bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor activity‐modifying protein 1 regulates mouse skin fibroblast proliferation via the Gαi3-PKA-CREB-YAP axis
Authors: Yin Siyuan , Song Ru , Ma Jiaxu , Liu Chunyan , Wu Zhenjie , Cao Guoqi , Liu Jian , Zhang Guang , Zhang Huayu , Sun Rui , Chen Aoyu , Wang Yibing 
Published: April 2022

Abstract
Background
Skin innervation is crucial for normal wound healing. However, the relationship between nerve receptors and wound healing and the intrinsic mechanism remains to be further identified. In this study, we investigated the role of a calcitonin gene-related peptide (CGRP) receptor component, receptor activity‐modifying protein 1 (RAMP1), in mouse skin fibroblast (MSF) proliferation.

Methods
In vivo, Western blotting and immunohistochemical (IHC) staining of mouse skin wounds tissue was used to detect changes in RAMP1 expression. In vitro, RAMP1 was overexpressed in MSF cell lines by infection with Tet-On-Flag-RAMP1 lentivirus and doxycycline (DOX) induction. An IncuCyte S3 Live-Cell Analysis System was used to assess and compare the proliferation rate differences between different treatment groups. Total protein and subcellular extraction Western blot analysis, quantitative real-time-polymerase chain reaction (qPCR) analysis, and immunofluorescence (IF) staining analysis were conducted to detect signalling molecule expression and/or distribution. The CUT & RUN assay and dual-luciferase reporter assay were applied to measure protein-DNA interactions.

Results
RAMP1 expression levels were altered during skin wound healing in mice. RAMP1 overexpression promoted MSF proliferation. Mechanistically, total Yes-associated protein (YAP) and nuclear YAP protein expression was increased in RAMP1-overexpressing MSFs. RAMP1 overexpression increased inhibitory guanine nucleotide-binding protein (G protein) α subunit 3 (Gαi3) expression and activated downstream protein kinase A (PKA), and both elevated the expression of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and activated it, promoting the transcription of YAP, elevating the total YAP level and promoting MSF proliferation.

Conclusions
Based on these data, we report, for the first time, that changes in the total RAMP1 levels during wound healing and RAMP1 overexpression alone can promote MSF proliferation via the Gαi3-PKA-CREB-YAP axis, a finding critical for understanding RAMP1 function, suggesting that this pathway is an attractive and accurate nerve target for skin wound treatment.
The implications of exosomes in pregnancy: emerging as new diagnostic markers and therapeutics targets
Authors: Ghafourian Mehri , Mahdavi Roya , Akbari Jonoush Zahra , Sadeghi Mahvash , Ghadiri Nooshin , Farzaneh Maryam , Mousavi Salehi Abdolah 
Published: April 2022

AbstractExtracellular vehicles (EVs) are a heterogeneous group of cell and membranous particles originating from different cell compartments. EVs participate in many essential physiological functions and mediate fetal-maternal communications. Exosomes are the smallest unit of EVs, which are delivered to the extracellular space. Exosomes can be released by the umbilical cord, placenta, amniotic fluid, and amniotic membranes and are involved in angiogenesis, endothelial cell migration, and embryo implantation. Also, various diseases such as gestational hypertension, gestational diabetes mellitus (GDM), preterm birth, and fetal growth restriction can be related to the content of placental exosomes during pregnancy. Due to exosomes' ability to transport signaling molecules and their effect on sperm function, they can also play a role in male and female infertility. In the new insight, exosomal miRNA can diagnose and treat infertilities disorders. In this review, we focused on the functions of exosomes during pregnancy.
CSF GFAP levels in double seronegative neuromyelitis optica spectrum disorder: no evidence of astrocyte damage
Authors: Hyun Jae-Won , Kim Yeseul , Kim Ki Hoon , Kim Su-Hyun , Olesen Mads Nikolaj , Asgari Nasrin , Siritho Sasitorn , Paul Friedemann , Kim Ho Jin 
Published: April 2022

Abstract
Background
Despite rigorous confirmation with reliable assays, some individuals showing the neuromyelitis optica spectrum disorder (NMOSD) phenotype remain negative for both aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies.

Objective
We aimed to investigate whether double seronegative NMOSD (DN-NMOSD) and NMOSD with AQP4 antibody (AQP4–NMOSD) share the same pathophysiological basis, astrocytopathy, by measurement of cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) levels as a marker of astrocyte damage.

Methods
Seventeen participants who (1) satisfied the 2015 diagnostic criteria for NMOSD, and (2) tested negative for AQP4 and MOG antibodies confirmed with repeated cell-based assays, and (3) had available CSF samples obtained at the point of clinical attacks, were enrolled from 4 medical centers (South Korea, Germany, Thailand, and Denmark). Thirty age-matched participants with AQP4–NMOSD, 17 participants with MOG antibody associated disease (MOGAD), and 15 participants with other neurological disorders (OND) were included as controls. The concentration of CSF GFAP was measured using enzyme-linked immunosorbent assay.

Results
CSF GFAP levels in the DN-NMOSD group were significantly lower than those in the AQP4–NMOSD group (median: 0.49 versus 102.9 ng/mL; p < 0.001), but similar to those in the OND (0.25 ng/mL) and MOGAD (0.39 ng/mL) control groups. The majority (90% (27/30)) of participants in the AQP4–NMOSD group showed significantly higher CSF GFAP levels than the highest level measured in the OND group, while no participant in the DN-NMOSD and MOGAD groups did.

Conclusions
These results suggest that DN-NMOSD has a different underlying pathogenesis other than astrocytopathy, distinct from AQP4–NMOSD.
Role of lipocalin-2 in surgery-induced cognitive decline in mice: a signal from neuron to microglia
Authors: Xiang Xuwu , Tang Xiaodong , Yu Yang , Xie Shulan , Liu Lu , Chen ManLi , Zhang Rong , Kang Xianhui , Zheng Yueying , Yang Guang , Gan Shuyuan , Zhu Shengmei 
Published: April 2022

Abstract
Background
Perioperative neurocognitive disorders (PNDs) are common complications observed among surgical patients. Accumulating evidence suggests that neuroinflammation is one of the major contributors to the development of PNDs, but the underlying mechanisms remain unclear.

Methods
qPCR and ELISA analysis were used for detecting LCN2 and cytokine levels. cx3cr1CreER/−:: R26iDTR/− crossed mouse line was used for microglia depletion; intracranial injection of recombinant LCN2 (rLCN2) and adeno-associated viruses (AAV)-mediated shRNA silencing approaches were used for gain and loss of function, respectively. Combing with in vitro microglia cell culture, we have studied the role of LCN2 in surgery-induced cognitive decline in mice.

Results
We revealed that Lcn2 mRNA and protein levels were greatly increased in mouse hippocampal neurons after surgery. This surgery-induced elevation of LCN2 was independent of the presence of microglia. Gain of function by intracranial injection of rLCN2 protein into hippocampus disrupted fear memory in naive mice without surgery. Conversely, silencing LCN2 in hippocampus by AAV-shRNA protected mice from surgery-induced microglia morphological changes, neuroinflammation and cognitive decline. In vitro, application of rLCN2 protein induced the expression of several pro-inflammatory cytokines in both BV-2 and primary microglia culture.

Conclusions
These data suggest LCN2 acts as a signal from neuron to induce proinflammatory microglia, which contributes to surgery-induced neuroinflammation and cognitive decline in mice.
Barriers to sexual and reproductive care among cisgender, heterosexual and LGBTQIA + adolescents in the border region: provider and adolescent perspectives
Authors: Hubach Randolph D. , Zipfel Rebecca , Muñoz Fatima A. , Brongiel Ilana , Narvarte Annabella , Servin Argentina E. 
Published: April 2022

Abstract
Introduction
The United States (U.S.) has higher rates of sexually transmitted infections (STIs) and adolescent pregnancy than most other industrialized countries. Furthermore, health disparities persist among racial and ethnic minority adolescents (e.g., African American and Latinx) and in counties located along the U.S.–Mexico border region—they demonstrate the highest rates of STIs and unintended pregnancy among adolescents.

Methods
Qualitative data were collected as part of formative research for the development of a mobile app that provides gender-inclusive sexual education to adolescents living in the U.S.—Mexico border region. From August 2019 to March 2020, the study team conducted 11 in-depth interviews with healthcare providers and three focus groups with cisgender, heterosexual, and SGM adolescents ages 15–18 (n = 20).

Results
Providers and adolescents reported similar barriers to accessing SRH in this region such as transportation, lack of insurance and cost of services or accessing services without their parent’s knowledge. However, providers shared that some adolescents in this region face extreme poverty, family separation (i.e., parent has been deported), have a mixed family legal status or are binational and have to travel every day from Mexico to the U.S. for school. These challenges further limit their ability to access SRH.

Conclusions
Adolescents in the U.S.-Mexico border region face unique economic and social challenges that further limit their access to SRH care, making them uniquely vulnerable to STIs and unintended pregnancy. The prototype of the app was developed based on the needs expressed by providers and adolescents, including providing comprehensive Sex Ed and mapping of free comprehensive and confidencial SRH services available in the region and is being pilot tested. Our findings provide further evidence for the need for interventions and service delivery, programs tailored for residents in the border region.
Increased expression of TIGIT and KLRG1 correlates with impaired CD56bright NK cell immunity in HPV16-related cervical intraepithelial neoplasia
Authors: Nie You , Liu Dandan , Yang Wen , Li Yazhuo , Zhang Lihua , Cheng Xia , Chen Ruyu , Yuan Bingbing , Zhang Guangzheng , Wang Hongwei 
Published: April 2022

Abstract
Background
The onset and progression of cervical intraepithelial neoplasia (CIN) are closely associated with the persistent infection of high-risk HPV (especially type16), which is mainly caused by immune escape. Natural killer (NK) cells play an important role against virally infected cells and tumor cells through a fine balance of signals from multiple surface receptors. Overexpression of non-MHC-I specific inhibitory receptors TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a on NK cells correlates with cellular exhaustion and immune evasion, but these receptors have not been investigated in CIN. The aim of the present study was to examine the potential role of NK cell non-MHC-I specific inhibitory receptors expression in immune escape from HPV16(+)CIN patients.

Methods
The subset distribution, IFN-γ and TNF-α expression levels and immunophenotype of TIGIT, KLRG1, Siglec-7, LAIR-1, and CD300a of NK cells were investigated in peripheral blood mononuclear cell samples by flow cytometry from 82 women who were HPV16(+) with CIN grades 0, I, II–III or HPV(−) CIN 0. Immunohistochemistry was applied to detect the expression of ligands for NK receptors in the cervical tissues. HPV types were identified by PCR assays.

Results
The HPV16(+) subjects with high-grade lesions had an increased number of circulating peripheral blood CD56bright NK cells with reduced functionality and IFN-γ secretion. The expression levels of the inhibitory molecules TIGIT and KLRG1 on CD56bright NK cells increased in parallel with increasing CIN grade. In addition, TIGIT and KLRG1 related ligands, Poliovirus receptor (PVR), N-Cadherin and E-Cadherin expression level was also elevated with increasing CIN grade.

Conclusions
Our results suggest that up-regulation of the inhibitory TIGIT, KLRG1 and their ligands may negatively regulate cervical CD56bright NK-mediated immunity to HPV16 and contribute to the progression of CIN. These results may facilitate the development of early-warning immune predictors and therapeutic strategies for HPV16(+) CIN based on the TIGIT and KLRG1 inhibitory pathways of NK cells.
Three-dimensional assessment of the favorability of maxillary posterior teeth intrusion in different skeletal classes limited by the vertical relationship with the maxillary sinus floor
Authors: Abdulghani Ehab A. , Al-Sosowa Abeer A. , Alhammadi Maged Sultan , Al-fakeh Hanan , Al-Gumaei Waseem Saleh , Almashraqi Abeer A. , Sharhan Hasan M. , Cao BaoCheng 
Published: April 2022

Abstract
Background
Understanding the anatomical relationship between the maxillary sinus floor (MSF) and the posterior maxillary teeth (PMT) is important when planning the orthodontic intrusion of the posterior teeth. This study aimed to determine the vertical relationship between posterior maxillary teeth and maxillary sinus floor in different skeletal classes in the Chinese adult population.

Methods
This is a retrospective cross-sectional study involved cone beam computed tomography images of 298 adult patients (145 males and 153 females) between 20 and 45 years old. The sample was categorized according to A point, Nasion, B point (ANB) angle into 102 Class I, 102 Class II, and 94 Class III malocclusion. Non-parametric Wilcoxon Mann–Whitney U and Kruskal–Wallis tests were used to compare the studied groups. The Intra-class Correlation Coefficient (ICC) was used to assess the intra- and inter-observer reliability analysis.

Results
Overall, there was a statistically significant difference in the mean distance between both genders (P < 0.001). The measured distance increased with age in all posterior tooth roots (P < 0.001). The root apex in the sagittal view appeared to be closer to the maxillary sinus than in the coronal view; 2.2 ± 4.3 and 3.1 ± 5.5 mm, respectively. The most frequent root scores were Type 1 and Type 2P. In both sagittal and coronal views, Class I demonstrated a higher Type 2P prevalence, whereas Class III showed a lower prevalence. The second molars’ mesiobuccal root had the largest number of penetration in the three examined skeletal classes.

Conclusions
Maxillary molars of Class I malocclusion with the majority of Type 2P root-sinus relationship have the highest possible risk of root resorption during molar intrusion due to cortical bone encroachment, while Class III malocclusion showed the least possible risk.
The influence of ossification morphology on surgery outcomes in patients with thoracic ossification of ligamentum flavum (TOLF)
Authors: Du Peiyu , Ma Lei , Ding Wenyuan 
Published: April 2022

Abstract
Background
To determine whether there is a correlation between the type of ossification and radiological parameters, modified thoracic JOA scores, and complications in patients with thoracic ossification of ligamentum flavum treated by posterior thoracic surgery.

Methods
This retrospective cohort study included 48 patients with thoracic myelopathy caused by single-level thoracic ossification of ligamentum flavum who underwent thoracic posterior approach surgery in our Hospital o between December 2013 to December 2018. Patients were divided into unilateral, bilateral, and bridged groups in axial position, and beak and round groups in sagittal position. The differences were analyzed according to the ossification morphology.

Results
In axial myelopathy, there was no significant difference in preop and postop JOA scores and RR among the three groups in axial position (P = 0.884). In sagittal view, there was no significant difference in preoperative JOA score between the two groups (P = 0.710), while the postop JOA score and the recovery rate in the beak group were significantly lower than that of the round group (P = 0.010, P = 0.034). Two-way ANOVA showed that sagittal morphology had a significant effect on postop JOA score (P = 0.028), but axial morphology don’t (P = 0.431); there was no interaction between them (P = 0.444). For the recovery rate, sagittal morphology also had a significant effect (P = 0.043), but axial ossification don’t (P = 0.998); there was no interaction between them (P = 0.479).

Conclusion
Sagittal morphology had a significant adverse effect on postop JOA score and surgical outcome, while axial morphology had no effect on surgical outcome, and there was no interaction between sagittal morphology and axial morphology.
Electroacupuncture vs topical diclofenac sodium gel for patients with hand osteoarthritis: study protocol for a randomized controlled trial
Authors: Wang Weiming , Yu Shudan , Long Zilin , Liu Yan , Yan Yan , Sun Tianheng , Liu Zhishun 
Published: April 2022

Abstract
Background
Hand osteoarthritis (OA) is a prevalent joint disorder and a great burden to both patients and society. While electroacupuncture (EA) and topical diclofenac sodium gel (DSG) are both currently used to treat OA, no head-to-head study of EA and topical DSG for hand OA exists. Thus, it remains unknown whether one intervention offers improved outcomes over the other. This study aims to compare the effects of EA and topical DSG in patients with hand OA.

Methods
A total of 108 participants with hand OA according to the American College of Rheumatology criteria will be recruited and randomly assigned to the EA group or topical DSG group with a 1:1 allocation ratio. Participants in the EA group will receive EA treatment thrice weekly for 4 weeks, followed by a 12-week follow-up. In the topical DSG group, topical DSG at a dose of 2 g over the affected joints per hand will be applied four times per day for 4 weeks. The outcomes will be measured at weeks 4, 8, and 16. The primary outcome will be the change in average overall finger joint pain intensity in the dominant hand from baseline to week 4. All outcome variables will be analyzed on an intention-to-treat principle. All statistical tests will be two-sided.

Discussion
This study will help determine which of the two treatment protocols, EA or topical DSG, is more effective for the clinical treatment of hand OA.
Trial registration ClinicalTrials.gov identifier: NCT04402047. Registered 16 May 2020, https://clinicaltrials.gov/ct2/show/NCT04402047
Successful cases of percutaneous left ventricular assist device “Impella” to fulminant myocarditis
Authors: Hori Takayuki , Iida Mitsuru , Uchiyama Masateru , Shimokawa Tomoki 
Published: April 2022

Abstract
Background
Fulminant myocarditis (FM) is a form of severe inflammatory carditis with rapidly developing acute heart failure.

Case presentation
We report three cases of successful intensive treatment by Impella of FM without any complications. In all cases, impairment of microcirculation as measured by blood lactate level and the hemodynamic value as indicated by cardiac index were improved within 24–48 h and 7 days after Impella implantation, respectively. Interestingly, our data also suggested that treatment by Impella CP or 5.0 may lead to faster recovery of microcirculation and cardiac function than treatment by Impella 2.5.

Conclusion
Our findings demonstrate that the appropriate selection of Impella devices guided by body surface area measurements may help to improve clinical outcomes of severe heart failure including FM.
A rare case of right upper lung cancer with azygos lobe and partial anomalous pulmonary venous return
Authors: Su Xiaoyang , Huang Qianzhun , Luo Zhiqiang , Fang Ning , Huang Jian 
Published: April 2022

Abstract
Background
The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer.

Case presentation
We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVR, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein.

Conclusions
AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction is more conducive to the correct performing of this type of surgery.
VCP suppresses proteopathic seeding in neurons
Authors: Zhu Jiang , Pittman Sara , Dhavale Dhruva , French Rachel , Patterson Jessica N. , Kaleelurrrahuman Mohamed Salman , Sun Yuanzi , Vaquer-Alicea Jaime , Maggiore Gianna , Clemen Christoph S. , Buscher William J. , Bieschke Jan , Kotzbauer Paul , Ayala Yuna , Diamond Marc I. , Davis Albert A. , Weihl Conrad 
Published: April 2022

Abstract
Background
Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem proteinopathy (MSP) is associated with dominant mutations in Valosin Containing Protein (VCP). MSP patients have muscle and neuronal degeneration characterized by aggregate pathology that can include αS, Tau and TDP-43.

Methods
We performed a fluorescent cell sorting based genome-wide CRISPR-Cas9 screen in αS biosensors. αS and TDP-43 seeding activity under varied conditions was assessed using FRET/Flow biosensor cells or immunofluorescence for phosphorylated αS or TDP-43 in primary cultured neurons. We analyzed in vivo seeding activity by immunostaining for phosphorylated αS following intrastriatal injection of αS seeds in control or VCP disease mutation carrying mice.

Results
One hundred fifty-four genes were identified as suppressors of αS seeding. One suppressor, VCP when chemically or genetically inhibited increased αS seeding in cells and neurons. This was not due to an increase in αS uptake or αS protein levels. MSP-VCP mutation expression increased αS seeding in cells and neurons. Intrastriatal injection of αS preformed fibrils (PFF) into VCP-MSP mutation carrying mice increased phospho αS expression as compared to control mice. Cells stably expressing fluorescently tagged TDP-43 C-terminal fragment FRET pairs (TDP-43 biosensors) generate FRET when seeded with TDP-43 PFF but not monomeric TDP-43. VCP inhibition or MSP-VCP mutant expression increases TDP-43 seeding in TDP-43 biosensors. Similarly, treatment of neurons with TDP-43 PFFs generates high molecular weight insoluble phosphorylated TDP-43 after 5 days. This TDP-43 seed dependent increase in phosphorlyated TDP-43 is further augmented in MSP-VCP mutant expressing neurons.

Conclusion
Using an unbiased screen, we identified the multifunctional AAA ATPase VCP as a suppressor of αS and TDP-43 aggregate seeding in cells and neurons. VCP facilitates the clearance of damaged lysosomes via lysophagy. We propose that VCP’s surveillance of permeabilized endosomes may protect against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP.