bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growing the Neonatal Nurse Practitioner Workforce Through Mentoring
Authors: Baker Lela A. , Moss Colleen , Bordelon Curry , Savin Michele K. 
Published: May 2024

Objective:
The purpose of this article is to highlight evidence specific to the neonatal nurse practitioner (NNP) workforce related to successful mentoring programs. Specifically, the authors of this article explored recent evidence of mentorship to improve job satisfaction and retention of the NNP workforce.

Background:
NNPs are valuable members of neonatal healthcare team. Because of the aging NNP workforce, methods to recruit, train, mentor, develop, and retain new NNPs are imperative.

Methods:
Using a quality appraisal tool from the PRISMA extension for scoping reviews, articles were identified through electronic database searches using search terms related to mentoring, nurse practitioners, recruitment, and retention. Studies published in English between 2013 and 2023 were included. Peer-reviewed quantitative and qualitative articles were synthesized and critically appraised by 4 reviewers.

Results:
The authors identified 46 articles with a focus on mentoring in nursing of which 12 articles include mentoring for nurse practitioners. Research indicates that mentoring relationships are valuable in many healthcare roles and professions. Evidence is limited indicating the impact of mentoring in the highly specialized role of the NNP.

Conclusion:
Mentoring is an invaluable component of professional nursing and counters incivility while advancing competency, job satisfaction, and retention. Additional research is needed regarding NNP-specific mentoring programs.
68Ga-PSMA-11 PET/CT in Cherry Hemangiomas
Authors: Betech-Antar Vicky , Urtasun-Iriarte César , Rosales Juan J. , Barrio-Piqueras Miguel , Rodriguez-Fraile Macarena 
Published: May 2024

Abstract
A 63-year-old man was remitted for a 68Ga-PSMA-11 PET/CT scan due to biochemical recurrence with a PSA of 0.32 ng/mL 1 year after radical prostatectomy of locally advanced Gleason 6 (3 + 3) ISUP 2 pT3a pN0 prostate cancer. 68Ga-PSMA-11 PET/CT showed multiple cutaneous and subcutaneous uptake foci in the upper body. Physical examination revealed numerous dome-shaped, ruby-red papules. These were consistent with a previous diagnosis of cutaneous hemangiomas. Cherry hemangiomas (also known as Campbell de Morgan spots) are the most common type of benign vascular proliferation of the skin. Due to the nonspecific 68Ga-PSMA-11 uptake of vascular lesions, careful interpretation should be considered in order to avoid a potential pitfall in nonmalignant conditions.
Relationship Between Pericarotid Fat Density and Pathology-Based Carotid Plaque Risk Characteristics
Authors: Dai An , Yao Weinan , Lei Jing , Yan Limin , Dang Lei , Zhao Haijun , Gu Jingshun , Li Jun , Nie Ying , Zheng Mengru , Wang Dongchun , Wang Qingwen 
Published: May 2024

Objectives:
In this study, the authors aimed to evaluate the relationship between pericarotid fat density (PFD) and pathologic carotid plaque risk characteristics.

Methods:
The authors retrospectively evaluated 58 patients (mean age: 66.66 ± 7.26 y, 44 males) who were subjected to both carotid endarterectomy and carotid artery computed tomography angiography (CTA) at the authors’ institution. The computed tomography values of the adipose tissue around the most severe stenosis carotid artery were measured, and the removed plaques were sent to the Department of Pathology for American Heart Association (AHA) classification. The Wilcoxon signed-rank test was used to detect the difference in PFD values between the operative and nonoperative sides. According to carotid plaque risk characteristics, the associations between PFD and 4 different risk characteristic subgroups were analyzed. The Student t test and χ2 test were used to compare differences between different risk subgroups. Receiver operating characteristic curve analysis was used to evaluate the predictive efficacy of PFD for carotid plaque risk characteristics.

Results:
The operative side had higher mean Hounsfield units (HU) values compared with the nonoperative side (P < 0.001). The AHA VI and the intraplaque hemorrhage (IPH) subgroups had higher mean HU values compared with the non-AHA VI and the non-IPH subgroups (P < 0.05). Male patients presented with IPH more than female patients (P = 0.047). The results of receiver operating characteristic curve analysis showed that the mean HU value (operative side; area under the curve: 0.729, Sensitivity (SE): 59.26%, Specificity (SP): 80.65%, P = 0.003) had a certain predictive value for diagnosing high-risk VI plaques. Pericarotid fat density ≥ −68.167 HU is expected to serve as a potential cutoff value to identify AHA VI and non-AHA VI subgroups.

Conclusion:
PFD was significantly associated with vulnerable plaques, high-risk AHA VI plaques, and IPH, which could be an indirect clinical marker for vulnerable plaques.
Evaluation of Regio Temporalis in 3 Steps in Terms of Interventional Procedures
Authors: Ok Fatma , Coşkun Osman , Yiğit Mehmet , Kale Ayşin , Sağ Fatma Beyza 
Published: May 2024

Regio temporalis is a site where botulinum neurotoxin is applied for various medical reasons, such as migraine, bruxism, and myofascial pain syndrome. The region is also one of the target regions in flap surgery. This study aimed to define the region topographically. In addition, it was aimed to reveal the intramuscular nerve distribution of the temporalis.11 fixed cephalus (cadaver head) and 2 fresh cephalus were used. The lateral canthus of the eye was marked as point A, and the middle of the ear tragus as point B. The transverse and vertical distances of the branching point of the superficial temporal artery to the A and B points were measured. Transverse distances of the superficial temporal artery and superficial temporal vein to A and B points were measured. The muscle was examined in 5 equal parts (L0–L1–L2–L3–L4), and each part’s vertical muscle and tendon lengths were examined. Intramuscular nerve density was demonstrated by applying the modified Sihler staining to fresh temporalis’. Superficial temporal artery had an average transverse distance of 8.56±1.9 mm in women and 12.56±1.94 mm in men from the middle of the ear tragus. The artery was 64.21±5.59 mm posterior in females and 63.48±6.53 mm in males from the lateral canthus of the eye. Our study determined that the branching point of the superficial temporal artery was below the upper level of the arcus zygomaticus in 10% of cases and above it in 90% of cases. In our study, the L2 point had the highest vertical muscle length at 45.67 mm, while the L3 point had the highest vertical tendon length at 41.25 mm. The point where the muscle length had the highest ratio with 1.49 compared to the tendon length, was the L2 point. The temporalis’ for which the modified Sihler staining was applied was examined in 5 quadrants. It was determined that the nerve densities were in the second and third quadrants from anterior to posterior. The distance of superficial landmarks to neurovascular structures is extremely important in interventions to the regio temporalis. Considering the average distances given in our study is important in avoiding damage in surgical procedures and not injecting into vascular structures. The point where the muscle length had the highest ratio of 1.49 compared to the tendon length was the L2 point. The area in line with this point is the most suitable area for injection. The L2 point is also the most suitable area for injection as it has the highest muscle length. Since the nerve densities were observed in the modified Sihler staining applied temporalis’ 2 and 3 quadrants from anterior to posterior, botulinum neurotoxin injections to these areas will give more effective results.
How to Set up and Run a Bad Bugs Bookclub group: resources and recommendations
Authors: Verran Joanna 
Published: May 2024

The Bad Bugs Bookclub is a public engagement initiative that enables scientists (microbiologists) and non-scientists to discuss the role of infectious disease and microorganisms in novels of fiction. The bookclub began in 2009 but since 2020 the meetings have taken place online, enabling international membership and occasional author participation. The bookclub has been shown through peer-reviewed publications to have impact and value to its members. For each book (the number now exceeds 100) a reading guide (questions to provoke discussion) and a meeting report (narrative of the discussion) have been produced. Previously hosted on a website, the reading guides from this rich archive and resource are now presented alongside this paper which provides tips on how to run a similar reading group.
Simulating pedigrees ascertained on the basis of observed IBD sharing
Authors: Jewett Ethan M. ,   the 23andMe Research Team
Published: May 2024

1.AbstractIn large genotyping datasets, individuals often have thousands of distant cousins with whom they share detectable segments of DNA identically by descent (IBD). The ability to simulate these distant relationships is important for developing and testing methods, carrying out power analyses, and performing population genetic analyses. Because distant relatives are unlikely to share detectable IBD segments by chance, many simulation replicates are needed to sample IBD between any given pair of distant relatives. Exponentially more samples are needed to simulate observable segments of IBD simultaneously among multiple pairs of distant relatives in a single pedigree. Using existing pedigree simulation methods that do not condition on the event that IBD is observed among certain pairs of relatives, the chances of sampling shared IBD patterns that reflect those observed in real data ascertained from large genotyping datasets are vanishingly small, even for pedigrees of modest size. Here, we show how to sample recombination breakpoints on a fixed pedigree while conditioning on the event that specified pairs of individuals share at least one observed segment of IBD. The resulting simulator makes it possible to sample genotypes and IBD segments on pedigrees that reflect those ascertained from biobank scale data.
A homozygousATP2A2variant alters sarcoendoplasmic reticulum Ca2+-ATPase 2 function in skeletal muscle and causes a novel vacuolar myopathy
Authors: Llansó Laura , Ravenscroft Gianina , Aceituno Cristina , Gutiérrez Antonio , Parmar Jevin , Gallano Pia , Caballero-Ávila Marta , Carbayo Álvaro , Vesperinas Ana , Collet Roger , Blanco Rosa , Laing Nigel , Hove-Madsen Leif , Gallardo Eduard , Olivé Montse 
Published: May 2024

AbstractBackgroundSarcoendoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), encoded byATP2A2, is a key protein involved in intracellular Ca2+homeostasis. The transcript SERCA2a is predominantly expressed in cardiac muscle and in type I myofibers, while SERCA2b is ubiquitously expressed including in skin cells. To date, variants in this gene were reported to be the cause of Darier disease, an autosomal dominant dermatologic disorder, but have never been linked to primary skeletal muscle disease. We describe four patients suffering from a novel hereditary myopathy caused by a homozygous missense variant inATP2A2.MethodsWe studied a family with four affected individuals suffering from an adult-onset progressive skeletal myopathy. We performed a comprehensive evaluation of the clinical phenotype, serum CK levels, muscle MRI, and muscle biopsy, with genetic workup by means of gene panel sequencing followed by whole genome sequencing and segregation analysis. Immunohistochemistry and western blot (WB) to evaluate SERCA2 and SERCA1 expression in skeletal muscle was performed. We evaluated kinetics of Ca2+handling following caffeine exposure or voltage-induced sarcolemma depolarization in patient myoblasts and myotubes, compared to healthy controls.ResultsFour siblings in their fifties developed in early adulthood symmetric proximal weakness in lower limbs, which was slowly progressive over time. They had no skin or cardiac involvement. Biopsy findings in two affected individuals showed small vacuoles restricted to type I myofibers. Ultrastructural analysis showed dilation and proliferation of T-tubules, swelling of sarcoplasmic reticulum and autophagic vacuoles. Genome sequencing revealed a homozygous variant inATP2A2(c.1117G>A, p.(Glu373Lys)) which segregated with the disease. Immunohistochemistry suggested SERCA2 mislocalization in patient myofibers compared to controls. WB did not show changes in the amount or molecular weight of the protein.In vitrofunctional studies revealed delayed sarcoendoplasmic reticulum Ca2+reuptake in patient myotubes, consistent with an altered pumping capacity of SERCA2 after cell stimulation with caffeine or depolarization.ConclusionsWe report a novel adult-onset vacuolar myopathy caused by a homozygous variant inATP2A2, resulting in a pure skeletal muscle phenotype with a limb-girdle distribution. Biopsy findings and functional studies demonstrating an impaired function of SERCA2 and consequent Ca2+dysregulation in slow-twitch skeletal myofibers highly support the pathogenicity of the variant.
Role of Lamin A/C on dendritic cell function in antiviral immunity
Authors: Herrero-Fernandez Beatriz , Bris Raquel Gómez , Zapero Marina Ortega , Saez Angela , Iborra Salvador , Zorita Virginia , Quintas Ana , Vazquez Enrique , Dopazo Ana , Sánchez-Madrid Francisco , Arribas Silvia Magdalena , Granado Jose Maria Gonzalez 
Published: May 2024

AbstractDendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing -CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primaryVaccinia virus(VACV) infection. Remarkably,in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NFκB-dependent transcription. Furthermore, lamin A/C ablation modifies the epigenetic signature of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and elucidates the molecular mechanisms through which lamin A/C modulates DC function via epigenetic and transcriptional regulation.
Imaging of MAP kinase dynamics reveals endocytic regulation of pulsatile signalling and network re-wiring in response to targeted therapy in EGFR-mutant non-small cell lung cancer
Authors: Le Marois Alix , Bailey Sasha , Hooper Steven , Kumar Sunil , Sparks Hugh , Alexandrov Yuriy , Caswell Deborah , Frӧhlich Fabian , Schlegelmilch Karin , Valand Karishma , Martin Matthew , Narvaez Ana , Swanton Charles , Downward Julian , Dunsby Christopher , French Paul , Sahai Erik 
Published: May 2024

AbstractA better understanding of the signalling mechanisms underlying transitions from drug-sensitive to drug-tolerant states is required to overcome therapy failure. We combined single-cell biosensor imaging with functional perturbations to investigate the regulation of oncogenic signalling in EGFR-mutant lung adenocarcinoma. We find that despite the constant presence of the mutant oncogene, ERK signalling exhibits pulsatile dynamics, with pulse characteristics determined by the endocytic machinery. Analysis of drug-tolerant persisters (DTPs) revealed that, after an initial phase of complete pathway shut-down, signalling was rewired leading to renewed ERK pulses that drive cell cycle progression. FAK- and SRC-regulated adhesion complexes replace mutant EGFR as the driver of reactivated ERK pulses in DTPs, yet they remain controlled by the membrane trafficking machinery. We show that DTPs rely on additional survival pathways including YAP signalling, and that the phosphatase PTPRS represents a key node in therapy resistant cells, coordinating regulation of ERK, the cytoskeleton, and YAP.
Lysineless HiBiT and NanoLuc Tagging Systems as Alternative Tools Monitoring Targeted Protein Degradation
Authors: Lin Hanfeng , Riching Kristin , Lai May Poh , Lu Dong , Cheng Ran , Qi Xiaoli , Wang Jin 
Published: May 2024

AbstractTarget protein degradation (TPD) has emerged as a revolutionary approach in drug discovery, leveraging the cell’s intrinsic machinery to selectively degrade disease-associated proteins. Proteolysis-Targeting Chimeras (PROTACs) exemplify this strategy, exploiting heterobifunctional molecules to induce ubiquitination and subsequent degradation of target proteins. The clinical advancement of PROTACs underscores their potential in therapeutic intervention, with numerous projects progressing through clinical stages. However, monitoring subtle changes in protein abundance induced by TPD molecules demands highly sensitive assays. Nano-luciferase (nLuc) fusion proteins, or the NanoBiT technology derived from it, offer a robust screening platform due to their high sensitivity and stability. Despite these advantages, concerns have arisen regarding potential degradation artifacts introduced by tagging systems due to the presence of lysine residues on them, prompting the development of alternative tools. In this study, we introduce HiBiT-RR and nLucK0, variants devoid of lysine residues, to mitigate such artifacts. Our findings demonstrate that HiBiT-RR maintains similar sensitivity and binding affinity with the original HiBiT. Moreover, the comparison between nLucWTand nLucK0constructs reveals variations in degradation patterns induced by certain PROTAC molecules, emphasizing the importance of choosing appropriate tagging systems to ensure the reliability of experimental outcomes in studying protein degradation processes.
SS18::SSX redistributes BAF chromatin remodelers selectively to activate and repress transcription
Authors: Li Jinxiu , Li Li , Smith-Fry Kyllie , Wilmot Zaki F. , Carroll Lara , Morrison Linda , Ge Xinyi , Nelson Mary , Hill Lesley A. , Zhang Xiaoyang , Nielsen Torsten O. , Hirst Martin , Underhill T. Michael , Cairns Bradley R. , Jones Kevin B. 
Published: May 2024

SUMMARYSynovial sarcoma (SyS) is driven by the expression of a chromosomal translocation-generated SS18::SSX fusion oncoprotein1,2. This oncoprotein fuses the SSX carboxy terminal tail that binds ubiquitylated histone H2A (H2AK119ub)3–6to the SS18 component of both canonical (CBAF) and non-canonical (GBAF, GLTSCR1-containing) BAF-family chromatin remodeling complexes7–11, wherein SS18::SSX reprograms the epigenetic landscape. Mice that express SS18::SSX develop tumors that faithfully recapitulate human SyS histopathologically and molecularly12–14, allowing dissection of transcriptional reprogrammingin vivo15,16. Here, we show that SS18::SSX redistributes GBAF complexes broadly to promoters and distal enhancers decorated by H2AK119ub, which uncharacteristically lack the transcription-silencing trimethylation of H3K27 that otherwise accompanies H2AK119ub. Fusion-GBAF instead associates with H2AK119ub and transcription-enabling H3K4 trimethylation (promoters), monomethylation (distal enhancers), and H3K27 acetylation (both). CBAF with the fusion redistributes away from typical loci, avoids H2AK119ub-bearing regions, and instead narrowly flanks transcription start sites (TSSs), co-distributed with polybromo BAF (PBAF). Accelerated tumorigenesis in our SyS mouse model followed deletion ofSmarcb1(PBAF and CBAF),Pbrm1(PBAF-specific), andArid1aorArid1b(CBAF-specific). While tumors lackingArid1a or Arid1bretained SyS character, loss ofSmarcb1orPbrm1resulted in tumors lacking SyS features. These findings suggest that SyS transcriptional reprogramming includes both improper GBAF localization and gene activation at H2AK119ub-bearing regulatory regions and improper gene silencing through loss of CBAF.
Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver
Authors: Gaither Kari A. , Singh Dilip Kumar , Yue Guihua , Trudeau Julia , Ponraj Kannapiran , Davydova Nadezhda Y. , Lazarus Philip , Davydov Dmitri R. , Prasad Bhagwat 
Published: May 2024

AbstractWe examined the effect of alcohol consumption and smoking on the abundance of drug-metabolizing enzymes and transporters (DMET) in human liver microsomes (HLM) isolated from liver tissues of 94 donors. Global proteomics analysis was performed and DMET protein levels were analyzed in relation to alcohol consumption levels, smoking history, and sex using non-parametric tests (p-value ≤ 0.05; cutoff of 1.25-fold change, FC). The examination of the alcohol-induced changes was further enforced by correlational analysis, where we used arbitrary alcohol consumption grade (ACG) scaling from 0 to 4 to establish a set of protein markers. We elaborated a provisional index of alcohol exposure (PIAE) based on a combination of relative abundances of four proteins (ER chaperone HSPA5, protein disulfide isomerases PDIA3 and P4HB, and cocaine esterase CES2) best correlating with ACG. The PIAE index was then used to find its correlations with the abundances of DMET proteins. Our results demonstrate considerable alcohol-induced changes in composition of the pool of cytochrome P450 enzymes in HLM. We observed significantly increased abundances of CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase. In contrast, CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b5protein levels were downregulated. Significant alteration in abundances of UDP-glucuronosyltransferase (UGT) were also detected, comprising of elevated UGT1A6, UGT1A9, and UGT2A1, and reduced UGT1A3, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 levels. Important alcohol-induced changes were also observed in the expression of non-CYP and non-UGT DMET. Additionally, tobacco smoke was associated with elevated CYP1A2, UGT1A6, UGT2A1, and UGT2B4 and decreased FMO3, FMO4, and FMO5 levels.