bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remote consultations in prison mental healthcare in England: impacts of COVID-19
Authors: Hewson Thomas , Robinson Louise , Khalifa Najat , Hard Jake , Shaw Jennifer 
Published: February 2021

Summary
Telemedicine has become increasingly used by prison mental health services throughout the COVID-19 pandemic. In this editorial, we explore the benefits and risks of the remote provision of forensic mental healthcare, with consideration of the clinical, financial, ethical and legal consequences.
Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
Authors: Nowakowski Grzegorz S. , Hong Fangxin , Scott David W. , Macon William R. , King Rebecca L. , Habermann Thomas M. , Wagner-Johnston Nina , Casulo Carla , Wade James L. , Nagargoje Gauri G. , Reynolds C. M. , Cohen Jonathon B. , Khan Nadia , Amengual Jennifer E. , Richards Kristy L. , Little R. F. , Leonard John P. , Friedberg Jonathan W. , Kostakoglu Lale , Kahl Brad S. , Witzig Thomas E. 
Published: February 2021

PURPOSE Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.
Downstream Revenue Generated by a Cancer Genetic Counselor
Authors: Mauer Caitlin B. , Reys Brian D. , Hall Reece E. , Campbell Connor L. , Pirzadeh-Miller Sara M. 
Published: February 2021

PURPOSE Enhanced cancer risk reduction measures are recommended for patients with hereditary predispositions to cancer. Providing these services within a healthcare institution (HI) generates downstream revenue (DSR). We evaluated the DSR for our institution after patients were identified to have a pathogenic variant by a genetic counselor (GC). METHODS Retrospective chart review identified patients with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) seen in the UT Southwestern Medical Center Cancer Genetics Clinic between November 1, 2009, and January 31, 2019. All billable encounters were recorded. Total revenue and work relative value units were calculated after patients met with a GC. RESULTS Four hundred twenty-five patients with HBOC and LS had financial data available for analysis. After GC visit, DSR totaled $32,798,000 in US dollars (USD). Patients unaffected with cancer (n = 176) generated $8,453,000 (USD). Patients (n = 96) whose first visit to the institution were for GC consultation (naïve patients) generated $5,933,000 (USD). Unaffected, naïve patients (n = 64) generated $3,190,000 (USD) in DSR. The 425 total patients generated 73,957 work relative value units at the institution after their appointment with a GC. CONCLUSION GCs bring in substantial DSR for their HI by identifying patients with HBOC or LS. Institution naïve and unaffected patients who continue care at the institution provide additional opportunities to generate DSR. If applied to additional pathogenic variant carriers, GCs can further increase DSR for an HI.
Total and Central Adiposity Are Associated With Age at Gonadarche and Incidence of Precocious Gonadarche in Boys
Authors: Pereira Ana , Busch Alexander S , Solares Fernanda , Baier Ingrid , Corvalan Camila , Mericq Veronica 
Published: February 2021

Abstract

Context
A close link between body mass index (BMI) and female pubertal onset is well established. However, observations in boys remain inconclusive.

Objective
We aim to determine whether BMI as well as total and central adiposity in prepubertal Chilean boys is associated with pubertal timing.

Methods
We performed a longitudinal study in which 494 boys from the Growth and Obesity Chilean Cohort Study were followed starting from birth and throughout puberty, including 5 prepubertal visits. The main outcome measures included anthropometric data and semi-annual clinical pubertal staging. The association between BMI, obesity (BMI standard deviation score [SDS] ≥ 2) and central adiposity (waist circumference ≥ 90th centile) with precocious puberty and age at gonadarche was analyzed using survival- and logistic regression models.

Results
BMI, prevalence of total obesity, and central obesity increased throughout childhood. Among the study population, 45 boys entered puberty before the age of 9 years (9.1%). Obesity at 4 to 7 years and childhood mean BMI SDS were significantly associated with precocious gonadarche. Mean age at testicular enlargement (≥4 mL), was 11.0 years (95% CI, 10.9-11.1) and was inversely associated with BMI SDS, waist circumference, and percentage fat mass in almost all prepubertal visits. Age at testicular enlargement in normal weight, overweight, and obese boys was 11.2 (11.0-11.3), 10.9 (10.6-11.1) and 10.7 (10.4-11.1) years, respectively.

Conclusion
Our observation supports the association of BMI SDS and obesity with pubertal timing and precocious gonadarche in boys, respectively. Early intervention controlling the obesity epidemic could be useful in decreasing detrimental impact on later health.
Predictors for Remission after Transsphenoidal Surgery in Acromegaly: A Dutch Multicenter Study
Authors: Coopmans Eva C , Postma Mark R , Wolters Thalijn L C , van Meyel Sebastiaan W F , Netea-Maier Romana , van Beek André P , Neggers Sebastian J C M M 
Published: February 2021

Abstract

Context
Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy.

Objective
To identify predictors for remission after TSS in acromegaly.

Methods
Large multicenter study with retrospective data collection from 3 tertiary neurosurgical referral centers in The Netherlands. We analyzed clinical data since 2000 from 3 cohorts (Groningen, Nijmegen, and Rotterdam, total n = 282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks to 1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex-normalized insulin-like growth factor 1 [IGF-1] and the absence of postoperative treatment until last follow-up), and relative IGF-1 and growth hormone [GH] reduction.

Results
A larger maximum tumor diameter (odds ratio [OR] 0.91, 95% CI 0.87-0.96, P ≤ .0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89-0.97, P = .0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96-0.99, P = .0053) were associated with a lower chance of long-term remission.

Conclusion
Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.
Mosaic CRISPR-stop enables rapid phenotyping of nonsense mutations in essential genes
Authors: Wang Guangqin , Li Chao , He Shunji , Liu Zhiyong 
Published: February 2021

ABSTRACT
CRISPR-stop converts protein-coding sequences into stop codons, which, in the appropriate location, results in a null allele. CRISPR-stop induction in one-cell-stage zygotes generates Founder 0 (F0) mice that are homozygous mutants; this avoids mouse breeding and serves as a rapid screening approach for nonlethal genes. However, loss of function of 25% of mammalian genes causes early lethality. Here, we induced CRISPR-stop in one of the two blastomeres of the zygote, a method we name mosaic CRISPR-stop, to produce mosaic Atoh1 and Sox10 F0 mice; these mice not only survived longer than regular Atoh1/Sox10 knockout mice but also displayed their recognized cochlear phenotypes. Moreover, by using mosaic CRISPR-stop, we uncovered a previously unknown role of another lethal gene, Rbm24, in the survival of cochlear outer hair cells (OHCs), and we further validated the importance of Rbm24 in OHCs by using our Rbm24 conditional knockout model. Together, our results demonstrated that mosaic CRISPR-stop is reliable and rapid, and we believe this method will facilitate rapid genetic screening of developmentally lethal genes in the mouse inner ear and also in other organs.
Fueling the cytoskeleton – links between cell metabolism and actin remodeling
Authors: DeWane Gillian , Salvi Alicia M. , DeMali Kris A. 
Published: February 2021

ABSTRACT
Attention has long focused on the actin cytoskeleton as a unit capable of organizing into ensembles that control cell shape, polarity, migration and the establishment of intercellular contacts that support tissue architecture. However, these investigations do not consider observations made over 40 years ago that the actin cytoskeleton directly binds metabolic enzymes, or emerging evidence suggesting that the rearrangement and assembly of the actin cytoskeleton is a major energetic drain. This Review examines recent studies probing how cells adjust their metabolism to provide the energy necessary for cytoskeletal remodeling that occurs during cell migration, epithelial to mesenchymal transitions, and the cellular response to external forces. These studies have revealed that mechanotransduction, cell migration, and epithelial to mesenchymal transitions are accompanied by alterations in glycolysis and oxidative phosphorylation. These metabolic changes provide energy to support the actin cytoskeletal rearrangements necessary to allow cells to assemble the branched actin networks required for cell movement and epithelial to mesenchymal transitions and the large actin bundles necessary for cells to withstand forces. In this Review, we discuss the emerging evidence suggesting that the regulation of these events is highly complex with metabolism affecting the actin cytoskeleton and vice versa.
Emerging functions of cytoskeletal proteins in immune diseases
Authors: Tur-Gracia Sara , Martinez-Quiles Narcisa 
Published: February 2021

ABSTRACT
Immune cells are especially dependent on the proper functioning of the actin cytoskeleton, and both innate and adaptive responses rely on it. Leukocytes need to adhere not only to substrates but also to cells in order to form synapses that pass on instructions or kill infected cells. Neutrophils literally squeeze their cell body during blood extravasation and efficiently migrate to the inflammatory focus. Moreover, the development of immune cells requires the remodeling of their cytoskeleton as it depends on, among other processes, adhesive contacts and migration. In recent years, the number of reports describing cytoskeletal defects that compromise the immune system has increased immensely. Furthermore, a new emerging paradigm points toward a role for the cellular actin content as an essential component of the so-called homeostasis-altering molecular processes that induce the activation of innate immune signaling pathways. Here, we review the role of critical actin-cytoskeleton-remodeling proteins, including the Arp2/3 complex, cofilin, coronin and WD40-repeat containing protein 1 (WDR1), in immune pathophysiology, with a special focus on autoimmune and autoinflammatory traits.
Vimentin tunes cell migration on collagen by controlling β1 integrin activation and clustering
Authors: Ostrowska-Podhorodecka Zofia , Ding Isabel , Lee Wilson , Tanic Jelena , Abbasi Sevil , Arora Pamma D. , Liu Richard S. , Patteson Alison E. , Janmey Paul A. , McCulloch Christopher A. 
Published: February 2021

ABSTRACT
Vimentin is a structural protein that is required for mesenchymal cell migration and directly interacts with actin, β1 integrin and paxillin. We examined how these interactions enable vimentin to regulate cell migration on collagen. In fibroblasts, depletion of vimentin increased talin-dependent activation of β1 integrin by more than 2-fold. Loss of vimentin was associated with reduction of β1 integrin clustering by 50% and inhibition of paxillin recruitment to focal adhesions by more than 60%, which was restored by vimentin expression. This reduction of paxillin was associated with 65% lower Cdc42 activation, a 60% reduction of cell extension formation and a greater than 35% decrease in cell migration on collagen. The activation of PAK1, a downstream effector of Cdc42, was required for vimentin phosphorylation and filament maturation. We propose that vimentin tunes cell migration through collagen by acting as an adaptor protein for focal adhesion proteins, thereby regulating β1 integrin activation, resulting in well-organized, mature integrin clusters.
This article has an associated First Person interview with the first author of the paper.
Differential activation of c-Fos and Egr1 during development of the mouse visual cortex
Authors: Ivanova Anna , Rogozin Pavel , Enikolopov Grigori , Anokhin Konstantin , Lazutkin Alexander 
Published: February 2021

Background: Critical periods (CP) in brain development are characterized by heightened neural plasticity in the relevant brain regions. They are associated with changes in gene expression cascades, in particular with altered expression of genes involved in plasticity regulation, such as immediate early genes. Here we examine the expression of the immediate early genes c-Fos and Egr1 at different stages of mouse visual cortex (VC) development. Methods: Mice 11, 25, and 50 days of age were maintained under standard light-dark conditions, deprived of light for 5 days, or deprived of light for 5 days and then exposed to light for 90 min. Their brains were analyzed at PND16 (before the onset of the CP), PND30 (during the CP) and PND55 (after the CP) to determine the changes in the number of cells expressing c-Fos and Egr1 in the binocular primary visual and primary somatosensory cortices. Results: We found highly specific induction of c-Fos expression in the primary VC in response to light. We also observed transient cross-modal activation of c-Fos in the barrel field of the primary somatosensory cortex in response to light before and during the CP; such activation disappeared after the CP. Expression of Egr1 was not induced by light in the VC before the CP, but was evident during and after the CP, although the induction was much less pronounced than that of c-Fos. Conclusions: Dynamic changes in c-Fos and Egr1 expression may reflect their contribution to the VC plasticity during the CPs of postnatal brain development.
SWAT 76 evaluation: randomised evaluation of sending pre-notification cards to trial participants before a face-to-face primary outcome measurement to increase attendance
Authors: Treweek Shaun , Gallant Stephanie , Anderson Annie S. 
Published: February 2021

Background: Retention is considered the second highest trial methods priority in the UK after recruitment. Methods: This Study Within A Trial (SWAT) evaluated whether sending a pre-notification card around one month before a face-to-face primary outcome measurement visit compared to not sending the card increased trial retention. The SWAT was a two-arm, parallel randomised (1:1 allocation ratio), stratified by centre, study. It was embedded within the ActWELL host trial, which evaluated whether women receiving lifestyle change counselling from volunteer coaches improved outcomes including weight and physical activity. The text on the card was not developed using formal behavioural change theory but did target factors thought to influence attendance. The SWAT primary outcome was the difference in the proportion of participants attending the host trial primary outcome measurement visit. The secondary outcome was the direct cost of sending cards. Host trial participants and research staff at the primary outcome visit were blind to the SWAT. Analysis was intention-to-treat. GRADE was used the assess the certainty of evidence. Results: 558 host trial participants took part in the SWAT and were included in the analysis. Sending a pre-notification card may result in a slight increase in attendance at a face-to-face primary outcome measurement visit: risk difference = 3.3% (95% confidence interval = -3.0% to 9.6%). This is GRADE low certainty evidence. A recording error meant it was unclear whether 17 participants allocated to the card were actually sent one but a sensitivity analysis did not change the overall result or conclusion. The direct cost of producing and sending the cards was £192 GBP (€213 EUR; $260 USD). Discussion: Trialists could consider using pre-notification as they may gain a slight increase in retention to face-to-face trial measurement visits but further evaluations are needed.
Z Factor: Drama as a tool to tackle mental health stigma: study design and protocol for community and public engagement in rural Zimbabwe
Authors: Gudyanga Denford , Palmer Tamaryn , Wright Nicola , O'Regan Eileen , Shonai Charity , Mlambo Nefasi , Maremera Melody , Mangezi Walter 
Published: February 2021

Background: Mental health is slowly gaining global significance as a key health issue, yet the stigma attached to psychosis is still a major problem. There has been little in-depth exploration of sustainable, cost-effective, and replicable community engagement strategies that address mental health myths and stigma, which are major barriers to early health-seeking behaviours. In low-income countries such as Zimbabwe, cultural and spiritual beliefs are at the centre of most mental health explanatory models, perpetuating an environment where mental health conversations are a cultural taboo. Mental health interventions should be accompanied by creative, evidence-based community engagement, ensuring that interventions are suitable for local settings and giving communities a voice in directing their health initiatives. Methods: Z Factor aimed to engage young adults and their support networks across a variety of socioeconomic groups in a rural district of Zimbabwe through their participation in an inter-ward five-staged drama competition. The focus was on psychosis, with subcategories of initial presentation/detection, seeking help/pathway to care, and the road to recovery/treatment. Each drama group’s composition included a young adult and a typical support network seeking treatment from the service provider of choice. Dramas were to act as discussion starters, paving the way toward broader and deeper psychosis treatment discussions among rural communities and gaining insight into service user expectations from health research. Conclusions: Outcomes of the pilot community engagement project will be instrumental in improving understanding community perceptions about psychosis treatment and recovery in rural Zimbabwe and increasing community awareness about psychosis, as well as paving the way for initiating service provider collaboration to promote early detection and encouraging early health-seeking behaviours. The above outcomes will also inform the design of models for more responsive community and public engagement initiatives in similar low resource settings in Zimbabwe and beyond.
The impact of certain factors on complications development in patients with multiple long bone fractures of lower extremities and severe associated trauma
Authors: Burianov Olexandr , Dubrov Sergii , Omelchenko Taras , Lianskorunskyi Volodymyr 
Published: February 2021

The aim: to determine the influence of individual factors on the development of complications in patients with polytrauma and multiple long bone fractures of lower extremities.Materials and methods: a prospective study conducted inKyivCityClinicalHospital №17 from December 2016 to January 2020. The study included 57 patients with polytrauma and multiple long bone fractures of lower extremities, treated according to the proposed algorithm.Results: the most common complications were: pneumonia (21.1%), acute respiratory distress syndrome (ARDS) (15.8%), multiple organ failure (MOF) (15.8%), sepsis (8.8%), mortality (12.3%). A number of factors influenced the development of complications in patients with multiple long bone fractures of lower extremities and polytrauma were identified and the correlation analysis was conducted. These factors included: age; sex; the Injury Severity Score (ISS); the Glasgow Coma Scale (GCS); the severity of a general condition of a patient according to the Clinical Grading Scale (CGS); trauma to the head, and neck, chest, abdomen, pelvis; head and neck, chest, abdomen, pelvis trauma in accordance with the Abbreviated Injury Scale (AIS); the number of segments of damaged limbs; Gustilo-Anderson fracture type; blood loss volume; massive blood transfusions; respiratory index; duration of mechanical ventilation (MV); treatment tactics; osteosynthesis method; conversion phasing.Conclusion: the analysis allowed to identify the most significant factors that lead to complications in patients with multiple long bone fractures of lower extremities and polytrauma. Informative parameters were:− for pneumonia: GCS and CGS; chest injury; AIS head and neck, chest ≥ 4; duration of MV; treatment tactics; conversion phasing (IC = 1.0-2.1).− for ARDS: GCS and CGS; AIS chest ≥ 4; fractures > 2 long bones; blood loss volume; massive blood transfusions; respiratory index; duration of MV; treatment tactics (IC = 1.2-4.6).− for sepsis: GCS; trauma to the chest, abdomen; AIS head and neck, abdominal cavity ≥ 4; fractures > 2 long bones; conversion phasing (IC = 1.1-3.2).− for MOF: GCS and CGS; abdominal trauma; AIS abdominal cavity ≥ 4; fractures > 2 long bones; massive blood transfusions; conversion phasing (IC = 1.2-2.2).− for mortality: age, ISS, GCS and CGS; abdominal trauma; AIS head and neck; chest, abdomen, pelvis ≥ 4; blood loss volume; massive blood transfusions; duration of MV (IC = 1,1-5,9).Among the factors there were those for which the diagnostic and treatment process:− affected: the choice of treatment tactics (IC = 1,1-1,3); use of massive blood transfusions (IC = 1.8-4.8); duration of MV (IC = 1,2-2,1); conversion of the fixation method (IC = 1.2-1.8).− did not affect: GCS (IC = 1,2-3,1), CGS (IC = 1,1-1,3), AIS (IC = 1,0-6,2).