The transcription factor E2A drives neural differentiation in pluripotent cells.

The intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via transcriptional upregulation of inhibitor of differentiation (Id) factors. We have previously identified the major binding partner of Id proteins in pluripotent cells as the basic helix-loop-helix (bHLH) transcription factor (TF) E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, including Sox1 and Foxd4, and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.

The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer? SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects. WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved. STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer. LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children. WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Survival after a cancer diagnosis among solid organ transplant recipients in the United States.

BACKGROUND: Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors' knowledge no study to date has comprehensively examined associations between transplantation status and mortality after a cancer diagnosis. METHODS: The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987-2014). Cox models were used to examine the association between transplantation status and cancer-specific mortality, adjusting for demographic characteristics and cancer stage. RESULTS: For the majority of cancers, cancer-specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [95% CI], 2.18-3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61-2.19), bladder (aHR, 1.85; 95% CI, 1.58-2.17), and colorectum (aHR, 1.77; 95% CI, 1.60-1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B-cell lymphoma (aHR range, 1.21-1.47). Associations remained significant after adjustment for first-course cancer treatment and generally were stronger among patients with local-stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94-4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07-3.70), breast (aHR, 2.08; 95% CI, 1.50-2.88), and prostate (aHR, 1.60; 95% CI, 1.12-2.29), despite the lack of an association for prostate cancer overall. CONCLUSIONS: For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.

Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.

Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.

Lead optimization of isocytosine-derived xanthine oxidase inhibitors.

We report our attempts at improving the oral efficacy of low-nanomolar inhibitors of xanthine oxidase from isocytosine series through chemical modifications. Our lead compound had earlier shown good in vivo efficacy when administered intraperitoneally but not orally. Several modifications are reported here which achieved more than twofold improvement in exposure. A compound with significant improvement in oral efficacy was also obtained.

Unintentional Child Injury in Rural and Urban Siddlagatta, Karnataka, India: A Community-Based Survey.

INTRODUCTION: Despite Indian children constituting approximately 31.4% of the population aged 0 to 14, a comprehensive exploration of childhood injuries within this demographic remains limited. This study aimed to examine the occurrence of unintentional injuries among children aged six months to 18 years in the Siddlagatta area and assess associated risk factors. METHODOLOGY: A community-based, cross-sectional study on unintentional child injuries was carried out from March 2018 to September 2020 across 11 sites in India. Employing a two-stage cluster sampling method with probability proportionate to size, 2341 urban and rural families were selected from each site. Data on unintentional injuries sustained over the past 12 months were collected using the WHO child injury questionnaire, tailored and validated for the Indian context. RESULTS: The study encompassed 10,335 individuals in households, including 2695 children aged 6 months to 18 years. Among them, 309 children experienced 390 unintentional injuries in the preceding year, excluding minor incidents. A prevalence rate of 11.5% (95% CI: 10.3-12.7) was identified for unintentional injuries among children, excluding minor cases. Falls were the most prevalent injury type (183 cases, 53.8%), while poisoning incidents were the least frequent (one case, 0.2%). More than 50% of incidents occurred within domestic settings. CONCLUSIONS: This study's outcomes underscore the prominence of fall-related injuries across all age groups and genders. Homes and schools emerged as primary settings for these injuries, highlighting the need for targeted preventive measures.

Prognostic significance of tetraspanin CD9 and oncogenic epidermal growth factor receptor in tongue squamous cell carcinoma survival.

The most prevalent locations for head and neck cancer is the tongue. The surviving patients who are receiving therapy have considerably compromised speech, taste, chewing, and swallowing. CD9 is a cell surface protein that has contradictory role in cancer progression. The objective of the study is to analyze the Cluster of Differentiation 9(CD9), Epidermal Growth Factor Receptor (EGFR) and Phosphorylated Akt (p-Akt) expression in tongue cancer specimens and its clinical significance.50 tongue cancer sections were used to analyze the expression of CD9,EGFR and p-Akt by immunohistochemistry. Data regarding the histological grade of the tumor, age, sex, and habits were recorded, and relation with CD9,EGFR and p-Akt expression was assessed. Data were expressed as mean ± SEM. Categorical data was analyzed by Chi-square test. Student t-test was used to check the significance of data between two groups.A significant increase in the CD9,EGFR and p-Akt expression (1.8 ± 0.11, 2.06 ± 0.18 and 2.3 ± 0.15 respectively) was seen in the tongue cancer specimens. CD9 and p-Akt expression had a significant association with the histological grade (p < 0.004 and p < 0.006 respectively). CD9 expression was higher in patients with the combination of addiction/habit compared to patients with single addictions(1.08 ± 0.11 and 0.75 ± 0.47). Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.

Burden of invasive cervical cancer in North Carolina.

OBJECTIVE: Cervical cancer causes over 4000 deaths yearly in the United States, although highly preventable through vaccination, screening, and early treatment. We aimed to determine demographic correlates for cervical cancer in North Carolina to identify target populations for interventions and to create a framework for state-level analyses. METHOD: Data on all reported invasive cervical cancer cases from 1998 to 2007 were obtained from the North Carolina Central Cancer Registry. Age-adjusted incidence and mortality rates were estimated using population data from the National Center for Health Statistics. RESULTS: Cervical cancer incidence and mortality rates varied greatly by county and were inversely associated with county prosperity. Hispanic women had the highest incidence rate, black women the highest mortality rate, although white women accounted for most cases. Incidence rates remained fairly steady above age 35 and mortality rates steadily increased with age. A later stage at diagnosis was more common for older women and for women without private insurance. CONCLUSION: Registry-based assessment illustrates the economic, racial, and age disparities associated with cervical cancer. This localized focus on demographic correlates is an important step toward eliminating this preventable disease and offers a template for cervical cancer prevention programs in other states.

Isocytosine-based inhibitors of xanthine oxidase: design, synthesis, SAR, PK and in vivo efficacy in rat model of hyperuricemia.

Structure-activity relationship studies were carried out for lead generation following structure-guided design approach from an isocytosine scaffold identified earlier for xanthine oxidase inhibition. A 470-fold improvement in in vitro IC(50) was obtained in the process. Five most potent compounds with nanomolar IC(50) values were selected for pharmacokinetics and in vivo experiments. The best compound showed good in vivo activity when administered intraperitoneally but was not active by oral route. The results suggest that improvement in oral exposure could improve the in vivo efficacy of this series.

Identification of novel isocytosine derivatives as xanthine oxidase inhibitors from a set of virtual screening hits.

In recent years, xanthine oxidase has emerged as an important target not only for gout but also for cardiovascular and metabolic disorders involving hyperuricemia. Contrary to popular belief, recent clinical trials with uricosurics have demonstrated that enhanced excretion of uric acid is, by itself, not adequate to treat hyperuricemia; simultaneous inhibition of production of uric acid by inhibition of xanthine oxidase is also important. Virtual screening of in-house synthetic library followed by in vitro and in vivo testing led to the identification of a novel scaffold for xanthine oxidase inhibition. In vitro activity results corroborated the results from molecular docking studies of the virtual screening hits. The isocytosine scaffold maintains key hydrogen bonding and pi-stacking interactions in the deep end of the xanthine-binding pocket, which anchors it in an appropriate pose to inhibit binding of xanthine and shows promise for further lead optimization using structure-based drug design approach.

Human Induced Pluripotent Stem Cell (iPSC) Handling Protocols: Maintenance, Expansion, and Cryopreservation.

Human induced pluripotent stem cells (iPSCs) have emerged as an invaluable resource for basic research, disease modeling, and drug discovery over recent years. Given the numerous advantages of iPSCs over alternative models-including their human origin, their ability to be differentiated into almost any cell type, and the therapeutic potential of patient-specific iPSCs in personalized medicine-many labs are now considering iPSC models for their studies. As the quality of the starting population of iPSCs is a key determinant in the success of any one of these applications, it is crucial to adhere to best practices in iPSC culture. In the following protocol, we offer a comprehensive guide to the culture, cryopreservation, and quality control methods required for the establishment and maintenance of high-quality iPSC cultures.

Indian Academy of Pediatrics Consensus Guidelines on Prevention and Management of Suicidal Behavior in Adolescents.

JUSTIFICATION: Suicide is an important cause of adolescent mortality and morbidity in India. As pediatricians are often the first point of contact for adolescents and their families in the healthcare system, they need guidelines to screen, assess, manage and prevent adolescent suicidal behavior to ensure survival, health and mental well-being of this vulnerable population. OBJECTIVES: To formulate guidelines to aid pediatricians for prevention and management of adolescent suicidal behavior. PROCESS: Indian Academy of Pediatrics, in association with Adolescent Health Academy, formed a multidisciplinary committee of subject experts in June, 2019 to formulate guidelines for adolescent suicide prevention and management. After a review of current scientific literature and preparation of draft guidelines, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by refining of draft guidelines, and discussions over e-mail where suggestions were incorporated and the final document was approved. GUIDELINES: Pediatricians should screen for mental distress, mental disorders and suicidal and para-suicidal (non-suicidal self-injury) behavior during adolescent health visits. Those with suicidal behavior should be referred to a psychiatrist after providing emergency healthcare, risk assessment, immediate counselling and formulation of a safety plan. Pediatricians should partner with the community and policymakers for primary and secondary prevention of adolescent suicide.

Indian Academy of Pediatrics Consensus Guidelines for Adolescent Friendly Health Services.

JUSTIFICATION: Adolescent health is critical to the current and future well- being of the world. Pediatricians need country specific guidelines in accordance with international and national standards to establish comprehensive adolescent friendly health services in clinical practice. PROCESS: Indian Academy of Pediatrics (IAP) in association with Adolescent Health Academy formed a committee of subject experts in June, 2019 to formulate guidelines for adolescent friendly health services. After a review of current scientific literature and drafting guidelines on each topic, a national consultative meeting was organized on 16 August, 2019 for detailed discussions and deliberations. This was followed by discussions over e-mail and refining of draft recommendations. The final guidelines were approved by the IAP Executive Board in December, 2021. OBJECTIVE: To formulate guidelines to enable pediatricians to establish adolescent friendly health services. Recommendations: Pediatricians should coordinate healthcare for adolescents and plan for transition of care to an adult physician by 18 years of age. Pediatricians should establish respectful, confidential and quality adolescent friendly health services for both out-patient and in-patient care. The healthcare facility should provide preventive, therapeutic, and health promoting services. Pediatricians should partner with the multidisciplinary speciality services, community, and adolescents to expand the scope and reach of adolescent friendly health services.

Cost of breast cancer treatment in Medicaid: implications for state programs providing coverage for low-income women.

BACKGROUND: To date, no study has reported on the cost of treating breast cancer among Medicaid beneficiaries younger than 65 years of age. This information is essential for assessing the funding required for treatment programs established by the Breast and Cervical Cancer Prevention and Treatment Act of 2000. OBJECTIVE: This study assesses the incremental cost of breast cancer treatment among Medicaid beneficiaries aged below 65 years. RESEARCH DESIGN: Administrative data from the North Carolina Medicaid program linked with cancer registry data were analyzed to derive monthly Medicaid costs for cancer patients and the incremental costs of breast cancer treatment at 6, 12, and 24 months from diagnosis. We compared 848 beneficiaries diagnosed with cancer during the years 2002 to 2004 with 1696 comparison cases matched on age. RESULTS: With the exception of in situ cancers, the cost of cancer care continued to increase beyond the initial 6-month period. The incremental costs at 6 months after diagnosis are $14,341, $24,002, and $34,469 for those with local, regional, and distant breast cancers, respectively; and these costs increased to $22,343, $41,005, and $117,033 at 24 months. CONCLUSIONS: The extended period of health care utilization, beyond the immediate 6-month period after diagnosis, indicates that Medicaid coverage may be required for many months after diagnosis to complete treatment. Continuous Medicaid coverage should be provided for an adequate time period to ensure that complete and comprehensive treatment is provided.

Spectrum of cancer risk among US solid organ transplant recipients.

CONTEXT: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. OBJECTIVE: To describe the overall pattern of cancer following solid organ transplantation. DESIGN, SETTING, AND PARTICIPANTS: Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES: Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS: The registry linkages yielded data on 175,732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10,656 cases and an incidence of 1375 per 100,000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100,000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100,000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100,000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100,000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100,000 person-years), liver (n = 930; incidence: 120.0 per 100,000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100,000 person-years), and kidney (n = 752; incidence: 97.0 per 100,000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100,000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). CONCLUSION: Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Depression in adolescents with chronic medical illness.

Chronic illness can lead to anxiety and depression in both parents and their adolescents. The identification of predictor variables would greatly assist pediatricians and parents in identifying children at risk for prolonged depression. Findings indicate that age and gender of the adolescent and duration of illness did not affect the depression score, but type of illness affected the score significantly. This article illustrates the fact that pediatricians can use the Beck Depression Inventory to identify depression and guide parents and adolescents to adequate medical care.

Global Health Education Amidst COVID-19: Disruptions and Opportunities.

This viewpoint examines the impact of COVID-19 travel bans and remote education on the global health education of students from high-income countries (HIC) and low- and middle-income countries (LMIC) and explores potential opportunities for strengthening global health education based upon more dispersed and equitable practices. Global health is unique in the opportunities it can offer to students during the pandemic if programs can manage and learn from the pandemic's many challenges. Global health educators can: shift to sustainable remote engagement and mobilize resources globally to facilitate this; collaborate with partners to support the efforts to deal with the current pandemic and to prepare for its next phases; partner in new ways with health care professional students and faculty from other countries; collaborate in research with partners in studies of pandemic related health disparities in any country; and document and examine the impact of the pandemic on health care workers and students in different global contexts. These strategies can help work around pandemic travel restrictions, overcome the limitations of existing inequitable models of engagement, and better position global health education and face future challenges while providing the needed support to LMIC partners to participate more equally.

Validity of state cancer registry treatment information for adolescent and young adult women.

BACKGROUND: Population-based cancer registries collect information on first course of treatment that may be utilized in research on cancer care quality, yet few studies have investigated the validity of this information. We examined the accuracy and completeness of registry-based treatment information in a cohort of adolescent and young adult women. METHODS: Women diagnosed with breast cancer, lymphoma, thyroid cancer, cervical/uterine cancer or ovarian cancer at ages 15-39 during 2003-2014 were identified using data from the North Carolina Central Cancer Registry (CCR) (N = 2342). CCR data were linked to Medicaid and private insurance claims data, and claims were reviewed for the 12 months following diagnosis to identify cancer treatments received. Using claims data as the gold standard, we calculated the sensitivity and positive predictive value (PPV) of CCR data for receipt of chemotherapy, radiation and hormone therapy. We also compared dates of treatment initiation between the two data sources. RESULTS: For all cancer types combined, the sensitivity of the CCR data was high for chemotherapy (86%) and moderate for radiation (74%). PPVs were 82% and 83% for chemotherapy and radiation, respectively. Both the sensitivity (67%) and PPV (70%) were lower for hormone therapy for breast cancer. For all three treatment types, dates of initiation in the registry and the claims differed by ≤30 days for most women. CONCLUSIONS: In this cohort of young women, population-based cancer registry data on chemotherapy receipt was reasonably accurate and complete in comparison with insurance claims. Radiation and hormone therapy appeared to be less complete.

Assessment of Birth Defects and Cancer Risk in Children Conceived via In Vitro Fertilization in the US.

Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF). Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally. Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020. Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries. Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups. Results: A total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group. Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.