bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical reliability of genomic data obtained from spinal metastatic tumor samples
Authors: Barzilai Ori , Martin Axel , Reiner Anne S , Laufer Ilya , Schmitt Adam , Bilsky Mark H
Published: January 2022

Background

The role of tumor genomic profiling is rapidly growing as it results in targeted, personalized, cancer therapy. Though routinely used in clinical practice, there are no data exploring the reliability of genomic data obtained from spine metastases samples often leading to multiple biopsies in clinical practice. This study compares the genomic tumor landscape between spinal metastases and the corresponding primary tumors as well as between spinal metastases and visceral metastases.

Methods

Spine tumor samples, obtained for routine clinical care from 2013 to 2019, were analyzed using MSK-IMPACT, a next-generation sequencing assay. These samples were matched to primary or metastatic tumors from the corresponding patients. A concordance rate for genomic alterations was calculated for matching sample pairs within patients for the primary and spinal metastatic tumor samples as well as for the matching sample pairs within patients for the spinal and visceral metastases. For a more robust and clinically relevant estimate of concordance, subgroup analyses of previously established driver mutations specific to the main primary tumor histologies were performed.

Results

Eighty-four patients contributed next-generation sequencing data from a spinal metastasis and at least one other site of disease: 54 from the primary tumor, 39 had genomic tumor data from another, nonspinal metastasis, 12 patients participated in both subsets. For the cohort of matched primary tumors and spinal metastases (n = 54) comprised of mixed histologies, we found an average concordance rate of 96.97% for all genetic events, 97.17% for mutations, 100% for fusions, 89.81% for deletions, and 97.01% for amplifications across all matched samples. Notably, >25% of patients harbored at least one genetic variant between samples tested, though not specifically for known driver mutations. The average concordance rate of driver mutations was 96.99% for prostate cancer, 95.69% (P = .0004513) for lung cancer, and 96.43% for breast cancer. An average concordance of 99.02% was calculated for all genetic events between spine metastases and non-spinal metastases (n = 41) and, more specifically, a concordance rate of 98.91% was calculated between spine metastases and liver metastases (n = 12) which was the largest represented group of nonspine metastases.

Conclusion

Sequencing data performed on spine tumor samples demonstrate a high concordance rate for genetic alterations between the primary tumor and spinal metastasis as well as between spinal metastases and other, visceral metastases, particularly for driver mutations. Spine tumor samples may be reliably used for genomic-based decision making in cancer care, particularly for prostate, NSCLC, and breast cancer.
Risk factors for treatment-refractory and relapsed optic pathway glioma in children with neurofibromatosis type 1
Authors: Kotch Chelsea , Avery Robert , Getz Kelly D , Bouffet Eric , de Blank Peter , Listernick Robert , Gutmann David H , Bornhorst Miriam , Campen Cynthia , Liu Grant T , Aplenc Richard , Li Yimei , Fisher Michael J
Published: January 2022

Background

Nearly one-third of patients with neurofibromatosis type 1-associated optic pathway glioma (NF1-OPG) fail frontline chemotherapy; however, little is known about risk factors for treatment failure.

Methods

We performed a retrospective multi-institutional cohort study to identify baseline risk factors for treatment-refractory/relapsed disease and poor visual outcome in children with NF1-OPG. Refractory/relapsed NF1-OPG was defined as a requirement of two or more treatment regimens due to progression or relapse.

Results

Of 111 subjects eligible for inclusion, adequate clinical and visual data were available for 103 subjects from 7 institutions. Median follow-up from the initiation of first chemotherapy regimen was 95 months (range 13-185). Eighty-four (82%) subjects received carboplatin-based frontline chemotherapy. Forty-five subjects (44%) experienced refractory/relapsed disease, with a median time of 21.5 months (range 2-149) from the initiation of first treatment to the start of second treatment. The proportion of patients without refractory/relapsed disease at 2 and 5 years was 78% and 60%. In multivariable analyses, age less than 24 months at initial treatment, posterior tumor location, and familial inheritance were associated with refractory/relapsed NF1-OPG by 2 years. Both age less than 24 months and posterior tumor location were associated with refractory/relapsed NF1-OPG by 5 years. Subjects with moderate to severe vision loss at last follow-up were more likely to have posterior tumor location, optic disc abnormalities, or abnormal visual acuity at initial treatment.

Conclusion

Young age, posterior tumor location, and optic disc abnormalities may identify patients with the greatest likelihood of refractory/relapsed NF1-OPG and poor visual outcomes, and who may benefit from newer treatment strategies.
Honor classes in China's higher education: perspectives from four universities
Authors: Zhao Weijie
Published: January 2022

Ever since the University of Science and Technology of China started the Special Class for the Gifted Young in 1978, many Chinese universities have set up their own honor classes under different names such as Gifted Young Class, Basic Science Class, Experimental Class or Elite Class. These are often small classes; some emphasize mathematics and physics, aiming to cultivate talents with broad basic knowledge, while others focus on a particular discipline, such as computer science. In 2011, the Chinese Ministry of Education started the Experimental Program for the Cultivation of Top Talents in Basic Sciences, which boosted a new round of honor classes.

How do these classes cultivate their students? Which kinds of special strategies are employed? Have they indeed fostered outstanding graduates? How did the students develop after graduation? On the other hand, are these classes a violation of the spirit of ‘equity in education’? Trying to answer these questions, in this NSR forum chaired by Professor Zhenjiang Hu, educators from four Chinese universities exchanged their experiences, views and perspectives on running the honor classes.

Baoquan Chen

Executive Director of the Center on Frontiers of Computing Studies, School of Electronics Engineering and Computer Science, Peking University. (Turing Class, Peking University.)

Changqing Chen

Professor and Head of the Department of Engineering Mechanics, Tsinghua University. (Tsien Excellence in Engineering Program, Tsinghua University.)

Zhenyu Li

Professor of the School of Chemistry and Materials Science, University of Science and Technology of China. (School of the Gifted Young, University of Science and Technology of China.)

Yong Yu

Professor of the Department of Computer Science and Engineering, Shanghai Jiao Tong University. (ACM Class, Shanghai Jiao Tong University.)

Ming Zhang

Chair of the ACM Special Interest Group of Computer Science Education (SIGCSE) China; Professor of the School of Electronics Engineering and Computer Science, Peking University.

Zhenjiang Hu (Chair)

Dean of School of Computer Science, Peking University.
A Systematic Review of Mental Health Professionals, Patients, and Carers’ Perceived Barriers and Enablers to Supporting Smoking Cessation in Mental Health Settings
Authors: Huddlestone Lisa , Shoesmith Emily , Pervin Jodi , Lorencatto Fabiana , Watson Jude , Ratschen Elena
Published: January 2022

Introduction

Evidence-based smoking cessation and temporary abstinence interventions to address smoking in mental health settings are available, but the impact of these interventions is limited.

Aims and Methods

We aimed to identify and synthesize the perceived barriers and enablers to supporting smoking cessation in mental health settings. Six databases were searched for articles reporting the investigation of perceived barriers and enablers to supporting smoking cessation in mental health settings. Data were extracted and coded using a mixed inductive/deductive method to the theoretical domains framework, key barriers and enablers were identified through the combining of coding frequency, elaboration, and expressed importance.

Results

Of 31 included articles, 56 barriers/enablers were reported from the perspectives of mental healthcare professionals (MHPs), 48 from patient perspectives, 21 from mixed perspectives, and 0 from relatives/carers. Barriers to supporting smoking cessation or temporary abstinence in mental health settings mainly fell within the domains: environmental context and resources (eg, MHPs lack of time); knowledge (eg, interactions around smoking that did occur were ill informed); social influences (eg, smoking norms within social network); and intentions (eg, MHPs lack positive intentions to deliver support). Enablers mainly fell within the domains: environmental context and resources (eg, use of appropriate support materials) and social influences (eg, pro-quitting social norms).

Conclusions

The importance of overcoming competing demands on staff time and resources, the inclusion of tailored, personalized support, the exploitation of patients wider social support networks, and enhancing knowledge and awareness around the benefits smoking cessation is highlighted.

Implications

Identified barriers and enablers represent targets for future interventions to improve the support of smoking cessation in mental health settings. Future research needs to examine the perceptions of the carers and family/friends of patients in relation to the smoking behavior change support delivered to patients.
The Essentials of Multiomics
Authors: Marshall John L , Peshkin Beth N , Yoshino Takayuki , Vowinckel Jakob , Danielsen Håvard E , Melino Gerry , Tsamardinos Ioannis , Haudenschild Christian , Kerr David J , Sampaio Carlos , Rha Sun Young , FitzGerald Kevin T , Holland Eric C , Gallagher David , Garcia-Foncillas Jesus , Juhl Hartmut
Published: January 2022

Within the last decade, the science of molecular testing has evolved from single gene and single protein analysis to broad molecular profiling as a standard of care, quickly transitioning from research to practice. Terms such as genomics, transcriptomics, proteomics, circulating omics, and artificial intelligence are now commonplace, and this rapid evolution has left us with a significant knowledge gap within the medical community. In this paper, we attempt to bridge that gap and prepare the physician in oncology for multiomics, a group of technologies that have gone from looming on the horizon to become a clinical reality. The era of multiomics is here, and we must prepare ourselves for this exciting new age of cancer medicine.
Genetic Evaluation for Hereditary Cancer Syndromes Among African Americans: A Critical Review
Authors: Khan Ambreen , Rogers Charles R , Kennedy Carson D , Lopez AnaMaria , Jeter Joanne
Published: January 2022

While hereditary cancer syndromes have been described and studied for centuries, the completion of the human genome project fueled accelerated progress in precision medicine due to the introduction of genetic testing in the 1990s, creating avenues for tailored treatments and medical management options. However, genetic testing has not benefited everyone equitably, with nearly all of the published work based on individuals of non-Hispanic White/European ancestry. There remains a gap in knowledge regarding the prevalence, penetrance, and manifestations of common hereditary cancer syndromes in the African-American population due to significant disparities in access and uptake of genetic testing. This review summarizes the available literature on genetic testing for breast, colon, and prostate cancers in the African-American population and explores the disparities in access to genetic testing between non-Hispanic White and African-American patients. This article also addresses the barriers to genetic testing and discrepancies in the uptake of recommendations for hereditary cancer syndromes in the African-American population when compared with non-Hispanic Whites. The review offers practice implications for many healthcare providers and demonstrates gaps in the existing knowledge to be addressed in future studies to help eliminate the persisting health disparities faced by the African-American population.
The UBP14-CDKB1;1-CDKG2 cascade controls endoreduplication and cell growth in Arabidopsis
Authors: Jiang Shan , Wei Jinwei , Li Na , Wang Zhibiao , Zhang Yilan , Xu Ran , Zhou Lixun , Huang Xiahe , Wang Li , Guo Siyi , Wang Yingchun , Song Chun-Peng , Qian Wei , Li Yunhai
Published: January 2022

Endoreduplication, a process in which DNA replication occurs in the absence of mitosis, is found in all eukaryotic kingdoms, especially plants, where it is assumed to be important for cell growth and cell fate maintenance. However, a comprehensive understanding of the mechanism regulating endoreduplication is still lacking. We previously reported that UBIQUITIN-SPECIFIC PROTEASE14 (UBP14), encoded by DA3, acts upstream of CYCLIN-DEPENDENT KINASE B1;1 (CDKB1;1) to influence endoreduplication and cell growth in Arabidopsis thaliana. The da3-1 mutant possesses large cotyledons with enlarged cells due to high ploidy levels. Here, we identified a suppressor of da3-1 (SUPPRESSOR OF da3-1 6; SUD6), encoding CYCLIN-DEPENDENT KINASE G2 (CDKG2), which promotes endoreduplication and cell growth. CDKG2/SUD6 physically associates with CDKB1;1 in vivo and in vitro. CDKB1;1 directly phosphorylates SUD6 and modulates its stability. Genetic analysis indicated that SUD6 acts downstream of DA3 and CDKB1;1 to control ploidy level and cell growth. Thus, our study establishes a regulatory cascade for UBP14/DA3-CDKB1;1-CDKG2/SUD6-mediated control of endoreduplication and cell growth in Arabidopsis.
Molecular and cellular dynamics of early embryonic cell divisions inVolvox carteri
Authors: von der Heyde Eva Laura , Hallmann Armin
Published: January 2022

Cell division is fundamental to all organisms and the green alga used here exhibits both key animal and plant functions. Specifically, we analyzed the molecular and cellular dynamics of early embryonic divisions of the multicellular green alga Volvox carteri (Chlamydomonadales). Relevant proteins related to mitosis and cytokinesis were identified in silico, the corresponding genes were cloned, fused to yfp, and stably expressed in Volvox, and the tagged proteins were studied by live-cell imaging. We reveal rearrangements of the microtubule cytoskeleton during centrosome separation, spindle formation, establishment of the phycoplast, and generation of previously unknown structures. The centrosomes participate in initiation of spindle formation and determination of spindle orientation. Although the nuclear envelope does not break down during early mitosis, intermixing of cytoplasm and nucleoplasm results in loss of nuclear identity. Finally, we present a model for mitosis in Volvox. Our study reveals enormous dynamics, clarifies spatio-temporal relationships of subcellular structures, and provides insight into the evolution of cell division.
The COVID-19 Infodemic and the Efficacy of Interventions Intended to Reduce Misinformation
Authors: Kreps Sarah E , Kriner Douglas L
Published: January 2022

The COVID-19 pandemic has prompted social media platforms to take unprecedented steps—ranging from false tags to journalistic factchecks—to stanch the flow of misinformation that could pose a health risk. However, there is little evidence about the relative efficacy of these approaches in this unique context of a pandemic. Using a pair of survey experiments, we examine whether false tags and journalistic factchecks reduce accuracy misperceptions and sharing propensity on social media that can spread false claims. False tags had little effect on subjects’ accuracy assessments and social media sharing. Journalistic factchecks that offer accurate information to counter misinformation were more effective in reducing both misperceptions and sharing on social media. Further, we find no evidence of partisan backfire effects, even in response to interventions against claims with a plausible partisan valence. Our results suggest that journalistic factchecks provide an effective counternarrative to COVID-19 misinformation even in the context of the increasing politicization of America’s pandemic response and polarization more generally.
Role of the axial U(1) anomaly in the chiral susceptibility of QCD at high temperature
Authors: Aoki S , Aoki Y , Fukaya H , Hashimoto S , Rohrhofer C , Suzuki K
Published: January 2022

The chiral susceptibility, or the first derivative of the chiral condensate with respect to the quark mass, is often used as a probe for the QCD phase transition since the chiral condensate is an order parameter of SU(2)L × SU(2)R symmetry breaking. However, the chiral condensate also breaks the axial U(1) symmetry, which is usually not studied as it is already broken by the anomaly and apparently has little impact on the transition. We investigate the susceptibilities in the scalar and pseudoscalar channels in order to quantify how much the axial U(1) breaking contributes to the chiral phase transition. Employing a chirally symmetric lattice Dirac operator and its eigenmode decomposition, we separate the axial U(1) breaking effects from others. Our result in two-flavor QCD indicates that both of the connected and disconnected chiral susceptibilities are dominated by axial U(1) breaking at temperatures T ≳ 190 MeV after the quadratically divergent constant is subtracted.
Lupus low disease activity state within 12 months is associated with favourable outcomes in severely active systemic lupus erythematosus
Authors: Kikuchi Jun , Hanaoka Hironari , Saito Shuntaro , Oshige Tatsuhiro , Hiramoto Kazuoto , Kaneko Yuko , Takeuchi Tsutomu
Published: January 2022

Objectives

To demonstrate the significance of the time to attain lupus low disease activity state (LLDAS) after remission induction therapy in patients with severely active SLE.

Methods

We enrolled 79 patients starting prednisolone ≥0.4 mg/kg/day for active lupus with a BILAG 2004 index of A ≥ 1 or B ≥ 2, or for severe flare based on the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI). The time to LLDAS attainment was divided into ≤6, 6–12 and >12 months and non-LLDAS; associations between the timing of LLDAS and flares, damage accrual and ≥50% LLDAS attainment were examined.

Results

The mean SLEDAI was 17; median starting dose of prednisolone, 0.95 mg/kg/day; and mean observational period, 39.7 months. Six (7.6%) and 41 (51.9%) patients achieved LLDAS within 6 and 12 months. Patients with a shorter time to LLDAS achievement were more likely to spend ≥50% of the time in LLDAS and had a lower cumulative prednisolone dose; no differences were observed in damage accrual. Patients requiring longer than 12 months to achieve LLDAS had a higher prevalence of thrombocytopenia and those with non-LLDAS had lower renal function and a higher starting dose of prednisolone and steroid pulse therapy than those who achieved LLDAS within 12 months.

Conclusion

Achieving LLDAS within 12 months of induction therapy may be favourable in patients with severely active SLE. The low frequency of LLDAS attainment in high-risk populations highlights the need for a new strategy for SLE treatment.
On the boundary of services and research collaborations in Japanese state-of-the-art academic research infrastructures
Authors: Onoda Takashi , Ito Yasunobu
Published: January 2022

Recently, research infrastructures (RIs) are recognized to take on a crucial role in the national innovation system in driving open innovation via shared use that include offering measurement service to external users. Generally, these services are performed by staff in line with the social division of labor as scientists and technicians in research institutes. However, services rarely lead to research collaborations because research collaborations generally do not stem from services per se and require researchers to engage more with partners in initiating collaboration. This article focuses on its boundary of services and research collaborations by conducting an ethnographic survey of four years since 2016 to analyze epistemic cultures in eight Japanese state-of-the-art RIs. It first examines what is occurring at the boundaries and offers two frameworks, i.e. the subject-driven approach and the user-driven approach, for finding potential solutions to the issues that impedes service from extending into research collaboration.
A National Study of Adult Women Sexually Abused by Clergy: Insights for Social Workers
Authors: Pooler David Kenneth , Barros-Lane Liza
Published: January 2022

Given the paucity of research on the experiences of women who are sexually abused by clergy as adults and the advent of the #ChurchToo movement in 2017, the results of a mixed-methods national study highlight the experiences of those who survived the abuse and report on what factors are most healing in their recovery. Internet-based surveys with both quantitative and qualitative items were completed by 159 respondents. Less than 10 percent reported receiving help and support from their congregation after they reported the abuse, and about half of the respondents were blamed for the abuse and ignored by people in their congregations. In spite of the poor responses from their churches, these respondents reported positive beliefs regarding their ability to recover and heal. Mental health counseling was listed as a primary mechanism for healing. Multiple regression was used to develop a model of resilience. Faith in God was the most salient predictor. Those who survived sexual abuse need social workers who can navigate the complex set of factors and issues at the intersection of religion/spirituality, mental health treatment, and policy advocacy, including the ability to see what has been helpful about religious experiences and what has not.
Skin cancer in immunosuppressed patients
Authors: Griffith Cynthia Faires
Published: January 2022

The number of people living with chronic immunosuppression is increasing in the United States. Patients with HIV, those who have had bone marrow or solid organ transplants, and patients taking biologics for autoimmune diseases are at increased risk for skin cancer. Skin cancer in these patients is more aggressive and more likely to metastasize and cause death. Medications and individual risk factors such as sex, age, and ethnicity are independent risk factors for the development of skin cancer. Routine screening and aggressive treatment of actinic keratoses and nonmelanoma skin cancers can reduce patients' skin cancer burden and improve patient outcomes.
Family satisfaction with telemedicine follow-up after pediatric plastic surgery
Authors: Roy Michelle G. , Dinnell Diana E. Guillen , Sequitin Jeromie D. , Davies Lesley W. , Tung Jessica S.
Published: January 2022

Objective:

One issue faced at institutions that serve a vast area is patients' ability to travel for perioperative care. Telemedicine is an innovative way of providing care while removing the inconvenience of travel or the hindrance of cost associated with travel. We initiated telemedicine as an option for certain postoperative encounters and assessed patient family satisfaction with this novel approach.

Methods:

Our practice offers telemedicine visits to patients who have had simple surgical procedures, identified by a fixed list of CPT codes. Visits are scheduled 7 to 14 days after surgery. Families completed a satisfaction survey after their encounter.

Results:

A pilot program was initiated from January 2019 to March 2020 using this method of postoperative follow-up. The initial response from families (N = 60) was extremely positive.

Conclusion:

We anticipate the option for telemedicine visits will make postoperative follow-ups more amendable to families, increase adherence rates, and increase access to care.
Sex Differences in Orthostatic Tolerance Are Mainly Explained by Blood Volume and Oxygen Carrying Capacity
Authors: Diaz-Canestro Candela , Pentz Brandon , Sehgal Arshia , Montero David
Published: January 2022

OBJECTIVES:

The reduced orthostatic tolerance (OT) that is characteristic of the female sex may be explained by multiple phenotypic differences between sexes. This study aimed to elucidate the mechanistic role of blood volume (BV) and oxygen carrying capacity on sex differences in OT.

DESIGN:

Experimental intervention.

SETTING:

University of Calgary, Main Campus, Calgary, AB, Canada.

SUBJECTS:

Healthy women and men (n = 90) throughout the adult lifespan (20–89 yr) matched by age and physical activity.

INTERVENTIONS:

Incremental lower body negative pressure (LBNP) in all individuals. Blood withdrawal and oxygen carrying capacity reduction in men to match with women’s levels.

MEASUREMENTS AND MAIN RESULTS:

Transthoracic echocardiography and central blood pressures were assessed throughout incremental LBNP for 1 hour or until presyncope. Blood uniformization resulted in a precise sex match of BV and oxygen carrying capacity (p ≥ 0.598). A third of women (14/45) and two thirds of men (31/45) prior to blood uniformization completed the orthostatic test without presyncopal symptoms (p-for-sex < 0.001). After blood uniformization, seven out of 45 men completed the test (p-for-sex = 0.081). Left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) were progressively reduced with LBNP in both sexes, with women showing markedly lower volumes than men (p < 0.001). Blood uniformization did not eliminate sex differences in LVEDV and SV.

CONCLUSIONS:

Sex differences in OT are not present when BV and oxygen carrying capacity are experimentally matched between sexes throughout the adult lifespan.
Surgical Dermatology and Private Equity: A Review of the Literature and Discussion
Authors: Fogel Alexander L. , Hogan Sara , Dover Jeffrey
Published: January 2022

BACKGROUND

While there has been substantial investment in dermatology by private equity (PE), the relevance of this trend to the dermatologic surgeon has not been assessed.

OBJECTIVE

The literature on PE investment in medicine was reviewed to provide interdisciplinary data relevant to the dermatologic surgeon.

MATERIALS AND METHODS

The PubMed database was queried for all peer-reviewed articles containing the term “private equity” and identified 70 unique articles across 18 medical specialties, comprising 20 original research articles and 50 commentary articles.

RESULTS

Significant PE growth across multiple medical specialties occurred in the 2010s. Private equity ownership was associated with higher levels of nonphysician providers relative to physicians. Pooled data suggest that PE ownership is associated with lower staffing levels, particularly for non–revenue-generating staff, as well as potentially lower levels of medical supplies on hand. Data on financial performance suggests that PE-ownership results in higher profits, revenues, and costs. Surveys of physicians demonstrate concern about autonomy, ethics, and career prospects.

CONCLUSION

For the dermatologic surgeon, issues related to consolidation, provider scope of practice, support staff availability, and supply management are important due to the nature of procedural intervention and the increased risk of adverse events.
Isoform-Selective HDAC Inhibitor Mocetinostat (MGCD0103) Alleviates Myocardial Ischemia/Reperfusion Injury Via Mitochondrial Protection Through the HDACs/CREB/PGC-1α Signaling Pathway
Authors: Wang Kaihao , Tang Ruijie , Wang Siyuan , Xiong Yuyan , Wang Wenyao , Chen Guihao , Zhang Kuo , Li Ping , Tang Yi-Da
Published: January 2022

Over the past decade, histone deacetylases (HDACs) has been proven to manipulate development and exacerbation of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiac hypertrophy, ventricular remodeling, and myocardial fibrosis. Inhibition of HDACs, especially class-I HDACs, is potent to the protection of ischemic myocardium after ischemia/reperfusion (I/R). Herein, we examine whether mocetinostat (MGCD0103, MOCE), a class-I selective HDAC inhibitor in phase-II clinical trial, shows cardioprotection under I/R in vivo and in vitro, if so, reveal its potential pharmacological mechanism to provide an experimental and theoretical basis for mocetinostat usage in a clinical setting. Human cardiac myocytes (HCMs) were exposed to hypoxia and reoxygenation (H/R), with or without mocetinostat treatment. H/R reduced mitochondrial membrane potential and induced HCMs apoptosis. Mocetinostat pretreatment reversed these H/R-induced mitochondrial damage and cellular apoptosis and upregulated CREB, p-CREB, and PGC-1α in HCMs during H/R. Transfection with small interfering RNA against PGC-1α or CREB abolished the protective effects of mocetinostat on cardiomyocytes undergoing H/R. In vivo, mocetinostat was demonstrated to protect myocardial injury posed by myocardial I/R via the activation of CREB and upregulation of PGC-1α. Mocetinostat (MGCD0103) can protect myocardium from I/R injury through mitochondrial protection mediated by CREB/PGC-1α pathway. Therefore, activation of the CREB/PGC-1α signaling pathway via the inhibition of Class-I HDACs may be a promising new therapeutic strategy for alleviating myocardial reperfusion injury.
Mammalian Target of Rapamycin as the Therapeutic Target of Vascular Proliferative Diseases: Past, Present, and Future
Authors: Huang Wen-Qian , Zou Yan , Tian Ying , Ma Xiao-Feng , Zhou Qin-Yi , Li Zhen-Yu , Gong Shao-Xin , Wang Ai-Ping
Published: January 2022

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key pathological characteristic of vascular proliferative diseases. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays an important role in regulating cell growth, motility, proliferation, and survival, as well as gene expression in response to hypoxia, growth factors, and nutrients. Increasing evidence shows that mTOR also regulates VSMC proliferation in vascular proliferative diseases and that mTOR inhibitors, such as rapamycin, effectively restrain VSMC proliferation. However, the molecular mechanisms linking mTOR to vascular proliferative diseases remain elusive. In our review, we summarize the key roles of the mTOR and the recent discoveries in vascular proliferative diseases, focusing on the therapeutic potential of mTOR inhibitors to target the mTOR signaling pathway for the treatment of vascular proliferative diseases. In this study, we discuss mTOR inhibitors as promising candidates to prevent VSMC-associated vascular proliferative diseases.
Changes in microRNA Expression Profiles in Diabetic Cardiomyopathy Rats Following H3 Relaxin Treatment
Authors: Zhang Xiaohui , Liu Mingming , Yang Kelaier , Chi Jinyu , Chen Wenjia , Shi Zhiyu , Liu Wenxiu , Ma Xiao , Yin Xinhua
Published: January 2022

MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the mechanisms of diabetic cardiomyopathy (DCM); however, whether human recombinant relaxin-3 (H3 relaxin) inhibits myocardial injury in DCM rats and the underlying mechanisms involving miRNAs remain unknown. miRNA expression profiles were detected using miRNA microarray and bioinformatics analyses of myocardial tissues from control, DCM, and H3 relaxin–administered DCM groups, and the regulatory mechanisms of the miRNAs were investigated. A total of 5 miRNAs were downregulated in the myocardial tissues of DCM rats and upregulated in H3 relaxin–treated DCM rats, and 1 miRNA (miRNA let-7d-3p) was increased in the myocardial tissue of DCM rats and decreased in H3 relaxin–treated DCM rats as revealed by miRNA microarray and validated by real-time polymerase chain reaction. Important signaling pathways were found to be triggered by the differentially expressed miRNAs, including metabolism, cancer, Rap1, PI3K-Akt, and MAPK signaling pathways. The study revealed that H3 relaxin improved glucose uptake in DCM rats, potentially via the regulation of miRNA let-7d-3p.
Consideration Regarding the Analysis of Randomized Controlled Trials in the Era of Evidence-based Medicine
Authors: Ennezat Pierre V. , Alavi Zarrin , Le Jemtel Thierry H. , Hansen Morten R.
Published: January 2022

Analysis of randomized controlled trials (RCTs) is the cornerstone of evidence-based medicine, therapeutic guidelines and ultimately daily practice. However, 2 issues contribute to cloud the analysis of RCTs. Industry-sponsored RCTs aim at capturing as large indications as possible and clinicians rely excessively on P value statistical significance for the evaluation of the findings. To be most valuable to practitioners, analysis of RCTs needs to provide absolute risk reduction, number of patients needed to treat, fragility index along with the estimation of lost to follow-up patients, and outcome postponement (gain in survival time). We analyzed few major cardiovascular RCTs and assessed the robustness of their findings. Our suggested analytic parameters may be further used in future systematic reviews and meta-analyses.
How CARE Tools Are Being Used to Address Brain Injury and Mental Health Struggles With Survivors of Domestic Violence
Authors: Kemble Hannah , Sucaldito Ana , Kulow Emily , Ramirez Rachel , Hinton Alice , Glasser Allison , Wermert Amy , Nemeth Julianna M.
Published: January 2022

Introduction:

CARE (
C
onnect,
A
cknowledge,
R
espond, and
E
valuate) is an advocacy framework developed for domestic violence service organization (DVSO) providers to address and accommodate domestic violence (DV) survivors with brain injury and mental health struggles. The CARE tools were designed for use by advocates and include the Just Breathe booklet, the Head Injury education card, and the Invisible Injuries booklet.

Objective:

The purpose of this study was to report findings on how CARE tools are being used by DVSO providers as well as their impact on DVSO advocacy practice.

Methods:

Post-CARE retrospective process evaluation online surveys (n = 60) and focus groups (n = 10 groups; 57 advocates) were conducted with consenting staff at 5 DVSOs in Ohio who partnered with the state coalition to develop and evaluate CARE, overseen by a university research partner. Rigorous, iterative coding qualitative analysis methods, endorsed by the Centers for Disease Control and Prevention, were used (Cohen's κ = 0.903 [stage 1] and 0.810 [stage 2]).

Results:

The use of CARE tools has been integral to DVSO providers' implementation of the CARE advocacy framework. DVSO advocates are using CARE tools to
C
onnect with self, survivors, and other systems; to
A
cknowledge that head trauma and mental health struggles are common among survivors and that ongoing education and self-care are necessary for advocates. Advocates have been able to provide a more holistic
R
esponse through accommodation within DVSOs and referral to other providers, often by using the CARE tools, including the Head Injury education card.

Conclusion:

CARE tools were designed for lay use to address head trauma, strangulation, and mental health struggles with DV survivors and are free for download at the Center on Partner Inflicted Brain Injury website: https://www.odvn.org/brain-injury. More widespread use of these tools by advocates has the potential to improve services for DV survivors and address what have historically been invisible injuries and mental health struggles in the population.
Examining the Association Between Childhood Trauma, Brain Injury, and Neurobehavioral Symptoms Among Survivors of Intimate Partner Violence: A Cross-Sectional Analysis
Authors: Saadi Altaf , Chibnik Lori , Valera Eve
Published: January 2022

Objective:

Understanding factors contributing to neurobehavioral symptom burden among intimate partner violence (IPV) survivors has important implications for prevention, screening, and intervention in this vulnerable population. This study aimed to (1) identify the relationship between childhood trauma and neurobehavioral symptoms among a shelter- and community-based sample of IPV survivors, including investigating the mediating role of posttraumatic stress symptoms and alexithymia in this relationship; (2) assess the association between IPV-related brain injury (BI) severity and neurobehavioral symptoms; and (3) assesses whether physical, emotional, or cognitive domains of neurobehavioral symptom burden show differential associations with childhood trauma or IPV-related BI.

Setting:

Community sites serving women who had experienced IPV such as domestic violence shelters and transitional housing sites.

Participants:

Women survivors of IPV with and without BI (n = 99), aged 18 to 54 years.

Design:

Retrospective, cross-sectional study design.

Measures:

The following self-reported questionnaires were used: Rivermead Post Concussion Questionnaire (RPQ); Childhood Trauma Questionnaire (CTQ); a modified version of the Conflict Tactics Scale; Brain Injury Severity Assessment (BISA); Clinician-Administered PTSD Scale for DSM IV; and Toronto Alexithymia Scale. The final multivariate regression model assessed the association between childhood abuse, BI severity, and neurobehavioral symptoms (as measured by the RPQ) adjusting for age, educational attainment, and abuse in the past year. We created separate models with total neurobehavioral symptom score as an outcome, as well as somatic, emotional, and cognitive symptom scores. We used structural equation modeling to assess whether posttraumatic stress and alexithymia mediated the effect of childhood trauma and neurobehavioral symptoms.

Results:

Childhood trauma was associated with higher levels (P < .01) of overall neurobehavioral symptom burden in women independent of BI and specifically associated with RPQ Emotional and Somatic subscale symptoms (P ≤ .05). BI was positively associated with somatic symptoms in the full sample and cognitive neurobehavioral symptoms in the sample of women with IPV-related BI (P < .05) independent of childhood trauma. Posttraumatic stress symptoms, but not alexithymia, partially mediated the effect of childhood trauma effect on neurobehavioral symptoms.

Conclusion:

Childhood trauma and BI should not be overlooked as part of efforts to meet the needs of IPV survivors who may experience a range of emotional, somatic, and cognitive symptoms.
Strangulation as an Acquired Brain Injury in Intimate–Partner Violence and Its Relationship to Cognitive and Psychological Functioning: A Preliminary Study
Authors: Valera Eve M. , Daugherty Julia C. , Scott Olivia C. , Berenbaum Howard
Published: January 2022

Objective:

The aim of this work was to examine the relationship between strangulation-related alterations in consciousness (AIC) and cognitive and psychological outcomes in women who have experienced intimate partner violence (IPV).

Setting:

Participants were recruited from a variety of settings, including women's shelters and support programs.

Participants:

A total of 99 women were enrolled in the study. After applying exclusion criteria for factors that could mask or confound the effects of strangulation, 52 women remained for analyses.

Design:

Cross-sectional, retrospective.

Main Measures:

We used several cognitive measures to assess learning, long-term and working memory, visuomotor speed, cognitive flexibility, and nonverbal cognitive fluency as well as several psychological measures to assess posttraumatic stress symptomatology, general distress, worry, anhedonic depression, and anxious arousal. We also used the Brain Injury Severity Assessment interview to examine the association between strangulation-related AICs and these measures of cognitive and psychological functioning.

Results:

Women who had experienced strangulation-related AICs performed more poorly on a test of long-term memory (P < .03) and had higher levels of depression (P < .03) and posttraumatic stress symptomatology (P < .02) than women who had not experienced strangulation-related AIC. When controlling for potential confounding variables, including number of IPV-related traumatic brain injuries, women who had experienced strangulation also performed more poorly on a measure of working memory.

Conclusion:

This is the first report to assess strangulation in this manner and demonstrate links to cognitive and psychological functioning. These preliminary data contribute to our knowledge of strangulation and its effects on women who have experienced IPV.
SEVERE RETINAL ISCHEMIA IN INFANT WITH NEUROFIBROMATOSIS TYPE 1
Authors: Rali Aditya S. , Bavinger J. Clay , Rao Prethy , Hubbard G. Baker
Published: January 2022

Purpose:

To report a case of severe retinal ischemia in an infant with neurofibromatosis type 1.

Methods:

Chart review, analysis of imaging studies, and review of literature.

Results:

A boy born at 37 weeks postmenstrual age with neurofibromatosis type 1 was noted to have a large plexiform neurofibroma with left-sided involvement of the cavernous sinus, internal carotid artery, orbit, and optic nerve. He was managed for left eye glaucoma with anti-hypertensive eye drops, and at 8 months of age, he was referred for retinal evaluation. Fluorescein angiography showed striking nonperfusion of the left retina with only a small area of perfused vessels in the posterior pole. A large frond of neovascularization extended anteriorly from the posterior pole. The right eye had a crescent of retinal nonperfusion in the far periphery but otherwise normal retinal vessels.

Conclusion:

This case demonstrates a severe form of retinal ischemia in the setting of a large neurofibroma because of neurofibromatosis type 1. We hypothesize that vascular compression from the tumor led to disruption of the neurovascular bundle with resultant severe nonperfusion, neovascularization, and retinal maldevelopment.
ACUTE MACULAR NEURORETINOPATHY FOLLOWING SARS-CoV-2 VACCINATION
Authors: Afonso Miguel Gonçalves , Marques João Heitor , Monteiro Sérgio , Lume Miguel , Abreu Ana Carolina , Maia Sofia
Published: January 2022

Purpose:

To report a case of acute macular neuroretinopathy (AMN) following SARS-CoV-2 vaccination.

Methods:

Case report.

Results:

An otherwise healthy 28-year-old white woman presented to an ophthalmology department with complaints of black paracentral vision scotomata on both eyes that appeared 2 days after receiving the first dose of Vaxzevria vaccine. Fundus examination revealed bilateral red brown petaloid lesions around the fovea. On spectral domain optical coherence tomography, a hyperreflective plaque between the outer plexiform and outer nuclear layers along with disruption of ellipsoid zone/interdigitation zone was observed. A diagnosis of AMN was made.

Conclusion:

AMN may be an extremely rare adverse event of SARS-COV-2 vaccination, especially in patients with other risk factors.

Synopsis:

An otherwise healthy 28-year-old white woman was diagnosed with AMN 2 days after SARS-CoV-2 vaccination.
Disseminated Juvenile Xanthogranuloma: A Case Report
Authors: Saher Najam Us , Qadri Palvisha , Naseem Zehra
Published: January 2022

Introduction:

Histiocytoses are localized or systemic diseases that can broadly be classified into Langerhans cell histiocytosis and non-Langerhans cell histiocytosis. Juvenile Xanthogranuloma (JXG) belongs to the latter group, which occurs in around 0.5% population younger than 5 years, and presents as solitary or multiple lesions.

Here, we present a case of disseminated JXG in an infant with the lesions regressing spontaneously.

Case presentation:

A 7-month-old boy presented with multiple erythematous nodular lesions over the body excluding limbs for 3 months. Initial laboratory work up was normal. Skin histopathology showed a dermal nodule with sheets of histiocytes exhibiting grooved vesicular nuclei and pale eosinophilic cytoplasm along with touton giant cells. Immunohistochemistry markers further confirmed the diagnosis. Lesions healed completely with symptomatic relief in 1.5 years and no recurrence occurred.

Discussion:

Disseminated JXG is a benign childhood disorder that can sometimes be associated with internal organs involvement mainly bones, eyes, and brain. Serious complications may follow in case of extracutaneous spread. Most frequently, JXG follows the occurrence of another neoplastic disorder but can sometimes appear de novo. Skin biopsy is required for the diagnosis and better education of the family.

Conclusion:

JXG in infancy is a rarity in South Asia. Therefore, along with the clinical judgment, clinicians must also get histological confirmation in order to manage this disorder successfully. Close surveillance for multiorgan involvement is also required to avoid any irreversible sequalae.
Diagnosing a Diffuse Blistering Rash
Authors: Nelson Jacob , Mengden Koon Stephanie , Fett Nicole
Published: January 2022

Blistering dermatoses can be difficult to clinically differentiate. Often extremely unpleasant for patients and potentially life threatening, a prompt and correct diagnosis is paramount. This photo quiz contains information that will aid readers in differentiating various blistering dermatoses.
Pragmatic Randomized Control Trial of a Coordinated Community Response: Increasing Access to Services for At-Risk Older Adults
Authors: Maxwell Christopher D. , Rodgers Kourtnie , Pickering Carolyn E. Z.
Published: January 2022

Background

Elder abuse, neglect, and financial exploitation (EANF) impacts over five million community-dwelling older adults. Yet, no evidence-based intervention models exist that prevent EANF.

Objectives

In this article, we describe the assessment of process outcomes for a Community Complex Care Response Team (C3RT) model developed, via a practitioner–researcher partnership, to reduce instances of EANF victimization among higher risk community-dwelling older adults by identifying and coordinating their service needs. Specifically, we evaluated whether this C3RT approach produced more service coordination among providers (measured as documented interagency communications), more referrals for services, and more enrollment in services.

Methods

A pragmatic randomized control trial using a 1:1 randomization scheme allocated participants to either the C3RT intervention (N = 74) or standard practice (N = 72) group offered by a local Area Agency on Aging. Outcome data were extracted from the participants' administrative service records.

Results

The participants assigned to C3RT had significantly more interagency communications and services provided (p < 0.05) than those in standard practice.

Conclusions

Communications and services increased across a broad range of multidisciplinary services, which attend to the social determinants of health. This study is the first to use objective outcome measures to evaluate the processes of a coordinated community response approach systematically.