brought about by COVID‐19 and the implementation of new guidelines for the management of tonsillitis and peritonsillar abscess (PTA), and to explore factors relating to unscheduled re‐presentations for patients discharged from the emergency department (ED).DesignProspective multicentre national audit over 12 weeks from 6 April 2020.SettingUK secondary care ENT departments.ParticipantsAdult patients with acute tonsillitis or PTA.Main outcome measuresRe‐presentation within 10 days for patients discharged from the ED.Results83 centres submitted 765 tonsillitis and 416 PTA cases. 54.4% (n = 410) of tonsillitis and 45.3% (187/413) of PTAs were discharged from ED. 9.6% (39/408) of tonsillitis and 10.3% (19/184) of PTA discharges re‐presented within 10 days, compared to 9.7% (33/341) and 10.6% (24/224) for those admitted from ED. The subsequent admission rate of those initially discharged from ED was 4.7% for tonsillitis and 3.3% for PTAs.IV steroids and antibiotics increased the percentage of patients able to swallow from 35.8% to 72.5% for tonsillitis (n = 270/754 and 441/608) and from 22.3% to 71.0% for PTA (n = 92/413 and 265/373).77.2% of PTAs underwent drainage (n = 319/413), with no significant difference in re‐presentations in those drained vs not‐drained (10.6% vs 9.5%, n = 15/142 vs 4/42, P = .846).Univariable logistic regression showed no significant predictors of re‐presentation within 10 days.ConclusionsManagement of tonsillitis and PTA changed during the initial peak of the pandemic, shifting towards outpatient care. Some patients who may previously have been admitted to hospital may be safely discharged from the ED.
Illegal fisheries, environmental crime, and the conservation of marine resources
Authors: Aceves‐Bueno Eréndira , Read Andrew J. , Cisneros‐Mata Miguel A. 
Published: December 2020

AbstractThe illegal harvest of marine species within exclusive economic zones can have a strong impact on the function of local ecosystems and livelihoods of coastal communities. The complexity of these problems is often overlooked in the development of solutions, leading to ineffective and sometimes harmful social and environmental outcomes. One‐dimensional, oversimplified perspectives can lead to conservation prescriptions that exacerbate social stressors. This is particularly critical in the case of international illegal trade of endangered, high‐value species, which generate a value chain in which artisanal fishers are the first operational and often the weakest link of an intricate web. We examined 2 illegal fisheries, totoaba (Totoaba macdonaldi) and sea cucumber (Isostichopus badionotusandHolothuria floridana), in Mexico. Although these are 2 separate and independent fisheries, important ecological (resource condition, fishery impacts at the ecosystem level) and social (governance, markets) similarities improve understanding of their complexity. Our findings are relevant globally and show the need for interdisciplinary decision‐making groups, community engagement, and the development of demand reduction measures.
Development of pluripotent stem cell‐based human tenocytes
Authors: Nakajima Taiki , Ikeya Makoto 
Published: December 2020

AbstractHuman pluripotent stem cells (PSCs) are used as a platform for therapeutic purposes such as cell transplantation therapy and drug discovery. Another motivation for studying PSCs is to understand human embryogenesis and development. All cell types that make up the body tissues develop through defined trajectories during embryogenesis. For example, paraxial mesoderm is considered to differentiate into several cell types including skeletal muscle cells, chondrocytes, osteocytes, dermal fibroblasts, and tenocytes. Tenocytes are fibroblast cells that constitute the tendon. The step‐wise narrowing fate decisions of paraxial mesoderm in the embryo have been modeled in vitro using PSCs; however, deriving tenocytes from human‐induced PSCs and their application in cell therapy have long been challenging. PSC‐derived tenocytes can be used for a source of cell transplantation to treat a damaged or ruptured tendon due to injury, disorder, or aging. In this review, we discuss the latest research findings on the use of PSCs for studying the biology of tenocyte development and their application in therapeutic settings.
Association of weight loss and weight loss maintenance following diabetes diagnosis by screening and incidence of cardiovascular disease and all‐cause mortality: An observational analysis of the ADDITION‐Europe trial
Authors: Strelitz Jean , Sharp Stephen J. , Khunti Kamlesh , Vos Rimke C. , Rutten Guy E. H. M. , Webb David R. , Witte Daniel R. , Sandbæk Annelli , Wareham Nicholas J. , Griffin Simon J. 
Published: December 2020

AbstractAimsShort‐term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis.Materials and methodsObservational analysis of the ADDITION‐Europe trial of 2730 adults with screen‐detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5‐year overall change in weight. Incident CVD events (n = 229) and all‐cause mortality (n = 225) from 5 to 10 years follow‐up were ascertained from medical records.ResultsGaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all‐cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30‐7.82)]. Losing ≥5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99‐6.21) and 2.72 (1.17‐6.30), respectively. Losing ≥10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m2 [4.62 (1.87‐11.42)]. Associations with CVD incidence were inconclusive.ConclusionsBoth weight loss and weight gain after screen‐detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted.
The effects of dipeptidyl peptidase‐4 inhibitors on kidney outcomes
Authors: O'Hara Daniel V. , Parkhill Thomas R. , Badve Sunil V. , Jun Min , Jardine Meg J. , Perkovic Vlado 
Published: December 2020

AbstractAimsTo summarize evidence from randomized controlled trials (RCTs) concerning the effects of dipeptidyl peptidase‐4 (DPP‐4) inhibitors on kidney outcomes in patients with type 2 diabetes mellitus (T2DM).MethodsThe Medline, EMBASE and Cochrane databases were searched for RCTs comparing DPP‐4 inhibitors with a placebo, active comparator or standard care, with at least 500 person‐years follow‐up in patients with T2DM and with reporting of kidney outcomes. Treatment effects were summarized using random‐effects meta‐analysis.ResultsTen trials including 47 955 patients (mean estimated glomerular filtration rate [eGFR] 71 mL/min/1.73m2, mean follow‐up 10 762 patient‐years per trial) were eligible for inclusion. DPP‐4 inhibitors were compared with placebo (five trials), active comparator (three trials), and standard care (two trials). Overall, treatment with DPP‐4 inhibitors was associated with a greater decline in eGFR than treatment with the comparators (weighted mean difference −1.12 mL/min/1.73m2, 95% confidence interval [CI] −1.61, −0.62; high‐certainty evidence). There were no detectable effects of DPP‐4 inhibitors on rates of doubling serum creatinine (risk ratio [RR] 1.10, 95% CI 0.90, 1.34; high‐certainty evidence), end‐stage kidney disease (RR 0.97, 95% CI 0.77, 1.23; high‐certainty evidence), death from kidney causes (RR 1.81, 95% CI 0.67, 4.93; low‐certainty evidence), or all‐cause mortality (RR 1.01, 95% CI 0.95, 1.09; high‐certainty evidence). DPP‐4 inhibitors significantly reduced the risks of the surrogate kidney outcome of new albuminuria (RR 0.88, 95% CI 0.8, 0.98; moderate‐certainty evidence) and worsening albuminuria (RR 0.88, 95% CI 0.82, 0.94; moderate‐certainty evidence). There was no difference in the safety outcome of acute kidney injury (RR 1.04, 95% CI 0.57, 1.87; high‐certainty evidence).ConclusionsDipeptidyl peptidase‐4 inhibitors are associated with a greater decline in eGFR, despite reducing the development and progression of albuminuria, and have no clear effect on other key kidney outcomes.
Cardiac hemangioma in a difficult anatomical location presented with ventricular tachycardia. A rare case report
Authors: Topel Çağdaş , Sevinç Samet , Onan Burak , Yıldız Mustafa , Güler Gamze Babur 
Published: December 2020

AbstractCardiac hemangioma is a benign and rare primary tumor of the heart. Though it has benign histopathological features, its complications can be life‐threatening. We report a young adult male without any prior structural heart disease or medical history who presented with ventricular tachyarrhythmia. Echocardiography revealed an echogenic mass located intramurally in the left lateral ventricle and its distinctive characteristics were revealed with further imaging modalities. Though simple complete removal of the mass is the preferred treatment, its firm texture and thinned encircling myocardium prevented the total excision. In this case report, we discussed cardiac hemangioma, its potential complications and treatment options.