bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in the study of exosomes derived from mesenchymal stem cells and cardiac cells for the treatment of myocardial infarction
Authors: Liu Yuchang , Wang Minrui , Yu Yang , Li Chunhong , Zhang Chunxiang 
Published: August 2023

AbstractAcute myocardial infarction has long been the leading cause of death in coronary heart disease, which is characterized by irreversible cardiomyocyte death and restricted blood supply. Conventional reperfusion therapy can further aggravate myocardial injury. Stem cell therapy, especially with mesenchymal stem cells (MSCs), has emerged as a promising approach to promote cardiac repair and improve cardiac function. MSCs may induce these effects by secreting exosomes containing therapeutically active RNA, proteins and lipids. Notably, normal cardiac function depends on intracardiac paracrine signaling via exosomes, and exosomes secreted by cardiac cells can partially reflect changes in the heart during disease, so analyzing these vesicles may provide valuable insights into the pathology of myocardial infarction as well as guide the development of new treatments. The present review examines how exosomes produced by MSCs and cardiac cells may influence injury after myocardial infarction and serve as therapies against such injury.Graphical Abstract
TNFSF14/LIGHT promotes cardiac fibrosis and atrial fibrillation vulnerability via PI3Kγ/SGK1 pathway-dependent M2 macrophage polarisation
Authors: Wu Yirong , Zhan Siyao , Chen Lian , Sun Mingrui , Li Miaofu , Mou Xuanting , Zhang Zhen , Xu Linhao , Xu Yizhou 
Published: August 2023

Abstract
Background
Tumour necrosis factor superfamily protein 14 (TNFSF14), also called LIGHT, is an important regulator of immunological and fibrosis diseases. However, its specific involvement in cardiac fibrosis and atrial fibrillation (AF) has not been fully elucidated. The objective of this study is to examine the influence of LIGHT on the development of myocardial fibrosis and AF.

Methods
PCR arrays of peripheral blood mononuclear cells (PBMCs) from patients with AF and sinus rhythm was used to identify the dominant differentially expressed genes, followed by ELISA to evaluate its serum protein levels. Morphological, functional, and electrophysiological changes in the heart were detected in vivo after the tail intravenous injection of recombinant LIGHT (rLIGHT) in mice for 4 weeks. rLIGHT was used to stimulate bone marrow-derived macrophages (BMDMs) to prepare a macrophage-conditioned medium (MCM) in vitro. Then, the MCM was used to culture mouse cardiac fibroblasts (CFs). The expression of relevant proteins and genes was determined using qRT-PCR, western blotting, and immunostaining.

Results
The mRNA levels of LIGHT and TNFRSF14 were higher in the PBMCs of patients with AF than in those of the healthy controls. Additionally, the serum protein levels of LIGHT were higher in patients with AF than those in the healthy controls and were correlated with left atrial reverse remodelling. Furthermore, we demonstrated that rLIGHT injection promoted macrophage infiltration and M2 polarisation in the heart, in addition to promoting atrial fibrosis and AF inducibility in vivo, as detected with MASSON staining and atrial burst pacing respectively. RNA sequencing of heart samples revealed that the PI3Kγ/SGK1 pathway may participate in these pathological processes. Therefore, we confirmed the hypothesis that rLIGHT promotes BMDM M2 polarisation and TGB-β1 secretion, and that this process can be inhibited by PI3Kγ and SGK1 inhibitors in vitro. Meanwhile, increased collagen synthesis and myofibroblast transition were observed in LIGHT-stimulated MCM-cultured CFs and were ameliorated in the groups treated with PI3Kγ and SGK1 inhibitors.

Conclusion
LIGHT protein levels in peripheral blood can be used as a prognostic marker for AF and to evaluate its severity. LIGHT promotes cardiac fibrosis and AF inducibility by promoting macrophage M2 polarisation, wherein PI3Kγ and SGK1 activation is indispensable.
A novel PRKDC mutation caused B lymphocytes V(D)J rearrangement disorder in the SLE-DAH like symptoms patient
Authors: Li Hongwei , Zhang Yawen , Zhang Biyun , Chen Dehui 
Published: August 2023

Abstract
Background
Analyzed the clinical features and treatment process of the patient suffering from immunodeficiency with systemic lupus erythematosus(SLE)-like syndrome in a novel mutation of PRKDC.

Case presentation
The patient had multiple positive auto-antibodies, chest CT and bronchoscopy showed Diffuse alveolar hemorrhage(DAH), and psychiatric symptoms showed brain atrophy by magnetic resonance imaging (MRI). Whole exon sequencing showed that novel complex heterozygous mutations of PRKDC gene (C. 1777 − 710_1777-709INSA (IVS16/IC16), C.1337T > A(p.Phe446Tyr). The mature B cell (CD19 + CD27 + CD38 dimIgD IgM-) were absent. The treatment of high-dose methylprednisolone (MP) and cyclophosphamide(CTX) can quickly relieve the symptoms of the patient.

Conclusion
We described the case of an infant immunodeficiency with SLE like-syndrome, which may cause by PRKDC mutation, treated successfully with high-dose MP and CTX.
Impairments of the ipsilesional upper-extremity in the first 6-months post-stroke
Authors: Smith Donovan B. , Scott Stephen H. , Semrau Jennifer A. , Dukelow Sean P. 
Published: August 2023

Abstract
Background
Ipsilesional motor impairments of the arm are common after stroke. Previous studies have suggested that severity of contralesional arm impairment and/or hemisphere of lesion may predict the severity of ipsilesional arm impairments. Historically, these impairments have been assessed using clinical scales, which are less sensitive than robot-based measures of sensorimotor performance. Therefore, the objective of this study was to characterize progression of ipsilesional arm motor impairments using a robot-based assessment of motor function over the first 6-months post-stroke and quantify their relationship to (1) contralesional arm impairment severity and (2) stroke-lesioned hemisphere.

Methods
A total of 106 participants with first-time, unilateral stroke completed a unilateral assessment of arm motor impairment (visually guided reaching task) using the Kinarm Exoskeleton. Participants completed the assessment along with a battery of clinical measures with both ipsilesional and contralesional arms at 1-, 6-, 12-, and 26-weeks post-stroke.

Results
Robotic assessment of arm motor function revealed a higher incidence of ipsilesional arm impairment than clinical measures immediately post-stroke. The incidence of ipsilesional arm impairments decreased from 47 to 14% across the study period. Kolmogorov–Smirnov tests revealed that ipsilesional arm impairment severity, as measured by our task, was not related to which hemisphere was lesioned. The severity of ipsilesional arm impairments was variable but displayed moderate significant relationships to contralesional arm impairment severity with some robot-based parameters.

Conclusions
Ipsilesional arm impairments were variable. They displayed relationships of varying strength with contralesional impairments and were not well predicted by lesioned hemisphere. With standard clinical care, 86% of ipsilesional impairments recovered by 6-months post-stroke.
Role of the protease-activated receptor-2 (PAR2) in the exacerbation of house dust mite-induced murine allergic lung disease by multi-walled carbon nanotubes
Authors: Lee Ho Young , You Dorothy J. , Taylor-Just Alexia , Tisch Logan J. , Bartone Ryan D. , Atkins Hannah M. , Ralph Lauren M. , Antoniak Silvio , Bonner James C. 
Published: August 2023

Abstract
Background
Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) has been reported to exert strong pro-inflammatory and pro-fibrotic adjuvant effects in mouse models of allergic lung disease. However, the molecular mechanisms through which MWCNTs exacerbate allergen-induced lung disease remain to be elucidated. We hypothesized that protease-activated receptor 2 (PAR2), a G-protein coupled receptor previously implicated in the pathogenesis of various diseases including pulmonary fibrosis and asthma, may play an important role in the exacerbation of house dust mite (HDM) allergen-induced lung disease by MWCNTs.

Methods
Wildtype (WT) male C57BL6 mice and Par2 KO mice were exposed to vehicle, MWCNTs, HDM extract, or both via oropharyngeal aspiration 6 times over a period of 3 weeks and were sacrificed 3-days after the final exposure (day 22). Bronchoalveolar lavage fluid (BALF) was harvested to measure changes in inflammatory cells, total protein, and lactate dehydrogenase (LDH). Lung protein and RNA were assayed for pro-inflammatory or profibrotic mediators, and formalin-fixed lung sections were evaluated for histopathology.

Results
In both WT and Par2 KO mice, co-exposure to MWCNTs synergistically increased lung inflammation assessed by histopathology, and increased BALF cellularity, primarily eosinophils, as well as BALF total protein and LDH in the presence of relatively low doses of HDM extract that alone produced little, if any, lung inflammation. In addition, both WT and par2 KO mice displayed a similar increase in lung Cc1-11 mRNA, which encodes the eosinophil chemokine CCL-11, after co-exposure to MWCNTs and HDM extract. However, Par2 KO mice displayed significantly less airway fibrosis as determined by quantitative morphometry compared to WT mice after co-exposure to MWCNTs and HDM extract. Accordingly, at both protein and mRNA levels, the pro-fibrotic mediator arginase 1 (ARG-1), was downregulated in Par2 KO mice exposed to MWCNTs and HDM. In contrast, phosphorylation of the pro-inflammatory transcription factor NF-κB and the pro-inflammatory cytokine CXCL-1 was increased in Par2 KO mice exposed to MWCNTs and HDM.

Conclusions
Our study indicates that PAR2 mediates airway fibrosis but not eosinophilic lung inflammation induced by co-exposure to MWCNTs and HDM allergens.
Adverse childhood experiences and trauma informed care for chiropractors: a call to awareness and action
Authors: Baca Kira J. , Salsbury Stacie A. 
Published: August 2023

Abstract
Background
Trauma is an emotional response to distressing events where coping and subsequent recovery are absent. Adverse Childhood Experiences (ACEs) are traumas, occurring before the age of 18 years, such as child abuse or neglect, caregiver instability, and household dysfunction. Sixty-four percent of the U.S. population report experiencing at least one ACE, with over 1 billion children experiencing abuse and neglect annually worldwide. Chronic exposure to stressful circumstances or multiple traumatic events has negative physiologic impacts. Persons who experience 3 or more ACEs in childhood are at greater risk of poor mental health outcomes and may be more likely to engage in high-risk behaviors, predisposing them to long-term health impacts, such as metabolic diseases, anxiety, depression, substance use, and chronic pain. Trauma informed care (TIC) is a recommended approach to healthcare delivery across professions, especially when a trauma history is suspected. This commentary aims to increase awareness of the impact of ACEs on health outcomes and introduce TIC concepts as they may apply to chiropractic care for adults with a history of ACEs.

Discussion
This commentary reviews an introductory model (4R's: realize, recognize, respond, resist re-traumatization) as one TIC framework used by healthcare practitioners. Prior trauma can lessen trust, alter perceptions of physical touch, and hands-on examinations and chiropractic treatments may trigger stress responses. Using TIC after appropriate training, includes referrals to multidisciplinary providers to address trauma-related concerns outside the scope of chiropractic, and screening for ACEs if deemed appropriate. Creating safe spaces, communicating clearly, avoiding victimizing language, explaining procedures, asking for consent before physical contact, and giving patients choice and control in their own care may avoid triggering prior traumas.

Conclusion
Given the high worldwide prevalence of persons experiencing 3 or more ACEs, TIC principles are practical adaptations to chiropractic care for use with many patient populations. As TIC and ACEs are emerging concepts within chiropractic, students and practitioners are encouraged to undertake additional training to better understand these complex and sensitive topics. Exploratory research on the incidence, presentation, and impacts of various trauma types, including ACEs, to support adoption of TIC in chiropractic settings is essential.
Impact of a double catastrophe, war and COVID-19, on health service utilization of a tertiary care hospital in Tigray: an interrupted time-series study
Authors: Abraha Hiluf Ebuy , Tequare Mengistu Hagazi , Teka Hale , Gebremedhin Micheal Berhe , Desta Kibrom Gebreselassie , Ebrahim Mohamedawel Mohamedniguss , Yemane Awol , Gebremariam Sintayehu Misgina , Gebresilassie Kibrom Berhanu , Tekle Tesfay Hailu , Atsbaha Mussie Tesfay , Berhe Ephrem , Berhe Bereket , Berhe Derbew Fikadu , Gebregziabher Mulugeta , Wall L. Lewis 
Published: August 2023

Abstract
Background
In developing nations with fragile healthcare systems, the effect of war is likely to be much worse than it would be in more developed countries. The presence of COVID-19 will also likely exacerbate the war’s impact. This study set out to determine the effect of armed conflict and the COVID-19 pandemic on health service utilization at Ayder Comprehensive Specialized Hospital, in the Tigray region of Ethiopia.

Methods
An interrupted time-series study design was used to analyze patient visits over forty-eight consecutive months (from July 2017 to June 2021) at inpatient, outpatient, and emergency departments. Data were analyzed using segmented regression analysis with a defined outcome of level and trend changes in the number of patient visits. In addition, negative binomial regression analysis was also used to estimate the impact of both COVID-19 and the war on patient flow.

Results
There were 59,935 admissions, 876,533 outpatient visits, and 127,872 emergency room visits. The effect of COVID-19 was seen as soon as the Tigray regional government imposed comprehensive restrictions. Immediately after COVID-19 appeared, all the service areas exhibited a significant monthly drop in visits; [-35.6% (95% CI: -48.2%, -23.1%)] for inpatient, [-60.6% (95% CI: -71.6%, -49.5%)] for outpatient, and [-44.1% (95% CI: -59.5%, -28.7%)] for emergency department visits. The impact of the war became apparent after a lag time of one month. Controlling the effects of time and COVID-19, the war led to a significant fall in inpatient visits [-44.3% (95% CI: -67.2%, -21.5%)], outpatients [-52.1% (95% CI: -82.7%, -21.5%)], and emergency-room attendances [-45.0% (95% CI: -74.8%, -15.2%)]. An upward trend in outpatient flow was observed after the war [1,219.4 (95% CI: 326.1, 2,112.8)].

Conclusions
The present study has clearly indicated that the war and COVID-19 have led to a large reduction in admissions, outpatient attendance, and emergency department visits. The evidence from this study suggests that due to this double catastrophe, thousands of patients could not gain access to healthcare, with probable negative consequences. Governments and organizations should implement measures to buttress the healthcare system to maintain pre-war status of service.
Challenges in the care of patients with RET-altered thyroid cancer: a multicountry mixed-methods study
Authors: Murray Suzanne , Subbiah Vivek , Sherman Steven I. , Péloquin Sophie , Sireci Anthony , Grohé Christian , Bubach Patrick , Lazure Patrice 
Published: August 2023

Abstract
Background
The discovery of driver oncogenes for thyroid carcinomas and the identification of genomically targeted therapies to inhibit those oncogenes have altered the treatment algorithm in thyroid cancer (TC), while germline testing for RET mutations has become indicated for patients with a family history of RET gene mutations or hereditary medullary TC (MTC). In the context of an increasing number of selective RET inhibitors approved for use, this paper aims to describe challenges and barriers affecting providers’ ability to deliver optimal care for patients with RET-altered TC across the patient healthcare journey.

Methods
A mixed-method educational and behavioral needs assessment was conducted in Germany (GER), Japan (JPN), the United Kingdom (UK), and the United States (US) prior to RET-selective inhibitor approval. Participants included medical oncologists (MO), endocrinologists (EN) and clinical pathologists (CP) caring for patients affected with TC. Data collection tools were implemented in three languages (English, German, Japanese). Qualitative data were coded and thematically analyzed in NVivo. Quantitative data were analyzed via frequency and crosstabulations in SPSS. The findings presented here were part of a broader study that also investigated lung cancer challenges and included pulmonologists.

Results
A total of 44 interviews and 378 surveys were completed. Suboptimal knowledge and skills were self-identified among providers, affecting (1) assessment of genetic risk factors (56%, 159/285 of MOs and ENs), (2) selection of appropriate genetic biomarkers (59%, 53/90 of CPs), (3) treatment plan initiation (65%, 173/275 of MOs and ENs), (4) management of side effects associated with multitargeted tyrosine kinase inhibitors (78%, 116/149 of MOs and ENs), and (5) transfer of patients into palliative care services (58%, 160/274 of MOs and ENs). Interviews underscored the presence of systemic barriers affecting the use of RET molecular tests and selective inhibitors, in addition to suboptimal knowledge and skills necessary to manage the safety and efficacy of targeted therapies.

Conclusion
This study describes concrete educational needs for providers involved in the care of patients with RET-altered thyroid carcinomas. Findings can be used to inform the design of evidence-based education and performance improvement interventions in the field and support integration into practice of newly approved RET-selective inhibitors.
Circulating 27-hydroxycholesterol, lipids, and steroid hormones in breast cancer risk: a nested case–control study of the Multiethnic Cohort Study
Authors: DeRouen Mindy C. , Yang Juan , Li Yuqing , Franke Adrian A. , Tome Anne N. , White Kami K. , Hernandez Brenda Y. , Shvetsov Yurii , Setiawan Veronica , Wu Anna H. , Wilkens Lynne R. , Le Marchand Loïc , Loo Lenora W. M. , Cheng Iona 
Published: August 2023

Abstract
Background
Laboratory studies have indicated that a cholesterol metabolite and selective estrogen receptor modulator, 27-hydroxycholesterol (27HC), may be important in breast cancer etiology and explain associations between obesity and postmenopausal breast cancer risk. Epidemiologic evidence for 27HC in breast cancer risk is limited, particularly in multiethnic populations.

Methods
In a nested case–control study of 1470 breast cancer cases and 1470 matched controls within the Multiethnic Cohort Study, we examined associations of pre-diagnostic circulating 27HC with breast cancer risk among African American, Japanese American, Native Hawaiian, Latino, and non-Latino White postmenopausal females. We used multivariable logistic regression adjusted for age, education, parity, body mass index, and smoking status. Stratified analyses were conducted across racial and ethnic groups, hormone receptor (HR) status, and use of lipid-lowering drugs. We assessed interactions of 27HC with steroid hormones.

Results
27HC levels were inversely related to breast cancer risk (odds ratio [OR] 0.80; 95% confidence interval [CI] 0.58, 1.12), but the association was not statistically significant in the full model. Directions of associations differed by racial and ethnic group. Results suggested an inverse association with HR-negative breast cancer (OR 0.46; 95% CI 0.20, 1.06). 27HC interacted with testosterone, but not estrone, on risk of breast cancer; 27HC was only inversely associated with risk among those with the highest levels of testosterone (OR 0.46; 95% CI 0.24, 0.86).

Conclusion
This is the first US study to examine circulating 27HC and breast cancer risk and reports a weak inverse association that varies across racial and ethnic groups and testosterone level.
SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models
Authors: Zhou Feng , Yang Guimei , Xue Liting , Liu Yajing , Guo Yao , Zhu Ji , Yuan Linlin , Gu Peng , Tang Feng , Shan Jinwen , Tang Renhong 
Published: August 2023

Abstract
Background
Targeted estrogen receptor degradation has been approved to effectively treat ER + breast cancers. Due to the poor bioavailability of fulvestrant, the first generation of SERD, many efforts were made to develop oral SERDs. With the approval of Elacestrant, oral SERDs demonstrated superior efficacy than fulvestrant. However, due to the poor ability of known SERDs to penetrate the blood–brain barrier (BBB), breast cancer patients with brain metastasis cannot benefit from clinical SERDs.

Methods
The ER inhibitory effects were evaluated on ERα protein degradation, and target genes downregulation. And anti-proliferation activities were further determined in a panel of ER + breast cancer cell lines. The subcutaneous and intracranial ER + tumor models were used to evaluate the efficacy of anti-tumor effects. Brain penetrability was determined in multiple animal species.

Results
SCR-6852 is a novel SERD and currently is under early clinical evaluation. In vitro studies demonstrated that it strongly induced both wildtype and mutant ERα degradation. It potently inhibited cell proliferation in a panel of ER + breast cancer cell lines, including the cell lines containing ESR1 mutations (Y537 and D538). Furthermore, SCR-6852 exhibited pure antagonistic activities on the ERɑ signal axis identified both in vitro and in vivo. Oral administration of SCR-6852 at 10 mg/kg resulted in tumor shrinkage which was superior to Fulvestrant at 250 mg/kg, notably, in the intracranial tumor model, SCR-6852 effectively inhibited tumor growth and significantly prolonged mice survival, which correlated well with the high exposure in brains. In addition to mice, SCR-6852 also exhibited high brain penetrability in rats and dogs.

Conclusions
SCR-6852 is a novel SERD with high potency in inducing ERα protein degradation and pure antagonistic activity on ERɑ signaling in vitro and in vivo. Due to the high brain penetrability, SCR-6852 could be used to treat breast patients with brain metastasis.