bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LightDock Server: Artificial Intelligence-powered modeling of macromolecular interactions
Authors: Jiménez-García Brian , Roel-Touris Jorge , Barradas-Bautista Didier 
Published: May 2023

Abstract
Computational docking is an instrumental method of the structural biology toolbox. Specifically, integrative modeling software, such as LightDock, arise as complementary and synergetic methods to experimental structural biology techniques. Ubiquitousness and accessibility are fundamental features to promote ease of use and to improve user experience. With this goal in mind, we have developed the LightDock Server, a web server for the integrative modeling of macromolecular interactions, along with several dedicated usage modes. The server builds upon the LightDock macromolecular docking framework, which has proved useful for modeling medium-to-high flexible complexes, antibody-antigen interactions, or membrane-associated protein assemblies. We believe that this free-to-use resource will be a valuable addition to the structural biology community and can be accessed online at: https://server.lightdock.org/
Crol contributes to PRE-mediated repression and Polycomb group proteins recruitment inDrosophila
Authors: Erokhin Maksim , Brown J Lesley , Lomaev Dmitry , Vorobyeva Nadezhda E , Zhang Liangliang , Fab Lika V , Mazina Marina Yu , Kulakovskiy Ivan V , Ziganshin Rustam H , Schedl Paul , Georgiev Pavel , Sun Ming-an , Kassis Judith A , Chetverina Darya 
Published: May 2023

AbstractThe Polycomb group (PcG) proteins are fundamental epigenetic regulators that control the repressive state of target genes in multicellular organisms. One of the open questions is defining the mechanisms of PcG recruitment to chromatin. In Drosophila, the crucial role in PcG recruitment is thought to belong to DNA-binding proteins associated with Polycomb response elements (PREs). However, current data suggests that not all PRE-binding factors have been identified. Here, we report the identification of the transcription factor Crooked legs (Crol) as a novel PcG recruiter. Crol is a C2H2-type Zinc Finger protein that directly binds to poly(G)-rich DNA sequences. Mutation of Crol binding sites as well as crol CRISPR/Cas9 knockout diminish the repressive activity of PREs in transgenes. Like other PRE-DNA binding proteins, Crol co-localizes with PcG proteins inside and outside of H3K27me3 domains. Crol knockout impairs the recruitment of the PRC1 subunit Polyhomeotic and the PRE-binding protein Combgap at a subset of sites. The decreased binding of PcG proteins is accompanied by dysregulated transcription of target genes. Overall, our study identified Crol as a new important player in PcG recruitment and epigenetic regulation.
PrismNet: predicting protein–RNA interaction using in vivo RNA structural information
Authors: Xu Yiran , Zhu Jianghui , Huang Wenze , Xu Kui , Yang Rui , Zhang Qiangfeng Cliff , Sun Lei 
Published: May 2023

Abstract
Fundamental to post-transcriptional regulation, the in vivo binding of RNA binding proteins (RBPs) on their RNA targets heavily depends on RNA structures. To date, most methods for RBP–RNA interaction prediction are based on RNA structures predicted from sequences, which do not consider the various intracellular environments and thus cannot predict cell type-specific RBP–RNA interactions. Here, we present a web server PrismNet that uses a deep learning tool to integrate in vivo RNA secondary structures measured by icSHAPE experiments with RBP binding site information from UV cross-linking and immunoprecipitation in the same cell lines to predict cell type-specific RBP–RNA interactions. Taking an RBP and an RNA region with sequential and structural information as input (‘Sequence & Structure’ mode), PrismNet outputs the binding probability of the RBP and this RNA region, together with a saliency map and a sequence–structure integrative motif. The web server is freely available at http://prismnetweb.zhanglab.net.
The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors
Authors: Tesileanu C Mircea S , Michaleas Sotirios , Gonzalo Ruiz Rocio , Mariz Segundo , Fabriek Babs O , van Hennik Paula B , Dedorath Jutta , Dekic Bruna , Unkrig Christoph , Brandt Andreas , Koenig Janet , Enzmann Harald , Delgado Julio , Pignatti Francesco 
Published: May 2023

Abstract
Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P = .029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence ≥ 5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Optimal large population Tullock contests
Authors: Lahkar Ratul , Mukherjee Saptarshi 
Published: May 2023

Abstract
We consider Tullock contests where contestants can be divided into a finite set of types according to their strategy cost function. Solving such contests is intractable if the number of players is finite but large and there are nonlinearities and asymmetries present. But by approximating the finite player contest with a large population model that can be solved in closed form, we can approximate equilibrium behavior in the finite player model. We then characterize the optimal bias parameters of the large population contest and interpret them as approximations of optimal bias parameters in finite player contests. We also identify conditions under which those parameters are increasing or decreasing according to the cost parameters. The parameters are biased in favor of high-cost agents if the cost functions are strictly convex and the likelihood of success is sufficiently responsive to strategy.
Adjusting to Macroprudential Policies: Loan-to-Value Limits and Housing Choice
Authors: Tzur-Ilan Nitzan 
Published: May 2023

Abstract
This study provides novel evidence regarding the effects of loan-to-value (LTV) limits on housing choices. Using a detailed loan-level dataset, I exploit the introduction of LTV limits in Israel. I find that the LTV limits led borrowers to choose housing units that were more affordable, farther from the central business district, and in lower socioeconomic neighborhoods. Additionally, these LTV limits increase interest rates and decrease loan amounts. The findings of this study indicate that macroprudential policies, which focus on the stability of the financial system, have micro implications on location choices, commuting costs, and movement to less-advantaged areas.
Timing and Preventability of Cardiovascular-Related Maternal Death
Authors: Diguisto Caroline , Choinier Pierre-Marie , Saucedo Monica , Bruyere Marie , Verspyck Eric , Morau Estelle , Bonnet Marie-Pierre , Deneux-Tharaux Catherine 
Published: May 2023

OBJECTIVE:
To describe the clinical profile, management, and potential preventability of maternal cardiovascular deaths.

METHODS:
We conducted a retrospective, descriptive study of all maternal deaths resulting from a cardiovascular disease during pregnancy or up to 1 year after the end of pregnancy in France from 2007 to 2015. Deaths were identified through the nationwide permanent enhanced maternal mortality surveillance system (ENCMM [Enquête Nationale Confidentielle sur les Morts Maternelles]). Women were classified into four groups based on the assessment of the national experts committee: those who died of a cardiac condition and those who died of a vascular condition and, within these two groups, whether the condition was known before the acute event. Maternal characteristics, clinical features and components of suboptimal care, and preventability factors, which were assessed with a standard evaluation form, were described among those four groups.

RESULTS:
During the 9-year period, 103 women died of cardiac or vascular disease, which corresponds to a maternal mortality ratio from these conditions of 1.4 per 100,000 live births (95% CI 1.1–1.7). Analyses were conducted on 93 maternal deaths resulting from cardiac (n=70) and vascular (n=23) disease with available data from confidential inquiry. More than two thirds of these deaths occurred in women with no known pre-existing cardiac or vascular condition. Among the 70 deaths resulting from a cardiac condition, 60.7% were preventable, and the main preventability factor was a lack of multidisciplinary prepregnancy and prenatal care for women with a known cardiac disease. For those with no known pre-existing cardiac condition, preventability factors were related mostly to inadequate prehospital care of the acute event, in particular an underestimation of the severity and inadequate investigation of the dyspnea. Among the 23 women who died of a vascular disease, three had previously known conditions. For women with no previously known vascular condition, 47.4% of deaths were preventable, and preventability factors were related mostly to wrong or delayed diagnosis and management of acute intense chest or abdominal pain in a pregnant woman.

CONCLUSION:
Most maternal deaths attributable to cardiac or vascular diseases were potentially preventable. The preventability factors varied according to the cardiac or vascular site and whether the condition was known before pregnancy. A more granular understanding of the cause and related risk factors for maternal mortality is crucial to identify relevant opportunities for improving care and training health care professionals.
When to stop medication in juvenile idiopathic arthritis
Authors: Abel Dori , Weiss Pamela F. 
Published: May 2023

Purpose of review
Disease-modifying antirheumatic drugs (DMARDs) have dramatically improved patient outcomes in juvenile idiopathic arthritis (JIA). However, these medications may also result in physical, psychologic, and economic burden, which must be balanced with risk of flare off treatment. Although some children remain in remission after medication discontinuation, evidence is sparse for if, when, and how medications should be de-escalated once achieving clinically inactive disease (CID). We review the data on medication discontinuation and the role of serologic and imaging biomarkers in JIA.

Recent findings
The literature uniformly supports early biologic DMARD initiation, although the optimal timing and strategy for medication withdrawal in patients with sustained CID remains unclear. In this review, we present the current data on flare frequency and time to flare, clinical factors associated with flare, and recapture data for each JIA category. We also summarize the current knowledge on the role of imaging and serologic biomarkers in guiding these treatment decisions.

Summary
JIA is a heterogenous disease for which prospective clinical trials are needed to address the question of when, how, and in whom to withdraw medication. Research investigating the roles of serologic and imaging biomarkers may help improve the ability to ascertain which children can successfully de-escalate medications.
Peritoneal interposition flap reduces symptomatic lymphocele following transperitoneal robot-assisted radical prostatectomy and pelvic lymph node dissection: An updated meta-analysis
Authors: de Pinho João Henrique Sendrete , Riscado Lorrane Vieira Siqueira , Manzano João Pádua 
Published: May 2023

Abstract

Background
Robot-assisted radical prostatectomy with intraoperative pelvic lymph node dissection is the criterion standard for surgical treatment of nonmetastatic intermediate- and high-risk prostate cancer. However, this method is associated with symptomatic lymphocele (SLC), which is an important morbidity factor. To overcome this complication, several modifications of the technique have been developed, including the peritoneal interposition flap (PIF). We performed an updated systematic review and meta-analysis to investigate the efficacy and safety of this technique for preventing SLC and lymphocele (LC) formation.

Materials and methods
Searches were performed using databases and references from included studies and previous systematic reviews. Only randomized controlled trials and nonrandomized cohorts were included. Primary outcomes were the incidence of SLC and LC formation, and safety outcomes were defined as operation time, estimated blood loss, length of hospital stay, and urinary incontinence. Quality assessment was performed using the Newcastle-Ottawa Scale and Cochrane Collaboration's tool. Pooled treatment effects were estimated using odds ratios with 95% confidence intervals (CIs) for binary endpoints. Heterogeneity was examined using Cochran's Q test and I
2 statistics; p values < 0.10 and I
2 > 25% were considered significant for heterogeneity. We used Mantel-Haenszel fixed-effect models in the analyses with low heterogeneity. Otherwise, the DerSimonian and Laird random-effects model was used.

Results
The initial search yielded 510 results. After the removal of duplicate records and application of the exclusion criterion, 9 studies were fully reviewed for eligibility. Three randomized controlled trials and 5 retrospective cohorts met all the inclusion criteria, comprising 2261 patients, of whom 1073 (47.4%) underwent PIF. Six studies reported a significant reduction in SLC in the PIF group, and 3 of the 4 studies reported LC formation yielded significant results in preventing this complication. The incidence of SLC and LC formation in a follow-up of ≥3 months was significantly different between the PIF and no PIF group (odds ratio, 0.34 [95% CI, 0.16–0.74; p = 0.006] and 0.48 [95% CI, 0.31–0.74; p = 0.0008]), respectively. The safety outcomes did not differ significantly between the 2 groups.

Conclusions
These results suggest that PIF is an effective and safe technique for preventing LC and SLC in patients undergoing transperitoneal robot-assisted radical prostatectomy and pelvic lymph node dissection.
Implementation of ED I-PASS as a Standardized Handoff Tool in the Pediatric Emergency Department
Authors: Yanni Evan , Calaman Sharon , Wiener Ethan , Fine Jeffrey S. , Sagalowsky Selin T. 
Published: May 2023

ABSTRACT

Introduction:
Communication, failures during patient handoffs are a significant cause of medical error. There is a paucity of data on standardized handoff tools for intershift transitions of care in pediatric emergency medicine (PEM). The purpose of this quality improvement (QI) initiative was to improve handoffs between PEM attending physicians (i.e., supervising physicians ultimately responsible for patient care) through the implementation of a modified I-PASS tool (ED I-PASS). Our aims were to: (1) increase the proportion of physicians using ED I-PASS by two-thirds and (2) decrease the proportion reporting information loss during shift change by one-third, over a 6-month period.

Methods:
After literature and stakeholder review, Expected Disposition, Illness Severity, Patient Summary, Action List, Situational Awareness, Synthesis by Receiver (ED I-PASS) was implemented using iterative Plan-Do-Study-Act cycles, incorporating: trained “super-users”; print and electronic cognitive support tools; direct observation; and general and targeted feedback. Implementation occurred from September to April of 2021, during the height of the COVID-19 pandemic, when patient volumes were significantly lower than prepandemic levels. Data from observed handoffs were collected for process outcomes. Surveys regarding handoff practices were distributed before and after ED I-PASS implementation.

Results:
82.8% of participants completed follow-up surveys, and 69.6% of PEM physicians were observed performing a handoff. Use of ED I-PASS increased from 7.1% to 87.5% (p < .001) and the reported perceived loss of important patient information during transitions of care decreased 50%, from 75.0% to 37.5% (p = .02). Most (76.0%) participants reported satisfaction with ED I-PASS, despite half citing a perceived increase in handoff length. 54.2% reported a concurrent increase in written handoff documentation during the intervention.

Conclusion:
ED I-PASS can be successfully implemented among attending physicians in the pediatric emergency department setting. Its use resulted in significant decreases in reported perceived loss of patient information during intershift handoffs.
Facilitators and barriers to the transition from registered nurse to nurse practitioner in Canada
Authors: El Hussein Mohamed Toufic , Ha Calla 
Published: May 2023

ABSTRACT

BACKGROUND:
Understanding factors that affect integration of NPs is likely to address barriers and provide reform strategies that shape a cost-effective, sustainable, accessible, and efficient health care system. There are a limited number of current and high-quality studies examining the transition process of registered nurses (RNs) to nurse practitioners (NPs), especially in Canada.

PURPOSE:
To explore the experiences of RNs transitioning to NPs in Canada.

METHODOLOGY:
Thematic analysis of audio-recorded semi-structured interviews was conducted to explore the experiences of 17 RNs as they transitioned to NPs. A purposive sampling of 17 participants was completed in 2022.

RESULTS:
Six main themes emerged from analysis of 17 interviews. The content of themes varied according to NPs' years of experience and the NP school they attended.

CONCLUSIONS:
Peer support and mentorship programs were facilitators in the transition from RN to NP. Conversely, shortcomings in education, financial stressors, and the lack of NP role definition were seen as barriers. Legislation and regulations supportive of NPs, diverse and comprehensive education, and improved availability of mentorship programs may strengthen transition facilitators and help NPs overcome related barriers.

IMPLICATIONS:
Legislation and regulations supportive of the NP role are needed, focusing on defining the NP role and establishing an independent and consistent remuneration structure for NPs. A more in-depth and diversified educational curriculum is needed, with increased support from faculty and educators and continual encouragement of initiation and perpetuation of peer support. A mentorship program is beneficial to reduce transition shock from the role of the RN to the NP.
The prothrombin time/international normalized ratio predicts prognosis in cardiogenic shock
Authors: Schupp Tobias , Behnes Michael , Rusnak Jonas , Dudda Jonas , Forner Jan , Ruka Marinela , Egner-Walter Sascha , Bertsch Thomas , Müller Julian , Akin Ibrahim 
Published: May 2023

Objective
The study investigates the prognostic impact of the prothrombin time/international normalized ratio (PT/INR) in patients with cardiogenic shock.

Background
Despite ongoing improvements regarding the treatment of cardiogenic shock patients, intensive care unit (ICU)-related mortality in cardiogenic shock patients remains unacceptably high. Limited data regarding the prognostic value of the PT/INR during the course of cardiogenic shock treatment is available.

Methods
All consecutive patients with cardiogenic shock from 2019 to 2021 were included at one institution. Laboratory values were collected from the day of disease onset (day 1) and days 2, 3, 4 and 8. The prognostic impact of the PT/INR was tested for 30-day all-cause mortality, as well as the prognostic role of PT/INR changes during course of ICU hospitalization. Statistical analyses included univariable t-test, Spearman’s correlation, Kaplan–Meier analyses, C-Statistics and Cox proportional regression analyses.

Results
Two hundred twenty-four cardiogenic shock patients were included with a rate of all-cause mortality at 30 days of 52%. The median PT/INR on day 1 was 1.17. The PT/INR on day 1 was able to discriminate 30-day all-cause mortality in cardiogenic shock patients [area under the curve 0.618; 95% confidence interval (CI), 0.544–0.692; P = 0.002). Patients with PT/INR > 1.17 were associated with an increased risk of 30-day mortality [62% vs. 44%; hazard ratio (HR) = 1.692; 95% CI, 1.174–2.438; P = 0.005], which was still evident after multivariable adjustment (HR = 1.551; 95% CI, 1.043–2.305; P = 0.030). Furthermore, especially patients with an increment of the PT/INR by ≥10% from day 1 to day 2 were associated with an increased risk of 30-day all-cause mortality (64% vs. 42%; log-rank P = 0.014; HR = 1.833; 95% CI, 1.106–3.038; P = 0.019).

Conclusion
Baseline PT/INR and an increase of the PT/INR during the course of ICU treatment were associated with the risk of 30-day all-cause mortality in cardiogenic shock patients.
Reaming the intramedullary canal during tibial nailing does not affect in vivo intramuscular pH of the anterior tibialis
Authors: Black Loren O. , Rushkin Megan , Lancaster Karalynn , Cheesman J. Samuel , Meeker James E. , Yoo Jung U. , Friess Darin M. , Working Zachary M. 
Published: May 2023

Objectives:
Many investigations have evaluated local and systemic consequences of intramedullary (IM) reaming and suggest that reaming may cause, or exacerbate, injury to the soft tissues adjacent to fractures. To date, no study has examined the effect on local muscular physiology as measured by intramuscular pH (IpH). Here, we observe in vivo IpH during IM reaming for tibia fractures.

Methods:
Adults with acute tibia shaft fractures (level 1, academic, 2019–2021) were offered enrollment in an observational cohort. During IM nailing, a sterile, validated IpH probe was placed into the anterior tibialis (<5 cm from fracture, continuous sampling, independent research team). IpH before, during, and after reaming was averaged and compared through repeated measures ANOVA. As the appropriate period to analyze IpH during reaming is unknown, the analysis was repeated over periods of 0.5, 1, 2, 5, 10, and 15 minutes prereaming and postreaming time intervals.

Results:
Sixteen subjects with tibia shaft fractures were observed during nailing. Average time from injury to surgery was 35.0 hours (SD, 31.8). Starting and ending perioperative IpH was acidic, averaging 6.64 (SD, 0.21) and 6.74 (SD, 0.17), respectively. Average reaming time lasted 15 minutes. Average IpH during reaming was 6.73 (SD, 0.15). There was no difference in IpH between prereaming, intrareaming, and postreaming periods. IpH did not differ regardless of analysis over short or long time domains compared with the duration of reaming.

Conclusions:
Reaming does not affect IpH. Both granular and broad time domains were tested, revealing no observable local impact.