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In vivo carrier protein tagging has recently become an attractive target for the site-specific modification of fusion systems and new approaches to natural product proteomics. A detailed study of pantetheine analogues was performed in order to identify suitable partners for covalent protein labeling inside living cells. A rapid synthesis of pantothenamide analogues was developed and used to produce a panel which was evaluated for in vitro and in vivo protein labeling. Kinetic comparisons allowed the construction of a structure—activity relationship to pinpoint the linker, dye, and bioorthogonal reporter of choice for carrier protein labeling. Finally bioorthogonal pantetheine analogues were shown to target carrier proteins with high specificity in vivo and undergo chemoselective ligation to reporters in crude cell lysate. The methods demonstrated here allow carrier proteins to be visualized and isolated for the first time without the need for antibody techniques and set the stage for the future use of carrier protein fusions in chemical biology. [ABSTRACT FROM AUTHOR]

Diverse marine animals undergo a metamorphic larval-to-juvenile transition in response to surface-bound bacteria. Although this host-microbe interaction is critical to establishing and maintaining marine animal populations, the functional activity of bacterial products and how they activate the host's metamorphosis program has not yet been defined for any animal. The marine bacterium Pseudoalteromonas luteoviolacea stimulates the metamorphosis of a tubeworm called Hydroides elegans by producing a molecular syringe called metamorphosis-associated contractile structures (MACs). MACs stimulate metamorphosis by injecting a protein effector termed metamorphosis-inducing factor 1 (Mif1) into tubeworm larvae. Here, we show that MACs bind to tubeworm cilia and form visible pores on the cilia membrane surface, which are smaller and less numerous in the absence of Mif1. In vitro , Mif1 associates with eukaryotic lipid membranes and possesses phospholipase activity. MACs can also deliver Mif1 to human cell lines and cause parallel phenotypes, including cell surface binding, membrane disruption, calcium flux, and mitogen-activated protein kinase activation. Finally, MACs can also stimulate metamorphosis by delivering two unrelated membrane-disrupting proteins, MLKL and RegIIIɑ. Our findings demonstrate that membrane disruption by MACs and Mif1 is necessary for Hydroides metamorphosis, connecting the activity of a bacterial protein effector to the developmental transition of a marine animal., Importance: This research describes a mechanism wherein a bacterium prompts the metamorphic development of an animal from larva to juvenile form by injecting a protein that disrupts membranes in the larval cilia. Specifically, results show that a bacterial contractile injection system and the protein effector it injects form pores in larval cilia, influencing critical signaling pathways like mitogen-activated protein kinase and calcium flux, ultimately driving animal metamorphosis. This discovery sheds light on how a bacterial protein effector exerts its activity through membrane disruption, a phenomenon observed in various bacterial toxins affecting cellular functions, and elicits a developmental response. This work reveals a potential strategy used by marine organisms to respond to microbial cues, which could inform efforts in coral reef restoration and biofouling prevention. The study's insights into metamorphosis-associated contractile structures' delivery of protein effectors to specific anatomical locations highlight prospects for future biomedical and environmental applications., Competing Interests: K.E.M., T.L.D., and N.J.S. are co-inventors on provisional U.S. patent application entitled "Protein and Peptide Delivery Systems and Methods for Using Them with Human Cells" and assigned to San Diego State University Research Foundation.

Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up testing efforts, as well as to reduce the use of vertebrate animals, great effort is being devoted to alternate laboratory models for testing DNT. A major mechanism of DNT is altered neuronal architecture resulting from chemical exposure during neurodevelopment. Caenorhabditis elegans is a nematode that has been extensively studied by neurobiologists and developmental biologists, and to a lesser extent by neurotoxicologists. The developmental trajectory of the nervous system in C. elegans is easily visualized, normally entirely invariant, and fully mapped. Therefore, we hypothesized that C. elegans could be a powerful in vivo model to test chemicals for the potential to alter developmental patterning of neuronal architecture. To test whether this might be true, we developed a novel C. elegans DNT testing paradigm that includes exposure throughout development, examines all major neurotransmitter neuronal types for architectural alterations, and tests behaviors specific to dopaminergic, cholinergic, and glutamatergic functions. We used this paradigm to characterize the effects of early-life exposures to the developmental neurotoxicants lead, cadmium, and benzo(a)pyrene (BaP) on dopaminergic, cholinergic, and glutamatergic architecture. We also assessed whether exposures would alter neuronal specification as assessed by expression of reporter genes diagnostic of specific neurotransmitters. We identified no cases in which the apparent neurotransmitter type of the neurons we examined changed, but many in which neuronal morphology was altered. We also found that neuron-specific behaviors were altered during C. elegans mid-adulthood for populations with measured morphological neurodegeneration in earlier stages. The functional changes were consistent with the morphological changes we observed in terms of type of neuron affected. We identified changes consistent with those reported in the mammalian DNT literature, strengthening the case for C. elegans as a DNT model, and made novel observations that should be followed up in future studies., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests.

Housing insecurity is a well-recognized social determinant of health, with poverty and homelessness significantly impacting health outcomes. When faced with unstable housing, health often becomes a lower priority for patients. We present the case of a 52-year-old homeless, morbidly obese female who arrived at the emergency department with worsening dyspnea. She required Bilevel Positive Airway Pressure (BiPAP) support for acute-on-chronic hypercapnic respiratory failure. Her discharge planning was complicated by the need for a BiPAP machine, which limited her options for placement in a receiving facility. The patient ultimately left against medical advice (AMA) after a seven-day hospitalization but was readmitted hours later with recurrent symptoms, highlighting the ongoing challenges posed by her chronic conditions and social determinants of health. This case highlights how the requirement for specialized medical equipment can serve as an additional barrier to securing shelter for individuals experiencing homelessness., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Santos-Rivera et al.)

Background: Central nervous system tumors (CNSTs) represent a significant oncological challenge in pediatric populations, particularly in developing regions where access to diagnostic and therapeutic resources is limited., Methods: This research investigates the epidemiology, histological classifications, and survival outcomes of CNST in a cohort of pediatric patients aged 0 to 19 years within a 25-year retrospective study at the Civil Hospital of Guadalajara, Mexico, from 1999 to 2024., Results: Data was analyzed from 273 patients who met inclusion criteria, revealing a higher incidence in males (51.6%) with a mean age at diagnosis of 8.2 years. Histological analysis revealed gliomas as the most common type (52.7%), followed by embryonal tumors (28.6%). High-grade tumors (WHO grade 4) comprised 49.8% of cases, demonstrating significantly poorer survival outcomes (median overall survival of 13.5 months) compared to lower-grade tumors (up to 57 months). The predominance of tumors in the supratentorial region and the notable differences in survival outcomes by tumor type underscore the varied impact of geographical and socioeconomic factors on pediatric oncology in Mexico., Conclusion: This study highlights the critical need for improved healthcare infrastructure and early diagnosis initiatives, as well as the importance of targeted research to address disparities in treatment and outcomes for pediatric CNST in this region., Competing Interests: Declarations. Ethics approval: Ethical approval was waived by the local Ethics Committee of Civil Hospital “Dr Juan I. Menchaca” (Registration codes: 17CI14039116 and 0483–21 HJCIM/2021). Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fanconi anemia (FA) is the most common hereditary bone marrow failure syndrome, with an incidence of 1 in 5,000,000. This disease is caused by an alteration in one of the 23 genes associated with the FA/BRCA DNA repair pathway, which is responsible for repairing interstrand bridges generated during homologous recombination. FA has been associated with a predisposition to other types of neoplasm. The current study aimed to present a pathogenic variant in FANCA observed in three Mexican siblings, as detected by next-generation sequencing (NGS). The results of an induced chromosomal breakage test showed chromosomal breaks and radial figures, which were compatible with FA, and a normal karyotype. NGS TruSight Hereditary Cancer Panel analysis resulted in the FANCA: c.3931_3932delAG variant being classified as pathogenic according to bioinformatics analysis. The present study reports a pathogenic variant in FANCA that was found in a Mexican family with FA, in which one of the siblings exhibited a suggestive mucosa-assisted lymphoid tissue lymphoma, which is an atypical presentation of neoplasia associated with FA., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2025 Cuero-Quezada et al.)

Congenital heart defects (CHDs) are caused by a complex interaction between numerous genetic and environmental risk factors, some of which may differ between different populations. A case-control study was conducted among 1232 newborns, including 308 patients with isolated CHDs (cases) and 924 infants without birth defects (controls), born all during the period 2009-2023 at the Hospital Civil de Guadalajara "Dr. Juan I. Menchaca" (Guadalajara, Mexico). Potential parental risk factors for CHDs were compared using multivariate logistic regression analysis to evaluate the deviance explained by different variables of interest. Consanguinity [adjusted odds ratio (aOR) = 3.3; 95% confidence interval (CI) 1.3-8.5], relatives with CHD (aOR = 8.5; 95% CI 5.3-13.8), maternal first-trimester exposure to diabetes (aOR = 3.5; 95% CI 2.4-5.1), hypertension (aOR = 2.6; 95% CI 1.5-4.4), alcohol consumption (aOR = 1.5; 95% CI 1.0-2.1), and illicit drug use (aOR = 2.4; 95% CI 1.2-5.3), as well as for the paternal history of alcohol consumption (aOR = 1.4; 95% CI 1.0-1.8) and illicit drug use (aOR = 2.7; 95% CI 1.7-4.1), were associated with CHDs. Contrarily, aOR for maternal age ≤19 years (aOR = 0.6; 95% CI 0.4-0.8) and maternal first-trimester coffee consumption (aOR = 0.7; 95% CI 0.5-0.9) have protective odds. Our results suggest that genetic factors, maternal diseases, environmental exposures, and reproductive factors can increase the occurrence of isolated CHDs in our sample, and they are discussed as clues in its pathogenesis., (© 2024 Japanese Teratology Society.)

Numerous individuals experiencing homelessness have a pet. When a homeless person is hospitalized for an emergency medical need, discharge planners are sometimes faced with tough options and a lack of resources for safe discharges from the hospital. We detail the case of a 64-year-old female patient who was admitted due to a witnessed syncopal event. The patient was admitted with her companion dog, which remained at the bedside through her hospitalization. The workup for her syncopal event was negative (CT brain, carotid US, ECG, troponins, orthostatic). Her discharge process was complicated by her need for a shelter placement that would accommodate her and her pet dog. The patient was discharged without finding a shelter that could accept her dog, which prevented her from receiving home health physical therapy. This case illustrates how pet ownership can create additional barriers to the transition of care for homeless individuals, limiting access to necessary follow-up services and impacting overall recovery outcomes. Thus, we would like to highlight this barrier that exists in this vulnerable population., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jimenez Garcia et al.)

Variants in the RB1 gene are associated with retinoblastoma (RB) development, and their presence in germline cells considerably increases the risk of subsequent malignant neoplasms (SMNs) in RB survivors. We report a female patient with bilateral RB who developed two SMNs in less than ten years, with a de novo pathogenic nonsense variant in RB1 [NM_000321.3:c.306T>A, p.(Cys102*)] in heterozygosity. The updated literature review of similar cases of SMN in patients with a previous diagnosis of RB reveals a wide range in both the type of subsequent malignancy and the age at which these SMNs develop. In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management.

The promise of large-scale, high-resolution datasets from Electron Microscopy (EM) and X-ray Microtomography (XRM) lies in their ability to reveal neural structures and synaptic connectivity, which is critical for understanding the brain. Effectively managing these complex and rapidly increasing datasets will enable new scientific insights, facilitate querying, and support secondary use across the neuroscience community. However, without effective neurodata standards that permit use of these data across multiple systems and workflows, these valuable and costly datasets risk being underutilized especially as they surpass petascale levels. These standards will promote data sharing through accessible interfaces, allow researchers to build on each other's work, and guide the development of tools and capabilities that are interoperable. Herein we outline a standards framework for creating and managing annotations originating and derived from high-resolution volumetric imaging and connectomic datasets, focusing on ensuring Findable, Accessible, Interoperable, and Reusable (FAIR) practices. The goal is to enhance collaborative efforts, boost the reliability of findings, and enable comparative analysis across growing datasets of different species and modalities. We have formed a global working group with academic and industry partners in the high-resolution volumetric data generation and analysis community, focused on identifying gaps in current EM and XRM data pipelines, and refining outlines and platforms for standardizing EM and XRM methods. This focus considers existing and past community approaches and includes examining neuronal entities, biological components, and associated metadata, while emphasizing adaptability and fostering collaboration.

Competing Interests: The authors declare no conflicts of interest.

Background: In Mexico, anemia prevalence among women of reproductive age (WRA) decreased from 16.4% in 2006 to 11.6% in 2012, only to increase to 18.3% in 2016. The factors associated with this fluctuation are uncertain., Objective: We conducted a systematic in-depth assessment of the quantitative and qualitative determinants of anemia among WRA in Mexico between 2006 and 2018., Methods: Using multivariate stepwise linear regression, we analyzed Mexico's Encuesta Nacional de Salud y Nutrición (ENSANUT) surveys from 2006, 2012, and 2018 to identify determinants of WRA anemia. We also conducted a review of anemia-relevant programs and policies, including financing documents, and conducted in-depth interviews and focus group discussions with key stakeholders in Mexico., Results: Among non-pregnant women (NPW) 15-49 years, mean hemoglobin (Hb) increased from 13.8 g/dL in 2006 to 14.0 g/dL in 2012, decreasing to 13.2 g/dL in 2018 (p<0.001). Inequities by geographical region and household wealth persisted throughout this period, with household wealth, urban residence and gravidity emerging as significant predictors of Hb among NPW. Qualitative analyses generally supported these findings. The most discussed program was Progresa-Oportunidades-Prospera (POP), where most resources for health were invested and most participants acknowledged that its cancellation in 2019 would lead to worsening in health and nutrition among the poor. Financing analyses showed a drop of funding for nutrition-related programs between 2014 and 2018. Cultural norms around gender roles were still prevalent, along with increasing rates of teenage pregnancy., Conclusions: Anemia prevention efforts need to refocus on poverty alleviation, continuity of adequate coverage and financing of nutrition programs, especially with safety nets, and increase in uptake of family planning, especially among adolescent girls., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Zulfiqar Bhutta reports financial support and article publishing charges were provided by Bill and Melinda Gates Foundation. Zulfiqar Bhutta reports financial support was provided by Gates Ventures. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Several studies in mothers of infants with Down syndrome (DS) (MoIDS) have suggested that the 677C>T and 1298A>C variants of the 5,10-methylentetrahydrofolate reductase ( MTHFR ) gene can increase the risk of having a child with DS. Aim: This study aimed to evaluate the MTHFR 677C>T and 1298A>C variants as potential maternal risk factors for DS. Materials and Methods: Using TaqMan allelic discrimination assay, we genotyped 95 MoIDS and 164 control mothers from western Mexico. Data were analyzed using logistic regression analysis. Results: We found that MoIDS had a significantly higher risk for the MTHFR 677TT genotype (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.1-10.6), and the MTHFR 677T allele (aOR = 1.5, 95% CI: 1.0-2.3), particularly in MoIDS <35 years of age. Conclusions: Our findings indicate that the presence of the 677TT genotype and 677T allele of the MTHFR 677C>T variant are maternal risk factors for DS in Mexican MoIDS.

Background and Objectives: Type 2 diabetes mellitus (T2DM) is a global health concern affecting more than 400 million people worldwide. Diabetic neuropathy, nephropathy, retinopathy, and cardiovascular complications lead to debilitating effects to patients. To prevent these, the treatment goal is to lower the blood sugar levels and maintain at a normal range which is achieved through conventional treatments like insulin and oral hypoglycemic agents. However, the high cost of these medications implicates patient treatment outcomes. Hence, alternatives are sought for including the use of herbal medicines. Momordica charantia (MC) and Lagerstroemia speciosa (LS) are common herbal medicines used to manage T2DM. In the Philippines, these herbal preparations are validated for their glucose lowering effects and are commonly found in combination in food supplements. The study aims to screen the possible mechanisms of compounds present in these herbal medicines which can offer possible explanations for their synergistic effects and rationalization of their combination in preparations., Methods: Network pharmacology was employed to determine pivotal proteins that are targeted by MC and LS compounds. Molecular docking was then done to evaluate the favorability of the binding of these compounds toward their target proteins., Results: Our results showed that TNF, HSP90AA1, MAPK3, ALDH2, GCK, AKR1B1, TTR and RBP4 are the possible pivotal targets of MC and LS compounds in T2DM., Conclusion: Terpenoids from MC and decanoic acid from LS are the compounds which showed favorable binding towards pivotal protein targets in T2DM. By binding towards the different key proteins in T2DM, they may exhibit their synergistic effects. However, the results of this study are bound to the limitations of computational methods and experimental validation are needed to verify our findings., Competing Interests: All authors declared no conflicts of interest., (© 2024 Acta Medica Philippina.)

The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD). We reviewed the phenotype of all reported individuals with TRAPPC11-opathies, including an additional Mexican patient with novel compound heterozygous missense variants in TRAPPC11 (c.751 T > C and c.1058C > G), restricted to the Latino population. In these 54 patients muscular dystrophy signs are common (early onset muscle weakness, increased serum creatine kinase levels, and dystrophic changes in muscle biopsy). They present two main phenotypes, one with a slowly progressive LGMD with or without GDD/ID (n = 12), and another with systemic involvement characterized by short stature, GDD/ID, microcephaly, hypotonia, poor speech, seizures, cerebral atrophy, cerebellar abnormalities, movement disorder, scoliosis, liver disease, and cataracts (n = 42). In 6 of them CMD was identified. Obstructive hydrocephaly, retrocerebellar cyst, and talipes equinovarus found in the individual reported here has not been described in TRAPPC11 deficiency. As in previous patients, membrane trafficking assays in our patient showed defective abnormal endoplasmic reticulum-Golgi transport as well as decreased expression of LAMP2, and ICAM-1 glycoproteins. This supports previous statements that TRAPPC11-opathies are in fact a congenital disorder of glycosylation (CDG) with muscular dystrophy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: To our knowledge, there are few examples of intrafamilial variability involving two different TP63 -linked morphopathies within a same family. Here, we describe a Mexican family in which the son had ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3), and his father acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63 . Additionally, we reviewed the clinical information reported for this TP63 genotype., Case Presentation: The son of this family presented ectodermal defects (thin and sparse hair, mild nail dysplasia), tetramelic ectrodactyly, syndactyly, and nasolacrimal duct obstruction (NLDO), indicative of an EEC3 diagnosis. His father, however, exhibited severe NLDO, facial freckling, dental abnormalities, mild nail dysplasia, and a history of micturition problems, compatible with ADULT syndrome. Both were heterozygous for the NM&#95;003722.5( TP63 ):c.797G>A (p.Arg266Gln) pathogenic variant in TP63 ., Discussion: This report expands the spectrum of intrafamilial variability confirming that this can include the expression of distinct types of TP63 -related disorders among different members of the same family, whose implications should be also considered in genetic counseling. From our review, we observed that p.Arg266Gln variant seems to correlate particularly with the presence of NLDO, sparse hair/eyebrows, ridged/dystrophic nails, anodontia/hypodontia, and micturition difficulties, as well as for a minor frequency of cleft lip/cleft palate., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

While diatoms are promising synthetic biology platforms, there currently exists a limited number of validated genetic regulatory parts available for genetic engineering. The standard method for diatom transformation, nonspecific introduction of DNA into chromosomes via biolistic particle bombardment, is low throughput and suffers from clonal variability and epigenetic effects. Recent developments in diatom engineering have demonstrated that autonomously replicating episomal plasmids serve as stable expression platforms for diverse gene expression technologies. These plasmids are delivered via bacterial conjugation and, when combined with modular DNA assembly technologies, provide a flexibility and speed not possible with biolistic-mediated strain generation. In order to expand the current toolbox for plasmid-based engineering in the diatom Phaeodactylum tricornutum , a conjugation-based forward genetics screen for promoter discovery was developed, and application to a diatom genomic DNA library defined 252 P. tricornutum promoter elements. From this library, 40 promoter/terminator pairs were delivered via conjugation on episomal plasmids, characterized in vivo, and ranked across 4 orders of magnitude difference in reporter gene expression levels.

Lead (Pb 2+ ) is an important developmental toxicant. The mitochondrial calcium uniporter (MCU) imports calcium ions using the mitochondrial membrane potential (MMP), and also appears to mediate the influx of Pb 2+ into the mitochondria. Since our environment contains mixtures of toxic agents, it is important to consider multi-chemical exposures. To begin to develop generalizable, predictive models of interactive toxicity, we developed mechanism-based hypotheses about interactive effects of Pb 2+ with other chemicals. To test these hypotheses, we exposed HepG2 (human liver) cells to Pb 2+ alone and in mixtures with other mitochondria-damaging chemicals: carbonyl cyanide- p -trifluoromethoxyphenylhydrazone (FCCP), a mitochondrial uncoupler that reduces MMP, and Ruthenium Red (RuRed), a dye that inhibits the MCU. After 24 hours, Pb 2+ alone, the mixture of Pb 2+ and RuRed, and the mixture of Pb 2+ and FCCP caused no decrease in cell viability. However, the combination of all three exposures led to a significant decrease in cell viability at higher Pb 2+ concentrations. After 48 hours, the co-exposure to elevated Pb 2+ concentrations and FCCP caused a significant decrease in cell viability, and the mixture of all three showed a clear dose-response curve with significant decreases in cell viability across a range of Pb 2+ concentrations. We performed ICP-MS analyses on isolated mitochondrial and cytosolic fractions and found no differences in Pb 2+ uptake across exposure groups, ruling out altered cellular uptake as the mechanism for interactive toxicity. We assessed MMP following exposure and observed a decrease in membrane potential that corresponds to loss of cell viability but is likely not sufficient to be the causative mechanistic driver of cell death. This research provides a mechanistically-based framework for understanding Pb 2+ toxicity in mixtures with mitochondrial toxicants.

Epilepsy is a chronic neurological disorder affecting around 1% of the global population, characterized by recurrent epileptic seizures. Accurate diagnosis and treatment are crucial for reducing mortality rates. Recent advancements in machine learning (ML) algorithms have shown potential in aiding clinicians with seizure detection in electroencephalography (EEG) data. However, these algorithms face significant challenges due to the patient-specific variability in seizure patterns and the limited availability of high-quality EEG data for training, causing erratic predictions. These erratic predictions are harmful, especially for high-stake domains in healthcare, negatively affecting patients. Therefore, ensuring safety in AI is of the utmost importance. In this study, we propose a novel ensemble method for uncertainty quantification to identify patients with low-confidence predictions in ML-based seizure detection algorithms. Our approach aims to mitigate high-risk predictions in previously unseen seizure patients, thereby enhancing the robustness of existing seizure detection algorithms. Additionally, our method can be implemented with most of the deep learning (DL) models. We evaluated the proposed method against established uncertainty detection techniques, demonstrating its effectiveness in identifying patients for whom the model's predictions are less certain. Our proposed method managed to achieve 87%, 89% and 75% in accuracy, specificity and sensitivity, respectively. This study represents a novel attempt to improve the reliability and robustness of DL algorithms in the domain of seizure detection. This study underscores the value of integrating uncertainty quantification into ML algorithms for seizure detection, offering clinicians a practical tool to gauge the applicability of ML models for individual patients.

MTSS2-related neurodevelopmental disorder (MTSS2-related NDD) (MIM 620086) is characterized by intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF). The only existing report to date described five individuals who exhibited an identical de novo c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. Herein, we report a new case of MTSS2-related NND in a male dizygotic twin who presented with IDDOF and severe intellectual disability. This patient also displayed additional clinical features, including low functioning autism, hypothyroidism, duodenal obstruction secondary to Ladd's bands, inguinal hernias, cryptorchidism, transient subperiosteal new bone formation, and short stature with delayed bone age, which had not been previously reported in association with the MTSS2-related NDD. Exome sequencing identified the recurrent c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. The mother and the other twin tested negative for the pathogenic variant, while the father's participation in the study was unavailable. This case confirms that the MTSS2-related NDD is caused by the recurrent MTSS2 missense variant p.Arg671Trp. The novel findings identified in our patient expand the phenotypic spectrum associated with this new autosomal dominant entity, but further studies on its genetic and clinical manifestations are still needed., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Preventable risk factors are responsible of at least 40% of cases and almost 45% of all cancer deaths worldwide. Cancer is already the leading cause of death in almost half of the Latin American and the Caribbean countries constituting a public health problem. Cost-effective measures to reduce exposures through primary prevention and screening of certain types of cancers are critical in the fight against cancer but need to be tailored to the local needs and scenarios. The Latin America and the Caribbean (LAC) Code Against Cancer, 1st edition, consists of 17 evidence-based recommendations for the general public, based on the most recent solid evidence on lifestyle, environmental, occupational, and infectious risk factors, and medical interventions. Each recommendation is accompanied by recommendations for policymakers to guide governments establishing the infrastructure needed to enable the public adopting the recommendations. The LAC Code Against Cancer has been developed in a collaborative effort by a large number of experts from the region, under the umbrella strategy and authoritative methodology of the World Code Against Cancer Framework. The Code is a structured instrument ideal for cancer prevention and control that aims to raise awareness and educate the public, while building capacity and competencies to policymakers, health professionals, stakeholders, to contribute to reduce the burden of cancer in LAC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aneurysmal coronary artery disease (ACAD) has been reported rarely in patients with neurofibromatosis type 1 (NF1), mostly in adults. We report on a female newborn affected by NF1 with ACAD disclosed during investigation for an abnormal prenatal ultrasound along with a review of the previously reported cases. The proposita had multiple café-au-lait spots and had no cardiac symptoms. Echocardiography, and cardiac computed tomography angiography confirmed aneurysms on the left coronary artery, left anterior descending coronary artery, and of the sinus of Valsalva. Molecular analysis detected the pathogenic variant NM&#95;001042492.3(NF1):c.3943C>T (p.Gln1315*). Literature findings on ACAD in NF1 indicated that this mostly occurs in males, showing predilection for the development of aneurysms at the left anterior descending coronary artery, and manifesting predominantly as acute myocardial infarction, inclusively in teenagers, though it may be also asymptomatic as in our case. This report documents the first case of ACAD in a patient with NF1 diagnosed at birth, emphasizing that its early diagnosis is essential to prevent potential life-threatening events attributable directly to coronary lesions., (© 2023 Wiley Periodicals LLC.)

Cutis verticis gyrata (CVG) is classified as primary or secondary according to the absence or presence of underlying soft tissue abnormalities. We report an infant with Turner syndrome (TS) who in addition presented with CVG on the scalp. The skin biopsy revealed a hamartoma-like lesion. We reviewed the clinical and histopathological findings of the 13 reported cases of congenital CVG in patients with TS, including ours. In 11 of them, CVG was localized on the skin of the scalp, mainly on the parietal region, and in two, on the forehead. Clinically, CVG had a flesh-colored aspect, with absent or sparse hair, and was not progressive. CVG was classified as primary in four patients who had skin biopsy and it was attributed to the intrauterine lymphedema of TS. However, histopathology in two of these patients identified dermal hamartoma as a secondary cause of CVG, and in three others, including ours, there were hamartomatous changes. Although further studies are required, previous findings support the proposal that some CVG may instead be dermal hamartomas. This report alerts clinicians to recognize CVG as a low-frequency manifestation of TS, but also to consider the possible co-occurrence of TS in all female infants with CVG., (© 2023 Wiley Periodicals LLC.)

Coal combustion byproducts are known to be enriched in arsenic (As) and selenium (Se). This enrichment is a concern during the handling, disposal, and reuse of the ash as both elements can be harmful to wildlife and humans if mobilized into water and soils. The leaching potential and bioaccessibility of As and Se in coal fly ash depends on the chemical forms of these elements and their association with the large variety of particles that comprise coal fly ash. The overall goal of this research was to determine nanoscale and microscale solid phase mineral associations and oxidation states of As and Se in fly ash. We utilized nanoscale 2D imaging (30-50 nm spot size) with the Hard X-ray Nanoprobe (HXN) in combination with microprobe X-ray capabilities (∼5 μm resolution) to determine the As and Se elemental associations. Speciation of As and Se was also measured at the nano- to microscale with X-ray absorption spectroscopy. The enhanced resolution of HXN showed As and Se as either diffusely located around or comingled with Ca- and Fe-rich particles. The results also showed nanoparticles of Se attached to the surface of fly ash grains. Overall, a comparison of As and Se species across scales highlights the heterogeneity and complexity of chemical associations for these trace elements of concern in coal fly ash., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Soil health is recognized as an important ecosystem property sensitive to human impact. As a concept, soil health cannot be directly measured, and so assessment and modeling efforts largely rely upon key biological, chemical, and physical indicators. Efforts to develop an overall soil health index are largely lacking due to significant statistical challenges and the necessity for regional calibration. Taken from the field of educational research, structural equation modeling (SEM) is an attractive approach to enhance the reliability and validity of soil health scoring. Therefore, SEM may be utilized to advance research efforts to understand management practices impacts on soil health. Our objectives were to develop a robust scoring function that (i) captures the concept of soil health and latent variables, (ii) adjusts scores by inherent soil properties and legacy of intensive land use to adequately reflect our regional conditions and contemporary land management, and (iii) meets the diverse practitioner needs. Through this process, we refined our minimum dataset of soil health indicators and reconceptualized soil health indicators into functional properties. Our results support the development of a robust single level or a multilevel SEM model-depending on the practitioner's goals-that accounts for repeated sampling or pseudoreplication. While the SEM scoring functions were highly related to the conventional scoring approach, SEM outperformed the conventional methods in terms of its wider distribution of scores-and thus enhanced discriminatory power on the lower and higher range of scores. We also confirmed that the SEM scoring function that includes adjustments for mineralogy and legacy of intensive land use successfully differentiates among contemporary management practices and land use. Therefore, we have confidence that the tool is reliable and appropriate to further examine more nuanced impacts of land use change and management practices within a given land use across time and space covering a diversity of soils. (300 words)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships influencing the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: PACS1 -related neurodevelopmental disorder ( PACS1- related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement., Case Presentation: Here, we describe 4 individuals with PACS1 -related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1 -related NDD., Discussion: We reviewed the ocular phenotypes reported in 74 individuals with PACS1 -related NDD and the overlaps with WDR37- and PACS2 -related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1 -related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37 - PACS1 - PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

Plants produce many high-value oleochemical molecules. While oil-crop agriculture is performed at industrial scales, suitable land is not available to meet global oleochemical demand. Worse, establishing new oil-crop farms often comes with the environmental cost of tropical deforestation. The field of metabolic engineering offers tools to transplant oleochemical metabolism into tractable hosts while simultaneously providing access to molecules produced by non-agricultural plants. Here, we evaluate strategies for rewiring metabolism in the oleaginous yeast Yarrowia lipolytica to synthesize a foreign lipid, 3-acetyl-1,2-diacyl-sn-glycerol (acTAG). Oils made up of acTAG have a reduced viscosity and melting point relative to traditional triacylglycerol oils making them attractive as low-grade diesels, lubricants, and emulsifiers. This manuscript describes a metabolic engineering study that established acTAG production at g/L scale, exploration of the impact of lipid bodies on acTAG titer, and a techno-economic analysis that establishes the performance benchmarks required for microbial acTAG production to be economically feasible., Competing Interests: Declaration of competing interest Authors declare that they have no competing interests., (Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Turner Syndrome is characterized by a normal X chromosome and the partial or complete absence of a second sexual chromosome. Small supernumerary marker chromosomes are present in 6.6% of these patients. Because of the wide range of Turner syndrome karyotypes, it is difficult to establish a relationship with the phenotype of the patients. We present the case of a female patient with Turner syndrome, insulin resistance, type 2 diabetes, and intellectual disability. The karyotype revealed the presence of mosaicism with a monosomy X cell line and a second line with a small marker chromosome. FISH of two different tissues was used to identify the marker chromosome with probes for X and Y centromeres. Both tissues presented mosaicism for a two X chromosome signal, differing in the percentage of the monosomy X cell percentage. Comparative genomic hybridization with the CytoScan TM HD assay was performed in genomic DNA from peripheral blood, allowing us to determine the size and breakage points of the small marker chromosome. The patient presents a phenotype that combines classic Turner syndrome features and unlikely ones as intellectual disability. The size, implicated genes, and degree of inactivation of the X chromosome influence the broad spectrum of phenotypes resulting from these chromosomes.

Adams-Oliver syndrome (AOS) is diagnosed in presence of aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). The autosomal recessive (AR) DOCK6-related form of AOS is most often associated with a severe phenotype including also central nervous system and ocular abnormalities. We report a sister and brother with different expression of the phenotype. Both were compound heterozygous pathogenic variants in the DOCK6 gene, including a heterozygous c.5939+2T > C intronic variant that was maternally inherited, and a heterozygous deletion of exons 10 to 21 that was paternally inherited. The sister had microcephaly, periventricular calcifications, minor retinal vasculopathy, and mild impaired neurodevelopment, but only very subtle limb abnormalities and no ACC. Her brother showed a classical DOCK6-related AOS phenotype, including a severe bilateral peripheral ischemic retinopathy. From a review of 22 molecularly confirmed cases with DOCK6-related AOS with ophthalmic examination, we found that 16 of them had retinal vascular pathology (72.7%), confirming as the major ocular anomaly. Documented intrafamilial variability in our family and the evidence revised from previous reports, confirm that AR DOCK6-related AOS expressivity can produce a "milder" phenotype without ACC or TTLD, which could be underdiagnosed in simplex cases because it is difficult to recognize out of a familial context. Therefore, in order to know its real magnitude is required the future inclusion of DOCK6 gene in NGS panels directed to the study of simplex cases of patients with microcephaly, periventricular calcifications, retinal vasculopathy, and/or cardiovascular defects., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Using a qualitative phenomenological design, the objective of this study was to explore in-depth how US-born Latinos provide social support to their immigrant counterparts during a time of heightened anti-immigrant rhetoric. A sample of 22 US-born Latino adult was recruited in 2019 for qualitative interviews, following a period of intense immigration raids. Eligible participants were adults who reported experiencing an immigration-related stressor and screened positive for a mental health concern or substance misuse. Open-ended questions focused on topics of immigration and health. Using a thematic analysis approach, interview transcripts were coded to identify common themes within the domains of social support: instrumental; informational; emotional; and appraisal. We found that US-born Latinos provide diverse forms of social support to immigrants with the intention of protecting them from immigration enforcement encounters (e.g. deportation), thereby safeguarding the livelihoods of their communities. US-born Latinos are integral pillars of support and resiliency for immigrant communities, and the domains identified within this study suggest important implications for immigrant health., (© 2022 John Wiley & Sons Ltd.)

Abstract: We investigated the influence of nursing students' sleep quality on their patient safety (PS) competence (i.e., knowledge of the dimensions of PS). The investigation surveyed 242 nursing students in a Saudi university. The majority of the surveyed students were characterized as having poor sleep quality. Notably, more male students experienced poor sleep quality than female students. The students reported the highest confidence in "culture of safety" and "managing safety risk"; they exhibited the poorest confidence in "working in teams." Increased length of sleep latency decreased sleep efficiency, and increased daytime sleepiness-related dysfunction was associated with reduced PS competence., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2022 National League for Nursing.)

Background: Severity of radiographic abnormalities on chest radiograph in subjects with COVID-19 has been shown to be associated with worse outcomes, but studies are limited by different scoring systems, sample size, subject age, and study duration. Data regarding the longitudinal evolution of radiographic abnormalities and its association with outcomes are scarce. We sought to evaluate these questions using a well-validated scoring system (the Radiographic Assessment of Lung Edema [RALE] score) using data over 6 months from a large, multihospital health care system., Methods: We collected clinical and demographic data and quantified radiographic edema on chest radiograph obtained in the emergency department (ED) as well as on days 1-2 and 3-5 (in those admitted) in subjects with a nasopharyngeal swab positive for SARS-CoV-2 by polymerase chain reaction (PCR) visiting the ED for coronavirus disease 2019 (COVID)-19-related complaints between March-September 2020. We examined the association of baseline and longitudinal evolution of radiographic edema with severity of hypoxemia and clinical outcomes., Results: Eight hundred and seventy subjects were included (median age 53.6; 50.8% female). Inter-rate agreement for RALE scores was excellent (interclass correlation coefficient 0.84 [95% CI 0.82-0.87], P < .001). RALE scores correlated with hypoxemia as quantified by S pO 2 /F IO 2 (r = -0.42, P < .001). Admitted subjects had higher RALE scores than those discharged (6 [2-11] vs 0 [0-3], P < .001). An increase of RALE score ≥ 4 was associated with worse 30-d survival ( P = .006). Larger increases in the RALE score were associated with worse survival., Conclusions: The RALE score was reproducible and easily implementable in adult subjects presenting to the ED with COVID-19. Its association with physiologic parameters and outcomes at baseline and longitudinally makes it a readily available tool for prognostication and early ICU triage, particularly in patients with worsening radiographic edema., Competing Interests: The authors have disclosed no conflicts of interests., (Copyright © 2022 by Daedalus Enterprises.)

Background: Filipino Americans underuse mental health and preventive care services even though studies have indicated that Filipino youth experience high rates of suicidal ideation, substance abuse, and teen pregnancies, whereas adults experience immigration stress, discrimination, and depression. Evidence-based parenting interventions provided in early childhood have proven to be effective in preventing the onset and escalation of child mental health disorders. In a pilot randomized controlled trial, we found that participation in the Incredible Years Basic Parent Training Program (IY) improved parenting stress and positive parenting practices and decreased child internalizing and externalizing symptoms among Filipino families. A fully powered trial is needed to determine the efficacy of IY as a prevention program among Filipino families., Objective: The aims of this study are to describe the design and rationale of a randomized controlled trial evaluating the effects of the web-based IY program among parents recruited from multiple community-based settings and its impact on parenting practices, parenting stress, and child problem behavior among Filipino Americans and describe the impact of COVID-19 on our study protocols., Methods: This study uses a randomized controlled 2-arm individually randomized group treatment pretest-posttest design for 180 parent-child dyads. Individuals are eligible if they are ≥18 years, live in California, and have at least one Filipino child aged 8-12 years. Consenting participants are randomly allocated to receive either the 12-week IY parenting intervention (intervention arm) or American Academy of Pediatrics' Bright Future handouts and placed on a waitlist to receive IY posttrial (waitlist control arm). Primary outcomes include the Parent Practices Interview and the Parenting Stress Index. Secondary outcomes will be measured using the Child Behavior Checklist (completed by parent) and will include child internalizing and externalizing behaviors and total problems. Data are collected at baseline and 3- and 6-month follow-ups., Results: Changes made to the protocol owing to COVID-19 include administration of surveys remotely and implementation of the intervention on the web. The pandemic has provided an opportunity to evaluate the effectiveness of a web-based version of IY that may improve access and increase use of the intervention. Recruitment and data collection procedures are still ongoing and are expected to be completed by December 2022., Conclusions: Our research will determine whether IY promotes positive parenting practices and prevents child internalizing and externalizing behaviors in healthy but high-risk populations such as Filipino families. It will also uplift cultural narratives and add to the evidence base for web-based parenting programs and their implementation in real-world settings. If found efficacious, IY has the potential to prevent behavioral health disparities in this understudied and high-risk Filipino population and can be scaled, adapted, and implemented in other at-risk racial and ethnic minority communities., Trial Registration: ClinicalTrials.gov NCT04031170; https://clinicaltrials.gov/ct2/show/NCT04031170., International Registered Report Identifier (irrid): DERR1-10.2196/21867., (©Samantha Reyes Macam, Wendy Mack, Lawrence Palinkas, Michele Kipke, Joyce Rivera Javier. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 17.02.2022.)

Malakoplakia is a chronic inflammatory process caused by a lysosomal defect in bacterial digestion. Although rare, it occurs more frequently in the genitourinary tract and in patients with immune dysfunction. The bladder is the most commonly affected site, although cases have been reported in other organs, including the prostate gland. Clinically, this lesion can be confused with malignant tumours, both on physical examination and imagining techniques. This is particularly pronounced in the prostate, making the differential diagnosis challenging. Histologically, characteristic aggregates of histiocytes with basophilic intracytoplasmic inclusions composed of calcium and iron salts are found. We present a case diagnosed on transrectal biopsy as acinar adenocarcinoma with a Gleason 5 + 5 = 10 score. Prostatectomy revealed an unusual association of diffuse prostate malakoplakia and an area of acinar adenocarcinoma with a Gleason score of 3 + 4 = 7., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)