bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Visegrád (V4) Countries
Authors: Šturma Pavel 
Published: August 2023

Abstract
The difficult historical developments of three of the Visegrád (V4) countries, namely the Czech Republic, Slovakia, and Hungary, influenced the role of international lawyers, both in academia and practice. Indeed, international law and its scholarship cannot be dissociated from politics, which is also true in this part of Europe. Their legal systems and academia had their roots in the Western European traditions. However, their development suffered because of almost six decades of totalitarian regimes (Nazi and communist) between 1939 and 1989. Even though they are now part of the European organizations, their relatively long isolation probably caused them to be viewed as semi-peripheral, from the point of view of the West. At the same time, the experience of these countries contributes to a higher sensitivity to the issues of peace, Statehood, and sovereignty. Since these values were not for long present, they are not taken for granted and need to be protected.
A Novel Home-Based Study of Circadian Rhythms: Design, Rationale, and Methods for the Circadia Study
Authors: Vlasac Irma M , Bormes Gregory W , Do Elizabeth , Benkhoukha Selma S , Diallo Naby , Fryou Noah L , Gioia Siena , Akeju Oluwaseun , Joseph Clarence , Kuan Anne , Lapan Jennifer , Oluwadara David , Team the Pepper , Rahman Shadab A , Saxena Richa , Scheer Frank A J L , Westover M Brandon , Winkelman John W , Woodson Faraji , Lane Jacqueline M 
Published: August 2023

Summary
The Circadia Study (Circadia) is a novel “direct-to-participant” research study investigating the genetics of circadian rhythm disorders of advanced and delayed sleep phase and non-24 hour rhythms. The goals of the Circadia Study are twofold: (i) to create an easy-to-use toolkit for at-home circadian phase assessment for patients with circadian rhythm disorders through the use of novel in-home based surveys, tests, and collection kits; and (ii) create a richly phenotyped patient resource for genetic studies that will lead to new genetic loci associated with circadian rhythm disorders revealing possible loci of interest to target in the development of therapeutics for circadian rhythm disorders. Through these goals, we aim to broaden our understanding and elucidate the genetics of circadian rhythm disorders across a diverse patient population while increasing accessibility to circadian rhythm disorder diagnostics reducing health disparities through self-directed at-home dim light melatonin onset (DLMO) collections.
Multiple Routes to Color Convergence in a Radiation of Neotropical Poison Frogs
Authors: Twomey Evan , Melo-Sampaio Paulo , Schulte Lisa M , Bossuyt Franky , Brown Jason L , Castroviejo-Fisher Santiago 
Published: August 2023

Abstract
Convergent evolution is defined as the independent evolution of similar phenotypes in different lineages. Its existence underscores the importance of external selection pressures in evolutionary history, revealing how functionally similar adaptations can evolve in response to persistent ecological challenges through a diversity of evolutionary routes. However, many examples of convergence, particularly among closely related species, involve parallel changes in the same genes or developmental pathways, raising the possibility that homology at deeper mechanistic levels is an important facilitator of phenotypic convergence. Using the genus Ranitomeya, a young, color-diverse radiation of Neotropical poison frogs, we set out to 1) provide a phylogenetic framework for this group, 2) leverage this framework to determine if color phenotypes are convergent, and 3) to characterize the underlying coloration mechanisms to test whether color convergence occurred through the same or different physical mechanisms. We generated a phylogeny for Ranitomeya using ultraconserved elements and investigated the physical mechanisms underlying bright coloration, focusing on skin pigments. Using phylogenetic comparative methods, we identified several instances of color convergence, involving several gains and losses of carotenoid and pterin pigments. We also found a compelling example of nonparallel convergence, where, in one lineage, red coloration evolved through the red pterin pigment drosopterin, and in another lineage through red ketocarotenoids. Additionally, in another lineage, “reddish” coloration evolved predominantly through structural color mechanisms. Our study demonstrates that, even within a radiation of closely related species, convergent evolution can occur through both parallel and nonparallel mechanisms, challenging the assumption that similar phenotypes among close relatives evolve through the same mechanisms.
Engaging Premedical Students in Medical Education Research: Benefits of Clinical Skills Observation Studies
Authors: Weingartner Laura A. , Noonan Emily J. , Shaw M. Ann , Fuselier Linda 
Published: August 2023

Purpose
Observations requiring evaluation and critical thinking can be powerful learning experiences. Video-recorded standardized patient encounters are underused resources for evaluation and research. The authors engaged premedical students in medical education research reviewing standardized patient encounters. This study aims to explore participant perceptions of the research experience and how they gained clinical skills.

Method
This mixed-method study was completed between 2019 and 2022. Premedical participants coded medical students’ clinical skills in video-recorded standardized patient encounters. Each participant also completed their own new patient history in a standardized patient encounter at both the beginning and end of their research project. Participants then completed an end-of-program debrief to discuss their experiences coding the clinical skills encounters. The authors coded communication skills implemented in the pre/postencounters and completed a thematic analysis of the debrief transcripts.

Results
All 21 participants demonstrated significant clinical skills gain after their research project, which included spending more time with the patient (pre-M=5 minutes, post-M=19 minutes, t=13.2, P<.001) and asking more questions (pre-M=13, post-M=40, t=9.3, P<.001). Prior clinical experience did not influence pre- or postoutcomes, but the number of videos coded was associated with asking more questions in the postencounter. Participants described learning actively and reflected that their clinical skills research project gave them greater insight into patient-care aspects of medical school and how medical students learn.

Conclusions
These data demonstrate that observational studies in which premedical students evaluate standardized patient encounters gave the students context to medical education while enabling them to develop and transfer their own clinical skills. Studies observing standardized patient encounters provide rich insight into clinical skills development, and this work generates both research outcomes and actionable program evaluation data for medical educators. Purposefully engaging premedical students in such experiential learning opportunities benefits the students and helps cultivate early medical education pathways for these learners.
How Do Academic Medicine Pathways Differ for Underrepresented Trainees and Physicians? A Critical Scoping Review
Authors: Russel Sarah M. , Carter Taylor M. , Wright Sarah T. , Hirshfield Laura E. 
Published: August 2023

Purpose
Academic medicine faces difficulty recruiting and retaining a diverse workforce. The proportion of medical students who are underrepresented in medicine (URiM) is smaller than the proportion of URiMs in the general population, and these numbers worsen with each step up the academic medicine ladder. Previously known as the “leaky pipeline,” this phenomenon may be better understood as disparate “pathways with potholes,” which acknowledges the different structural barriers that URiM trainees and faculty face in academic medicine. This critical scoping review analyzed current literature to determine what variables contribute to the inequitable “pathways and potholes” URiM physicians experience in academic medicine.

Method
The authors combined scoping review methodology with a critical lens. The comprehensive search strategy used terms about academic medicine, underrepresented groups, and leaving academic medical careers. One reviewer conducted screening, full-text review, and data extraction while in consultation with members of the research team. Data extraction focused on themes related to pathways and potholes, such as attrition, recruitment, and retention in academic medicine. Themes were iteratively merged, and quality of contribution to the field and literature gaps were noted.

Results
Included papers clustered into attrition, recruitment, and retention. Those pertaining to attrition noted that URiM faculty are less likely to get promoted even when controlling for scholarly output, and a hostile work environment may exacerbate attrition. Recruitment and retention strategies were most effective when multipronged approaches changed every step of the recruitment and promotion processes.

Conclusions
These studies provide examples of various “potholes” that can affect representation in academic medicine of URiM trainees and faculty. However, only a few studies examined the link between isolating and hostile work environments, the so-called “chilly climate,” and attrition from academic medicine. Understanding these concepts is key to producing the most effective interventions to improve diversity in medicine.
Botulinum Toxin for Scalp Conditions: A Systematic Review
Authors: Nguyen Betty , Perez Sofia M. , Tosti Antonella 
Published: August 2023

BACKGROUND
Many reports have described the use of botulinum toxin (BTX) in the treatment of scalp conditions, but no studies have synthesized these collective findings.

OBJECTIVE
We conducted a systematic review to summarize the scalp conditions for which treatment with BTX has been described.

METHODS
We searched PubMed/MEDLINE and Scopus for articles in English published before November 1, 2022, using the keywords “hair” or “scalp” and BTX-related search terms. Articles that described patients who received injections of BTX for the management of scalp conditions were included.

RESULTS
Twenty-four original articles (12 case reports, 9 clinical trials, and 3 case series) were identified that described 309 patients with a scalp condition treated with BTX. Androgenetic alopecia, craniofacial hyperhidrosis, and scalp hyperseborrhea had the most robust data supporting the clinical efficacy of BTX.

CONCLUSION
The current quality of evidence is highly variable and, for many conditions, limited to small observational studies. Botulinum toxin may be a promising therapeutic option for patients with various scalp conditions, but future studies are needed to better understand its efficacy and safety.
Population Pharmacokinetic Modeling and Determination of Individual Exposure to Avalglucosidase Alfa in Adolescent and Adult Patients With Late-Onset Pompe Disease: Analysis of Pooled Data From Phase I to III Clinical Trials
Authors: Tuffal Gilles , Tiraboschi Gilles , Hurbin Fabrice , Boittet Pascale , Palmer Rachel , Martinez Jean-Marie , Fabre David 
Published: August 2023

Background:
Pompe disease is a rare genetic disorder caused by a deficiency of a lysosomal enzyme called acid alpha-glucosidase and is classified into infantile and late-onset forms. Since 2006, an enzyme replacement therapy involving alglucosidase alfa has been available. In 2021, a new enzyme replacement therapy involving avalglucosidase alfa demonstrated improved clinical benefits. In this article, the authors describe the pharmacokinetics of avalglucosidase alfa using a population pharmacokinetic approach.

Methods:
The population pharmacokinetic model was developed using a data set that included 75 patients and 2042 plasma drug concentrations determined through enzymatic activity assay from 3 studies (phases I/II and III) and involved 3 dose levels (5, 10, and 20 mg/kg). The analysis was performed using NONMEM software.

Results:
Two sequences were observed in the plasma drug concentration profile: the first kinetic driving exposure, and after 12 hours postdose, a slight rebound addressing very low concentrations that lasted up to 2 weeks. Following model screening, a model with a central compartment with parallel linear and nonlinear elimination and 2 concatenated peripheral compartments was proposed. A putative back-redistribution of a marginal fraction of the drug from the second peripheral compartment to the central compartment may explain the slight rebound in concentration. The final model's mean bias and precision for individual predictions were −2.66% and 30.7%, respectively, and −0.433% and 38.9%, respectively, for population predictions.

Conclusions:
A concatenated 3-compartment model was developed to describe the avalglucosidase alfa concentrations in patients with late-onset Pompe disease. None of the covariates tested could explain the interindividual variability.
Functional Chimeric Double-barrel Fibula and Reinnervated Peroneus Brevis Osteomyocutaneous Flap for One-stage Forearm Reconstruction
Authors: Lai Yeu-Her , Lee Yao-Chou 
Published: August 2023

Summary:
Reconstructing a mangled limb is complex and requires expertise in both bone and soft-tissue reconstruction, particularly when there is significant muscle loss. Typically, multistage surgery is necessary, starting with soft-tissue coverage, followed by bone grafting and tendon transfers. Sometimes, microsurgical techniques such as vascularized bone grafts and free functional muscle transfers are necessary, especially when there is a bone defect of over 6 cm; the soft-tissue environment is infected, scarred, or poorly vascularized; or there are extensive musculotendinous injuries. We treated a 34-year-old man who had a crushed left forearm resulting in an 18 × 8 cm open wound, 5-cm radius and 7-cm ulna bone defects, loss of the extensor pollicis longus and brevis muscles, and extensive injuries to the other musculotendinous structures of the forearm. To accomplish a one-stage reconstruction, we used a chimeric fibula osteomyocutaneous flap that included a 20 × 10 cm skin flap, peroneus brevis muscle with its motor nerve, and two segments of fibula. The proximal and distal fibula segments were used for ulnar and radial bone reconstruction, respectively, preserving forearm supination and pronation. The peroneus brevis tendon was sutured to the extensor pollicis longus tendon, and its motor nerve was coaptated with the posterior interosseous nerve to restore thumb extension. The skin flap provided complete coverage of all exposed bone and tendon structures. At the 12-month follow-up, the patient regained full extension of the thumb, and there were no difficulties with forearm supination and pronation or with foot eversion and plantar flexion at the donor leg.
A Comparison between the Use of Patient-worn Virtual Reality in Wound Care and Hand Surgery: How Does Virtual Reality Work?
Authors: Park Sean K. , Oakes Tannur C. , Lin Judith C. , Chahal Ruby , Clarkson James H.W. 
Published: August 2023

Background:
As virtual reality (VR) technology becomes smaller and more affordable, it is gaining in popularity as a tool to address the patient experience of pain and anxiety during invasive procedures. In this study, we explore the effect of VR on the patient experience in two clinical environments of different anxiety levels to propose a possible mechanism of VR on pain and anxiety reduction.

Method:
Twenty-five wound care patients were randomly assigned to either a VR group or non-virtual reality (NVR) group, singly blinded. Pre-debridement, peri-debridement, and immediately postdebridement anxiety, fun, and pain scores were collected using a Likert scale (0 = least; 10 = most) from each group of patients. These measurements were compared among the VR versus NVR group in the setting of routine wound debridement procedures. The results are compared with our previously published data on patients who underwent wide awake local anesthesia no tourniquet (WALANT) hand surgery.

Results:
The WALANT surgery patients using VR experienced significant reduction in anxiety and increase in fun compared with the NVR group. In the wound debridement group with VR, there was improved fun, but no statistically significant reduction in pain or anxiety when compared with the NVR group. The mean score for anxiety was higher for awake hand surgery than for wound debridement cases (3.3 versus 1.7, P = 0.004).

Conclusions:
VR seems to be more effective in higher anxiety settings, could VR work via a neurological mechanism akin to the Melzack and Wall gate control theory of pain? VR may act primarily on the anxiety axis, providing negative feedback via cortical pathways to the amygdala.
Therapeutic strategies targeting the endothelial glycocalyx
Authors: Machin Daniel R. , Sabouri Mostafa , Zheng Xiangyu , Donato Anthony J. 
Published: August 2023

Purpose of review
This review will highlight recent studies that have examined the endothelial glycocalyx in a variety of health conditions, as well as potential glycocalyx-targeted therapies.

Recent findings
A degraded glycocalyx is present in individuals that consume high sodium diet or have kidney disease, diabetes, preeclampsia, coronavirus disease 2019 (COVID-19), or sepsis. Specifically, these conditions are accompanied by elevated glycocalyx components in the blood, such as syndecan-1, syndecans-4, heparin sulfate, and enhanced heparinase activity. Impaired glycocalyx barrier function is accompanied by decreased nitric oxide bioavailability, increased leukocyte adhesion to endothelial cells, and vascular permeability. Glycocalyx degradation appears to play a key role in the progression of cardiovascular complications. However, studies that have used glycocalyx-targeted therapies to treat these conditions are scarce. Various therapeutics can restore the glycocalyx in kidney disease, diabetes, COVID-19, and sepsis. Exposing endothelial cells to glycocalyx components, such as heparin sulfate and hyaluronan protects the glycocalyx.

Summary
We conclude that the glycocalyx is degraded in a variety of health conditions, although it remains to be determined whether glycocalyx degradation plays a causal role in disease progression and severity, and whether glycocalyx-targeted therapies improve patient health outcomes. Future studies are warranted to investigate therapeutic strategies that target the endothelial glycocalyx.
Donor-derived infections in solid organ transplant recipients
Authors: Peghin Maddalena , Grossi Paolo Antonio 
Published: August 2023

Purpose of review
The potential for transmission of donor-derived infections (DDIs) is impossible to eliminate, but a thoughtful and systematic approach to donor evaluation can mitigate the risk. Prevention is a key issue and clinicians must maintain a high index of suspicion and remain vigilant in staying up to date on emerging infections. COVID-19 and Monkeypox have represented a new challenge for infectious disease screening and recommendations have been evolving, as knowledge in the field has grown. Additional considerations for pretransplant deceased donor screening include testing for neglected and endemic infectious diseases such as strongyloidiasis and HTLV 1/2. Molecular diagnostic tests have improved awareness on pathogenicity of mollicutes and fungi in the setting of DDIs. The aim of this review is to provide an update on the most recent literature on DDI with a special focus on these emerging hot topics.

Recent findings
Donor screening for uncommon pathogens must be guided by knowledge of changing epidemiology of infectious disease and availability of new diagnostic methods.

Summary
Appropriate screening, early recognition, timely reporting, close monitoring, and appropriate management are essential to help reducing the risk of emerging DDIs.
Adjuvant gemcitabine after resection of pancreatic cancer without significant difference in overall survival: a retrospective cohort study
Authors: Bauer Katrin , Büchler Peter , Henne-Bruns Doris , Manzini Giulia 
Published: August 2023

Background:
International guidelines recommend adjuvant chemotherapy after resection of pancreatic adenocarcinoma. The administration of gemcitabine has become part of the interdisciplinary treatment concept. The authors aim to prove whether the benefit in overall survival (OS) reported in randomized controlled trials (RCTs) could be reached also for patients treated in their department.

Materials and methods:
The authors retrospectively analyzed the OS of all patients who underwent pancreatic resection at their clinic because of ductal adenocarcinoma between January 2013 and December 2020 in dependence on adjuvant treatment with gemcitabine.

Results:
Overall 133 pancreatic resections were performed between 2013 and 2020 due to malignant pancreatic pathology. Seventy-four patients had ductal adenocarcinoma. Forty patients received adjuvant gemcitabine chemotherapy postoperatively, 18 patients underwent only surgical resection, and 16 patients received other chemotherapy regimens. The authors compared the group receiving adjuvant gemcitabine (n=40) with the group undergoing surgery alone (n=18). The median age was 74 years (range: 45–85), and the median OS was 16.5 months [95% confidence interval (CI) 13–27]. Follow-up time was at least 23 months (range 23–99). No statistically significant difference in median OS was observed in the group who received adjuvant chemotherapy compared to the operation-only group [17.5 months (range: 5–99, 95% CI 14–27) versus 12.5 months (range: 1–94, 95% CI 5–66), P=0.75].

Conclusion:
OS with and without adjuvant chemotherapy with gemcitabine was comparable to the results of those RCTs which serve as the basis of guideline recommendations. However, the analyzed patient cohort did not profit significantly from the adjuvant treatment.
Prognostic significance of the preoperative platelet-lymphocyte ratio in nonmetastatic renal cell carcinoma: cross-sectional study
Authors: Ouanes Yassine , Chaker Kays , Nouira Yassine 
Published: August 2023

Introduction:
The prognostic significance of the platelet-lymphocyte ratio (PLR) in nonmetastatic renal cell carcinoma (RCC) is controversial, although it has been established as a prognostic factor in several cancers.

Objective:
The objective of our study was to evaluate the prognostic significance of the PLR in patients with nonmetastatic RCC.

Patients and methods:
The authors performed a retrospective analysis of patients with nonmetastatic RCC who were operated between 2004 and 2020. Five years recurrence-free survival and metastasis-free survival were calculated. The prognostic significance of the preoperative PLR was assessed. The Kaplan–Meier method was utilized to graphically display survivor functions. Univariate and multivariate Cox’s proportional hazards regression models were utilized to analyze the association between PLR and oncological outcomes. Differences were considered significant if P<0.05.

Results:
Two hundred and two patients were included. The mean follow-up was 56.8±3 months. Patients with a higher PLR had larger tumors (P=0.02), higher ASA score (P=0.001), symptomatic forms (P=0.01), and more frequent tumor necrosis (P=0.02). Recurrence-free survival and metastasis-free survival rates were significantly lower in patients with high PLR than in those with low ratios (each P<0.005). Multivariate analysis identified PLR as an independent predictor of recurrence-free survival (P=0.002) and metastasis-free survival (P<0.001).

Conclusion:
A higher PLR was associated with aggressive renal cancer. In addition, the PLR was a significant prognostic factor for both recurrence-free survival and metastasis-free survival in patients with nonmetastatic RCC.