bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic variant SLC2A1-rs1105297 is associated with the differential analgesic response to a glucose-based treatment in newborns
Authors: Farinella Riccardo , Falchi Fabio , Tavanti Arianna , Tuoni Cristina , Di Nino Maria Grazia , Filippi Luca , Ciantelli Massimiliano , Rizzato Cosmeri , Campa Daniele 
Published: September 2023

Abstract
Neonatal pain is a critical issue in clinical practice. The oral administration of glucose-based solutions is currently one of the most common and effective nonpharmacologic strategies for neonatal pain relief in daily minor procedures. However, a varying degree of analgesic efficacy has been reported for this treatment. Environmental, maternal, and genetic factors may explain this variability and potentially allow for a personalized analgesic approach, maximizing therapeutic efficacy and preventing side effects. We investigated the exposome (ie, the set of clinical and anthropometric variables potentially affecting the response to the therapy) and the genetic variability of the noradrenaline transporter gene (solute carrier family 6 member 2 [SLC6A2]) and 2 glucose transporter genes (solute carrier family 2 member 1 [SLC2A1] and 2 [SLC2A2]) in relation to the neonatal analgesic efficacy of a 33% glucose solution. The study population consisted in a homogeneous sample of more than 1400 healthy term newborns. No association for the exposome was observed, whereas a statistically significant association between the G allele of SLC2A1-rs1105297 and a fourfold decreased probability of responding to the therapy was identified after multiple-testing correction (odds ratio of 3.98, 95% confidence interval 1.95-9.17; P = 4.05 × 10−4). This allele decreases the expression of SLC2A1-AS1, causing the upregulation of SLC2A1 in the dorsal striatum, which has been suggested to be involved in reward-related processes through the binding of opioids to the striatal mu-opioid receptors. Altogether, these results suggest the involvement of SLC2A1 in the analgesic process and highlight the importance of host genetics for defining personalized analgesic treatments.
Prader–Willi syndrome: an update
Authors: Duis Jessica 
Published: September 2023

Purpose of review
Sleep disorders in Prader–Willi syndrome (PWS) range from respiratory to neurological disorders of sleep. We now recognize the role of excessive daytime sleepiness (present in the infant period and throughout life), and a modified narcolepsy phenotype with or without cataplexy. Disordered sleep in PWS may present with symptoms pervasive to daily function, including inattention at school, irritability, and behavioral outbursts. This review highlights the spectrum of sleep disordered breathing and neurological disorders of sleep in individuals with PWS as well as the current knowledge of management.

Recent findings
This article covers the literature characterizing sleep disorders in PWS, including treatment strategies.

Summary
The review highlights the importance of considering disorders of sleep in PWS and the current treatment options.
Be aware of the “O” sign in the bipolar cup dissociation during closed reduction of bipolar dislocation: A case report
Authors: Sim Seung-Bo , Son Sang-Woo , Shim Bum-Jin 
Published: September 2023

Rationale:
Bipolar cup dissociation following hip hemiarthroplasty is a rare complication of which only a few cases have been reported, and it usually requires revision surgery because of difficulties in closed reduction.

Patient concerns:
We report the case of a 57-year-old man who underwent bipolar hemiarthroplasty 2 months ago caused by a left femoral neck fracture. Postoperatively, bipolar dislocation occurred thrice, and the patient showed bipolar cup dissociation during closed reduction maneuver at the recent visit. At the time of this event, no consideration was given to the shape of the prosthesis on the radiograph.

Diagnoses:
The patient was diagnosed with early bipolar cup dissociation.

Interventions:
The patient underwent revision surgery to replace and reassemble the femoral head component.

Outcomes:
No further dislocation occurred following the surgery.

Lessons:
To avoid dissociation of the components during closed reduction, it would be helpful to have knowledge of the “O” sign, a concentric circle shape of the prosthesis on the radiograph.

Level of evidence:
Level V, case report.
Demonstration Projects to Test Built Environment Changes: A Systematic Review
Authors: Balis Laura E. , Porter Gwenndolyn , Grocke-Dewey Michelle 
Published: September 2023

Context:
Built environment interventions (pedestrian/bicycle infrastructure and enhanced access) mitigate barriers to physical activity by making the healthy choice the default choice. Demonstration projects (eg, temporary pedestrian lanes or sidewalks marked with tape) are used to test these interventions before making permanent changes. However, it is unknown whether demonstration projects lead to desired built environment changes.

Objective:
To systematically review the literature to determine outcomes and overall public health impacts of demonstration projects and whether they lead to permanent changes to the built environment.

Design:
Systematic review, conducted from March to September 2022 by searching PubMed and EBSCOhost for peer-reviewed literature and Google for gray (non–peer-reviewed) literature. Inclusion criteria were policy, systems, or environmental interventions; temporary implementation; and presence of evaluation data. Exclusion criteria were individual/interpersonal-level interventions, permanent implementation, and absence of evaluation data. Two authors coded for inclusion/exclusion and resolved discrepancies, coded a portion of included sources and resolved discrepancies, refined coding guide definitions, and coded remaining sources.

Main Outcome Measures:
Data were extracted based on the expanded RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, which incorporates constructs of the Implementation Outcomes Framework (acceptability, appropriateness, feasibility).

Results:
Gray (N = 23) and peer-reviewed (N = 1) sources describing unique demonstration projects (N = 31) met inclusion criteria. Projects tested built environment interventions including traffic calming measures, crosswalks, bike lanes, intersection design, and trails. Sources primarily reported effectiveness (typically improved safety), maintenance, acceptability, and appropriateness. Most sources did not report projects leading to permanent changes to the built environment.

Conclusions:
Based on inconsistent reporting of key outcomes (number of community members reached, changes to physical activity levels), overall impacts are unknown. Most demonstration projects captured community members' feedback, which was typically positive, but it is unknown whether feedback led to long-term changes. We recommend providing improved demonstration project guidance for practitioners to facilitate robust data collection, including suggested evaluation methods and tools.
68Ga-FAPI–Avid Submental Ectopic Papillary Thyroid Carcinoma and Lateral Neck Lymphadenopathy With Low 18F-FDG Uptake
Authors: Shi Yuan , Tang Linglin , Fei Mengjia , Liu Jianjun , Wang Zhuoying 
Published: September 2023

Abstract
Ectopic thyroid tissue is rare and generally occurs along the thyroglossal duct or in lateral cervical region. We reported 18F-FDG and 68Ga-FAPI findings of a 28-year-old woman with previously diagnosed BRAF-mutated lateral lymph node metastasis of unknown primary site. Low 18F-FDG but increased 68Ga-FAPI uptake was seen in a submental pretracheal nodular lesion. Postsurgical pathologic report verified the diagnosis of ectopic papillary thyroid carcinoma. High FAP expression in the tumor sample corresponded to its imaging manifestations.
Pharmacologic inhibition of BAF chromatin remodeling complexes as a therapeutic approach to transcription factor-dependent cancers
Authors: Centore Richard C. , Soares Luis M. M. , Topal Salih , Vaswani Rishi G. , Ichikawa Kana , Li Zhifang , Fan Hong , Setser Jeremy W. , Lahr David L. , Zawadzke Laura E. , Chen Xueying , Barnash Kimberly D. , Muwanguzi Jordana , Anthony Neville , Sandoval Gabriel J. , Feldman Katharine , Elliott GiNell , Adam Ammar , Huang David , Davenport Yunji , Schiller Shawn , Wilson Kevin J. , Voigt Johannes , Xu Lan , Hentemann Martin , Millan David S. , Chan Ho Man , Decicco Carl P. , Kruger Ryan G. , Bellon Steven F. 
Published: September 2023

AbstractThe BRG/Brahma-associated factors (BAF or mSWI/SNF) family of chromatin remodeling complexes are critical regulators of gene expression and are major determinants of cancer and other diseases. Two paralog ATPases, SMARCA4 and SMARCA2 (BRG1 and BRM, respectively), provide the enzymatic activity required for chromatin remodeling. Here, we discover and characterize a novel series of compounds that potently and selectively inhibit SMARCA4/SMARCA2. Mutational and biochemical studies demonstrate that these inhibitors act through a unique mode of inhibition, distinct from reported SMARCA4/SMARCA2 inhibitors. Across a range of cancer cell lines, SMARCA4/SMARCA2 inhibition resulted in lineage-specific changes in chromatin accessibility at binding sites for key transcription factors (TFs). In uveal melanoma (UM), BAF inhibition resulted in loss of enhancer occupancy of SOX10 and MITF, two essential TFs, leading to down-regulation of the melanocytic gene expression program. In a mouse xenograft model of UM, SMARCA4/SMARCA2 inhibition was well tolerated and resulted in dose-dependent tumor regression correlating with pharmacodynamic modulation of BAF-target gene expression. These data provide the foundation for first-in-human studies of BAF ATPase inhibition as a novel therapeutic to treat TF-dependent cancers.
Sclerostin blockade inhibits bone resorption through PDGF receptor signaling in osteoblast lineage cells
Authors: Thouverey Cyril , Apostolides Pierre , Brun Julia , Caverzasio Joseph , Ferrari Serge 
Published: September 2023

AbstractWhile sclerostin-neutralizing antibodies (Scl-Ab) transiently stimulate bone formation by activating Wnt signaling in osteoblast lineage cells, they exert sustained inhibition of bone resorption, suggesting an alternate signaling pathway by which Scl-Ab control osteoclast activity. Since sclerostin can activate platelet-derived growth factor receptors (PDGFRs) in osteoblast lineage cells in vitro and PDGFR signaling in these cells induces bone resorption through M-CSF secretion, we hypothesized that the prolonged anti-catabolic effect of Scl-Ab could result from PDGFR inhibition. We show here that inhibition of PDGFR signaling in osteoblast lineage cells is sufficient and necessary to mediate prolonged Scl-Ab effect on M-CSF secretion and osteoclast activity in mice. Indeed, sclerostin co-activates PDGFRs independently of Wnt/β-catenin signaling inhibition, by forming a ternary complex with LRP6 and PDGFRs in pre-osteoblasts. In turn, Scl-Ab prevents sclerostin-mediated co-activation of PDGFR signaling and consequent M-CSF up-regulation in pre-osteoblast cultures, thereby inhibiting osteoclast activity in pre-osteoblast/osteoclast co-culture assays. These results provide a new potential mechanism explaining the dissociation between anabolic and anti-resorptive effects of long-term Scl-Ab.
Ligand requirements for immunoreceptor triggering
Authors: Barton Michael I. , Paterson Rachel L. , Denham Eleanor M. , Goyette Jesse , van der Merwe P. Anton 
Published: September 2023

AbstractLeukocytes interact with other cells using cell surface receptors. The largest group of such receptors are non-catalytic tyrosine phosphorylated receptors (NTRs), also called immunoreceptors. NTR signalling requires phosphorylation of cytoplasmic tyrosine residues by SRC-family tyrosine kinases. How ligand binding to NTRs induces this phosphorylation, also called NTR triggering, remains controversial, with roles suggested for size-based segregation, clustering, and mechanical force. Here we exploit a recently developed cell-surface generic ligand system to explore the ligand requirements for NTR triggering. We examine the effect of varying the ligand’s length, mobility and valency on the activation of representative members of four NTR families: SIRPβ1, Siglec 14, NKp44 and TREM-1. Increasing the ligand length impairs activation via NTRs, despite enhancing cell-cell conjugation, while varying ligand mobility has little effect on either conjugation or activation. Increasing the valency of the ligand, while enhancing cell-cell conjugation, does not enhance activation at equivalent levels of conjugation. These findings are more consistent with a role for size-based segregation, rather than mechanical force or clustering, in NTR triggering, suggesting a role for the kinetic-segregation model.
Regulation of human interferon signaling by transposon exonization
Authors: Pasquesi Giulia Irene Maria , Allen Holly , Ivancevic Atma , Barbachano-Guerrero Arturo , Joyner Olivia , Guo Kejun , Simpson David M. , Gapin Keala , Horton Isabella , Nguyen Lily , Yang Qing , Warren Cody J. , Florea Liliana D. , Bitler Benjamin G. , Santiago Mario L. , Sawyer Sara L. , Chuong Edward B. 
Published: September 2023

SummaryInnate immune signaling is essential for clearing pathogens and damaged cells, and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues, and functions as a decoy receptor that potently inhibits interferon signaling including in cells infected with SARS-CoV-2. Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.
Snow Buntings, an arctic cold-specialist passerine, risk overheating under intense activity even at low air temperatures
Authors: O’Connor Ryan S. , Love Oliver P. , Regimbald Lyette , Gerson Alexander R. , Elliott Kyle H. , Hargreaves Anna L. , Vézina François 
Published: September 2023

AbstractBirds maintain some of the highest body temperatures (Tb) among endothermic animals. Often deemed a selective advantage for heat tolerance, high Tbalso limits the capacity to increase Tbbefore reaching lethal levels. Recent thermal modelling suggests that sustained effort in Arctic birds might be restricted at mild air temperatures (Ta) during energetically demanding life history stages, which may force reductions in activity to avoid overheating, with expected negative impacts on reproductive performance. Consequently, understanding how Arctic birds will cope with increasing Tahas become an urgent concern. We examined within-individual changes in Tbin response to an experimental increase in activity in outdoor captive Arctic cold-specialised snow buntings (Plectrophenax nivalis), exposed to naturally varying Tafrom -15 to 36 °C. Calm buntings exhibited a modal Tbrange from 39.9 – 42.6 °C. However, we detected a dramatic increase in Tbwithin minutes of shifting birds to active flight, with strong evidence for a positive effect of Taon Tb(slope = 0.04 °C/°C). Importantly, by Taof 9 °C, flying buntings were already generating Tb≥ 45°C, approaching the upper thermal limits of organismal performance (i.e., Tb= 45 - 47 °C). Under scenarios of elevated Tb, buntings must increase rates of evaporative water loss and/or reduce activity to avoid overheating. With known limited evaporative heat dissipation capacities, we argue buntings operating at peak energy levels will increasingly rely on behavioral thermoregulatory strategies (i.e., reducing activity) to regulate Tb, at the potential detriment to nestling growth and survival.
Magnetically Powered Microwheel Thrombolysis of Occlusive Thrombi in Zebrafish
Authors: Pontius M. Hao Hao , Ku Chia-Jui , Osmond Matthew , Disharoon Dante , Liu Yang , Marr David W.M. , Neeves Keith B. , Shavit Jordan A. 
Published: September 2023

AbstractTissue plasminogen activator (tPA) is the only FDA approved treatment for ischemic stroke but carries significant risks, including major hemorrhage. Additional options are needed, especially in small vessel thrombi which account for ∼25% of ischemic strokes. We have previously shown that tPA-functionalized colloidal microparticles can be assembled into microwheels (µwheels) and manipulated under the control of applied magnetic fields to enable rapid thrombolysis of fibrin gels in microfluidic models of thrombosis. Providing a living microfluidic analog, transparent zebrafish larvae have a highly conserved coagulation cascade that enables studies of hemostasis and thrombosis in the context of intact vasculature, clotting factors, and blood cells. Here we show that tPA-functionalized µwheels can perform rapid and targeted recanalizationin vivo. This effect requires both tPA and µwheels, as minimal to no recanalization is achieved with tPA alone, µwheels alone, or tPA-functionalized microparticles in the absence of a magnetic field. We evaluated tPA-µwheels in CRISPR-generated plasminogen (plg) heterozygous and homozygous mutants and confirmed that tPA-µwheels are dose-dependent on plasminogen for lysis. We have found that magnetically powered µwheels as a targeted tPA delivery system are dramatically more efficient at plasmin-mediated thrombolysis than systemic deliveryin vivo. Further development of this system in fish and mammalian models could enable a less invasive strategy for alleviating ischemia that is safer than directed thrombectomy or systemic infusion of tPA.
Sclerotic prostate cancer bone metastasis: woven bone lesions with a twist
Authors: Eltit-Guersetti Felipe , Wang Qiong , Jung Naomi , Munshan Sheryl , Xie Dennis , Xu Samuel , Mojtahedzadeh Bita , Liu Danmei , Corey Eva , True Lawrence D , Morrissey Colm , Wang Rizhi , Cox Michael E. 
Published: September 2023

ABSTRACTBone metastasis (BM) are the most severe and prevalent consequences of prostate cancer (PC) affecting more than 80% of patients with advanced PC. PCBM generate pain, pathological fractures, and paralysis. As modern therapies increase survival, more patients are suffering from these catastrophic consequences of PCBM. Radiographically, PCBM are predominantly osteosclerotic, but the mechanisms of abnormal bone formation, and how this “more and new” bone is related to fractures is unclear. In this study, we conducted a comprehensive analysis on a cohort of 76 cadaveric PCBM samples and 12 from non-PC donors as control. We used μ-CT to determine three-dimensional organization and quantify bone characteristics, quantitative backscattering electron microscopy to characterize mineral content and details in bone structure, nano indentation to determine mechanical properties, and we finalize with histological and immunohistochemical analysis of bone structure and composition. We define 4 phenotypes of PCBM, osteolytic, mixed lytic-sclerotic, and two subgroups of osteosclerotic lesions, those with residual trabeculae, and others without residual trabeculae. The osteosclerotic lesions are characterized by the presence of abnormal bone within the trabeculae surfaces and intertrabecular spaces. This abnormal bone is characterized by higher lacunae density, abnormal lacunae morphology and orientation. However, we observed no significant difference between this irregular bone and residual trabeculae in terms of mineral content, hardness, and elastic modulus at micron-scale. The collagen matrix of this abnormal bone presents with irregular organization and is accompanied by increased proteoglycan and phosphorylated glycoprotein content. These characteristics suggests the presence of woven bone in PCBM. However, the lack of subsequent bone remodelling, absence of lamellar bone deposition on its surface, absence of markers of matrix vesicles but evidence of alkaline phosphatase dominated mineralization and collagen-III structure, set up differences from woven bone, while the role of PC cells in inducing this irregular bone phenotype remains unclear.
Oligodendroglia generate vascular mural cells and neurons in the adult mouse brain
Authors: Yu Qingting , Yang Kairan , Fan Zhouling , Huang Maojiao , Xu Ting , Yang Yanzhuo , Yang Zuisu , He Xiaosong , Yuan Falei 
Published: September 2023

AbstractBACKGROUNDOligodendroglia encompass oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs). In the grey matter of the cortex, nearly all OPCs divide slowly, yet they don’t differentiate solely into mature OLs, leaving the exact role of these OPCs in the grey matter enigmatic.METHODSOligodendroglia, including OPCs, were traced using the Sox10 Cre-ERT2reporter mice. We compared the effect of tamoxifen dissolved in different solvents on the fate of Sox10 cells. We also compared the effect of tamoxifen dosage on the fate of Sox10 cells. The differentiation of labeled red fluorescent protein (RFP) cells was analyzed using immunofluorescence staining.RESULTSTwo groups of RFP cells, type A Sox10 (Sox10-A) cells, and type B Sox10 (Sox10-B) cells, were identified in the cortex, striatum, hippocampus, thalamus, and hypothalamus. Sox10-A cells differentiate into platelet-derived growth factor receptor-β (PDGFRβ)+, CD13+ pericytes, and smooth muscle myosin heavy chain 11 (MYH11) + smooth muscle cells when the mice received ethanol or high-dose tamoxifen. Sox10-B cells transform into glutamatergic neurons when the mice received high-dose tamoxifen. Sox10-B cells include perineurona OPCs and OLs.CONCLUSIONSThis investigation provides evidence that a substantial proportion of oligodendroglia in the grey matter serve as mural cell precursors and neuronal precursors. These two phenomena may contribute to our understanding of neurodegenerative diseases.Graphic abstract