bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study
Authors: Vukusic Sandra , Ionescu Iuliana , Cornu Catherine , Bossard Nadine , Durand-Dubief Françoise , Cotton François , Durelli Luca , Marignier Romain , Gignoux Laurence , Laplaud David-Axel , Moreau Thibault , Clavelou Pierre , De Seze Jérôme , Debouverie Marc , Brassat David , Pelletier Jean , Lebrun-Frenay Christine , Le Page Emmanuelle , Castelnovo Giovanni , Berger Eric , Hautecoeur Patrick , Heinzlef Olivier , Trojano Maria , Patti Francesco , Baulieu Etienne-Emile , Remontet Laurent , El-Etr Martine 
Published: December 2020

Background: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. Objective: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. Methods: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. Results: Recruitment was stopped prematurely due to slow inclusions ( n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58–1.39), placebo = 0.97 (0.63–1.50) ( p = 0.79)). Conclusion: POPARTMUS failed showing efficacy of a NOMAc–E2 combination in preventing post-partum relapses.
Distribution of sickness absence risk across different levels and patterns of drinking: findings from the Stockholm Public Health Cohort
Authors: Landberg Jonas , Ramstedt Mats 
Published: November 2020

Aim: This study estimated (i) the risk function between different indicators of alcohol use and long-term sickness absence, adjusting for possible confounding factors, (ii) whether the risk function between average volume of consumption and sickness absence is modified by heavy episodic drinking (HED), and (iii) to what extent the risk for sickness absence among abstainers is due to health selection bias. Data and methods: The study was based on data from the Stockholm Public Health Cohort 2006, with an analytical sample of 16,477 respondents aged 18–64 years. The outcome included register-based long-term (> 14 days) sickness absence. Negative binominal regression was used to estimate the association between sickness absence and average weekly volume of consumption, frequency of HED, and both in interaction. Results: Abstainers, chronic heavy drinkers and respondents with the highest frequency of HED had approximately two-fold higher rates of sickness absence relative to the reference groups, i.e., moderate drinkers and those with HED one to 6 times per year. Adjustment for confounding factors did not materially affect the shape of the risk function. After exclusion of abstainers with alcohol-related problems, or poor health, the estimates for abstainers became non-significant. Moderate drinkers with HED did not have significantly higher rates of sickness absence than moderate drinkers without HED. Conclusions: Our results suggest a significant association between alcohol use and sickness absence. There were indications that the U-shaped risk function may largely be due to health selection bias among abstainers. We found no indication of effect modification of HED on moderate drinking.
A comparative assessment of transfer accuracy of two indirect bonding techniques in patients undergoing fixed mechanotherapy: A randomised clinical trial
Authors: Chaudhary Vivek , Batra Puneet , Sharma Karan , Raghavan Sreevatsan , Gandhi Vikram , Srivastava Amit 
Published: December 2020

Objectives To assess the transfer accuracy of three-dimensional (3D) printed transfer trays and compare them with transfer trays made up of polyvinyl siloxane (PVS) for use in indirect bonding. Design: This was a two-arm parallel prospective randomised controlled trial. Setting: The trial was undertaken at the outpatient department of a dental college. Participants: A total of 30 patients (18 men, 12 women) were randomly allocated to two groups. Methods: The inclusion criteria included patients with permanent and fully erupted dentition (age range = 17–24 years), Angles class I malocclusion with crowding <3 mm requiring non-extraction treatment, good oral hygiene and no previous history of orthodontic treatment. Blinding was applicable only for outcome assessment. Indirect bonding was performed by the primary investigator for both the groups. Digital images of the pre-transfer and post-transfer brackets were obtained by means of an intra-oral scanner and compared using software. Superimpositions of pre- and post-transfer images were done to determine the transfer error for linear and angular variables for all tooth types. Results: A total of 600 teeth were bonded, 300 each for both groups. Statistically significant differences were observed in all dimension between the two groups, with 3D-printed trays being more accurate than PVS trays except in the vertical dimension ( P < 0.05). The prevalence of clinically unacceptable transfer errors revealed that most of the transfer errors were in the vertical dimensions for 3D-printed trays. Conclusion: 3D-printed trays are more accurate than PVS trays except for transfers in vertical dimension.
Remembering love: Memory work of orphaned children in the Philippine drug war
Authors: Ofreneo Mira Alexis , Canoy Nico , Martinez Luz Maria , Fortin Pacita , Mendoza Merlie , Yusingco Mara Patricia , Aquino Michaela Grace 
Published: November 2020

Summary The “war on drugs” in the Philippines has left a generation of Filipino orphaned children in deep grief and social disarray. Using feminist memory work as critical methodology and intervention design, this study examines accounts of 56 orphaned children and how they exercise agency embedded in the collective remembering of a traumatic past (i.e. rooted in painful memories of tokhang or community police operations) and to identify social structures that marginalize their present and future lifeworld. Findings Findings show three overarching themes namely: (1) reclaiming stripped agency in the loss and injustice of the past, (2) holding on to crippled agency in the sadness and insecurity of the present, and (3) carrying on with agency to hope for healing and justice in a reimagined future. Applications Insights and recommendations to critical praxis of social work in light of an ongoing drug war are further discussed which include strengthening civil societies and intersectoral collaborations, integrating specific social provisions for tokhang survivors in the creation of a national orphan policy, and using digital memorialization. Guided by enacting ethics and politics of caring for and with the marginalized, social workers working alongside expanded communities of care are called to remember love despite traumatic pains and to restore homes for orphaned children in the midst of state insecurity.
Serum miR-185 Is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer
Authors: Liu Jinghao , Han Yueting , Liu Xingyu , Wei Sen 
Published: November 2020

Objective: MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC. Methods: Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored. Results: The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC. Conclusions: Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.
Technical aspects of combined intrasaccular and endoluminal flow diversion
Authors: White Timothy G , Shah Kevin , Turpin Justin , Link Thomas , Dehdashti Amir R , Katz Jeffrey M , Woo Henry H 
Published: November 2020

Introduction The concurrent use of endoluminal flow diversion with coils is a viable option when treating complex or large aneurysms. Alternatives to coil embolization as an adjunctive treatment are currently limited. The Food and Drug Administration recently approved the Woven EndoBridge (WEB) device (Microvention, Aliso Viejo, California) as an intrasaccular flow diverter for wide-neck bifurcation aneurysms. We present the technical aspects of combined WEB device plus endoluminal flow diversion for the treatment of complex wide-necked intracranial aneurysms. Methods A retrospective chart review of all patients treated via intrasaccular flow diversion at a single institution over the last 12 months was performed. Results In total, seven patients underwent treatment of eight aneurysms via combined intrasaccular and endoluminal flow diversion. Of the seven patients, six were treated in a single setting. The most common aneurysm location was the posterior communicating artery. The majority of the aneurysms required steam shaping of the Via deployment catheter to place the WEB device orthogonally to the aneurysm dome. There were no complications. Conclusions We believe this is one of the first series reporting the combined use of the WEB device and endoluminal flow diversion for the treatment of intracranial aneurysms. This series demonstrates that the concurrent use of the WEB device with endoluminal flow diversion is safe for achieving immediate aneurysm treatment and may enhance the long-term durability in complex aneurysms.
Protecting the Well-Being of Medical Residents and Faculty Physicians During the COVID-19 Pandemic: Making the Case for Accessible, Comprehensive Wellness Resources
Authors: Ey Sydney , Soller Marie , Moffit Mary 
Published: December 2020

Accounts of frontline health care workers experiencing distress in the midst of the COVID-19 pandemic highlight the need for accessible psychological support for them. Prior to the pandemic, medical residents and physicians often experienced difficulty receiving counseling due to concerns about confidentiality, stigma, cost, time, and reportability to licensure/credentialing bodies. Since 2004, the OHSU Resident and Faculty Wellness Program (RFWP) team has sought to reduce these barriers by providing on-site free, confidential, individual counseling and medication management. Utilization of this program is high with over 500 physicians a year seeking care; 38% of all OHSU residents/fellows and 7% of all faculty eligible for our services participated in 2019-20. In the present essay, we describe how our model of care for trainees and faculty was a key wellness resource during COVID-19. Similar to other accounts of lower help-seeking by health professionals initially during the pandemic, we experienced a slight downturn in utilization rates during the initial weeks of when the pandemic struck our area, but quickly returned to normal and exceeded prior levels. All appointments shifted to telehealth visits and a number of physicians expressed gratitude for the opportunity to talk through concerns and strengthen coping. A number of physicians requested medication consultations to address severe insomnia, anxiety, and depression. We hope that being present in our physicians’ lives when they are exposed to COVID-related stress or trauma will keep them safe, help them cope with difficult experiences and losses, and ultimately facilitate both recovery and post-traumatic growth.
Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin
Authors: Marcellino Bridget K. , Farnoud Noushin , Cassinat Bruno , Lu Min , Verger Emanuelle , McGovern Erin , Patel Minal , Medina-Martinez Juan , Levine Max Fine , Arango Ossa Juanes E. , Zhou Yangyu , Kosiorek Heidi , Mehrotra Meenakshi , Houldsworth Jane , Dueck Amylou , Rossi Michael , Mascarenhas John , Kiladjian Jean-Jacques , Rampal Raajit K. , Hoffman Ronald 
Published: December 2020

AbstractActivation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analysis of raw sequencing data of baseline samples was performed and revealed that a subset of these mutations was present at baseline and expanded during treatment with idasanutlin. Follow-up samples were obtained from 4 of 5 patients in this cohort, and we observed that after cessation of idasanutlin, the variant allele frequency (VAF) of 8 of 9 TP53 mutations decreased. Furthermore, disease progression to myelofibrosis or myeloproliferative neoplasm blast phase was not observed in any of these patients after 19- to 32-month observation. These data suggest that idasanutlin treatment may promote transient TP53 mutant clonal expansion. A larger study geared toward high-resolution detection of low VAF mutations is required to explore whether patients acquire de novo TP53 mutations after idasanutlin therapy.
Che-1/AATF-induced transcriptionally active chromatin promotes cell proliferation in multiple myeloma
Authors: Bruno Tiziana , De Nicola Francesca , Corleone Giacomo , Catena Valeria , Goeman Frauke , Pallocca Matteo , Sorino Cristina , Bossi Gianluca , Amadio Bruno , Cigliana Giovanni , Ricciardi Maria Rosaria , Petrucci Maria Teresa , Spugnini Enrico Pierluigi , Baldi Alfonso , Cioce Mario , Cortese Giancarlo , Mattei Elisabetta , Merola Roberta , Gianelli Umberto , Baldini Luca , Pisani Francesco , Gumenyuk Svitlana , Mengarelli Andrea , Höpker Katja , Benzing Thomas , Vincenzi Bruno , Floridi Aristide , Passananti Claudio , Blandino Giovanni , Iezzi Simona , Fanciulli Maurizio 
Published: December 2020

Abstract
Multiple myeloma (MM) is a hematologic malignancy produced by a clonal expansion of plasma cells and characterized by abnormal production and secretion of monoclonal antibodies. This pathology exhibits an enormous heterogeneity resulting not only from genetic alterations but also from several epigenetic dysregulations. Here we provide evidence that Che-1/AATF (Che-1), an interactor of RNA polymerase II, promotes MM proliferation by affecting chromatin structure and sustaining global gene expression. We found that Che-1 depletion leads to a reduction of “active chromatin” by inducing a global decrease of histone acetylation. In this context, Che-1 directly interacts with histones and displaces histone deacetylase class I members from them. Strikingly, transgenic mice expressing human Che-1 in plasma cells develop MM with clinical features resembling those observed in the human disease. Finally, Che-1 downregulation decreases BRD4 chromatin accumulation to further sensitize MM cells to bromodomain and external domain inhibitors. These findings identify Che-1 as a promising target for MM therapy, alone or in combination with bromodomain and external domain inhibitors.
Mesenchymal stromal cells in hematopoietic cell transplantation
Authors: Burnham Andre J. , Daley-Bauer Lisa P. , Horwitz Edwin M. 
Published: December 2020

Abstract
Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow–derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.
Renal outcome in patients with newly diagnosed multiple myeloma: results from the UK NCRI Myeloma XI trial
Authors: Rana Ritika , Cockwell Paul , Drayson Mark , Cook Mark , Pratt Guy , Cairns David A. , Pawlyn Charlotte , Jackson Graham , Davies Faith , Morgan Gareth , Pinney Jennifer Helen 
Published: December 2020

Abstract
Renal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were &lt;70 years old, male, had an average eGFR &lt;60 mL per minute per 1.73 m2 and a higher baseline free light chain level &gt;1000 mg/L, and/or a free light chain response of &gt;90%. It did not correlate with monoclonal–protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852.
Follicular lymphoma t(14;18)-negative is genetically a heterogeneous disease
Authors: Nann Dominik , Ramis-Zaldivar Joan Enric , Müller Inga , Gonzalez-Farre Blanca , Schmidt Janine , Egan Caoimhe , Salmeron-Villalobos Julia , Clot Guillem , Mattern Sven , Otto Franziska , Mankel Barbara , Colomer Dolors , Balagué Olga , Szablewski Vanessa , Lome-Maldonado Carmen , Leoncini Lorenzo , Dojcinov Stefan , Chott Andreas , Copie-Bergman Christiane , Bonzheim Irina , Fend Falko , Jaffe Elaine S. , Campo Elias , Salaverria Itziar , Quintanilla-Martinez Leticia 
Published: December 2020

Abstract
Fifty-five cases of t(14;18)− follicular lymphoma (FL) were genetically characterized by targeted sequencing and copy number (CN) arrays. t(14;18)− FL predominated in women (M/F 1:2); patients often presented during early clinical stages (71%), and had excellent prognoses. Overall, t(14;18)− FL displayed CN alterations (CNAs) and gene mutations carried by conventional t(14;18)+ FL (cFL), but with different frequencies. The most frequently mutated gene was STAT6 (57%) followed by CREBBP (49%), TNFRSF14 (39%), and KMT2D (27%). t(14;18)− FL showed significantly more STAT6 mutations and lacked MYD88, NOTCH2, MEF2B, and MAP2K1 mutations compared with cFL, nodal marginal zone lymphoma (NMZL), and pediatric-type FL (PTFL). We identified 2 molecular clusters. Cluster A was characterized by TNFRSF14 mutations/1p36 alterations (96%) and frequent mutations in epigenetic regulators, with recurrent loss of 6q21-24 sharing many features with cFL. Cluster B showed few genetic alterations; however, a subgroup with STAT6 mutations concurrent with CREBBP mutations/16p alterations without TNFRSF14 and EZH2 mutations was noted (65%). These 2 molecular clusters did not distinguish cases by inguinal localization, growth pattern, or presence of STAT6 mutations. BCL6 rearrangements were demonstrated in 10 of 45 (22%) cases and did not cluster together. Cases with predominantly inguinal presentation (20 of 50; 40%) had a higher frequency of diffuse growth pattern, STAT6 mutations, CD23 expression, and a lower number of CNAs, in comparison with noninguinal cases (5.1 vs 9.1 alterations per case; P &lt; .05). STAT6 mutations showed a positive correlation with CD23 expression (P &lt; .001). In summary, t(14;18)− FL is genetically a heterogeneous disorder with features that differ from cFL, NMZL, and PTFL.