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The TeLeo Program offers a free-access 2-year online learning program to support fellowship programs in pediatric oncology, enhance networking opportunities, and facilitate the exchange of context-specific, educational content within the pediatric oncology community in training in Latin America. In its first edition beginning in 2021, 185 fellows from 40 centers in 12 Latin American countries were enrolled. Additional courses for other healthcare professionals related to oncology in the region were produced to further support the program. A digital platform was created to allow users to easily access learning activities after registration, with 7075 professionals currently registered., (© 2024 Wiley Periodicals LLC.)

Background: Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults., Objective: This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults., Methods: This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m 2 ) and prediabetes or well-controlled T2DM (hemoglobin A 1c 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and β galactosidase staining., Results: The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024., Conclusions: Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide., Trial Registration: ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521., International Registered Report Identifier (irrid): DERR1-10.2196/62667., (©Tiffany M Cortes, Libia Vasquez, Monica C Serra, Ronna Robbins, Allison Stepanenko, Kevin Brown, Hannah Barrus, Annalisa Campos, Sara E Espinoza, Nicolas Musi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.09.2024.)

Most of spectroscopic signals are specified by the nonlinear laser-induced polarization. In recent years, population-detection of signals becomes a trend in femtosecond spectroscopy. Polarization-detected (PD) and population-detected signals are fundamentally different, because they are determined by photoinduced processes acting on disparate time scales. In this work, we consider the fluorescence-detected (FD) N -wave-mixing ( N WM) signal as a representative example of population-detected signals, derive a rigorous expression for this signal, and discuss its approximate variants suitable for numerical simulations. This leads us to the definition of the phenomenological FD (PFD) signal, which contains as a special case all definitions of FD signals available in the literature. Then we formulate and prove the population-polarization equivalence (PPE) theorem, which states that PFD N WM signals produced by (possibly strong) laser pulses can be evaluated as conventional PD signals in which the effective polarization is determined by the PFD transition dipole moment operator. We use the PPE theorem for the construction of the ab initio protocol for the simulation of PFD 4WM signals. As an example, we calculate electronic two-dimensional (2D) PFD spectra of the gas-phase pyrazine and compare them with the corresponding PD 2D spectra.

Background: The International Society of Paediatric Oncology Society Global Mapping Program aims to describe the local pediatric oncology capacities. Here, we report the data from Latin America., Methods: A 10-question survey was distributed among chairs of pediatric oncology services. Centers were classified according to patient volume into high- (HVC; 100 or more new cases per year), medium- (MVC; 31-99 cases), and low-volume centers (LVC; 30 cases or less), respectively. National referral centers (NRC) were identified., Results: Total 307 centers in 20 countries were identified (271 responded), and 264 responses were evaluable, accounting for 78% of the expected cases (21,359 cases per year). Seventy-seven percent of patients are treated in public centers, including additional support by civil society organizations. We found that 66% of the patients are treated in 70 centers of excellence, including 21 NRC. There was a median of one pediatric oncologist every 21 newly diagnosed patients (44 for NRC), and in 84% of the centers, nurses rotated to other services. A palliative care team was lacking in 25% of the centers. LVC with public funding have significantly lower probability of having a palliative care team or trained pediatric oncology surgeons. Psychosocial, pharmacy, and nutrition services were available in more than 93% of the centers. No radiotherapy facility was available on campus in nine of 21 NRC., Conclusions: Most children with cancer in Latin America are treated in public HVC. There is a scarcity of pediatric oncologists, specialized nurses and surgeons, and palliative care teams, especially in centers with public funding., (© 2024 Wiley Periodicals LLC.)

With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue ( n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (T H ) cells and cytotoxic (T C ) cells of early (CD57-) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. T C and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ T C -cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL.

Background: Latin American countries are improving childhood cancer care, showing strong commitment to implement the Global Initiative for Childhood Cancer, but there are scant publications of the situation at a continental level., Methods: As part of the International Society of Paediatric Oncology Global Mapping project, delegates of each country participating in the Latin American Society of Pediatric Oncology (SLAOP) and chairs of national pediatric oncology societies and cooperative groups were invited to provide information regarding availability of national pediatric cancer control programs (NPCCP), pediatric oncology laws, pediatric oncology tumor registries, and training programs and support to diagnosis and treatment., Results: Nineteen of the 20 countries participating in SLAOP responded. National delegates reported nine countries with NPCCP and four of them were launched in the past 5 years. National pediatric tumor registries are available in eight countries, and three provided published survival results. Fellowship programs for training pediatric oncologists are available in 12 countries. National delegates reported that eight countries provide support to most essential diagnosis and treatments and 11 provide partial or minimal support that is supplemented by civil society organizations. Seven countries have a pediatric oncology law. There are three international cooperative groups and four national societies for pediatric oncology., Conclusion: Despite many challenges, there were dramatic advances in survivorship, access to treatment, and availability of NPCCP in Latin America. Countries with highest social development scores in general provide more complete support and are more likely to have NPCCP, training programs, and reported survival results., (© 2024 Wiley‐Liss, Inc., A Wiley Company.)

Multiple myeloma is a heterogeneous hematological disease that originates from the bone marrow and is characterized by the monoclonal expansion of malignant plasma cells. Despite novel therapies, multiple myeloma remains clinically challenging. A common feature among patients with poor prognosis is the increased activity of the epigenetic silencer EZH2, which is the catalytic subunit of the PRC2. Interestingly, the recruitment of PRC2 lacks sequence specificity and, to date, the molecular mechanisms that define which genomic locations are destined for PRC2-mediated silencing remain unknown. The presence of a long non-coding RNA (lncRNA)-binding pocket on EZH2 suggests that lncRNA could potentially mediate PRC2 recruitment to specific genomic regions. Here, we coupled RNA immunoprecipitation sequencing, RNA-sequencing and chromatin immunoprecipitation-sequencing analysis of human multiple myeloma primary cells and cell lines to identify potential lncRNA partners to EZH2. We found that the lncRNA plasmacytoma variant translocation 1 (PVT1) directly interacts with EZH2 and is overexpressed in patients with a poor prognosis. Moreover, genes predicted to be targets of PVT1 exhibited H3K27me3 enrichment and were associated with pro-apoptotic and tumor suppressor functions. In fact, PVT1 inhibition independently promotes the expression of the PRC2 target genes ZBTB7C, RNF144A and CCDC136. Altogether, our work suggests that PVT1 is an interacting partner in PRC2-mediated silencing of tumor suppressor and pro-apoptotic genes in multiple myeloma, making it a highly interesting potential therapeutic target.

Objective: To create an interdisciplinary curriculum to teach key topics at the intersection of women's health, gender-affirming care, and health disparities to internal medicine (IM) residents. Materials and Methods: A core team of faculty from IM, Obstetrics and Gynecology, and Surgery partnered with faculty and fellows from other disciplines and with community experts to design and deliver the curriculum. The resulting curriculum consisted of themed half-day modules, each consisting of three to four inter-related topics, updated and repeated on an ∼3-year cycle. Health equity was a focus of all topics. Module delivery used diverse interactive learning strategies. Modules have been presented to ∼175 residents annually, beginning in 2015. To assess the curriculum, we used formative evaluation methods, using primarily anonymous, electronic surveys, and collected quantitative and qualitative data. Most surveys assessed resident learning by quantifying residents' self-reported comfort with skills taught in the module pre- and postsession. Results: Of 131 residents who completed an evaluation in 2022/23, 121 (90%) "somewhat" or "strongly" agreed with their readiness to perform a range of skills taught in the module. In all previous years where pre- and postsurveys were used to evaluate modules, we observed a consistent meaningful increase in the proportion of residents reporting high levels of comfort with the material. Residents particularly valued interactive teaching methods, and direct learning from community members and peers. Conclusion: Our interdisciplinary curriculum was feasible, valued by trainees, and increased resident learning. The curriculum provides a template to address equity issues across a spectrum of women's and gender-affirming care conditions that can be used by other institutions in implementing similar curricula.

Ethnic differences exist in the United States in the interrelated problems of diabetes (DM), peripheral arterial disease (PAD), and leg amputations. The purpose of this study was to determine the prevalence and risk factor associations for subclinical PAD in a population sample of Mexican Americans using the ankle brachial (ABI) index. The ABI-High (higher of the two ankle pressures/highest brachial pressure) and ABI-Low (lower of the two ankle pressures/highest brachial pressure) were calculated to define PAD. Toe brachial index (TBI) was also calculated. 746 participants were included with an age of 53.4 ± 0.9 years, 28.3 % had diabetes mellitus (DM), 12.6 % were smokers, and 51.2 % had hypertension (HTN). Using ABI-High ≤ 0.9, the prevalence of PAD was 2.7 %. This rose to 12.7 % when an ABI-Low ≤ 0.9 was used; 4.0 % of the population had an ABI-High > 1.4. The prevalence of TBI < 0.7 was 3.9 %. DM was a significant risk factor for ABI-High ≤ 0.9 and ABI-High > 1.4, and TBI < 0.7. Increased age, HTN, smoking was associated with ABI-High ≤ 0.9, while being male was associated with ABI-High > 1.4. Increased age, smoking, and lower education were all associated with abnormal TBI. Despite relatively younger mean age than other studied Hispanic cohorts, the present population has a high burden of ABI abnormalities. DM was a consistent risk factor for PAD. These abnormalities indicate an important underlying substrate of vascular and metabolic disease that may predispose this population to the development of symptomatic PAD and incident amputations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

This study examined the impact of child abuse on intimate partner violence (IPV) among a representative sample of 3,296 women using the Violence Against Women National Survey data from El Salvador. We found that child physical, sexual, and psychological abuse were independently associated with IPV, and experiencing child polyvictimization, along with having a controlling husband increased the risk of IPV victimization. To prevent child abuse (poly)victimization and IPV, and its negative consequences in El Salvador, implementing programs that focus on group training for women and men, as well as, community mobilizations that involve multiple stakeholders with multiple approaches would be beneficial., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Social media platforms contribute to the dissemination of information and encourage communication between health agencies and the public, especially during health crises. Public health agencies must engage in carefully crafted educational, communicative, and interactive practices to be effective in their messaging to build relationships with the public. Using quantitative content, social network, and thematic analysis, this study examined 2,500 tweets from April to August 2020 that included the hashtag #YoMeInformoPMA. Panama's Public Health Ministry created the #YoMeInformoPMA hashtag to keep citizens informed and engaged during the COVID-19 pandemic. Research on social media use and implementation in Latin America during the COVID-19 pandemic, to inform and engage the public, is limited. Therefore, the aim of this investigation was to analyze strategies, themes, multimedia formats, key actors, and overall communications patterns of a Latin American health community hashtag. Our results determined that actors using the hashtag #YoMeInformoPMA mainly used an interactive strategy, a message that aims to promote casual conversations, advice, and problem-solving. Findings highlighted evidence of a communication strategy by specific actors in this network, supporting recent studies that indicate engagement between the public and health agencies can take place on social media. Practical implications and recommendations for communication preparation via social media for future health crises are discussed.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the Cure All framework, which can be replicated in low- and middle-income countries., Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services., Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology., Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

This article aims to describe the activities conducted by the National Childhood Cancer Plan Working Group to support the development of national childhood cancer plans in Latin America and the Caribbean in the period 2019-2022, and to present the stage of plan development. The Working Group activities were supported by the Pan American Health Organization and St. Jude Children's Research Hospital, which is the World Health Organization (WHO) Collaborating Centre for Childhood Cancer. Year after year, the workshops and activities developed with the Working Group mobilized key stakeholders: pediatric oncologists, representatives of the Ministry of Health, foundations supporting childhood cancer initiatives, and hospital administrators. As of February 2023, one regional framework is in place, approved by the Council of Ministries of Health of Central America and the Dominican Republic, nine countries are currently implementing national plans or laws that include childhood cancer, and ten countries are writing new plans. The WHO three-step framework helped to guide the Working Group activities. All plans were supported by a situational analysis, which highlighted the importance of having systematized data for evidence-based policies. To increase implementation success, an accompanying budget and timeline help to ensure the adequate implementation of the interventions. More than anything, committed stakeholders remain the most fundamental element to successfully write and approve a national childhood cancer plan. This is an opportunity to share these countries' experience so the strategy can be adapted to support other countries developing a childhood cancer plan and extended to other public health areas.

Background: Education for parents and caregivers of children with cancer is one of the fundamental roles of nurses to avoid complications, provide quality care, promote adherence to treatment and maintain basic standards of care. This study aimed to design educational material for parents and caregivers of children with cancer in Peru on general information about childhood cancer and its care. Method: Within the framework of the WHO Global Initiative for Childhood Cancer in Peru, a multicenter working group was convened by the Peruvian Ministry of Health. A comprehensive needs assessment of parents and caregivers of children with cancer was performed through a survey in June and July 2020. The survey was conducted online (via Google Forms) and in person at nine hospitals to examine the preferred method of delivery and content of information. Results: Based on the findings from the parent needs assessment, a national nursing working group developed Spanish-language audiovisual materials (i.e., diagnosis and treatment videos for nurses to educate parents and caregivers). A total of 365 parents and caregivers were included. Most respondents (56.9%) were parents of children receiving treatment. Main topics were childhood cancer overview and side effects (85%), food and nutrition (75%), and palliative care (67%); most (70.9%) preferred information through talks and videos (64.7%). Twenty-three videos were developed with support by the Pan American Health Organization and the Ministry of Health. Discussion: Assessing the educational needs of parents and caregivers of children with cancer provides a starting point in the design of targeted strategies.

Intimate partner violence (IPV) victims tend to suffer from various mental health issues. Mental health issues, including suicidal thoughts and attempts caused by IPV victimization, might be more severe among women in El Salvador, where violence against women is prevalent overall. Although polyvictimization, which is defined as experiencing more than one type of violence by one or multiple partners, is associated with more severe mental health consequences than victimization by just a single form of violence due to accumulative trauma, not enough attention has been paid to this phenomenon among Salvadoran women. Thus, guided by trauma theory, this study aimed to examine the impact of polyvictimization from different types of violence (i.e., physical, sexual, emotional, and economic) on suicidal thoughts and attempts among Salvadoran women using the 2017 Violence Against Women National Survey. A nationally representative sample of 3,074 Salvadoran women aged 15 years or older and who had experienced an intimate relationship in their lifetime, recruited through a multistage random sampling design, was analyzed in this study using logistic regression analyses. We found that psychological and economic violence, along with physical and sexual violence, had statistically significant associations with suicidal thoughts and attempts, and polyvictimization increased suicidal thoughts and attempts. Based on this study's findings, we recommend effective research and practice or intervention implementation for addressing IPV and associated mental health problems among Salvadoran women.

Introduction: The diagnosis of vascular graft infections and infected aneurysms via conventional methods such as computed tomography (CT) and ultrasound (US) can often be challenging. Nuclear medicine imaging techniques can detect infection in these difficult cases. We aim to evaluate the diagnostic value of technetium-99m-labelled leukocyte scans in diagnosing vascular graft infections in our centre., Methods: There were 164 patient-scans identified over a 16-year period. The electronic clinical records, laboratory findings and radiology of these patients were reviewed. An adapted case definition of infection was defined using the criteria proposed by the Management of Aortic Graft Infection Collaboration. There were 43 patients identified to have vascular indications and had sufficient information to be divided into infected and non-infected groups. Imaging and reports of the leucocyte scans in these patients were analysed to calculate specificity and sensitivity., Results: Overall sensitivity of leucocyte scans to detect vascular infection was 78.1% and specificity of 81.8% with a positive likelihood ratio of 4.30 and negative likelihood ratio of 0.27. Two false positives in patients with aortic grafts; one patient possibly had concurrent gastrointestinal infection and continued antibiotic treatment. The other patient had persistent uptake around an endoleak and was treated with lifelong antibiotics for aortic vascular graft infection on the basis of the leucocyte scan; no other clinical or laboratory evidence was found to fulfil the case definition of the vascular graft infection., Conclusion: Technetium-99m-labelled leukocyte scan can be a useful adjuvant test in diagnosing suspected vascular infections in this uncommon presentation., (© 2022 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Background: Pediatric Early Warning Systems (PEWS) aid in identification of deterioration in hospitalized children with cancer but are underutilized in resource-limited settings. Proyecto EVAT is a multicenter quality improvement (QI) collaborative in Latin America to implement PEWS. This study investigates the relationship between hospital characteristics and time required for PEWS implementation., Methods: This convergent mixed-methods study included 23 Proyecto EVAT childhood cancer centers; 5 hospitals representing quick and slow implementers were selected for qualitative analysis. Semi-structured interviews were conducted with 71 stakeholders involved in PEWS implementation. Interviews were recorded, transcribed and translated to English, then coded using a priori and novel codes. Thematic content analysis explored the impact of hospital characteristics and QI experience on time required for PEWS implementation and was supplemented by quantitative analysis exploring the relationship between hospital characteristics and implementation time., Results: In both quantitative and qualitative analysis, material and human resources to support PEWS significantly impacted time to implementation. Lack of resources produced various obstacles that extended time necessary for centers to achieve successful implementation. Hospital characteristics, such as funding structure and type, influenced PEWS implementation time by determining their resource-availability. Prior hospital or implementation leader experience with QI, however, helped facilitate implementation by assisting implementers predict and overcome resource-related challenges., Conclusions: Hospital characteristics impact time required to implement PEWS in resource-limited childhood cancer centers; however, prior QI experience helps anticipate and adapt to resource challenges and more quickly implement PEWS. QI training should be a component of strategies to scale-up use of evidence-based interventions like PEWS in resource-limited settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Abutineh, Graetz, Muniz-Talavera, Ferrara, Puerto-Torres, Chen, Gillipelli, Elish, Gonzalez-Ruiz, Alfonso Carreras, Alvarez, Arce Cabrera, Arguello Vargas, Armenta Cruz, Barra, Calderon Sotelo, Carpio, Chavez Rios, Covarrubias, de Leon Vasquez, Diaz Coronado, Fing Soto, Gomez-Garcia, Hernandez, Juarez Tobias, Leon, Loeza Oliva, Mendez, Miller, Montalvo Cozar, Negroe Ocampo, Penafiel, Pineda, Rios, Rodriguez Ordonez, Soto Chavez, Devidas and Agulnik.)

Background: Undergraduate nursing students will play a pivotal role in caring for the rising numbers of older adults and people living with dementia (PLWD). However, many do not receive training in geriatrics or dementia and do not enter this field post-graduation, contributing to the workforce shortage., Objective: We aimed to capture students' interest and intention to work with PLWD, their suggestions about training, and to evaluate interest in a new elective long-term care (LTC) externship., Methods: We developed and administered a survey to Bachelor of Science in Nursing students consisting of questions modified from the Dementia Attitude Scale and related to respondents' health care experience, attitudes about caring for older adults, comfort working with PLWD, and willingness to develop geriatric and dementia care skills. We then conducted focus groups about desired curricular and clinical content., Results: Seventy-six students completed the survey. The majority reported low interest in working with and low knowledge of caring for older adults and PLWD. Six focus group participants expressed interest in participating in hands-on learning opportunities. Participants identified specific training components to attract students to geriatrics education., Conclusions: Our findings informed the development, piloting, and evaluation of a new LTC externship at the University of Washington Schoool of Nursing., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Childhood central nervous system (CNS) tumors have longer delays in diagnosis than do other pediatric malignancies because health care providers (HCPs) lack awareness about clinical presentation of these tumors. To evaluate the knowledge gap among HCPs, we conducted a global cross-sectional survey. The survey consisted of a set of CNS tumor knowledge questions focused on symptoms, signs, and imaging indications. The survey was disseminated to HCPs via email (November 2018-March 2020). Participants had to complete a pre-test survey, attend an education seminar on CNS tumors, and complete a post-test survey. The knowledge gap was evaluated using pre-test and post-test scores. We received 889 pre-test and 392 post-test responses. Most respondents were from Asia (73.1% of pre-test responses; 87.5% of post-test responses). The median pre-test score was 40.0% (range: 13.1-92.9%). A high percentage of correct answers were given in post-test responses (median score: 77.1%, range: 14.9-98.2%). In the pre-test, 18.7% of participants accurately responded that Cushing's triad was a less common symptom, and 15.0% recognized that children aged > 10 years are at risk of late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignancy experienced the longest pre-diagnostic symptom interval, and 54.5% of respondents wrongly selected medulloblastoma as the most common CNS tumor. Overall, pediatricians demonstrated a greater knowledge gap on both surveys than did other specialties.  Conclusion: Pre- and post-test surveys revealed significant knowledge gaps in childhood CNS tumors among HCPs. Thus, raising professional awareness on clinical presentations of CNS tumors through educational strategies is important to address this knowledge deficit. What is Known: • Diagnostic delay in childhood central nervous system (CNS) tumors continues to be a significant problem that negatively impacts the quality of life and treatment sequelae. • Lack of medical education on CNS tumors is a contributing factor to this problem. What is New: • Most health care providers do not realize that low-grade tumors are the most common neoplasm in children. • Health care providers fail to recognize that teenagers and adolescents are a vulnerable age group for diagnostic delays, with the longest pre-diagnostic symptom interval., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis ( M. tuberculosis ). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R 2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a - e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl- β - D -ribose-2'-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of -71.3 to -12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a - e was evaluated against M. bovis , M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis . All compounds exhibited good to excellent activity against all the families of M. tuberculosis . Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

Early detection of cancer will improve survival rates. The blood biomarker 5-hydroxymethylcytosine has been shown to discriminate cancer. In a large covariate-controlled study of over two thousand individual blood samples, we created, tested and explored the properties of a 5-hydroxymethylcytosine-based classifier to detect colorectal cancer (CRC). In an independent validation sample set, the classifier discriminated CRC samples from controls with an area under the receiver operating characteristic curve (AUC) of 90% (95% CI [87, 93]). Sensitivity was 55% at 95% specificity. Performance was similar for early stage 1 (AUC 89%; 95% CI [83, 94]) and late stage 4 CRC (AUC 94%; 95% CI [89, 98]). The classifier could detect CRC even when the proportion of tumor DNA in blood was undetectable by other methods. Expanding the classifier to include information about cell-free DNA fragment size and abundance across the genome led to gains in sensitivity (63% at 95% specificity), with similar overall performance (AUC 91%; 95% CI [89, 94]). We confirm that 5-hydroxymethylcytosine can be used to detect CRC, even in early-stage disease. Therefore, the inclusion of 5-hydroxymethylcytosine in multianalyte testing could improve sensitivity for the detection of early-stage cancer., (© 2022. The Author(s).)

Background: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year., Method: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners., Results: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability., Conclusion: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic., (© 2022 Wiley Periodicals LLC.)

Background: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group., Methods: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues., Results: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge., Conclusions: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients., (© 2022 Wiley Periodicals LLC.)

The circumstances of transferred electrons across organic/inorganic interfaces have attracted intensive interest because of the distinctive electronic structure properties of those two components. Leveraging ab initio nonadiabatic molecular dynamics methods in conjunction with spin dynamics induced by spin-orbital couplings (SOCs), this study reports two competitive channels during photoinduced dynamical processes in the prototypical ZnPc/monolayer MoS 2 heterojunction. Interestingly, the electron-transfer and relaxation processes occur simultaneously because of the enhancement of electron-phonon couplings and expansion of dynamical pathways by SOCs, suggesting that the electron-transfer rate and relaxation processes can be tuned by SOCs, hence yielding the performance promotion of photovoltaic and photocatalytic devices. Additionally, approximately half of the transferred electrons flip their spin within 1.6 ps because of strong SOCs in MoS 2 , achieving great agreement with experimental measurements. This investigation provides instructive perspectives for designing novel devices and applications based on organic/inorganic heterojunctions, demonstrating the importance of spin dynamics simulations in exploring sophisticated photoinduced processes in materials.

Transgenerational inheritance of environmentally induced epigenetic marks can have significant impacts on eco-evolutionary dynamics, but the phenomenon remains controversial in ecological model systems. We used whole-genome bisulfite sequencing of individual water fleas ( Daphnia magna ) to assess whether environmentally induced DNA methylation is transgenerationally inherited. Genetically identical females were exposed to one of three natural stressors, or a de-methylating drug, and their offspring were propagated clonally for four generations under control conditions. We identified between 70 and 225 differentially methylated CpG positions (DMPs) in F1 individuals whose mothers were exposed to a natural stressor. Roughly half of these environmentally induced DMPs persisted until generation F4. In contrast, treatment with the drug demonstrated that pervasive hypomethylation upon exposure is reset almost completely after one generation. These results suggest that environmentally induced DNA methylation is non-random and stably inherited across generations in Daphnia , making epigenetic inheritance a putative factor in the eco-evolutionary dynamics of freshwater communities., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The purpose of this study was to evaluate the acceptability of and satisfaction with an interprofessional educational workshop to teach family caregivers of persons living with dementia to provide complex care. The workshop was developed by a team that included nursing, occupational therapy, speech-language pathology, nutrition and dental hygiene. Caregivers who attended the workshop completed an evaluation to describe their satisfaction and acceptability using a Likert-type scale, as well as open ended comments about their learning needs and feedback about the workshop. Semi-structured interviews were conducted with family caregivers and members of the interprofessional team to analyze and evaluate how the workshop may have improved their confidence in performing complex tasks and to obtain their perspectives on offering this program as a virtual workshop in the future. Family caregivers (n=171) reported high satisfaction with the workshop and strongly agreed that the workshop provided them with useful information to support their caregiving roles. Themes identified from the content of the interviews were: i) building understanding; ii) mastering new skills; and iii) learning skills together. Our results suggest and emphasize the importance and the benefits of an interprofessional team approach to support family caregivers and build confidence with complex care.

The resolution of causal genetic variants informs understanding of disease biology. We used regulatory quantitative trait loci (QTLs) from the BLUEPRINT, GTEx and eQTLGen projects to fine-map putative causal variants for 12 immune-mediated diseases. We identify 340 unique loci that colocalize with high posterior probability (≥98%) with regulatory QTLs and apply Bayesian frameworks to fine-map associations at each locus. We show that fine-mapping credible sets derived from regulatory QTLs are smaller compared to disease summary statistics. Further, they are enriched for more functionally interpretable candidate causal variants and for putatively causal insertion/deletion (INDEL) polymorphisms. Finally, we use massively parallel reporter assays to evaluate candidate causal variants at the ITGA4 locus associated with inflammatory bowel disease. Overall, our findings suggest that fine-mapping applied to disease-colocalizing regulatory QTLs can enhance the discovery of putative causal disease variants and enhance insights into the underlying causal genes and molecular mechanisms., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Irregular applications can be found in different scientific fields. In computer-aided drug design, molecular docking simulations play an important role in finding promising drug candidates. AutoDock is a software application widely used for predicting molecular interactions at close distances. It is characterized by irregular computations and long execution runtimes. In recent years, a hardware-accelerated version of AutoDock, called AutoDock-GPU, has been under active development. This work benchmarks the recent code and algorithmic enhancements incorporated into AutoDock-GPU. Particularly, we analyze the impact on execution runtime of techniques based on early termination. These enable AutoDock-GPU to explore the molecular space as necessary, while safely avoiding redundant computations. Our results indicate that it is possible to achieve average runtime reductions of 50% by using these techniques. Furthermore, a comprehensive literature review is also provided, where our work is compared to relevant approaches leveraging hardware acceleration for molecular docking., Competing Interests: Declaration of interests X The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

An isotope fractionation analysis of organic groundwater pollutants can assess the remediation at contaminated sites yet needs to consider physical processes as potentially confounding factors. This study explores the predictability of water-air partitioning isotope effects from experiments and computational predictions for benzene and trimethylamine (both H-bond acceptors) as well as chloroform (H-bond donor). A small, but significant, isotope fractionation of different direction and magnitude was measured with ε = -0.12‰ ± 0.07‰ (benzene), ε C = 0.49‰ ± 0.23‰ (triethylamine), and ε H = 1.79‰ ± 0.54‰ (chloroform) demonstrating that effects do not correlate with expected hydrogen-bond functionalities. Computations revealed that the overall isotope effect arises from contributions of different nature and extent: a weakening of intramolecular vibrations in the condensed phase plus additional vibrational modes from a complexation with surrounding water molecules. Subtle changes in benzene contrast with a stronger coupling between intra- and intermolecular modes in the chloroform-water system and a very local vibrational response with few atoms involved in a specific mode of triethylamine. An energy decomposition analysis revealed that each system was affected differently by electrostatics and dispersion, where dispersion was dominant for benzene and electrostatics dominated for chloroform and triethylamine. Interestingly, overall stabilization patterns in all studied systems originated from contributions of dispersion rather than other energy terms.

Objective: We conducted a systematic literature review of e-mental health technologies in juvenile justice contexts., Hypotheses: Our exploratory research questions were as follows: First, what types of e-mental health exist for justice-involved youth, their caregivers, and juvenile justice professionals? Second, what are the characteristics of studies that have examined these technologies? Third, what have studies found about the effectiveness, reliability, or validity of e-mental health in treating and assessing juvenile justice populations? And fourth, what advantages and disadvantages exist for e-mental health use in juvenile justice?, Method: We screened 759 articles and retained 36 for review. We included articles that investigated e-mental health for the assessment or treatment of justice-involved youth and their caregivers. We excluded technologies not directly related to assessment or treatment as well as samples of at-risk youth with no justice involvement., Results: We identified four types of e-mental health technologies: Interventions with technology-facilitated interpersonal communication (e.g., telehealth and mHealth), digitized intervention programs, simulation games, and computerized assessments. Most study designs were experimental/quasi-experimental or qualitative/descriptive, followed closely by repeated measures/pretest-posttest. A majority of evidence suggested that e-mental health technologies were potentially effective or valid for treatment and assessment, especially telehealth. Advantages included positive opinions of users, increased access to care, and efficiency; disadvantages included barriers to accessing technology, privacy concerns, and lack of clear effectiveness, reliability, or validity data., Conclusions: Although the available evidence for e-mental health for juvenile justice is promising, the current literature base appears generally underdeveloped and nuanced. Worthwhile future directions include continued development of technologies and more rigorously conducted studies to support further implementation of e-mental health for juvenile justice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).