Melanin-concentrating hormone receptor: A therapeutic target for novel anxiolytics.

Anxiety disorders are chronic, disabling psychiatric disorders, and there is a growing medical need for the development of novel pharmacotherapeutic agents showing improved efficacy and an improved side effect profile as compared with the currently prescribed anxiolytic drugs. In the course of the search for next-generation anxiolytics, neuropeptide receptors have garnered interest as potential therapeutic targets, underscored by pivotal roles in modulating stress responses and findings from animal studies using pharmacological tools. Among these neuropeptide receptors, the type 1 receptor for melanin-concentrating hormone (MCH1), which has been demonstrated to be involved in an array of physiological processes, including the regulation of stress responses and affective states, has gained attraction as a therapeutic target for drugs used in the treatment of psychiatric disorders, including anxiety disorders. To date, a plethora of MCH1 antagonists have been synthesized, and studies using MCH1 antagonists and genetically manipulated mice lacking MCH1 have revealed that the blockade of MCH1 produces anxiolytic-like effects across diverse rodent paradigms. In addition, MCH1 antagonists have been demonstrated to show a rapid onset of antidepressant-like effects; therefore, they may be effective for conditions commonly encountered in patients with anxiety disorders, which is an advantage for anxiolytic drugs. Notably, MCH1 antagonists have not manifested the undesirable side effects observed with the currently prescribed anxiolytics. All these preclinical findings testify to the potential of MCH1 antagonists as novel anxiolytics. Although there are still issues that need to be resolved prior to the initiation of clinical trials, such as elucidating the precise neuronal mechanisms underlying their anxiolytic effects and exploring pertinent biomarkers that can be used in clinical trials, MCH1 blockade appears to be an attractive way to tackle anxiety disorders.

Maternal and Child Health Services Utilization During COVID-19 in Eastern Ethiopia.

Objectives: This study aimed to describe the impact of COVID-19 on maternal and child health service utilization in the Eastern part of Ethiopia. Methods: Comparative analysis was used to examine 2 years of maternal and child health service utilization. Data were extracted from client registers. A traditional Expert Modeler and one-way Analysis of Variance were used to compare service utilization before and during the COVID-19 pandemic. Results: A total of 34,576 client records were reviewed, of which 17,100 (49.5%) and 17,476 (50.5%) had visited the MCH service before and during the COVID-19 pandemic, respectively. The total client visit has shown a 2% percentage point increase. However, postnatal care and child immunization services showed a decrease. Moreover, there was a significant difference between service visits before and during COVID-19 (f = 4.6, p < 0.04). Conclusion: Mothers and children have missed or unattended facility appointments due to protective impositions or fear of getting infected with COVID-19, which might suggest a higher proportion of MCH issues were not addressed during the pandemic. The health system should therefore improve its resilience and strengthen its access at the lowest health care inlets.

Zeolite Membrane-Based Low-Temperature Dehydrogenation of a Liquid Organic Hydrogen Carrier: A Key Step in the Development of a Hydrogen Economy.

Methylcyclohexane (MCH) dehydrogenation is an equilibrium-limited reaction that requires high temperatures (>300 °C) for complete conversion. However, high-temperature operation can degrade catalytic activity and produce unwanted side products. Thus, a hybrid zeolite membrane (Z) is prepared on the inner surface of a tubular support and used it as a wall in a membrane reactor (MR) configuration. Pt/C catalysts is packed diluted with quartz sand inside the Z-coated tube and applied the MR for MCH dehydrogenation at low temperatures (190-250 °C). Z showed a remarkable H2-permselectivity in the presence of both toluene and MCH, yielding separation factors over 350. The Z-based MR achieved higher MCH conversion (75.3% ± 0.8% at 220 °C) than the conventional packed-bed reactor (56.4% ± 0.3%) and the equilibrium state (53.2%), owing to the selective removal of H2 through Z. In summary, the hybrid zeolite MR enhances MCH dehydrogenation at low temperatures by overcoming thermodynamic limitations and improves the catalytic performance and product selectivity of the reaction.

An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking.

Background: Identifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. Methods: Surface EEG signals and real-time Ca2+ activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. Results: An EEG waveform derivative - a modified theta-to-delta ratio (EEG Ratio) - accurately tracks real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions. Conclusions: The identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.

An Electroencephalogram Signature of Melanin-Concentrating Hormone Neuron Activities Predicts Cocaine Seeking.

BACKGROUND: Identifying biomarkers that predict substance use disorder propensity may better strategize antiaddiction treatment. Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus critically mediate interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers. METHODS: Surface EEG signals and real-time calcium (Ca2+) activities of lateral hypothalamus MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCH using EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCH either before or after cocaine experience were used to predict future drug-seeking behaviors. RESULTS: An EEG waveform derivative-a modified theta-delta-theta peak ratio (EEGTDT ratio)-accurately tracked real-time Ca2+MCH in rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through vigilance states, sleep manipulations, and circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEGTDT ratio, suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEGTDT ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEGTDT ratio also exhibited advantages over conventional REMS measures for the predictions. CONCLUSIONS: The identified EEGTDT ratio may serve as a noninvasive measure for assessing MCH neuron activities in vivo and evaluating REMS; it may also serve as a potential biomarker for predicting drug use propensity.

Neuroanatomical, electrophysiological, and morphological characterization of melanin-concentrating hormone cells coexpressing cocaine- and amphetamine-regulated transcript.

Melanin-concentrating hormone (MCH) cells in the hypothalamus regulate fundamental physiological functions like energy balance, sleep, and reproduction. This diversity may be ascribed to the neurochemical heterogeneity among MCH cells. One prominent subpopulation of MCH cells coexpresses cocaine- and amphetamine-regulated transcript (CART), and as MCH and CART can have opposing actions, MCH/CART+ and MCH/CART- cells may differentially modulate behavioral outcomes. However, it is not known if there are differences in the cellular properties underlying their functional differences; thus, we compared the neuroanatomical, electrophysiological, and morphological properties of MCH cells in male and female Mch-cre;L10-Egfp reporter mice. Half of MCH cells expressed CART and were most prominent in the medial hypothalamus. Whole-cell patch-clamp recordings revealed differences in their passive and active membrane properties in a sex-dependent manner. Female MCH/CART+ cells had lower input resistances, but male cells largely differed in their firing properties. All MCH cells increased firing when stimulated, but their firing frequency decreases with sustained stimulation. MCH/CART+ cells showed stronger spike rate adaptation than MCH/CART- cells. The kinetics of excitatory events at MCH cells also differed by cell type, as the rising rate of excitatory events was slower at MCH/CART+ cells. By reconstructing the dendritic arborization of our recorded cells, we found no sex differences, but male MCH/CART+ cells had less dendritic length and fewer branch points. Overall, distinctions in topographical division and cellular properties between MCH cells add to their heterogeneity and help elucidate their response to stimuli or effect on modulating their respective neural networks.

Peroxisome deficiency underlies failures in hepatic immune cell development and antigen presentation in a severe Zellweger disease model.

Peroxisome biogenesis disorders (PBDs) represent a group of metabolic conditions that cause severe developmental defects. Peroxisomes are essential metabolic organelles, present in virtually every eukaryotic cell and mediating key processes in immunometabolism. To date, the full spectrum of PBDs remains to be identified, and the impact PBDs have on immune function is unexplored. This study presents a characterization of the hepatic immune compartment of a neonatal PBD mouse model at single-cell resolution to establish the importance and function of peroxisomes in developmental hematopoiesis. We report that hematopoietic defects are a feature in a severe PBD murine model. Finally, we identify a role for peroxisomes in the regulation of the major histocompatibility class II expression and antigen presentation to CD4+ T cells in dendritic cells. This study adds to our understanding of the mechanisms of PBDs and expands our knowledge of the role of peroxisomes in immunometabolism.

A role for MCH neuron firing in modulating hippocampal plasticity threshold.

It has been revealed that hypothalamic neurons containing the peptide, melanin-concentrating hormone (MCH) can influence learning [1] and memory formation [2], but the cellular mechanisms by which they perform this function are not well understood. Here, we examine the role of MCH neural input to the hippocampus, and show in vitro that optogenetically increasing MCH axon activity facilitates hippocampal plasticity by lowering the threshold for synaptic potentiation. These results align with increasing evidence that MCH neurons play a regulatory role in learning, and reveal that this could be achieved by modulating plasticity thresholds in the hippocampus.

Promoting Innovation in State and Territorial Maternal and Child Health Policymaking.

INTRODUCTION: The Association of Maternal & Child Health Programs (AMCHP) and the Association of State and Territorial Health Officials (ASTHO) launched the PRISM (Promoting Innovation in State and Territorial MCH Policymaking) Learning Community, funded by the U.S. Department of Health and Human Services (HHS), Health Resources and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB). The goal of PRISM was to build state and territorial health agency program and policy-making capacity to address substance use and mental health in the maternal and child health (MCH) population. Expanding access to care and treatment for perinatal substance use disorders (SUD) emerged as the issue of greatest need for state teams. METHODS: The PRISM Learning Community consisted of three major components: (1) intensive capacity building for cross-agency state teams, which involved action planning, peer-to-peer learning, and technical assistance; (2) programming to inform the MCH field broadly about innovations in perinatal SUD policy and practice; and (3) a program evaluation involving pre-, mid-, and post-assessments and follow-up key informant interviews with state teams. This manuscript is not based on clinical study or patient data, therefore IRB approval was not required. RESULTS: States reported that their knowledge of perinatal SUDs increased and their cross-agency partnerships were strengthened as a result of their participation in PRISM. States identified four key priorities for their continued work: to improve multisector collaborations, to institute equitable SUD screening practices for pregnant people, to strengthen the perinatal behavioral health workforce, and to enhance Medicaid coverage for perinatal SUD prevention and treatment services. The need to respond to urgent demands of COVID-19 and the stigma associated with perinatal SUDs were the most significant barriers to advancing state action plan goals. DISCUSSION: Since 2018, the PRISM project has supported nine jurisdictions across two cohorts. Participation in PRISM advanced state policies and programs to improve perinatal SUD care through capacity building, technical assistance, and virtual programming. Findings and lessons learned from PRISM may inform the activities of other states seeking to address perinatal substance use disorders.

Seeking Health in a Digital World: Exploring Immigrant Parents' Quest for Child Health Information-A Scoping Review.

During pregnancy and early parenthood, parents' strong interest in pediatric health information presents a valuable opportunity to positively impact long-term health-seeking behavior and overall child health. In line with the increasing prevalence of digital transformation, a scoping review was conducted to explore two key aspects: (1) information seeking and use of digital health information among immigrant parents, and (2) associated reasons and factors. The literature search covered the period until July 2022, using Web of Science, MEDLINE, and CINAHL Complete databases. Out of 625 articles, 12 were included, comprising six qualitative, five quantitative studies, and one review. The majority of studies focused on immigrants in North America, primarily from Latin America and Asia. The studies varied in topics and methodologies, making it challenging to draw general conclusions. Nevertheless, while most immigrant parents rely on digital information on child health, they often prefer human sources such as family, friends, or healthcare providers. Trustworthiness and accessibility emerged as critical criteria for health resources. Two focus group discussions, derived from the results of the review, confirmed these findings for migrant mothers in Switzerland.

Orexin and MCH neurons: regulators of sleep and metabolism.

Sleep-wake and fasting-feeding are tightly coupled behavioral states that require coordination between several brain regions. The mammalian lateral hypothalamus (LH) is a functionally and anatomically complex brain region harboring heterogeneous cell populations that regulate sleep, feeding, and energy metabolism. Significant attempts were made to understand the cellular and circuit bases of LH actions. Rapid advancements in genetic and electrophysiological manipulation help to understand the role of discrete LH cell populations. The opposing action of LH orexin/hypocretin and melanin-concentrating hormone (MCH) neurons on metabolic sensing and sleep-wake regulation make them the candidate to explore in detail. This review surveys the molecular, genetic, and neuronal components of orexin and MCH signaling in the regulation of sleep and metabolism.

Utilization of preconception care and associated factors among pregnant women attending ANC in private MCH Hospitals in Addis Ababa, Ethiopia.

BACKGROUND: Despite its benefit in promoting maternal health and the health of her developing fetus, little is known about preconception care practice and its associated factors in Ethiopia. Moreover, preconception care utilization in private hospitals is not known. The purpose of this study, therefore, is to determine the utilization of preconception health care services and its associated factors among pregnant women following antenatal care in the private Maternal and Child Health hospitals in Addis Ababa. METHODS: A Hospital based cross-sectional study was conducted from April 1 to April 30,2022 among 385 women attending ANC in private MCH hospitals. Bestegah and Hemen MCH hospitals were selected by convenience method. Data were collected by a pretested self-administered semi-structured questionnaire. To identify the factors associated with the utilization of preconception care, bivariable and multivariable logistic regression analysis were performed. Adjusted odds ratios with 95% confidence interval were estimated to assess the strength of associations, and statistical significance was declared at a p-value < 0.05. RESULTS: The utilization of preconception care among the pregnant mothers according to our study was 40%. Professional/technical/managerial occupation (AOR = 4.3, 95%CI = 1.13, 16.33, P < 0.032), having good knowledge on preconception care (AOR = 3.5, 95%CI = 1.92, 6.53, P < 0.000), having unintended pregnancy (AOR = 0.1, 95%CI = 0.03, 0.42, P < 0.001), history of family planning use before conception (AOR = 3.9, 95%CI = 1.20, 12.60, P < 0.023), having pre-existing medical disease(s) (AOR = 8.4, 95%CI = 2.83, 24.74, P < 0.002), and having adverse pregnancy outcome(s) in previous pregnancies (AOR = 3.2, 95%CI = 1.55, 6.50, P < 0.000) were significantly associated with preconception care utilization. CONCLUSIONS: This study found out that the utilization of preconception care in the private MCH hospitals is still low i.e., only 40%. Occupation, level of knowledge, having unintended pregnancy, history of family planning use before conception, having adverse pregnancy outcome(s) in previous pregnancy and having pre-existing medical disease(s) were independently associated with preconception care utilization. Lack of awareness about the availability of the services and having an unintended pregnancy were the main reasons for not utilizing preconception care.

History and Metamorphosis of Hand Surgery India.

The advent of hand surgery in India reads like a fortuitous saga, a continuum of the hand deformity correction on leprosy patients pioneered by Dr. Paul Wilson Brand at the Christian Medical College (CMC) Vellore, Madras State (Tamil Nadu [TN]), in 1948. The "Hand Research Unit," established in 1951, became the largest repository for hand reconstructive surgeries and with its head-start drew in most hand dysfunctions in the country. Early industrialization and disorderly road traffic generated hand injuries that threatened workforce in India. Propitiously, a hand injury service was opened in 1971 at the Government Stanley Medical College Hospital, Chennai. The inexorable growth of hand surgery continued and incorporated the gamut of conditions that required hand care and rehabilitation, including brachial plexus injuries. Continuing Medical Education programs, Hand Surgery workshops, Indian Society for Surgery of the Hand meetings, Hand Fellowships, etc., increased the number of "hand surgery" practitioners, which drew the attention of the Medical Council of India to commence a postgraduate Hand Surgery program that it eventually gazetted. The sagacity of the members of the Board of Studies of TN Medical University honored the historical role of CMC Vellore in hand surgery and allowed it to commence the first Master of Chirurgiae Hand Surgery course in India in 2015. An intuitive understanding of 70 years of hand surgery accomplishments that redesigned and restored deformed and injured hands and protected livelihoods have made young surgeons increasingly take hand surgery as a career.

Neurosurgery training in Nepal: then and now.

Introduction: Neurosurgery training lacks uniformity across the world. Differences in the methods of training adopted during the training period is one of the major problems encountered in the field of neurosurgery all over the world. Moreover, neurosurgery is not "one neurosurgery"; in other words, it is not a unified whole. Material and methods: In this study, we attempt to evaluate the present conditions of neurosurgery training in Nepal by exploring different institutions providing the training. Results: Due to various factors and challenges, the neurosurgery training provided in Nepal varies in different institutions. Many travel abroad for training due to a lack of sufficient seats in training institutions. Discussion and conclusions: Despite the challenges, the future is bright for neurosurgery training in Nepal. With continued investment in education and training, and the adoption of new technologies and techniques, it is likely that the field of neurosurgery will continue to thrive and make a positive impact on the health and well-being of the Nepali population.

Access to Maternal and Child Health Services during the COVID-19 Pandemic: An Explorative Qualitative Study in Odisha, India.

Background: Maternal and child health (MCH) care is one of the essential routine healthcare services, which got affected during the coronavirus disease 2019 (COVID-19) pandemic. Modeled projections had anticipated an 8.3%-38.6% rise in maternal mortality from different countries globally. In view of limited studies pertaining to issues related to accessing MCH services in the event of a pandemic, this study was carried out on pregnant and postnatal mothers in Odisha, India. Methods: An explorative qualitative study through 36 in-depth interviews (IDIs) was conducted among 16 (44.4%) antenatal and 20 (55.5%) postnatal mothers in six of thirty districts of Odisha, India, from February to April 2021. The districts and blocks were randomly selected for better representativeness. The IDIs were conducted using a predesigned and pretested guide among mothers who had undergone delivery or availed of antenatal, postnatal, or child health services from October 2020 to April 2021. The IDIs were conducted till data saturation. The data were analyzed using MAXQDA software. Results: The average age of mothers was 27.6 (+/- 2.2) years. Among the participants, 16 (44.4%) were antenatal and 20 (55.6%) were postnatal mothers; 19 (52.8%) were primipara and 17 (47.2%) were multipara. The majority explained that they received enormous support including door-to-door services from the community health workers (CHWs) even during the difficult times of the pandemic. Reduced transportation facility and fear of contracting the infection were reasons behind the unwillingness to visit health facilities and preference for home delivery. Furthermore, the pandemic had physical, mental, social, and financial impacts among pregnant and postnatal women. Conclusion: The unprecedented COVID-19 pandemic has affected access to MCH services by antenatal and postnatal mothers. Health system preparedness and appropriate strategies including better community engagement and participation could avert such challenges in the future.

"HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex".

HLA-C, a gene located within the major histocompatibility complex, has emerged as a prominent target in biomedical research due to its involvement in various diseases, including cancer and autoimmune disorders; even though its recent addition to the MHC, the interaction between HLA-C and KIR is crucial for immune responses, particularly in viral infections. This review provides an overview of the structure, origin, function, and pathological implications of HLA-C in the major histocompatibility complex. In the last decade, we systematically reviewed original publications from Pubmed, ScienceDirect, Scopus, and Google Scholar. Our findings reveal that genetic variations in HLA-C can determine susceptibility or resistance to certain diseases. However, the first four exons of HLA-C are particularly susceptible to epigenetic modifications, which can lead to gene silencing and alterations in immune function. These alterations can manifest in diseases such as alopecia areata and psoriasis and can also impact susceptibility to cancer and the effectiveness of cancer treatments. By comprehending the intricate interplay between genetic and epigenetic factors that regulate HLA-C expression, researchers may develop novel strategies for preventing and treating diseases associated with HLA-C dysregulation.

Early effects of COVID-19 on maternal and child health service disruption in Mozambique.

This article is part of the Research Topic 'Health Systems Recovery in the Context of COVID-19 and Protracted Conflict'. Introduction: After the World Health Organization declared COVID-19 a pandemic, more than 184 million cases and 4 million deaths had been recorded worldwide by July 2021. These are likely to be underestimates and do not distinguish between direct and indirect deaths resulting from disruptions in health care services. The purpose of our research was to assess the early impact of COVID-19 in 2020 and early 2021 on maternal and child healthcare service delivery at the district level in Mozambique using routine health information system data, and estimate associated excess maternal and child deaths. Methods: Using data from Mozambique's routine health information system (SISMA, Sistema de Informação em Saúde para Monitoria e Avaliação), we conducted a time-series analysis to assess changes in nine selected indicators representing the continuum of maternal and child health care service provision in 159 districts in Mozambique. The dataset was extracted as counts of services provided from January 2017 to March 2021. Descriptive statistics were used for district comparisons, and district-specific time-series plots were produced. We used absolute differences or ratios for comparisons between observed data and modeled predictions as a measure of the magnitude of loss in service provision. Mortality estimates were performed using the Lives Saved Tool (LiST). Results: All maternal and child health care service indicators that we assessed demonstrated service delivery disruptions (below 10% of the expected counts), with the number of new users of family planing and malaria treatment with Coartem (number of children under five treated) experiencing the largest disruptions. Immediate losses were observed in April 2020 for all indicators, with the exception of treatment of malaria with Coartem. The number of excess deaths estimated in 2020 due to loss of health service delivery were 11,337 (12.8%) children under five, 5,705 (11.3%) neonates, and 387 (7.6%) mothers. Conclusion: Findings from our study support existing research showing the negative impact of COVID-19 on maternal and child health services utilization in sub-Saharan Africa. This study offers subnational and granular estimates of service loss that can be useful for health system recovery planning. To our knowledge, it is the first study on the early impacts of COVID-19 on maternal and child health care service utilization conducted in an African Portuguese-speaking country.

Neuronal responses of melanin-concentrating hormone and corticotropin-releasing hormone to background color in the self-fertilizing fish, Kryptolebias marmoratus.

We examined neuronal responses of hypothalamic melanin-concentrating hormone (MCH) and corticotropin-releasing hormone (CRH) to background color in the self-fertilizing fish, Kryptolebias marmoratus. Fish were individually reared in lidless white or black cylindrical plastic containers for 15 days. The number of MCH-immunoreactive (ir) cell bodies in the nucleus lateralis tuberis (NLT) of the hypothalamus was significantly greater in the white-acclimated fish, while no significant differences were observed in the nucleus anterior tuberis (NAT) of the hypothalamus. Significant differences were not seen in the number of CRH-ir cell bodies in the NLT between the groups. The body of the white- and black-acclimated fish appeared lighter and darker, respectively, compared with the baseline color. In the black-acclimated fish, feeding activity was significantly greater with a tendency toward higher specific growth rate compared with the observations in white-acclimated fish. No significant inter-group cortisol level differences were observed. These results indicate that background color affects MCH neuronal activity in the NLT as well as body color adaptation but does not affect CRH neuronal activity in K. marmoratus.

Predicting thalassemia using deep neural network based on red blood cell indices.

BACKGROUND AND OBJECTIVE: The traditional statistical screening method for thalassemia based on red blood cell (RBC) indices is being replaced by machine learning. Here, we developed deep neural networks (DNNs) that outperformed the traditional method for predicting thalassemia. METHOD: Using a dataset of 8693 records comprising genetic tests and other 11 features we constructed 11 DNN models and 4 traditional statistical models and then compared their performances and analysed feature importance for interpreting DNN models. RESULTS: The area under the receiver operating characteristic curve, accuracy, Youden's index, F1 score, sensitivity, specificity, positive predictive value and negative predictive value, were 0.960, 0.897, 0.794, 0.897, 0.883, 0.911, 0.914, and 0.882, respectively, for our best model, and compared with the traditional statistical model based on the mean corpuscular volume, these values were increased by 10.22%, 10.09%, 26.55%, 8.92%, 4.13%, 16.90%, 13.86% and 6.07%, respectively, and by 15.38%, 11.70%, 31.70%, 9.89%, 3.05%, 22.13%, 17.11% and 5.94%, respectively, for the mean cellular haemoglobin model. The DNN model performance will reduce without age, RBC distribution width (RDW), sex, or both WBC and PLT. CONCLUSIONS: Our DNN model outperformed the current screening model. In 8 features, RDW and age were the most useful, followed by sex and the combination of WBC and PLT, the remaining nearly useless.

Conviction and Compassion Creates the Federal Children's Health Insurance Program.

INTRODUCTION: For a quarter century, the Children's Health Insurance Program (CHIP) has provided essential health care coverage for children and pregnant women in working families. Established as part of the Balanced Budget Act of 1997, CHIP provides critical coverage for children living in families with incomes falling between eligibility for Medicaid and employment-based coverage. Since its enactment, CHIP has markedly reduced the number of children who were uninsured in 2020 to approximately 3.7 million children (5.0%), an extraordinary 67% reduction. This article traces the history of the federal CHIP legislation based in large part upon the success of Pennsylvania's innovative efforts. METHODS: Review of the literature. Personal Communications. RESULTS: Since its enactment, CHIP has markedly reduced the number of children who were uninsured in 2020 to approximately 3.7 million children (5.0%), an extraordinary 67% reduction. DISCUSSION: This article traces the history of the federal CHIP legislation based in large part upon the success of Pennsylvania's innovative efforts. The authors certify that the material presented in this article was prepared in accord with prevailing ethical principles.

While CHIP has been heralded for greatly improving access to health coverage, little is known about its origins, especially the contribution of the Pennsylvania CHIP, and the history of prior efforts. This article reviews the history of providing insurance coverage for children and recounts the personal involvement of the authors for CHIP's enactment.