bluuebunny/crossref_metadata_2025 huggingface dataset:
JNK signaling during IL-3–mediated differentiation contributes to the c-kit–potentiated allergic inflammatory capacity of mast cells
Authors: Hicks Natalie J , Crozier Robert W E , MacNeil Adam J
Published: May 2023

Mast cells are leukocytes that mediate various aspects of immunity and drive allergic hypersensitivity pathologies. Mast cells differentiate from hematopoietic progenitor cells in a manner that is largely IL-3 dependent. However, molecular mechanisms, including the signaling pathways that control this process, have yet to be thoroughly investigated. Here, we examine the role of the ubiquitous and critical mitogen-activated protein kinase signaling pathway due to its position downstream of the IL-3 receptor. Hematopoietic progenitor cells were harvested from the bone marrow of C57BL/6 mice and differentiated to bone marrow–derived mast cells in the presence of IL-3 and mitogen-activated protein kinase inhibitors. Inhibition of the JNK node of the mitogen-activated protein kinase pathway induced the most comprehensive changes to the mature mast cell phenotype. Bone marrow–derived mast cells differentiated during impaired JNK signaling expressed impaired c-kit levels on the mast cell surface, first detected at week 3 of differentiation. Following 1 wk of inhibitor withdrawal and subsequent stimulation of IgE-sensitized FcεRI receptors with allergen (TNP-BSA) and c-kit receptors with stem cell factor, JNK-inhibited bone marrow–derived mast cells exhibited impediments in early-phase mediator release through degranulation (80% of control), as well as late-phase secretion of CCL1, CCL2, CCL3, TNF, and IL-6. Experiments with dual stimulation conditions (TNP-BSA + stem cell factor or TNP-BSA alone) showed that impediments in mediator secretion were found to be mechanistically linked to reduced c-kit surface levels. This study is the first to implicate JNK activity in IL-3–mediated mast cell differentiation and also identifies development as a critical and functionally determinative period.
Development of an automated mosquito pupae counter
Authors: Esnault Jérémy , Scussel Sarah , Gaudillat Benjamin , Lejarre Quentin , Toussaint Matéo , Duployer Marianne , Gárdos Miklós , Bán Péter , Mavingui Patrick , Tortosa Pablo , Cattel Julien
Published: May 2023

The production of mosquitoes for control programs or basic research is facilitated by the standardization of rearing conditions allowing the daily manipulation of thousands of individuals. It is crucial to develop mechanical or electronic systems for controlling the density of mosquitoes at each development stage with the aim of reducing costs, time, and human errors. We present herein an automatic mosquito counter using a recirculating water system allowing rapid and reliable counting of pupae without detectable increased mortality. Using Aedes albopictus pupae, we determined the density of pupae and the time of counting for which the device is most accurate, and evaluated the time saved using this device. Lastly, we discuss how this mosquito pupae counter can be useful in small-scale or mass-rearing contexts enabling a number of applications for research purposes as well as operational mosquito control programs.
Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes
Authors: Kalam Faiza , James Dara L , Li Yun Rose , Coleman Michael F , Kiesel Violet A , Cespedes Feliciano Elizabeth M , Hursting Stephen D , Sears Dorothy D , Kleckner Amber S
Published: May 2023

Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, preclinical, and clinical studies in cancer published between January 2020 and August 2022 and propose avenues for future research. An outstanding concern regarding the use of intermittent fasting among cancer patients is that fasting often results in caloric restriction, which can put patients already prone to malnutrition, cachexia, or sarcopenia at risk. Although clinical trials do not yet provide sufficient data to support the general use of intermittent fasting in clinical practice, this summary may be useful for patients, caregivers, and clinicians who are exploring intermittent fasting as part of their cancer journey for clinical outcomes and symptom management.
Body composition and endometrial cancer outcomes
Authors: Arteaga Diana P , DeKraker Corina , Ennis Marguerite , Dewey Nicole , Goebel Emily A , Welch Stephen , Pimentel Isabel , Ippolito Joseph E , Lohmann Ana Elisa
Published: May 2023

Background

Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT).

Methods

In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area.

Results

Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer–specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89).

Conclusion

Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.
The ‘omics of obesity in B-cell acute lymphoblastic leukemia
Authors: Geitgey Delaney K , Lee Miyoung , Cottrill Kirsten A , Jaffe Maya , Pilcher William , Bhasin Swati , Randall Jessica , Ross Anthony J , Salemi Michelle , Castillo-Castrejon Marisol , Kilgore Matthew B , Brown Ayjha C , Boss Jeremy M , Johnston Rich , Fitzpatrick Anne M , Kemp Melissa L , English Robert , Weaver Eric , Bagchi Pritha , Walsh Ryan , Scharer Christopher D , Bhasin Manoj , Chandler Joshua D , Haynes Karmella A , Wellberg Elizabeth A , Henry Curtis J
Published: May 2023

The obesity pandemic currently affects more than 70 million Americans and more than 650 million individuals worldwide. In addition to increasing susceptibility to pathogenic infections (eg, SARS-CoV-2), obesity promotes the development of many cancer subtypes and increases mortality rates in most cases. We and others have demonstrated that, in the context of B-cell acute lymphoblastic leukemia (B-ALL), adipocytes promote multidrug chemoresistance. Furthermore, others have demonstrated that B-ALL cells exposed to the adipocyte secretome alter their metabolic states to circumvent chemotherapy-mediated cytotoxicity. To better understand how adipocytes impact the function of human B-ALL cells, we used a multi-omic RNA-sequencing (single-cell and bulk transcriptomic) and mass spectroscopy (metabolomic and proteomic) approaches to define adipocyte-induced changes in normal and malignant B cells. These analyses revealed that the adipocyte secretome directly modulates programs in human B-ALL cells associated with metabolism, protection from oxidative stress, increased survival, B-cell development, and drivers of chemoresistance. Single-cell RNA sequencing analysis of mice on low- and high-fat diets revealed that obesity suppresses an immunologically active B-cell subpopulation and that the loss of this transcriptomic signature in patients with B-ALL is associated with poor survival outcomes. Analyses of sera and plasma samples from healthy donors and those with B-ALL revealed that obesity is associated with higher circulating levels of immunoglobulin-associated proteins, which support observations in obese mice of altered immunological homeostasis. In all, our multi-omics approach increases our understanding of pathways that may promote chemoresistance in human B-ALL and highlight a novel B-cell–specific signature in patients associated with survival outcomes.
Genome-Wide Identification of Gene Loss Events Suggests Loss Relics as a Potential Source of Functional lncRNAs in Humans
Authors: Wen Zheng-Yang , Kang Yu-Jian , Ke Lan , Yang De-Chang , Gao Ge
Published: May 2023

Gene loss is a prevalent source of genetic variation in genome evolution. Calling loss events effectively and efficiently is a critical step for systematically characterizing their functional and phylogenetic profiles genome wide. Here, we developed a novel pipeline integrating orthologous inference and genome alignment. Interestingly, we identified 33 gene loss events that give rise to evolutionarily novel long noncoding RNAs (lncRNAs) that show distinct expression features and could be associated with various functions related to growth, development, immunity, and reproduction, suggesting loss relics as a potential source of functional lncRNAs in humans. Our data also demonstrated that the rates of protein gene loss are variable among different lineages with distinct functional biases.
KREH1 RNA helicase activity promotes utilization of initiator gRNAs across multiple mRNAs in trypanosome RNA editing
Authors: Dubey Ashutosh P , Tylec Brianna L , Mishra Amartya , Sortino Katherine , Chen Runpu , Sun Yijun , Read Laurie K
Published: May 2023

Mitochondrial U-indel RNA editing in kinetoplastid protozoa is directed by trans-acting gRNAs and mediated by a holoenzyme with associated factors. Here, we examine the function of the holoenzyme-associated KREH1 RNA helicase in U-indel editing. We show that KREH1 knockout (KO) impairs editing of a small subset of mRNAs. Overexpression of helicase-dead mutants results in expanded impairment of editing across multiple transcripts, suggesting the existence of enzymes that can compensate for KREH1 in KO cells. In depth analysis of editing defects using quantitative RT-PCR and high-throughput sequencing reveals compromised editing initiation and progression in both KREH1-KO and mutant-expressing cells. In addition, these cells exhibit a distinct defect in the earliest stages of editing in which the initiator gRNA is bypassed, and a small number of editing events takes place just outside this region. Wild type KREH1 and a helicase-dead KREH1 mutant interact similarly with RNA and holoenzyme, and overexpression of both similarly disorders holoenzyme homeostasis. Thus, our data support a model in which KREH1 RNA helicase activity facilitates remodeling of initiator gRNA-mRNA duplexes to permit accurate utilization of initiating gRNAs on multiple transcripts.
The LightDock Server: Artificial Intelligence-powered modeling of macromolecular interactions
Authors: Jiménez-García Brian , Roel-Touris Jorge , Barradas-Bautista Didier
Published: May 2023

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

The 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

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

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

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

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.

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

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

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

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.
Comparing the volume of vascular intersection of two femoral neck fracture fixation implants using an In silico technique
Authors: Putnam Matthew D. , Rau Andrew , Frohbergh Michael , Ong Kevin , Bushelow Michael , Blauth Michael
Published: May 2023

Background:

Femoral neck fracture displacement with subsequent vascular disruption is one of the factors that contribute to trauma-induced avascular necrosis of the femoral head. Iatrogenic damage of the intraosseous arterial system during fixation of femoral neck fracture is another possible cause of avascular necrosis that is less well understood. Recently, Zhao et al (2017) reconstructed 3D structures of intraosseous blood supply and identified the epiphyseal and inferior retinacular arterial system to be important structures for maintaining the femoral head blood supply after femoral neck fracture. The authors therefore recommended placing implants centrally to reduce iatrogenic vascular injuries. Our in vitro study compared the spatial footprint of a traditional dynamic hip screw with an antirotation screw versus a newly developed hip screw with an integrated antirotation screw on intraosseous vasculature.

Methods:

Three dimensional (3D) µCT angiograms of 9 cadaveric proximal femora were produced. Three segmented volumes—porous or cancellous bone, filled or cortical bone, and intraosseous vasculature—were converted to surface files. 3D in silico models of the fixation systems were sized and implanted in silico without visibility of the vascular maps. The volume of vasculature that overlapped with the devices was determined. The ratio of the vascular intersection to the comparator device was calculated, and the mean ratio was determined. A paired design, noninferiority test was used to compare the devices.

Results:

Results indicate both significant (P < 0.001) superiority and noninferiority of the hip screw with an integrated antirotation screw when compared with a dynamic hip screw and antirotation screw for the volume of vasculature that overlapped with each device in the femoral neck.

Conclusions:

Combining established methods of vascular visualization with newer methods enables an implant's impact on vascular intersection to be assessed in silico. This methodology suggests that when used for femoral neck fracture management, the new device intersects fewer blood vessels than the comparator. Comparative clinical studies are needed to investigate whether these findings correlate with the incidence of avascular necrosis and clinical outcomes.
Long-distance Wnt transport in axons highlights cell type-specific modes of Wnt transportin vivo
Authors: Pani Ariel M , Favichia Michelle , Goldstein Bob
Published: May 2023

Wnt signaling performs critical functions in development, homeostasis, and disease states. Wnt ligands are secreted signaling proteins that often move between cells to activate signaling across a range of distances and concentrations. In different animals and developmental contexts, Wnts utilize distinct mechanisms for intercellular transport including diffusion, cytonemes and exosomes [1]. Mechanisms for intercellular Wnt dispersal remain controversial in part due to technical challenges with visualizing endogenous Wnt proteinsin vivo, which has limited our understanding of Wnt transport dynamics. As a result, the cell-biological bases for long-range Wnt dispersal remain unknown in most instances, and the extent to which differences in Wnt transport mechanisms vary by cell type, organism, and/or ligand remain uncertain. To investigate processes underlying long-range Wnt transportin vivo, we utilizedC. elegansas an experimentally tractable model where it is possible to tag endogenous Wnts with fluorescent proteins without disrupting signaling [2]. Live imaging of two endogenously tagged Wnt homologs revealed a novel mode for long-distance Wnt movement in axon-like structures that may complement Wnt gradients generated by diffusion and highlighted cell type-specific Wnt transport processesin vivo.
Conditional independence as a statistical assessment of evidence integration processes
Authors: Salinas Emilio , Stanford Terrence R
Published: May 2023

Intuitively, combining multiple sources of evidence should lead to more accurate decisions than considering single sources of evidence individually. In practice, however, the proper computation may be difficult, or may require additional data that are inaccessible. Here, based on the concept of conditional independence, we consider expressions that can serve either as recipes for integrating evidence based on limited data, or as statistical benchmarks for characterizing evidence integration processes. Consider three events,A, B, andC. We find that, ifAandBare conditionally independent with respect toC, then the probability thatCoccurs given that bothAandBare known,P(C|A, B), can be easily calculated without the need to measure the full three-way dependency betweenA, B, andC. This simplified approach can be used in two general ways: to generate predictions by combining multiple (conditionally independent) sources of evidence, or to test whether separate sources of evidence are functionally independent of each other. These applications are demonstrated with four computer-simulated examples, which include detecting a disease based on repeated diagnostic testing, inferring biological age based on multiple biomarkers of aging, discriminating two spatial locations based on multiple cue stimuli (multisensory integration), and examining how behavioral performance in a visual search task depends on selection histories. Besides providing a sound prescription for predicting outcomes, this methodology may be useful for analyzing experimental data of many types.
An invertible seven-dimensional Dirichlet cell characterization of lattices
Authors: Bernstein Herbert J. , Andrews Lawrence C. , Xerri Mario
Published: May 2023

Characterization of crystallographic lattices is an important tool in structure solution, crystallographic database searches and clustering of diffraction images in serial crystallography. Characterization of lattices by Niggli-reduced cells (based on the three shortest non-coplanar lattice vectors) or by Delaunay-reduced cells (based on four non-coplanar vectors summing to zero and all meeting at obtuse or right angles) is commonly performed. The Niggli cell derives from Minkowski reduction. The Delaunay cell derives from Selling reduction. All are related to the Wigner–Seitz (or Dirichlet, or Voronoi) cell of the lattice, which consists of the points at least as close to a chosen lattice point as they are to any other lattice point. The three non-coplanar lattice vectors chosen are here called the Niggli-reduced cell edges. Starting from a Niggli-reduced cell, the Dirichlet cell is characterized by the planes determined by 13 lattice half-edges: the midpoints of the three Niggli cell edges, the six Niggli cell face-diagonals and the four body-diagonals, but seven of the lengths are sufficient: three edge lengths, the three shorter of each pair of face-diagonal lengths, and the shortest body-diagonal length. These seven are sufficient to recover the Niggli-reduced cell.
Mission drift or mission fulfillment? Examining microfinance's financial and social performance with growth curve modeling and variance decomposition
Authors: Jia Peiyi , Sun Sunny Li
Published: May 2023

Purpose

Examining multilevel effects of financial and social performance of microfinance institutions (MFIs), the authors aim to investigate microfinance mission drift from the trend effect. The authors also seek to move the literature forward by decomposing the performance variance at different levels and examining whether and how much each level of analysis matters.

Design/methodology/approach

Growth curve modeling and variance decomposition analysis were conducted using a dataset consisting of 17,953 observations of 2,902 microfinance institutions in 122 countries from 1999 to 2017.

Findings

The study's result shows no evidence of mission drift in the microfinance industry. While MFIs improve their economic returns, they also increase the depth of outreach. In addition, firm-level heterogeneity is the dominant effect which explains 44% of the variance in microfinance financial performance (ROA) and 39% of the variance in social performance (Depth of outreach). The country-level is more critical in explaining financial performance (ROA) than social performance (Depth of outreach), accounting for 11 and 32% of the total variance, respectively. In particular, the interplay between the country-level and organizational-category level accounts for 9 and 11% of the total variance in financial performance (ROA) and social performance (Depth of outreach), respectively.

Originality/value

This study’s multilevel analysis of microfinance performances moves the literature forward by responding to the debate on microfinance mission drift and providing a comprehensive overview of both social and financial performance. By focusing on the trend effect, the result of our models shows that MFIs improve both financial and social performance to fulfill dual missions. The microfinance business model becomes sustainable over time. The study's results of country effect and its interaction effect with different organizational categories reveal the prominence of a good policy design on MFI's mission fulfillment.
Reminiscence and wellbeing – reflecting on past festival experiences during Covid lockdowns
Authors: Wood Emma Harriet , Kinnunen Maarit
Published: May 2023

Purpose

To explore the value in reminiscing about past festivals as a potential way of improving wellbeing in socially isolated times.

Design/methodology/approach

The paper uses previous research on reminiscence, nostalgia and wellbeing to underpin the analysis of self-recorded memory narratives. These were gathered from 13 pairs of festivalgoers during Covid-19 restrictions and included gathering their individual memories and their reminiscences together. The participant pairs were a mix of friends, family and couples who had visited festivals in the UK, Finland and Denmark.

Findings

Four key areas that emerged through the analysis were the emotions of nostalgia and anticipation, and the processes of reliving emotions and bonding through memories.

Research limitations/implications

Future studies could take a longitudinal approach to see how memory sharing evolves and the impact of this on wellbeing. The authors also recommend undertaking similar studies in other cultural settings.

Practical implications

This study findings have implications for both post-festival marketing and for the further development of reminiscence therapy interventions.

Originality/value

The method provides a window into memory sharing that has been little used in previous studies. The narratives confirm the value in sharing memories and the positive impact this has on wellbeing. They also illustrate that this happens through positive forms of nostalgia that centre on gratitude and lead to hope and optimism. Anticipation, not emphasised in other studies, was also found to be important in wellbeing and was triggered through looking back at happier times.
How frequent and visible criminal violence affects housing prices: evidence from Mexico City (2007–2011)
Authors: Atuesta Laura H. , Carrasco Monserrat
Published: May 2023

Purpose

Between 2006 and 2012, Mexico implemented a “frontal war against organized crime”. This strategy increased criminal violence and triggered negative consequences across the country’s economic, political and social spheres. This study aims to analyse how the magnitude and visibility of criminal violence impact the housing market of Mexico City.

Design/methodology/approach

The authors used different violent proxies to measure the effect of the magnitude and visibility of violence in housing prices. The structure of the data set is an unbalanced panel with no conditions of strict exogeneity. To address endogeneity, the authors calculate the first differences to estimate an Arellano–Bond estimator and use the lags of the dependent variable to instrumentalise the endogenous variable.

Findings

Results suggest that the magnitude of violence negatively impacts housing prices. Similarly, housing prices are negatively affected the closer the property is to visible violence, measured through narcomessages placed next to the bodies of executed victims. Lastly, housing prices are not always affected when a violent event occurs nearby, specifically, when neighbours or potential buyers consider this event as sporadic violence.

Originality/value

There are only a few studies of violence in housing prices using data from developing countries, and most of these studies are conducted with aggregated data at the municipality or state level. The authors are using geocoded information, both violence events and housing prices, to estimate more disaggregated effects. Moreover, the authors used different proxies to measure different characteristics of violence (magnitude and visibility) to estimate the heterogeneous effects of violence on housing prices.