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12/5/2017Lynn YoungDivision of Library ServicesJournal
Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception.

Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli.
Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction
6/6/2017Patricia ZerfasDivision of Veterinary ResourcesArticle
T cells undergo metabolic reprogramming with major changes in cellular energy metabolism during activation. In summary, the findings presented herein emphasize the role of COX particularly in T cells as a metabolic checkpoint for cell fate decisions following T cell activation, with heterogeneous effects in T cell subsets.

In addition, our studies highlight the utility of translational models that recapitulate human mitochondrial disease for understanding immunometabolism.
Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation.
2/1/2016Patricia ZerfasDivision of Veterinary ResourcesJournal
Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explain impaired neuromuscular and secretory cells’ functions that mediate regulated exocytosis.

Here, we analyzed several forms of regulated exocytosis in a mouse model of MLIV and, opposite to expectations, we found enhanced exocytosis in secretory glands due to enlargement of secretory granules in part due to fusion with lysosomes.
Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV.
5/2/2016Patricia ZerfasDivision of Veterinary ResourcesArticle
In this paper we describe individuals with biallelic mutations in LAMA1, all of whom had the cerebellar dysplasia, myopia and retinal dystrophy, in addition to obsessive compulsive traits, tics and anxiety. Patient-derived fibroblasts have impaired adhesion, reduced migration, abnormal morphology and increased apoptosis due to impaired activation of Cdc42, a member of the Rho family of GTPases that is involved in cytoskeletal dynamics. LAMA1 knockdown in human neuronal cells also showed abnormal morphology and filopodia formation, supporting the importance of LAMA1 in neuronal migration, and marking these cells potentially useful tools for disease modelling and therapeutic target discovery.
Cystic cerebellar dysplasia and biallelic LAMA1 mutations
7/2/2015Patricia ZerfasDivision of Veterinary ResourcesArticle
Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations.

Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor’s DNA binding.
Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes
9/9/2015Patricia ZerfasDivision of Veterinary ResourcesArticle
Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp(-/-) molar teeth.
Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein
9/1/2015Casey Skvorc, PhD, JDDivision of Occupational Health and SafetyArticle
Until recently, academic institutions and Principal Investigators (PIs) maintained a de-facto immunity from criminal prosecution for worker injuries and deaths attributed to unsafe laboratory practices. This status quo changed in 2011 when a state prosecutor filed felony charges for statutory and regulatory safety violations against the Regents of a state university system and a tenured professor.

This article presents sentinel factors associated with the prosecution and settlement of the prosecution, with a discussion of resulting implications for academic institutions/institutes and PIs.
Criminal Prosecution—A Jumpstart for Laboratory Safety Accountability?
5/16/2019Patricia ZerfasDivision of Veterinary ResourcesArticle
During infection, hepatocytes must undergo a reprioritization of metabolism, termed metabolic reprogramming. Hepatic metabolic
reprogramming in response to infection begins within hours of infection, suggesting a mechanism closely linked to
pathogen recognition.

This work not only addresses a key component of end-organ physiology, but also raises questions about the side effects of biologics in the treatment of inflammatory diseases.
Macrophage Derived TNFa Promotes Hepatic Reprogramming to Warburg-like Metabolism
7/15/2017Patricia ZerfasDivision of Veterinary ResourcesArticle
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family.

In this study, we used genome editing to knockout the two mcoln1 genes present in Danio rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis.
Novel Degenerative and Developmental Defects in a Zebrafish Model of Mucolipidosis Type IV
5/29/2015Patricia ZerfasDivision of Veterinary ResourcesArticle
By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in β-oxidation.

Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection.

BBA Molecular Basis of Disease
11/1/2015CC, Dr. Steven Solomon Medical Arts BranchJournal
7/18/2017NEI, Dr. Anthony St Leger Medical Arts BranchJournal
Immunity Volume 47
3/11/2021Xizhong Cui, Junfeng Sun, Samuel J. Minkove, Yan Li, Diane Cooper, Zoe Couse, Peter Q. Eichacker, Parizad Torabi‐PariziDivision of Library ServicesArticle
Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non‐SARS‐CoV2 infection supported the use of these agents in the present SARS‐CoV2 outbreak.
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5/20/2020Abhimanyu A. Amarnani, Katlin R. Poladian, Beatriz E. Marciano, Janine R. Daub, Sandra G. Williams, Alicia A. Livinski, Amy P. Hsu, Cindy L. Palmer, Cara M. Kenney, Daniele N. Avila, Steven M. Holland & James D. KatzDivision of Library ServicesArticle
This study characterizes rheumatological manifestations of GATA2 deficiency. Results: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17.8%). Twenty-two of those patients (78.6%) reported symptom onset prior to or in conjunction with the molecular diagnosis of GATA2 deficiency.
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6/11/2020Stephanie Chidester, Alicia A. Livinski, Anne F. Fish and Paule V. JosephDivision of Library ServicesArticle
This review was conducted to determine what is known from the literature about the effect of EV crosstalk on pancreatic β-cell function and viability in the pathogenesis of diabetes mellitus, to perform a gap analysis for future research directions, and to discuss implications of available evidence for diabetes care. The literature search yielded 380 studies from which 31 studies were determined to meet eligibility criteria.
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4/8/2021Li JiaDivision of Library ServicesArticle
Adoptive T cell therapy (ACT) using ex vivo–expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39−CD69−) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence.

Other authors and affiliations: Sri Krishna, Frank J. Lowery, Amy R. Copeland, Erol Bahadiroglu, Ratnadeep Mukherjee, James T. Anibal, Abraham Sachs, Serifat O. Adebola, Devikala Gurusamy1, View ORCID ProfileZhiya Yu1, Victoria Hill, Jared J. Gartner, Yong F. Li, Maria Parkhurst, Biman Paria1, Pia Kvistborg, Michael C. Kelly, Stephanie L. Goff, Grégoire Altan-Bonnet, Paul F. Robbins, Steven A. Rosenberg
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4/1/2021Candace Norton, Alicia A. LivinskiDivision of Library ServicesArticle
Bibliometric analyses are commonly used to measure the productivity of researchers or institutions but rarely used to assess the scientific contribution of national surveys/datasets. We applied bibliometric methods to quantify the contributions of the National Survey of Children's Health (NSCH) and the National Survey of Children with Special Health Care Needs (NS-CSHCN) to the body of pediatric health-related research. We also examined dissemination to nonresearch audiences by analyzing media coverage of statistics and research produced from the surveys.
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4/11/2023Mengbi Yang, Amy Q. Wang, Elias C. Padilha, Pranav Shah, Natalie R. Hagen, China Ryu, Khalida Shamim, Wenwei Huang and Xin XuDivision of Veterinary ResourcesArticle
The Division of Veterinary Resources (DVR) continually supports the Intramural Research Program at the NIH, oftentimes behind the scenes of groundbreaking research. Two recent publications highlight DVR’s dedication and contributions. DVR was specifically recognized in the Acknowledgement sections of recently published work describing effective treatments against COVID-19. These were performed in Dr. Xin Xu’s lab with the National Center for Advancing Translational Sciences (NCATS). DVR’s very own Nida Delbe and Danitra Brathwaite, as well as the rodents we care for, were integral to the drug discovery now being investigated in humans. These studies include an oral formulation of Remdesivir1 and development of physiological based pharmacokinetic model in mice accurately predicting lung tissue concentrations in humans2.
1/26/2023William H. Herman  ORCID logo  ; Dean Schillinger; Shari Bolen; John M. Boltri; Ann Bullock; William Chong; Paul R. Conlin  ORCID logo  ; J. William Cook, IV; Ayotunde Dokun  ORCID logo  ; Naomi Fukagawa; Jasmine Gonzalvo  ORCID logo  ; M. Carol Greenlee;Division of Library ServicesArticle
The National Clinical Care Commission (NCCC) was established by Congress to make recommendations to leverage federal policies and programs to more effectively prevent and treat diabetes and its complications. The NCCC developed a guiding framework that incorporated elements of the Socioecological and Chronic Care Models. It surveyed federal agencies and conducted follow-up meetings with representatives from 10 health-related and 11 non–health-related federal agencies.
Diabetes care cover
1/5/2023Diane CooperDivision of Library ServicesArticle
Research has demonstrated that solid tumor patients experience high levels of psychological distress at the time of diagnosis. While distress has been associated with many adverse clinical outcomes, little is known about how this symptom may influence the disease trajectory for cancer patients, affecting outcomes such as progression, recurrence, and survival. The purpose of this systematic review was to explore the literature linking distress with survival in solid tumor patients, which may guide future work exploring clinical outcomes as a function of distress.
Findings from this review suggest that psychological distress may have an impact on disease-related outcomes, including (but not limited to) survival.
1/13/2023Brigit SullivanDivision of Library ServicesArticle
Chronic granulomatous disease (CGD) is a rare inborn error of immunity, resulting from a defect in nicotinamide adenine dinucleotide phosphate oxidation and decreased production of phagocyte reactive oxygen species. The main clinical manifestations are recurrent infections and chronic inflammatory disorders. Current approaches to management include antimicrobial prophylaxis and control of inflammatory complications. Hematopoietic stem cell transplantation or gene therapy can provide definitive treatment.
his review describes the various clinical findings and the latest studies in management of gastrointestinal and hepatic manifestations in CGD, as well as the management experience at the National Institutes of Health.
1/19/2023Diane CooperDivision of Library ServicesArticle
The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, “High-grade neuroepithelial tumor with MN1 alteration” (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene.
Improving our Understanding of the Management and Pathogenesis of Rare and Neglected Tumors of the Central and Peripheral Nervous System
3/2/2023Gisela ButeraDivision of Occupational Health and SafetyArticle
We found considerable variation in reported information and in the thoroughness of the case reports. Reports tended to be inadequate in full assessment of the patient’s kratom use. As kratom use continues to increase in the USA, consistent and detailed reporting, usage of biospecimen testing and kratom product assays, consultation of experts to aid with patient workup, usage of causality assessment tools, and acknowledgement of limitations will improve the quality of case reports.
In this systematic review, we examined case reports of patients who use kratom and evaluated their rigor based on reporting of clinically relevant information.
3/8/2023Alicia A. LivinskiDivision of Library ServicesArticle
 The meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect).
Results provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which requir
2/7/2023Alicia A. LivinskiDivision of Library ServicesArticle
Caregiving has been robustly linked to caregiver health through the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in the context of caregiving for an adult with a chronic illness. However, little research examines the physiological impact of caregiving for a child with a chronic illness despite high burden and unique stressors. In this review, we explore the links of caregiving for a child with a congenital, chromosomal, or genetic disorder to the regulation or dysregulation of the HPA axis. A search was conducted in PubMed, Embase, and the Web of Science and 15 studies met inclusion criteria.
This review sought to summarize the current state of the literature to understand what is currently known about the impact of chronic stress on the HPA axis in the context of caregiving for a child with a congenital, chromosomal, or genetic condition. Ove
4/5/2023Gisela ButeraDivision of Library ServicesArticle
Many reports were difficult to interpret due to missing information. Despite the lack of standardized assessment and diagnostic tools for kratom addiction, withdrawal, or dependence, medications for opioid use disorder were frequently prescribed, which is problematic for opioid naïve patients. Findings suggest that case reports involving kratom should include established standardized assessments of history and symptomatology, incorporating laboratory testing where possible. Development of best practices for treatment of kratom-associated dependence or addiction is warranted.
This systematic review examines case reports of kratom physical dependence or addiction, focusing on assessment, diagnosis, and treatment methods and the completeness of the clinical data presented.
4/24/2023Diane CooperDivision of Library ServicesArticle
Two reviewers (S.M and P.Q.E) independently assessed included studies for quality of evidence using a modified version of the Systemic Review Centre for Laboratory Animal Experimentation (SYRCLE) grading system [26, 27]. Studies were examined to determine if the following information was provided: a primary outcome; sample size or power calculation; randomization of challenges; confirmation of baseline similarity of study groups (e.g., age, weight); blinding of challenges and outcome assessments; and randomized animal housing.
Limited animal studies have investigated FiO2 ≤ 0.60/ > 0.21 with clinically relevant models and endpoints but suggest even these lower FiO2s may be injurious. Given the influence animal studies examining FiO2 > 0.60 have had on clinical practice, additio
5/4/2023Diane CooperDivision of Library ServicesArticle
Collectively, the reports included in this review suggest that inflammatory pathways related to the proliferation of immune cells at the time of diagnosis and treatment are associated with frailty development and symptomology. Limited reports (one each) also implicate telomere shortening and epigenetic alterations such as perturbations in aging miRNAs as potential correlates of deficit accumulation frailty. Additionally, metabolic pathways underlying deficit accumulation frailty may be of potential value when identifying target biomarkers. Given the paucity of evidence across the diverse set of biomarkers searched, the field of frailty biomarkers in solid tumors is largely underexplored. Future studies will benefit from longitudinal studies with a comprehensive set of biomarkers adjusted for cancer stages, time since diagnosis and treatment, and type of treatment; larger sample sizes, robust control groups, and multiple time points by sex, gender, and race/ethnicity. Such investigations will aid the development of robust biomarker profiles, early identification of cancer survivors at risk for developing frailty, and timely referral to therapeutic interventions.

Author contributions
This review examines the current literature to identify biomarkers of frailty across patients with solid tumors. We conducted the systematic review using preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA). PubMed, Web o
6/3/2023Alicia A. LivinskiDivision of Library ServicesArticle
Most strategies to maintain cancer services during the COVID-19 pandemic centred around cancer treatment, with few strategies on maintaining cancer prevention services, early detection, palliative care and research services. The most mentioned challenge during the pandemic was fear of exposure to COVID-19 infection at the health facility during diagnosis, treatment or follow-up for cancer care. Other challenges were disruptions to service delivery, inaccessibility of cancer treatment, disruption of research activities and a lack of psychosocial support for COVID-19 related fear/anxiety. Significantly, this analysis shows that the COVID-19 related mitigation measures exacerbated existing predicaments in Africa, such as inadequate attention to cancer prevention strategies, psychosocial and palliative services and cancer research. The Africa Cancer ECHO recommends African countries to leverage the infrastructure developed in response to COVID-19 pandemic to strengthen the health system along the entire cancer control continuum. This calls for urgent action to develop and implement evidence-based frameworks and comprehensive National Cancer Control Plans that will withstand any future disruptions.
The COVID-19 related mitigation measures adversely affected various cancer control activities in Africa, with cancer prevention and screening activities amongst the most significantly impacted. When the COVID-19 pandemic struck, the Africa Cancer Research
9/1/2023Alicia A. LivinskiDivision of Library ServicesArticle
An increasing number of cancer epidemiology studies use metabolomics assays. This scoping review characterizes trends in the literature in terms of study design, population characteristics, and metabolomics approaches and identifies opportunities for future growth and improvement, including needs for standardized race and ethnicity reporting, more diverse study populations, and larger studies.
Cancer Epidemiology, Biomarkers & Prevention
8/2/2023Amanda L. Vogel; Brittany M. Haynes; Shadab F. Hussain; Lameese D. Akacem; Marcus G. Hodges; Gisela Butera; Jessica M. Faupel-BadgerDivision of Library ServicesArticle
Translational science education and training (E&T) aims to prepare the translational workforce to accelerate progress along the translational pipeline toward solutions that improve human health. In 2020–2021, the National Center for Advancing Translational Sciences (NCATS) Education Branch conducted a scoping review of the E&T literature with this focus. This review highlights strengths and opportunities for growth in translational science E&T. Enhancements to content, expansion of participants and modalities, and rigorous evaluations will contribute to building a highly qualified, diverse translational science workforce.
Clinical and Translational Science
9/14/2023Alicia A. LivinskiDivision of Library ServicesArticle
The burden of cancer and access to effective treatment are not experienced equally by all in the United States. For underserved populations that often access the health-care system when their cancers are in advanced disease stages, radiation oncology services are essential. In 2001, the National Cancer Institute’s (NCI’s) Radiation Research Program created and implemented the Cancer Disparities Research Partnership Program (CDRP). CDRP was a pioneering funding model whose goal was to increase participation of medically underserved populations in NCI clinical trials. CDRP’s Cooperative Agreement funding supported for awardees the planning, development, and conduct of radiation oncology clinical research in institutions not traditionally involved in NCI-sponsored research and cared for a disproportionate number of medically underserved, health-disparities populations. Six CDRP awards were made over two 5-year funding periods ending in 2013, with the end-of-program accomplishments previously reported. With the current focus on addressing equity, diversity, and inclusion, the 6 principal investigators were surveyed, 5 of whom responded about the impact of CDRP on their institutions, communities, and personal career paths. This article provides a 20-year retrospective of the experiences and observations from those principal investigators that can inform those now planning, building, and implementing equity, diversity, and inclusion programs.
JNCI: Journal of the National Cancer Institute
3/25/2023Esteban Astiazaran-Symonds; Gina M. Ney; Cecilia Higgs; Leatrisse Oba; Radhika Srivastava; Alicia A. Livinski; Philip S. Rosenberg & Douglas R. Stewart Division of Library ServicesArticle
Costello syndrome (CS) is a cancer-predisposition disorder caused by germline pathogenic variants in HRAS. We conducted a systematic review using case reports and case series to characterise cancer risk in CS.
British Journal of Cancer
1/1/2024Alicia A. LivinskiDivision of Library ServicesArticle
Sickle cell disease and beta thalassemia are some of the first targets for potentially curative cell-based therapies. Currently, bone marrow transplants, stem cell transplants, and gene therapy are being researched and utilized for people living with these hemoglobinopathies. Although these therapies are often described as curative, there is not a clear definition of what cure means for these hemoglobinopathies.
Genetics in Medicine Open
11/8/2023Jennifer M P Woo, Jennifer L Ish, Kemi Ogunsina, Che-Jung Chang, Camryn M Cohen, Amrita L Ramanathan, et alDivision of Library ServicesArticle
Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research.
JNCI Monographs
11/15/2023Alicia A. LivinskiDivision of Library ServicesArticle
The transfer of innovations from low and middle-income countries (LMICs) to high-income countries (HICs) has received little attention, leaving gaps in the understanding of the process, its benefits and the factors influencing it. This scoping review, part of a National Institutes of Health (NIH) project and the focus for a 2022 NIH-sponsored workshop on Global Health Reciprocal Innovation, sought to identify publications describing health innovations that were researched, developed and implemented in LMICs and adapted to address similar health challenges in HICs. Our results highlighted the underexplored field of LMIC to HIC innovation transfer and exchange and lay the foundation for future research studies.
BMJ Global Health
12/11/2023Alicia A. LivinskiDivision of Library ServicesArticle
Racially and ethnically minoritized (REM) women experience social and structural factors that may affect their response to mental health treatment and menopausal symptoms during the menopause transition (MT). This scoping review on mental health during the MT for REM women in the United States was conducted to characterize factors associated with mental health challenges.
Journal of Women's Health
12/12/2023Alicia A. LivinskiDivision of Library ServicesArticle
The COVID-19 pandemic has had drastic effects on worldwide mental health and laid bare health disparities and inequities among marginalised groups and racial/ethnic minoritised communities in the USA. This is especially the case among Hispanic/Latino/a immigrants who face numerous structural and socioeconomic barriers to well-being. The increased mental health burden on Hispanic/Latino/a immigrants may have far reaching effects if left unaddressed. Thus, by understanding further Hispanic/Latino/a immigrant mental health during the pandemic, communities and health providers may be able to better address this growing issue. This scoping review aims to assess and outline the current literature on the pandemic’s effects on Hispanic/Latino/a immigrant mental health in the USA, identify research gaps and areas of urgent concern, and inform future research and public health interventions and guidelines.
BMJ Open