Searching for studies: A guide to information retrieval for Campbell systematic reviews.

This guide outlines general issues in searching for studies; describes the main sources of potential studies; and discusses how to plan the search process, design, and carry out search strategies, manage references found during the search process and document and report the search process.

Perceived Acceptability of Technology Modalities for the Provision of Universal Child and Family Health Nursing Support in the First 6-8 Months After Birth: Cross-Sectional Study.

BACKGROUND: Child and Family Health Nursing (CFHN) services provide universal care to families during the first 2000 days (conception: 5 years) to support optimal health and developmental outcomes of children in New South Wales, Australia. The use of technology represents a promising means to encourage family engagement with CFHN services and enable universal access to evidenced-based age and stage information. Currently, there is little evidence exploring the acceptability of various models of technology-based support provided during the first 2000 days, as well as the maternal characteristics that may influence this. OBJECTIVE: This study aims to describe (1) the acceptability of technology-based models of CFHN support to families in the first 6 months, and (2) the association between the acceptability of technology-based support and maternal characteristics. METHODS: A cross-sectional survey was undertaken between September and November 2021 with women who were 6-8 months post partum within the Hunter New England Local Health District of New South Wales, Australia. Survey questions collected information on maternal demographics and pregnancy characteristics, perceived stress, access to CFHN services, as well as preferences and acceptability of technology-based support. Descriptive statistics were used to describe the characteristics of the sample, the proportion of women accessing CFHN services, maternal acceptability of technology-based support from CFHN services, and the appropriateness of timing of support. Multivariable logistic regression models were conducted to assess the association between maternal characteristics and the acceptability of technology-based CFHN support. RESULTS: A total of 365 women participated in the study, most were 25 to 34 years old (n=242, 68%), had completed tertiary level education or higher (n=250, 71%), and were employed or on maternity leave (n=280, 78%). Almost all (n=305, 89%) women reported accessing CFHN services in the first 6 months following their child's birth. The majority of women (n=282-315, 82%-92%) "strongly agreed or agreed" that receiving information from CFHN via technology would be acceptable, and most (n=308) women "strongly agreed or agreed" with being provided information on a variety of relevant health topics. Acceptability of receiving information via websites was significantly associated with maternal employment status (P=.01). The acceptability of receiving support via telephone and email was significantly associated with maternal education level (adjusted odds ratio 2.64, 95% CI 1.07-6.51; P=.03 and adjusted odds ratio 2.90, 95% CI 1.20-7.00; P=.02, respectively). Maternal age was also associated with the acceptability of email support (P=.04). CONCLUSIONS: Technology-based CFHN support is generally acceptable to mothers. Maternal characteristics, including employment status, education level, and age, were found to modify the acceptability of specific technology modalities. The findings of this research should be considered when designing technology-based solutions to providing universal age and stage child health and developmental support for families during the first 2000 days.

Effects of perfluoroalkyl sulfonic acids on developmental, physiological, and immunological measures in northern leopard frog tadpoles.

The chronic toxicity of short chain perfluoroalkyl sulfonic acids (PFSAs), such as perfluorobutanesulfonic acid (PFBS) and perfluorohexanesulfonic acid (PFHxS), are relatively understudied despite the increasing detection of these compounds in the environment. We investigated the chronic toxicity and bioconcentration of PFBS and PFHxS using northern leopard frog (Rana [Lithobates] pipiens) tadpoles. We exposed Gosner stage (GS) 25 tadpoles to either PFBS or PFHxS at nominal concentrations of 0.1, 1, 10, 100, and 1000 µg/L until metamorphosis (GS42). We then assessed tadpole growth, development, stress, and immune metrics, and measured fatty acid (FA) composition and PFSA concentrations in liver and whole-body tissues. Tadpole growth and development measures were relatively unaffected by PFSA exposure. However, tadpoles exposed to 1000 µg/L PFBS or PFHxS had significantly increased hepatosomatic indexes (HSI) relative to controls. Further, tadpoles from the 1000 µg/L PFHxS treatment had altered FA profiles relative to controls, with increased total FAs, saturated FAs, monounsaturated FAs, and omega-6 polyunsaturated FAs. In addition, tadpoles from the 1000 µg/L PFHxS treatment had a higher probability of waterborne corticosterone detection. These results suggest that PFBS and PFHxS influence the hepatic health of tadpoles, and that PFHxS may alter lipid metabolism in tadpoles. We also observed a higher probability of tadpoles being phenotypically female after exposure to an environmentally relevant concentration (0.1 µg/L) of PFHxS, suggesting that PFHxS may exert endocrine disrupting effects on tadpoles during early development. The measured bioconcentration factors (BCFs) for both compounds were ≤10 L kg-1 wet weight, suggesting low bioconcentration potential for PFBS and PFHxS in tadpoles. Many of the significant effects observed in this study occurred at concentrations several orders of magnitude above those measured in the environment; however, our work shows effects of PFSAs exposure on amphibians and provides essential information for ecological risk assessments of these compounds.

Searching and reporting in Campbell Collaboration systematic reviews: A systematic assessment of current methods.

The search methods used in systematic reviews provide the foundation for establishing the body of literature from which conclusions are drawn and recommendations made. Searches should aim to be comprehensive and reporting of search methods should be transparent and reproducible. Campbell Collaboration systematic reviews strive to adhere to the best methodological guidance available for this type of searching. The current work aims to provide an assessment of the conduct and reporting of searches in Campbell Collaboration systematic reviews. Our objectives were to examine how searches are currently conducted in Campbell systematic reviews, how search strategies, search methods and search reporting adhere to the Methodological Expectations of Campbell Collaboration Intervention Reviews (MECCIR) and PRISMA standards, and identify emerging or novel methods used in searching in Campbell systematic reviews. We also investigated the role of information specialists in Campbell systematic reviews. We handsearched the Campbell Systematic Reviews journal tables of contents from January 2017 to March 2024. We included all systematic reviews published since 2017. We excluded other types of evidence synthesis (e.g., evidence and gap maps), updates to systematic reviews when search methods were not changed from the original pre-2017 review, and systematic reviews that did not conduct their own original searches. We developed a data extraction form in part based on the conduct and reporting items in MECCIR and PRISMA. In addition, we extracted information about the general quality of searches based on the use of Boolean operators, keywords, database syntax and subject headings. Data extraction included information about reporting of sources searched, some aspects of search quality, the use and reporting of supplementary search methods, reporting of the search strategy, the involvement of information specialists, date of the most recent search, and citation of the Campbell search methods guidance. Items were rated as fully, partially or not conducted or reported. We cross-walked our data extraction items to the 2019 MECCIR standards and 2020 PRISMA guidelines and provide descriptive analyses of the conduct and reporting of searches in Campbell systematic reviews, indicating level of adherence to standards where applicable. We included 111 Campbell systematic reviews across all coordinating groups published since 2017 up to the search date. Almost all (98%) included reviews searched at least two relevant databases and all reported the databases searched. All reviews searched grey literature and most (82%) provided a full list of grey literature sources. Detailed information about databases such as platform and date range coverage was lacking in 16% and 77% of the reviews, respectively. In terms of search strategies, most used Boolean operators, search syntax and phrase searching correctly, but subject headings in databases with controlled vocabulary were used in only about half of the reviews. Most reviews reported at least one full database search strategy (90%), with 63% providing full search strategies for all databases. Most reviews conducted some supplementary searching, most commonly searching the references of included studies, whereas handsearching of journals and forward citation searching were less commonly reported (51% and 62%, respectively). Twenty-nine percent of reviews involved an information specialist co-author and about 45% did not mention the involvement of any information specialist. When information specialists were co-authors, there was a concomitant increase in adherence to many reporting and conduct standards and guidelines, including reporting website URLs, reporting methods for forward citation searching, using database syntax correctly and using subject headings. No longitudinal trends in adherence to conducting and reporting standards were found and the Campbell search methods guidance published in 2017 was cited in only twelve reviews. We also found a median time lag of 20 months between the most recent search and the publication date. In general, the included Campbell systematic reviews searched a wide range of bibliographic databases and grey literature, and conducted at least some supplementary searching such as searching references of included studies or contacting experts. Reporting of mandatory standards was variable with some frequently unreported (e.g., website URLs and database date ranges) and others well reported in most reviews. For example, database search strategies were reported in detail in most reviews. For grey literature, source names were well reported but search strategies were less so. The findings will be used to identify opportunities for advancing current practices in Campbell reviews through updated guidance, peer review processes and author training and support.

Redox-responsive CpG-dextran conjugate enhances anti-tumour immunity following intratumoral administration.

Conjugation of a therapeutic agent to a polymer for enhanced delivery into target cells followed by its intracellular triggered release has proved to be an effective drug delivery approach. This approach is applied to the delivery of the immune-stimulatory unmethylated cytosine-phosphate-guanine (CpG) oligonucleotide for an anti-tumour immune response after intratumoral administration. On average four CpG-1668 molecules were covalently linked to a 40-kDa amino-functionalised dextran polymer via either a non-reversible (CpG-dextran) or an intracellular redox-responsive disulfide linkage (CpG-SS-dextran). Dynamic light scattering analysis showed that both conjugates had a similar particle size and surface charge of 17 nm and -10 mV, respectively. Agarose gel electrophoresis analysis showed that CpG-SS-dextran was stable in the extracellular low glutathione (GSH) concentration range (i.e. 10-20 µM) and was cleaved at the higher intracellular GSH concentration (5 mM), while CpG-dextran was stable in both GSH concentrations. Uptake and activation assays on bone-marrow-derived dendritic cells showed no significant difference between free CpG, CpG-dextran and CpG-SS-dextran. In a mouse subcutaneous colorectal tumour model the CpG-SS-dextran showed a statistically significantly greater inhibition of tumour growth (p < 0.03) and prolonged survival (p < 0.001) compared to CpG-dextran or free CpG. These results demonstrate that the redox-triggered intracellular release of CpG from a dextran polymer carrier has promise for intratumoral therapeutic vaccination against cancer.

Whole exome sequencing reveals a dual diagnosis of BCAP31-related syndrome and glutaric aciduria III.

Background: Biochemical testing is a common first-tier approach in the setting of genetic evaluation of patients with unexplained developmental delay. However, results can be unclear, and a plan for second-tier analysis must be determined based on the patient's biochemical results and clinical presentation - in many cases, triggering a diagnostic odyssey. Case presentation: A male patient from the United States presenting with unexplained developmental delay, microcephaly, hypotonia, and feeding difficulties was referred for clinical genetic evaluation at age 8 months. Biochemical testing revealed an isolated marked elevation of glutaric acid on urine organic acid profile, without elevations of related metabolites. Further testing included GCDH sequencing, a neurometabolic gene panel, chromosomal microarray, Prader Willi/Angelman testing, and lysosomal disease enzyme panel, all of which were non-diagnostic. The patient had persistent developmental delay and hypotonia, dystonia, sensorineural hearing loss, and abnormal brain myelination on magnetic resonance imaging. Whole exome sequencing (WES) was performed and revealed a dual diagnosis of glutaric aciduria III (GA III) and BCAP31-related disorder, an X-linked intellectual disability syndrome, caused by a novel pathogenic variant. Conclusions: GA III has historically been considered clinically benign, with few reported cases. This patient's presenting symptoms were similar to those commonly seen in GA I and GA II, however the biochemical abnormalities were not consistent with these disorders, prompting additional molecular and biochemical testing. Ultimately, WES confirmed a diagnosis of BCAP31-related syndrome, a rare neurological disorder, which explained the patient's presenting symptoms. WES also identified a secondary diagnosis of GA III. We present a patient with two rare genetic conditions, highlighting the importance of deep phenotyping and the utility of WES in the setting of a patient with dual genetic diagnoses.

Value chain interventions for improving women's economic empowerment: A mixed-methods systematic review and meta-analysis: A systematic review.

Background: Value chain interventions have become widespread throughout the international development sector over the last 20 years, and there is a need to evaluate their effectiveness in improving women's welfare across multiple dimensions. Agricultural value chains are influenced by socio-cultural norms and gender dynamics that have an impact on the distribution of resources, benefits, and access to opportunities. While women play a critical role in agriculture, they are generally confined to the least-valued parts of the value chain with the lowest economic returns, depending on the local, social and institutional contexts. Objectives: The review assesses the effectiveness of approaches, strategies and interventions focused on women's engagement in agricultural value chains that lead to women's economic empowerment in low- and middle-income countries. It explores the contextual barriers and facilitators that determine women's participation in value chains and ultimately impact their effectiveness. Search Methods: We searched completed and on-going studies from Scopus, Web of Science Core Collection (Social Sciences Citation Index [SSCI], Science Citation Index Expanded [SCI-EXPANDED], Conference Proceedings Citation Index - Science [CPCI-S], Conference Proceedings Citation Index - Social Science & Humanities [CPCI-SSH], and Emerging Sources Citation Index [ESCI]), International Bibliography of the Social Sciences, EconLit, Business Source Premier, APA PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane, Database of Systematic Reviews, CAB Abstracts and Sociological Abstracts. We also searched relevant websites such as Consortium of International Agricultural Research Centers (CGIAR); the International Fund for Agricultural Development (IFAD); AgriProFocus; the Bill & Melinda Gates Foundation (BMGF); Donor Committee for Enterprise Development; the UN Food and Agriculture Organisation (FAO); the International Labour Organisation (ILO); the Netherlands Development Organisation; USAID; the Swiss Agency for Development and Cooperation; the International Food Policy Research Institute; World Agroforestry; the International Livestock Research Institute; the Foreign, Commonwealth & Development Office; the British Library for Development Studies (BLDS); AGRIS; the IMMANA grant database; the 3ie impact evaluation database; Innovations for Poverty Action (IPA); The Abdul Latif Jameel Poverty Action Lab (J-PAL); the World Bank IEG evaluations; the USAID Development Data Library; Experience Clearinghouse; the proceedings of the Agriculture, Nutrition and Health Academy conference; the proceedings of the Centre for the Study of African Economies (CSAE) Conference; the proceedings of the North East Universities Development Consortium (NEUDC) Conference; and the World Bank Economic Review. The database search was conducted in March 2022, and the website search was completed in August 2022. Selection Criteria: The review includes value chain interventions evaluating the economic empowerment outcomes. The review includes effectiveness studies (experimental and non-experimental studies with a comparison group) and process evaluations. Data Collection and Analysis: Two review authors independently assessed studies for inclusion, extracted data, critically appraised the studies, and synthesised findings. Results: We found that value chain interventions are successful in improving the economic conditions of their intended beneficiaries. The interventions were found to improve women's economic outcomes such as income, assets holdings, productivity, and savings, but these effects were small in size and limited by low confidence in methodological quality. The meta-analysis suggests that this occurs more via the acquisition of skills and improved inputs, rather than through improvement in access to profitable markets. The qualitative evidence on interventions points to the persistence of cultural barriers and other constraints. Those interventions implemented in Sub-Saharan Africa and South Asia are consistently more successful for all outcomes considered, although there are few studies conducted in other areas of the world. Conclusions: The review concludes that value chain interventions empower women, but perhaps to a lesser extent than expected. Economic empowerment does not immediately translate into empowerment within families and communities. Interventions should either moderate their expectations of empowerment goals, or they should be implemented in a way that ensures higher rates of participation among women and the acquisition of greater decision-making power.

Racial and Ethnic Disparities in Occult Hypoxemia Prevalence and Clinical Outcomes Among Hospitalized Patients: A Systematic Review and Meta-analysis.

BACKGROUND: There is growing concern that pulse oximeters are routinely less accurate in hospitalized patients with darker skin pigmentation, in turn increasing risk of undetected (occult) hypoxemia and adverse clinical outcomes. The aim of this systematic review and meta-analysis was to synthesize evidence on racial and ethnic disparities in occult hypoxemia prevalence and clinical impacts of undetected hypoxemia. METHODS: Ovid MEDLINE, Embase, and CINAHL databases were searched for relevant articles published through January 2024. Eligible studies must have been conducted among adults in inpatient or outpatient settings and report occult hypoxemia prevalence stratified by patient race or ethnicity, or clinical outcomes stratified by patient race or ethnicity and occult hypoxemia status. Screening for inclusion was conducted independently by two investigators. Data extraction and risk of bias assessment were conducted by one investigator then checked by a second. Outcome data were synthesized using random-effects meta-analyses. RESULTS: Fifteen primary studies met eligibility criteria and reported occult hypoxemia prevalence in 732,505 paired oximetry measurements from 207,464 hospitalized patients. Compared with White patients, occult hypoxemia is likely more common among Black patients (pooled prevalence ratio = 1.67, 95% CI 1.47 to 1.90) and among patients identifying as Asian, Latinx, Indigenous, multiracial, or other race or ethnicity (pooled prevalence ratio = 1.39, 95% CI 1.19 to 1.64). Findings from studies reporting clinical outcomes suggest that Black patients with undetected hypoxemia may experience poorer treatment delivery outcomes than White patients with undetected hypoxemia. No evidence was found from outpatient settings. DISCUSSION: This review and included primary studies rely on self-identified race or ethnicity, which may obscure variability in occult hypoxemia risk. Findings underscore that clinicians should be aware of the risk of occult hypoxemia in hospitalized patients with darker skin pigmentation. Moreover, oximetry data from included studies suggests that the accuracy of pulse oximeters could vary substantially from patient to patient and even within individual patients. TRIAL REGISTRATION: PROSPERO ( CRD42023402152 ).

The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.

Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.

Intravenous push lacosamide: Successful implementation and patient outcomes across a health system.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Intravenous administration of the antiseizure medication lacosamide can be delayed given operational challenges related to short beyond-use-dating and controlled substance requirements. The purpose of this study was to describe the steps required to successfully transition from intravenous piggyback administration to intravenous push administration and demonstrate that workflow changes improved time to administration without compromising patient safety. METHODS: This multicenter study had 2 components; the first portion was a prospective description of the implementation and operationalization process, while the second was a retrospective cohort analysis comparing patients who received intravenous piggyback and intravenous push lacosamide. After the transition, the default administration route for adult patients for lacosamide doses of 400 mg or less was intravenous push. While the primary objective was to describe the implementation process, secondary objectives included comparison of time to administration and safety, using a composite and incidence of PR prolongation. RESULTS: Success in implementation and operationalization across a large health system was achieved by following a 6-month timeline. A total of 102 patients were included in the cohort study, with 869 individual administrations analyzed (519 intravenous piggyback and 350 intravenous push). Time from verification to administration was significantly decreased when comparing intravenous piggyback (median, 159 minutes) to intravenous push (median, 88 minutes) administrations (P = 0.008). No significant difference was found in the safety composite or PR prolongation. CONCLUSION: Transitioning intravenous lacosamide administration from piggyback to push administration is feasible and decreases time from verification to administration without increased incidence of adverse effects.

Improving Transition of Care for Pediatric Patients With Chronic Kidney Disease: A Pilot Project.

Introduction Transition is the process of preparing an adolescent or young adult for the adult model of care. Poor transitions have been linked to increased medical utilization and poorer kidney outcomes. There are limited studies evaluating predictors of transition readiness or interventions in pediatric patients with chronic kidney disease (CKD). Methods We enrolled 42 non-dialysis, non-transplant patients with CKD stage 2 or higher and 14 years and older receiving care in our pediatric nephrology clinic. Data collected included demographics, clinical information, and transition readiness as measured by the Transition Readiness Assessment Questionnaire (TRAQ). Patients were provided with a structured, remote curriculum with resources that addressed areas of need. Patients were followed every three to six months. Repeat TRAQ questionnaires were administered six months after enrollment. Results Our study found that younger age and male gender were risk factors for poor transition. Age was consistently a positive predictor of higher TRAQ scores in the medication, appointment, and total score domains (p < 0.05). Male gender was a risk factor for lower TRAQ scores in the appointment and communication domains (p < 0.05). Additionally, our curriculum was effective at improving scores across all TRAQ domains, with an average increase of about 25% in six months. There was no difference in patients who had a three-month follow-up as compared to a six-month follow-up (p > 0.05). Conclusion Our study finds that younger age and male gender are risk factors for poor transition. Additionally, a structured, remote curriculum is effective at improving transition readiness.

Ten tips on how to care for your CKD patients in episodes of extreme heat.

Climate change is responsible for ≈75% of extreme heat events throughout the world. Heat events are associated with an increased risk for acute kidney injury, which contributes to the development of chronic kidney disease (CKD) and cardiovascular events. Patients with CKD are especially vulnerable to heat stress for a variety of reasons. A disproportionate percentage of patients with CKD live in poverty; experience homelessness, mental illness or disabilities; work outside or are elderly, all demographics that overlap with populations most susceptible to episodes of extreme heat. Therefore, it is reasonable to conclude that exposure to episodes of extreme heat can lead to the progression of CKD and increases morbidity and mortality. Given these concerns, clinicians must be prepared to promptly recognize complications of heat in CKD patients and to help patients appropriately acclimate. We propose the following tips for clinicians to effectively care for their CKD patients during extreme heat days.

Corrigendum: Late-stage MC38 tumours recapitulate features of human colorectal cancer - implications for appropriate timepoint selection in preclinical studies.

[This corrects the article DOI: 10.3389/fimmu.2023.1152035.].

Multi-center study on sellar reconstruction after endoscopic transsphenoidal pituitary surgery.

INTRODUCTION: Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques. METHODS: A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test. RESULTS: Five hundred and one patients were identified. The median tumor size was 2.1 cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3 cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p < 0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication. CONCLUSION: The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks.

Exploratory mapping of tumor associated macrophage nanoparticle article abstracts using an eLDA topic modeling machine learning approach.

The role of macrophages in regulating the tumor microenvironment has spurned the exponential generation of nanoparticle targeting technologies. With the large amount of literature and the speed at which it is generated it is difficult to remain current with the most up-to-date literature. In this study we performed a topic modeling analysis of 854 abstracts of peer-reviewed literature for the most common usages of nanoparticle targeting of tumor associated macrophages (TAMs) in solid tumors. The data spans 20 years of literature, providing a broad perspective of the nanoparticle strategies. Our topic model found 6 distinct topics: Immune and TAMs, Nanoparticles, Imaging, Gene Delivery and Exosomes, Vaccines, and Multi-modal Therapies. We also found distinct nanoparticle usage, tumor types, and therapeutic trends across these topics. Moreover, we established that the topic model could be used to assign new papers into the existing topics, thereby creating a Living Review. This type of "birds-eye-view" analysis provides a useful assessment tool for exploring new and emerging themes within a large field.

PROTOCOL: Abortion and mental health outcomes: A systematic review and meta-analysis.

This is a protocol for a systematic review and meta-analysis of research on mental health outcomes of abortion. Does abortion increase the risk of adverse mental health outcomes? That is the central question for this review. Our review aims to inform policy and practice by locating, critically appraising, and synthesizing empirical evidence on associations between abortion and subsequent mental health outcomes. Given the controversies surrounding this topic and the complex social, political, legal, and ideological contexts in which research and reviews on abortion are conducted, it is especially important to conduct this systematic review and meta-analysis with comprehensive, rigorous, unbiased, and transparent methods. We will include a variety of study designs to enhance understanding of studies' methodological strengths and weaknesses and to identify potential explanations for conflicting results. We will follow open science principles, providing access to our methods, measures, and results, and making data available for re-analysis.

Blood flow regulates acvrl1 transcription via ligand-dependent Alk1 activity.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by the development of arteriovenous malformations (AVMs) that can result in significant morbidity and mortality. HHT is caused primarily by mutations in bone morphogenetic protein receptors ACVRL1/ALK1, a signaling receptor, or endoglin (ENG), an accessory receptor. Because overexpression of Acvrl1 prevents AVM development in both Acvrl1 and Eng null mice, enhancing ACVRL1 expression may be a promising approach to development of targeted therapies for HHT. Therefore, we sought to understand the molecular mechanism of ACVRL1 regulation. We previously demonstrated in zebrafish embryos that acvrl1 is predominantly expressed in arterial endothelial cells and that expression requires blood flow. Here, we document that flow dependence exhibits regional heterogeneity and that acvrl1 expression is rapidly restored after reinitiation of flow. Furthermore, we find that acvrl1 expression is significantly decreased in mutants that lack the circulating Alk1 ligand, Bmp10, and that, in the absence of flow, intravascular injection of BMP10 or the related ligand, BMP9, restores acvrl1 expression in an Alk1-dependent manner. Using a transgenic acvrl1:egfp reporter line, we find that flow and Bmp10 regulate acvrl1 at the level of transcription. Finally, we observe similar ALK1 ligand-dependent increases in ACVRL1 in human endothelial cells subjected to shear stress. These data suggest that ligand-dependent Alk1 activity acts downstream of blood flow to maintain or enhance acvrl1 expression via a positive feedback mechanism, and that ALK1 activating therapeutics may have dual functionality by increasing both ALK1 signaling flux and ACVRL1 expression.

A 3D-Printed and Freely Available Device to Measure the Zebrafish Optokinetic Response Before and After Injury.

Zebrafish eyes are anatomically similar to humans and have a higher percentage of cone photoreceptors more akin to humans than most rodent models, making them a beneficial model organism for studying vision. However, zebrafish are different in that they can regenerate their optic nerve after injury, which most other animals cannot. Vision in zebrafish and many other vertebrate animals, including humans, can be accessed using the optokinetic response (OKR), which is an innate eye movement that occurs when tracking an object. Because fish cannot use an eye chart, we utilize the OKR that is present in virtually all vertebrates to determine if a zebrafish has vision. To this end, we have developed an inexpensive OKR setup that uses 3D-printed and off-the-shelf parts. This setup has been designed and used by undergraduate researchers and is also scalable to a classroom laboratory setup. We demonstrate that this setup is fully functional for assessing the OKR, and we use it to illustrate the return of the OKR following optic nerve injury in adult zebrafish.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.