bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generating, modeling and evaluating a large-scale set of CRISPR/Cas9 off-target sites with bulges
Authors: Yaish Ofir , Orenstein Yaron 
Published: May 2024

Abstract
The CRISPR/Cas9 system is a highly accurate gene-editing technique, but it can also lead to unintended off-target sites (OTS). Consequently, many high-throughput assays have been developed to measure OTS in a genome-wide manner, and their data was used to train machine-learning models to predict OTS. However, these models are inaccurate when considering OTS with bulges due to limited data compared to OTS without bulges. Recently, CHANGE-seq, a new in vitro technique to detect OTS, was used to produce a dataset of unprecedented scale and quality. In addition, the same study produced in cellula GUIDE-seq experiments, but none of these GUIDE-seq experiments included bulges. Here, we generated the most comprehensive GUIDE-seq dataset with bulges, and trained and evaluated state-of-the-art machine-learning models that consider OTS with bulges. We first reprocessed the publicly available experimental raw data of the CHANGE-seq study to generate 20 new GUIDE-seq experiments, and hundreds of OTS with bulges among the original and new GUIDE-seq experiments. We then trained multiple machine-learning models, and demonstrated their state-of-the-art performance both in vitro and in cellula over all OTS and when focusing on OTS with bulges. Last, we visualized the key features learned by our models on OTS with bulges in a unique representation.
Intermittent fasting as a dietary intervention with potential sexually dimorphic health benefits
Authors: Rius-Bonet Julia , Macip Salvador , Closa Daniel , Massip-Salcedo Marta 
Published: May 2024

Abstract
Intermittent fasting (IF) has proven to be a feasible dietary intervention for the wider population. The recent increase in IF clinical trials highlights its potential effects on health, including changes in body composition, cardiometabolic status, and aging. Although IF may have clinical applications in different populations, studies suggest there may be sex-specific responses in parameters such as body composition or glucose and lipid metabolism. Here, the existing literature on IF clinical trials is summarized, the application of IF in both disease prevention and management is discussed, and potential disparities in response to this type of diet between men and women are assessed. Moreover, the potential mechanisms that may be contributing to the sexually dimorphic response, such as age, body composition, tissue distribution, or sex hormones are investigated. This review underscores the need to further study these sex-specific responses to IF to define the most effective time frames and length of fasting periods for men and women. Tailoring IF to specific populations with a personalized approach may help achieve its full potential as a lifestyle intervention with clinical benefits.
Prolonged complete response to adjuvant tepotinib in a patient with newly diagnosed disseminated glioblastoma harboring mesenchymal-epithelial transition fusion
Authors: Pham Lily C , Weller Lauryn , Gann Claudia N , Schumacher Karl Maria , Vlassak Soetkin , Swanson Todd , Highsmith Kaitlin , O’Brien Barbara J , Nash Sebnem , Aaroe Ashley , de Groot John F , Majd Nazanin K 
Published: May 2024

Abstract
The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.
Challenges to CVAs
Authors: Smith Tom , Judd Daniel 
Published: May 2024

Abstract
This chapter notes the challenges of CVAs, primarily under Section 6 of the 1986 Act. Challenges to a CVAS may come in the forms of jurisdiction or two statutory grounds of challenge under section 6 of the 1986 Act. The basis of challenges varies from unfair prejudice to material irregularity. The challenge under the grounds of unfair prejudice looks into the effect of a CVA's contents on the rights of creditors, while a material irregularity challenge is focused on the circumstances and process by the approval of the CVA. A limit of 28 days is the required observance period when challenging a CVA under the aforementioned grounds.
Rational and ambitious legislators? Role theory, between open questions and new applicability
Authors: Gambacciani Paolo 
Published: May 2024

Abstract
Role theory utilizes sociological and political science tools to study parliamentary functioning and parliamentarians’ behavior. While scholars in the USA (1960–70) and Europe (1990–2010) have extensively applied it, this review focuses on its enduring theoretical validity. It introduces a role choice typology, categorizing parliamentarians in empirical studies. The analysis highlights role theory strengths and weaknesses, highlighting that the goal of reelection represents only one potential explanation of parliamentarian behavior. The article suggests reconsidering the sociological concept of role to derive testable hypotheses. In addition, the article extends role theory applications to studying legislative careers and less institutionalized legislatures.
Interrogating ‘Parriah Arrack’: Anxieties Over Health, Race and Drinking in Early Colonial Calcutta
Authors: Mitra Sarbajit 
Published: May 2024

Summary
The colonial authorities in India had always been watchful of the drinking activities of the European soldiers and sailors, expressing concerns about their moral and physical health. The article suggests that such anxieties motivated the European population in India, particularly in its early days, to investigate the drinking practices of the local population and examine the effects of locally distilled liquor on their health and constitution. Through an analysis of a petition and a Commission report, the paper explores a dialogue between a group of European distillers and the Fort William Medical Board in early nineteenth-century Calcutta, focussing on the topics of drinking and health. The article argues that these early interrogations on the local drink not just reinforced the racial stereotypes concerning taste and technology but also consolidated the idea of the ‘tropic’ that continued to inform Anglo-Indian medical discourses in subsequent years.
Mast cell conditions and drug allergy: when to suspect and how to manage
Authors: Olivieri Bianca , Ghilarducci Alessandro , Nalin Francesca , Bonadonna Patrizia 
Published: May 2024

Purpose of review
Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe anaphylactic responses. Hypersensitivity reactions (HRs) to drugs are a major cause of anaphylaxis in these patients, who often worry about triggering mast cell degranulation when taking medications. The aim of this review is to explore the complex interactions between mast cell disorders and drug HRs, focusing on the clinical challenges of managing these conditions effectively to enhance understanding and guide safer clinical practices.

Recent findings
Among the drugs most commonly associated with hypersensitivity reactions in patients with mast cell disorders are non-steroidal anti-inflammatory drugs, antibiotics, and perioperative agents. Recent studies have highlighted the role of Mas-related G-protein coupled receptor member X2 (MRGPRX2) – a receptor involved in non-immunoglobulin E mediated mast cell degranulation – in exacerbating HRs. Investigations reveal varied drug tolerance among patients, underscoring the need for individual risk assessments.

Summary
Tailored diagnostic approaches are crucial for confirming drug allergies and assessing tolerance in patients with mastocytosis, preventing unnecessary medication avoidance and ensuring safety before acute situations arise.
Predictive models and applicability of artificial intelligence-based approaches in drug allergy
Authors: Núñez Rafael , Doña Inmaculada , Cornejo-García José Antonio 
Published: May 2024

Purpose of review
Drug allergy is responsible for a huge burden on public healthcare systems, representing in some instances a threat for patient's life. Diagnosis is complex due to the heterogeneity of clinical phenotypes and mechanisms involved, the limitations of in vitro tests, and the associated risk to in vivo tests. Predictive models, including those using recent advances in artificial intelligence, may circumvent these drawbacks, leading to an appropriate classification of patients and improving their management in clinical settings.

Recent findings
Scores and predictive models to assess drug allergy development, including patient risk stratification, are scarce and usually apply logistic regression analysis. Over recent years, different methods encompassed under the general umbrella of artificial intelligence, including machine and deep learning, and artificial neural networks, are emerging as powerful tools to provide reliable and optimal models for clinical diagnosis, prediction, and precision medicine in different types of drug allergy.

Summary
This review provides general concepts and current evidence supporting the potential utility of predictive models and artificial intelligence branches in drug allergy diagnosis.
Findings Associated With Nonaccidental Trauma in Children With Isolated Femoral Diaphyseal Fractures
Authors: Ina Jason , Dumaine Anne M. , Flanagan Christopher , Haase Lucas , Moore Rebecca , Rimnac Clare , Gilmore Allison 
Published: May 2024

Background:
Pediatric patients with isolated femoral diaphyseal fractures are difficult to assess for nonaccidental trauma (NAT). The purpose of this study was to determine (1) if there are any demographic features of isolated femoral diaphyseal fractures associated with suspected NAT and (2) if there are clinical signs associated with isolated femoral diaphyseal fractures associated with suspected NAT.

Methods:
All patients with femoral diaphyseal fractures from January 2010 to June 2018 were reviewed. We included patients younger than 4 years old with isolated femoral diaphyseal fractures. We excluded patients 4 years old and older, polytraumas, motor vehicle collisions, and patients with altered bone biology. Diagnosis of suspected NAT was determined by review of a documented social work assessment. We recorded fracture characteristics including location along femur as well as fracture pattern and presence of associated findings on NAT workup including the presence of retinal hemorrhage, subdural hematoma, evidence of prior fracture, or cutaneous lesions. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these associated findings were calculated.

Results:
Totally, 144 patients met the inclusion criteria. Social work was consulted on 50 patients (35%). Suspected NAT was diagnosed in 27 patients (19%). The average age of patients with suspected NAT was 0.82 and 2.25 years in patients without NAT (P<0.01). The rate and type of skin lesions present on exam were not different between the 2 groups. Patients with suspected NAT had no findings of retinal hemorrhage or subdural hematoma, but 5 of 27 patients (19%) had evidence of prior fracture on skeletal survey. The sensitivities of retinal hemorrhage, subdural, and skeletal survey were 0%, 0%, and 19% and the specificities of all were 100%. The NPVs were 39%, 27%, and 63%, respectively. The PPV of skeletal survey was 100%. Since there were no patients in this study with positive findings of retinal hemorrhage or subdural hematoma, the PPV for these could not be assessed.

Conclusions:
In the current study, signs of NAT such as skin lesions, retinal hemorrhage, subdural hematoma, and evidence of prior fracture on skeletal survey may not be helpful to diagnosis suspected NAT in patients with an isolated femoral diaphyseal fracture.

Level of Evidence:
Level III—diagnostic study.
Clinical Performance and Persistence on Dual Pathway Inhibition with Rivaroxaban and Aspirin in Real-World Setting
Authors: Russo Vincenzo , Fabiani Dario , Imbalzano Egidio , De Michele Mario , Castellano Paola , Colaiori Iginio , Parisi Valentina , D'Andrea Antonello , Attena Emilio 
Published: May 2024

Abstract:The dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin in patients with stable atherosclerotic vascular disease reduces the occurrence of cardiovascular events, with no significant increase of intracranial or other critical organ bleedings. Our observational study aimed to describe the clinical performance, adherence, and persistence of DPI therapy among a real-world setting of patients with an established diagnosis of coronary artery (CAD) and/or peripheral artery disease (PAD). We prospectively included all consecutive patients with an established diagnosis of CAD and/or PAD treated with aspirin (ASA) 100 mg once daily and rivaroxaban 2.5 mg twice daily. Clinical evaluation was performed at baseline, before starting treatment, at 1 month, and every 6 months after the study drug administration. A total of 202 consecutive patients (mean age 66 ± 10 years; male 80%) eligible to DPI therapy were included. During a mean follow-up of 664 ± 177 days, the incidence rate of major bleedings and of major adverse cardiovascular events was 0.8 and 1.1 per 100 patients/year, respectively. The adherence to pharmacological treatment was 99%. Additionally, 13.4% of patients suspended the DPI therapy during the follow-up. Minor bleedings resulted the most common cause of both temporary and permanent DPI therapy discontinuation. This observational study supports the safety of DPI with low-dose rivaroxaban and aspirin among patients with CAD and PAD in a real-world setting, showing high persistence and maximum adherence to medical treatment.
Outcomes of Mastectomy and Immediate Reconstruction Managed with Closed-incision Negative Pressure Therapy Applied Over the Whole Breast
Authors: Gabriel Allen , Chan Vivian 
Published: May 2024

Background:
Incision healing after mastectomy and immediate reconstruction can be supported with closed-incision negative pressure therapy (ciNPT). Studies have reported patients receiving postoperative care with ciNPT after breast surgery exhibited lower rates of dehiscence, infection, necrosis, and seroma, compared with standard dressings. A recent approach to ciNPT involves the application of negative pressure to the incision and a wider area of surrounding tissue. In this retrospective review, we investigated the outcomes of ciNPT using full-coverage dressings over the entire breast after mastectomy and reconstruction.

Methods:
Patients underwent mastectomies and immediate prepectoral breast reconstruction with an implant or tissue expander. After surgery, patients received oral antibiotics and ciNPT with full-coverage foam dressings at −125 mm Hg.

Results:
All 54 patients (N = 105 incisions) were women, with a mean age of 53.5 years and 29.1 kg per m2 body mass index. Common comorbidities included prior chemotherapy (31.3%) or radiation (21.6%), hypertension (14.8%), and diabetes (5.6%). Procedures included skin-reducing (34.3%), skin-sparing (7.6%), and nipple-sparing (58.1%) mastectomies. Lymph nodes were removed in 38 (36.2%) incisions. All patients were discharged home with ciNPT on postoperative day (POD) 1, and ciNPT was discontinued on POD 5–7. At POD 30, three patients developed seromas, requiring revision. Of these, one required removal of the left tissue expander. The remaining 102 incisions (97.1%) healed without complication.

Conclusions:
Among this cohort, the use of ciNPT with full-dressing coverage of the breast incisions and surrounding soft tissue was effective in supporting incisional healing after mastectomy and immediate reconstruction.
Willingness of Patients With End-Stage Renal Disease to Accept a Kidney Transplant and Related Factors
Authors: CHENG Yin , LAI Hsiang-Ru , CHEN I-Hui , CHIU Yen-Ling , LEE Pei-I , PETERS Kath , LEE Pi-Hsia 
Published: May 2024

ABSTRACT

Background
The prevalence of end-stage renal disease (ESRD) in Taiwan is among the highest in the world. Although kidney transplant is the most effective treatment for ESRD, the willingness of patients with ESRD to undergo kidney transplantation is low in Taiwan. The factors associated with willingness to accept kidney transplantation remain unclear, and studies on kidney transplant willingness and associated factors among Taiwanese patients with ESRD are scarce.

Purpose
The aim of this study was to assess willingness to undergo a kidney transplant and related factors among patients with ESRD in Taiwan.

Methods
A cross-sectional design was employed. Two hundred fourteen participants from a single medical center in Taiwan were recruited, and 209 valid questionnaires were collected (valid response rate: 97.7%). The study instruments included a kidney transplant knowledge scale, a kidney transplant attitude scale, and a kidney transplant willingness scale. Data were analyzed using Pearson's product–moment correlations, t tests, one-way analyses of variance, and multiple regressions.

Results
The mean kidney transplant willingness in the sample was 13.23 (out of 20). Being male, younger, married, or employed; having a college education or above; and having a shorter dialysis duration were all associated with higher kidney transplant willingness. Sociodemographics, dialysis duration, knowledge, and attitudes explained 45.4% of the variance in kidney transplant willingness, with two of these, kidney transplant attitudes (β = .61, p < .001) and dialysis duration (β = −.11, p = .041), identified as significant.

Conclusions/Implications for Practice
The findings support the important role of cultivating positive attitudes in patients with ESRD to increasing willingness to undergo kidney transplantation interventions.
Clinical Nurse Leader Practice Development
Authors: Salinas Brianna , Leger J. Michael 
Published: May 2024

Background:
The Clinical Nurse Leader (CNL) is a skilled clinician qualified in outcomes-based practice and quality improvement. Publications describe the CNL training, integration, and outcomes. However, CNL practice development and its impact has not been fully explored.

Purpose:
This review aimed to synthesize existing literature related to CNL practice development and identify what influences on the care environment and nursing care outcomes.

Methods:
An integrative literature review was conducted in 5 bibliographic databases for sources published in English from January 2012 to March 2023.

Results:
Fifteen publications identified 3 interrelated themes of CNL practice, outcomes, and practice development. Staff development needs were identified across various levels of expertise.

Conclusion:
There is a need to further explore CNL practice development and how it can impact the care environment and care outcomes.
SERUM TRANSACTIVE RESPONSE DNA BINDING PROTEIN 43 ASSOCIATES WITH POOR SHORT-TERM NEUROLOGIC OUTCOME AFTER RETURN OF SPONTANEOUS CIRCULATION FOLLOWING CARDIAC ARREST
Authors: Sun Zhangping , Yu Dongping , Li Peijuan , Wang Ling , Chen Yushu , Wei Xiaojun , Gong Ping 
Published: May 2024

ABSTRACTObjective: To explore the association of serum transactive response DNA binding protein 43 (TDP-43) with 28-day poor neurologic outcome in patients with return of spontaneous circulation (ROSC) after cardiac arrest.Methods: We performed a study between January and December 2023. Eligible patients with ROSC following cardiac arrest were enrolled. Their baseline characteristics were collected, and serum levels of TDP-43, tumor necrosis factor-α, interleukin-6 and 10, C-reactive protein, and neuron-specific enolase (NSE) at 24 h after ROSC were measured. The neurologic function was assessed by the cerebral performance category scores on day 28 after ROSC.Results: A total of 92 patients were included, with 51 and 41 patients in the good and poor neurologic outcome groups, respectively. Serum TDP-43 was significantly higher in the poor than the good neurologic outcome group (P< 0.05). Univariate and multivariate logistic regression analyses showed that TDP-43, Witnessed CA, IL-6, and NSE were associated with poor 28-day neurologic outcome (allP< 0.05). Restricted cubic spline analysis revealed that TDP-43 at the serum level of 11.64 pg/mL might be an ideal cutoff value for distinguishing between good and poor neurologic outcomes. Area under curve of serum TDP-43 (AUC = 0.78) was close to that of serum NSE (AUC = 0.82). A dynamic nomogram prediction model that combined TDP-43, Witnessed CA, IL-6, and NSE was constructed and validated.Conclusion: Elevated serum TDP-43 level was associated with and could be used together with Witnessed CA, IL-6, and NSE to predict poor 28-day neurologic outcome in patients after ROSC following cardiac arrest.
Effect of Plastic Stents Following Lumen-Apposing Metal Stent Placement on Recurrence of Pancreatic Fluid Collections in Disconnected Pancreatic Duct Syndrome: A Systematic Review and Meta-Analysis
Authors: Liu Jiawen , Wei Zhengjie , Huang Qing , Yang Shizhong , Fang Yanbin , Ren Yutang , Jiang Xuan , Jiang Bo 
Published: May 2024

Background and Aim:
Lumen-apposing metal stents (LAMS) are preferred to initial drainage in pancreatic fluid collections (PFCs) patients with disconnected pancreatic duct syndrome (DPDS) in recent years. However, unlike plastic stents, the long-term placement of LAMS is not recommended due to a high risk of local complications. This meta-analysis attempted to evaluate the effect of using plastic stents for prolonged drainage after LAMS removal on recurrence of PFCs in DPDS.

Methods:
A comprehensive literature search was conducted from inception until January 2023, to identify articles investigating the endoscopic ultrasound (EUS)-guided treatment of plastic stents compared with no plastic stents following LAMS removal in patients with PFCs and DPDS. The primary outcome measures included recurrence of PFCs and need for reintervention.

Results:
We identified 3 eligible articles including 520 patients with PFCs, 246 of whom with DPDS. There was a total of 143 and 103 patients in the plastic stents group and in the no plastic stents group, respectively. The plastic stents group exhibited a lower rate of PFCs recurrence following LAMS removal after PFCs resolution compared with the no plastic stents group (OR 0.15; 95% CI 0.03-0.75; P=0.02). However, there was no difference in the rates of reintervention between the two groups (OR 0.52; 95% CI 0.15-1.83; P=0.31). There was no severe adverse events and mortality associated with stent placement or exchange in all patients.

Conclusion:
Deployment of plastic stents for long-term drainage after LAMS replacement can decrease the risk of PFCs recurrence in patients with DPDS following resolution, but it does not impact reintervention rates.