bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3K4 Methyltransferase Smyd3 Mediates Vascular Smooth Muscle Cell Proliferation, Migration, and Neointima Formation
Authors: Yang Di , Su Zhenghua , Wei Gang , Long Fen , Zhu Yi-Chun , Ni Ting , Liu Xinhua , Zhu Yi Zhun 
Published: April 2021

Objective:
Smyd3 (SET and MYND domain-containing protein 3) is an H3K4 (histone H3 lysine 4) dimethyltransferase and trimethyltransferase that activates the transcription of oncogenes and cell cycle genes in human cancer cells. We discovered its overexpression in proliferative vascular smooth muscle cells (VSMCs). However, whether Smyd3 plays a role in vascular remodeling remains unanswered. The objective of this study is to investigate the role and underlying mechanism of Smyd3 in phenotypic transition of VSMCs (such as proliferation and migration) and vascular remodeling (such as neointima formation).

Approach and Results:
We discovered upregulation of Smyd3 in both PDGF (platelet-derived growth factor) BB–induced vascular cell proliferation model and balloon injury–induced neointima formation model. Knockdown of Smyd3 or blockade of its enzymatic activity suppressed VSMCs proliferation and migration ability, whereas Smyd3 overexpression promoted VSMC migration and proliferation. Mechanistically, RNA-seq and ChIP-seq analysis revealed Smyd3 promoted neointimal formation by directly binding and increasing H3K4me3 to the promoter regions of target genes that are associated with cell proliferation and migration, cell cycle control. Furthermore, Smyd3 knockout mice profoundly ameliorated carotid artery ligation–induced neointimal hyperplasia, consistently, local knocking down Smyd3 in rats relieved balloon injury–induced neointimal formation, while restored VSMC contractile protein expression, suggesting that Smyd3 plays a critical role in vivo.

Conclusions:
Our results demonstrate that Smyd3 promotes VSMC proliferation and migration during injury-induced vascular remodeling, which provide a potential therapeutic target for preventing neointimal hyperplasia in proliferative vascular diseases.
Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction
Authors: Kondreddy Vijay , Magisetty Jhansi , Keshava Shiva , Rao L. Vijaya Mohan , Pendurthi Usha R. 
Published: April 2021

Objective:
In response to inflammatory insult, endothelial cells express cell adhesion molecules and TF (tissue factor), leading to increased adhesion of leukocytes to the endothelium and activation of coagulation. Enhanced coagulation could further exacerbate inflammation. Identifying key signaling molecule(s) that drive both inflammation and coagulation may help devise effective therapeutic strategies to treat inflammatory and thrombotic disorders. The aim of the current study is to determine the role of Gab2 (Grb2-associated binder2), which is known to play a crucial role in the signaling evoked by growth factors and antigen receptors, in inflammatory signaling pathways and its contribution to vascular dysfunction.

Approach and Results:

WT (wild type) and Gab2-silenced endothelial cells were treated with TNFα (tumor necrosis factor alpha), IL (interleukin)-1β, or lipopolysaccharide (LPS). Activation of key signaling proteins in the inflammatory signaling pathways and expression of cell adhesion molecules, TF, and inflammatory cytokines were analyzed. Gab2
−/
−
and WT littermate mice were challenged with LPS or
S
pneumoniae (Streptococcus pneumoniae
), and parameters of inflammation and activation of coagulation were assessed. Gab2 silencing in endothelial cells markedly attenuated TNFα-induced, IL-1β–induced, and LPS-induced expression of TF, cell adhesion molecules, and inflammatory cytokines/chemokines. Gab2 silencing suppressed TNFα-induced, IL-1β–induced, and LPS-induced phosphorylation and ubiquitination of TAK1 (transforming growth factor beta-activated kinase 1) and activation of MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor kappa B). Immunoprecipitation studies revealed that the Src kinase Fyn phosphorylates Gab2. Gab2
−/−
mice are protected from LPS or
S
pneumoniae
–induced vascular permeability, neutrophil infiltration, thrombin generation, NET formation, cytokine production, and lung injury.

Conclusions:
Our studies identify, for the first time, that Gab2 integrates signaling from multiple inflammatory receptors and regulates vascular inflammation and thrombosis.
Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits
Authors: Vasconcellos Luiz Ricardo C. , Martimiano Letícia , Dantas Danillo Pereira , Fonseca Filipe Mota , Mata-Santos Hilton , Travassos Leonardo , Mendez-Otero Rosalia , Bozza Marcelo Torres , Pimentel-Coelho Pedro Moreno 
Published: April 2021

Background and Purpose:
Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model.

Methods:
Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls.

Results:

Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in
Nlrp3
knockout mice in comparison to wild-type mice.

Conclusions:
Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.
Prionotropis xausi, a new species of Thrinchinae (Orthoptera: Pamphagidae) from Catalonia (northeast of the Iberian Peninsula)
Authors: OLMO-VIDAL JOSEP MARIA 
Published: April 2021

A new species of the genus Prionotropis Fieber, 1853 is described from Catalonia (Northeast of the Iberian Peninsula). Prionotropis xausi n. sp. was collected in a steppic calcareous grassland with low shrubs and scattered rocks, dominated by Buxus, Arctostaphylos uva-ursi, Thymus and Poa species. P. xausi n. sp. is characterized by the pronotum in dorsal view narrow and in lateral view with the principal transverse sulcus between prozona and metazona clearly incised. Females squamipterous with the tegmina extending at most to the end of second abdominal segment. Males sub-brachypterous with the tegmina reaching the 5th abdominal tergite and the epiproct visible. Inside hind femora at the base to the middle part and inside hind tibia red. Phallic complex with the epiphallus more long than wide with short posterior edge and the penis valves long. This new species is compared to the similar species P. rhodanica Uvarov, 1923 , P. azami Uvarov, 1923 and P. hystrix (Germar, 1817) and to the species presents in Catalonia P. flexuosa (Serville, 1838) and P. ancosae Olmo-Vidal, 2017. P. xausi is the species of the genus Prionotropis with the smallest males.
A new species, genus and tribe of cicada (Hemiptera: Cicadoidea: Cicadidae: Tibicininae) from Chile with a list of Chilean cicada fauna
Authors: SANBORN ALLEN F. 
Published: April 2021

Citroriginini n. tribe. is formed for the Chilean cicada Citroriginis elongata n. gen., n. sp. Males differ from other South American Tibicininae Distant, 1905a because they lack timbal organs. The new species has fore wings that are similar in general appearance to the Nearctic Platypediini Kato, 1932 and genitalia with a superficial resemblance to the Tettigadini Distant, 1905c and the Chilean Chilecicadini Sanborn, 2014 but the new species is divergent from the both tribes in the fore wing venation, fore wing cell shape, general body proportions and male genitalia. A female exuvia is described representing the first description of a Chilean cicada exuvia. A list of Chilean cicada species is also provided with Calliopsida cinnabarina (Berg, 1879) removed from the Chilean cicada fauna.
Morbidity and Mortality in the Obese Trauma Intensive Care Unit Patient
Authors: Conrad Hope L. , Hutchinson Robert A. , Pittman Jessica , Ewing Joseph A. , Cull John D. 
Published: April 2021

Introduction Obesity is an epidemic in the United States, known to be associated with comorbidities. However, some data show that obesity may be a protective factor in some instances. The purpose of this study is to determine if there are differences in morbidity and mortality when comparing the obese and non-obese critically ill trauma patient populations. Materials and Methods This was a retrospective study conducted at Prisma Health Upstate in Greenville, South Carolina, an Adult Level 1 Trauma Center. Patients over the age of 18 years admitted due to trauma from February 6, 2016 to February 28, 2019 were included in this study. Burn patients were excluded. An online trauma database was used to obtain age, sex, body mass index, Glasgow coma score (GCS), injury severity score (ISS), revised trauma score (RTS), days on mechanical ventilation, hospital length of stay (LOS), and intensive care unit (ICU) LOS. Results There were 2365 critically ill trauma patients who met inclusion criteria for this study. 1570 patients were men (66.38%) and mean age was 53.2 ± 20.9. Of the patients, 2166 patients had blunt trauma (91.59%). Median GCS was 15 (interquartilerange [IQR]: 12, 15), median RTS was 12 (IQR: 11, 12), and median ISS was 17 (IQR: 9, 22). Obese critically ill trauma patients had significantly lower odds of mortality than nonobese (OR .686, CI 0.473-.977). Penetrating traumas (OR: 4.206, CI: 2.478, 6.990), increased ISS (OR: 1.095, CI: .473, 1.112), and increased age (OR: 1.036, CI: 1.038, 1.045) were associated with significantly increased odds of mortality. Discussion The obesity paradox is observed in the obese critically ill trauma patient population.
Tissue Diagnosis Is Associated With Worse Survival in Hepatocellular Carcinoma: A National Cancer Database Analysis
Authors: Dahdaleh Fadi S. , Naffouje Samer A. , Sherman Scott K. , Kamarajah Sivesh K. , Salti George I. 
Published: April 2021

Background Biopsy to achieve tissue diagnosis (TD) of hepatocellular carcinoma (HCC) risks needle tract seeding. With chest wall and peritoneal recurrences reported, TD could worsen cancer outcomes. We investigated HCC outcomes after TD compared to clinical diagnosis (CD), hypothesizing that TD adversely affects overall survival (OS). Methods The National Cancer Database (NCDB) Participant User File for liver cancer was reviewed, including patients with nonmetastatic HCC treated with major hepatectomy or transplantation. Clinical diagnosis patients were matched 1:1 to TD patients per propensity score. Survival was examined in the unmatched and matched cohorts. Results Of 172 283 cases, 16 366 met inclusion criteria. Mean age was 60.8 years, 12 100 (73.9%) were male, and 48.4% of patients received hepatectomies. Clinical diagnosis occurred in 70.4% of cases, and 29.6% underwent TD. Cox regression confirmed the diagnostic method as an independent predictor of OS in addition to age, Charlson-Deyo score, grade, delay of surgery, lymphovascular invasion, nodal stage, and procedure type, favoring transplantation over hepatectomy. After propensity matching on these factors, 4251 patients were matched from each group. In the matched cohort, patients with TD had a significantly lower OS than patients with CD (median: 65.5 vs. 85.6 ± 2.7 months, P < .001). The corresponding 5-year survival was lower in the TD group (47.6% vs. 60.9% P < .001). Conclusion Hepatocellular carcinoma patients with preoperative TD had decreased OS compared to CD, which persisted after propensity matching. This study supports avoiding biopsy for HCC whenever possible.
Reducing stigma associated with mental health problems among university students in the Asia-Pacific: A video content analysis of student-driven proposals
Authors: Withers Mellissa , Jahangir Tasfia , Kubasova Ksenia , Ran Mao-Sheng 
Published: April 2021

Introduction: Studies have demonstrated that mental health problems among university students may be increasing in both prevalence and severity. This study aimed to identify ways to reduce stigma and improve students’ utilization of mental health services. Methods: We performed a content analysis on video proposals to address stigma and mental health at universities, submitted by 15 teams from nine Asian-Pacific countries as part of a case competition. We examined five domains: (1) tone; (2) cultural context; (3) mental health issue of focus; (4) prevention versus secondary prevention; and (5) main intervention strategies. Results: Five main intervention strategies emerged: (1) educational campaigns; (2) peer interaction and support; (3) counseling; (4) screening; and (5) self-management. The results suggest that mental health literacy is low among students. Educational campaigns and events to increase awareness and reduce stigma were the most commonly incorporated strategy, through film screenings, mental health days, and social media. Building empathy through personal stories from celebrities and other students was also highly recommended. Second, counseling was incorporated in 80% of proposals, with a preference for peers and staff support, and web-based therapy over professional counselors, except in severe cases. Programs to increase social contact were the third most common strategy, suggesting students may feel isolated and disconnected. Creating common spaces for students to interact and pairing of students with and without mental health issues were widely suggested. The use of technology was recommended for self-management of mental health and for mandatory mental health screening, which was generally only recommended for incoming students. Conclusions: Our analysis provides insight into student-generated intervention approaches to prevent and address stigma associated with mental health issues among students. A greater university commitment is needed to provide a range of resources, including education and counseling, to leverage technology, and to foster stronger support networks among students.
Understanding the palliative care needs and experiences of people with mesothelioma and their family carers: An integrative systematic review
Authors: Harrison Madeleine , Gardiner Clare , Taylor Bethany , Ejegi-Memeh Stephanie , Darlison Liz 
Published: April 2021

Background: People with mesothelioma and their families have palliative care needs throughout the relatively short trajectory of their illness. Aim: To describe the palliative care needs and experiences of people with mesothelioma and their family carers. Design: Integrative systematic review with narrative synthesis (PROSPERO: CRD42020190115). Data sources: MEDLINE, CINAHL, PsycINFO and the Cochrane Library were searched for articles published between 01 January 2000 and 10 May 2020. Articles were included if they presented empirical studies or comprehensive reviews including information about the palliative care needs and experiences of people with mesothelioma and their family carers. Results: The search yielded 508 articles, 14 were included in the analysis. A cross cutting theme of ‘uncertainty’ was identified encompassing five themes: (1) organisation and co-ordination of services, (2) communication and information needs, (3) management of care needs and high symptom burden, (4) consideration of the impact of seeking compensation and (5) family carer needs. Our findings demonstrate that people with mesothelioma want a co-ordinated, team-based approach to palliative care with a named point of contact. Whilst carers value and benefit from early referral to specialist palliative care, this does not necessarily reflect the outcomes and views of patients. Conclusion: The evidence base around the palliative care needs and experiences of people with mesothelioma and their carers needs to be strengthened. The results of this review support the need to develop a greater understanding about the role non-specialist palliative care clinicians’ play in providing generalist palliative care for people with mesothelioma and their carers.
Effect of “drip-and-ship” and “drip-and-drive” on endovascular treatment of acute ischemic stroke with large vessel occlusion: a single-center retrospective study
Authors: Hang Yu , Jia Zhen Yu , Zhao Lin Bo , Cao Yue Zhou , Huang Huang , Shi Hai-Bin , Liu Sheng 
Published: April 2021

Background Patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) were usually transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (drip-and-ship [DS]), while driving the doctor from a CSC to a PSC to perform a procedure is an alternative strategy (drip-and-drive [DD]). Purpose To compare the efficacy and prognosis of the two strategies. Material and Methods From February 2017 to June 2019, 62 patients with LVO received endovascular treatment via the DS and DD models and were retrospectively analyzed from the stroke alliance based on our CSC. Primary endpoint was door-to-reperfusion (DTR) time. Secondary endpoints included puncture-to-recanalization (PTR) time, modified Thrombolysis in Cerebral Infarction (mTICI) rates at the end of the procedure, and modified Rankin Scale (mRS) at 90 days. Results Forty-one patients received the DS strategy and 21 patients received the DD strategy. The DTR time was significantly longer in the DS group compared to the DD group (315.5 ± 83.8 min vs. 248.6 ± 80.0 min; P < 0.05), and PTR time was shorter (77.2 ± 35.9 min vs. 113.7 ± 69.7 min; P = 0.033) compared with the DD group. Successful recanalization (mTICI 2b/3) was achieved in 89% (36/41) of patients in the DS group and 86% (18/21) in the DD group ( P = 1.000). Favorable functional outcomes (mRS 0–2) were observed in 49% (20/41) of patients in the DS group and 71% (15/21) in the DD group at 90 days ( P = 0.089). Conclusion Compared with the DS strategy, the DD strategy showed more effective and a trend of better clinical outcomes for AIS patients with LVO.
Genetic mutations in patients with nonsyndromic hearing impairment of minority and Han Chinese ethnicities in Qinghai, China
Authors: Duan Shihong , Guo Yufen , Chen Xingjian , Li Yong 
Published: April 2021

Objective Mutations in GJB2, SLC26A4, and mitochondrial (mt)DNA 12S rRNA genes are the main cause of nonsyndromic hearing impairment. The present study analyzed these mutations in ethnic minority and Han Chinese patients with nonsyndromic hearing impairment from Qinghai, China. Methods The SNPscan assay was used to analyze mutation spectra and frequencies in the two patient groups. Results GJB2 mutations were detected in 9.5% (20/210) of minority patients and 20.88% (48/230) of Han Chinese patients. The most common Han Chinese GJB2 variants were c.235delC and c.299_300delAT, whereas c.235delC and c.109G > A were the most prevalent in minority patients. SLC26A4 mutations were detected in 5.71% (12/210) of minority patients and 14.35% (33/230) of Han Chinese patients, and mtDNA 12S rRNA mutations were detected in 4.28% (9/210) of minority patients and 9.13% (21/230) of Han Chinese patients. Conclusions These data indicate that the mutation frequencies of three deafness-associated genes were significantly higher in Han Chinese patients than in minority patients. Moreover, the GJB2 mutation spectrum was shown to differ between these two patient groups.
Are individual stock returns predictable?
Authors: Zeng Hui , Marshall Ben R , Nguyen Nhut H , Visaltanachoti Nuttawat 
Published: April 2021

We show that the previously documented predictability of macroeconomic and technical variables for market returns is also evident in individual stock returns. Technical variables generate better predictability on firms with high limits to arbitrage (small, illiquid, volatile firms), while macroeconomic variables better predict firms with low limits to arbitrage. Technical predictors show a stronger predictive power for high limits to arbitrage firms across the business cycle, whereas macroeconomic variables capture more predictive information for firms with low limits to arbitrage during recessions. JEL Classification: C58, E32, G11, G12, G17
Ulnar Collateral Ligament Laxity After Repetitive Pitching: Associated Factors in High School Baseball Pitchers
Authors: Hattori Hiroshi , Akasaka Kiyokazu , Otsudo Takahiro , Hall Toby , Sakaguchi Katsunobu , Tachibana Yomei 
Published: April 2021

Background: Medial elbow injury is common in baseball pitchers, with evidence of elbow valgus instability after only 60 consecutive pitches. However, the tissue-specific effects of repetitive pitching on medial elbow stabilizers are largely unknown. Purpose/Hypothesis: This study aimed to investigate changes in the ulnar collateral ligament (UCL) and forearm flexor-pronator muscles (FPMs) during repetitive pitching and factors that relate to identified change. We hypothesized that repetitive pitching would increase elasticity of the medial elbow stabilizers and therefore induce laxity. Study Design: Descriptive laboratory study. Methods: A total of 30 high school baseball pitchers participated (mean ± SD age, 16.6 ± 0.5 years). Each participant pitched 100 times (5 blocks of 20 pitches). The strain ratio, indicating elasticity in the UCL and FPMs, was measured using ultrasound before pitching and after every 20-pitch block. Data for each pitch block were compared using analysis of variance. Multiple regression analysis was used to investigate factors related to the change rate of the strain ratio. Results: The strain ratio of the UCL after 100 pitches was significantly less than that before pitching (before pitching, 4.83 ± 1.70; after 100 pitches, 3.59 ± 1.35; P = .013), but this was not the case for the FPMs (before pitching, 0.57 ± 0.24; after 100 pitches, 0.43 ± 0.18; P = .07). The ratio of the strain ratio in the UCL and FPMs (UCL/FPMs) before pitching (β = −0.385; P = .031) and the elbow flexion range of motion before pitching (β = −0.352; P = .046) were significantly and independently correlated with the change rate of the UCL. Conclusion: Elasticity significantly increased for the UCL, indicating laxity, but not for the FPMs after 100 pitches. Furthermore, the ratio of elasticity (UCL/FPMs) and the elbow flexion range of motion before pitching were significantly related to the change rate of UCL elasticity. Clinical Relevance: To reduce laxity of the UCL, pitchers should be limited to <100 pitches per game. Sustaining a lower level of relative FPMs to UCL elasticity at rest and maintaining a large muscle volume to avoid excessive elbow flexion range of motion may prevent UCL laxity that develops during repetitive pitching.