bluuebunny/crossref_metadata_2025_split huggingface dataset:
The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency
Authors: Sheridan Mathew , Maqbool Muhammad Ahmad , Largeot Anne , Clayfield Liam , Xu Jingru , Moncaut Natalia , Sellers Robert , Whittle Jessica , Paggetti Jerome , Iqbal Mudassar , Aucagne Romain , Delva Laurent , Baker Syed Murtuza , Lie-a-Ling Michael , Kouskoff Valerie , Lacaud Georges 
Published: October 2024

Abstract
Background
The epigenetic factors KAT6A (MOZ/MYST3) and KMT2A (MLL/MLL1) interact in normal hematopoiesis to regulate progenitors’ self-renewal. Both proteins are recurrently translocated in AML, leading to impairment of critical differentiation pathways in these malignant cells. We evaluated the potential of different KAT6A therapeutic targeting strategies to alter the growth of KAT6A and KMT2A rearranged AMLs.

Methods
We investigated the action and potential mechanisms of the first-in-class KAT6A inhibitor, WM-1119 in KAT6A and KMT2A rearranged (KAT6Ar and KMT2Ar) AML using cellular (flow cytometry, colony assays, cell growth) and molecular (shRNA knock-down, CRISPR knock-out, bulk and single-cell RNA-seq, ChIP-seq) assays. We also used two novel genetic murine KAT6A models combined with the most common KMT2Ar AML, KMT2A::MLLT3 AML. In these murine models, the catalytic activity of KAT6A, or the whole protein, can be conditionally abrogated or deleted. These models allowed us to compare the effects of specific KAT6A KAT activity inhibition with the complete deletion of the whole protein. Finally, we also tested these therapeutic approaches on human AML cell lines and primary patient AMLs.

Results
We found that WM-1119 completely abrogated the proliferative and clonogenic potential of KAT6Ar cells in vitro. WM-1119 treatment was associated with a dramatic increase in myeloid differentiation program. The treatment also decreased stemness and leukemia pathways at the transcriptome level and led to loss of binding of the fusion protein at critical regulators of these pathways. In contrast, our pharmacologic and genetic results indicate that the catalytic activity of KAT6A plays a more limited role in KMT2Ar leukemogenicity, while targeting the whole KAT6A protein dramatically affects leukemic potential in murine KMT2A::MLLT3 AML.

Conclusion
Our study indicates that inhibiting KAT6A KAT activity holds compelling promise for KAT6Ar AML patients. In contrast, targeted degradation of KAT6A, and not just its catalytic activity, may represent a more appropriate therapeutic approach for KMT2Ar AMLs.
Cardiometabolic risk in children and adolescents with obesity: a position paper of the Italian Society for Pediatric Endocrinology and Diabetology
Authors: Valerio Giuliana , Di Bonito Procolo , Calcaterra Valeria , Cherubini Valentino , Corica Domenico , De Sanctis Luisa , Di Sessa Anna , Faienza Maria Felicia , Fornari Elena , Iughetti Lorenzo , Licenziati Maria Rosaria , Manco Melania , del Giudice Emanuele Miraglia , Morandi Anita , Salerno Mariacarolina , Street Maria Elisabeth , Umano Giuseppina Rosaria , Wasniewska Malgorzata , Maffeis Claudio 
Published: October 2024

AbstractDespite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the “Childhood Obesity study group” within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality.
Evaluation of statistical process control charts for infant mortality monitoring in Brazilian cities with different population sizes
Authors: Souza Jéssica , Boccolini Cristiano , Baroni Lais , Belloze Kele , Bezerra Eduardo , Pedroso Marcel , Alves Ronaldo Fernandes Santos , Ogasawara Eduardo 
Published: October 2024

Abstract
Objectives
The control chart is a classic statistical technique in epidemiology for identifying trends, patterns, or alerts. One meaningful use is monitoring and tracking Infant Mortality Rates, which is a priority both domestically and for the World Health Organization, as it reflects the effectiveness of public policies and the progress of nations. This study aims to evaluate the applicability and performance of this technique in Brazilian cities with different population sizes using infant mortality data.

Results
In this article, we evaluate the effectiveness of the statistical process control chart in the context of Brazilian cities. We present three categories of city groups, divided based on population size and classified according to the quality of the analyses when subjected to the control method: consistent, interpretable, and inconsistent. In cities with a large population, the data in these contexts show a lower noise level and reliable results. However, in intermediate and small-sized cities, the technique becomes limited in detecting deviations from expected behaviors, resulting in reduced reliability of the generated patterns and alerts.
Differences in the DNA methylome of T cells in adults with asthma of varying severity
Authors: Liao Yixuan , Cavalcante Raymond G. , Waller Jonathan B. , Deng Furong , Scruggs Anne M. , Huang Yvonne J. , Atasoy Ulus , Chen Yahong , Huang Steven K. 
Published: October 2024

Abstract
Background
DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity are less well-defined.

Objective
To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation.

Methods
Peripheral blood T cells from 35 adults with asthma in Beijing, China, were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores.

Results
Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway.

Conclusion
These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to differences in clinical indices of asthma.
Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report
Authors: Stalter Johannes , Gies Ursula , Mathys Christian , Witt Karsten 
Published: October 2024

Abstract
Background
Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life.

Case presentation
In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene.

Conclusion
This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.
Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia – a narrative review
Authors: Desai Sanjay , Sharma Digvijay , Srinivas Rajesh , Balaji Venugopal , Thakore Vijay , Bedi Varinder Singh , Jindal Ravul , Sugumaran Amarnath , Mohanasundaram Senthilnathan , Gogtay Jaideep , Gupta Pawan Kumar , Bhuiyan Aniruddha , Atturu Gnaneswar 
Published: October 2024

AbstractChronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or “no-option” CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of “no-option” Atherosclerotic Peripheral Arterial disease / Buerger’s disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.
A protocol for identifying the needs related to drug use, health and social (re)integration of people living in prison within five European countries
Authors: Plettinckx Els , Berndt Nadine , Seixas Rita , De Smet Stefaan , Antoine Jérôme , Bruggeman Helena , Harth Nina , Papadopoulou Athanasia , Bafi Ioulia , Fotiou Anastasios , Pridotkienė Evelina , Kalinauskaitė Rima , Rašimaitė Brigita , Tsiakkirou Myria , Balcaen Margot , Fernandez Kim , Gremeaux Lies , Dirkx Nicky , De Ridder Karin , Yiasemi Ioanna , Mavrou Josefina 
Published: October 2024

Abstract
Background
Compared to the general population, people living in prison are at an increased risk to experience negative (mental) health outcomes. Moreover, delinquency and drug use have many risk factors in common. A need exists for increasing the knowledge about health needs, drug use patterns and the coverage of drug-related interventions in prison within Europe. The current protocol describes the design of a study about wellbeing, drug use and related care in prison.

Methods/design
A multicentre mixed method design is implemented in five European countries (Belgium, Cyprus, Greece, Lithuania and Luxembourg). Qualitative and quantitative data collection tools are combined in order to generate complementary and comprehensive results. First, a cross-sectional survey among people living in prison is conducted. This survey is based on a model questionnaire, the European Questionnaire on Drug use among people living in Prison, developed by the European Monitoring Centre for Drug and Drugs Addiction. Second, people living in prison and people who have been recently released from prison are involved in qualitative semi-structured face-to-face interviews. The main topics of interest are the use of drugs and other health related topics such as loneliness, anxiety, depression, infectious diseases, suicide and treatment. Third, data regarding health and social reintegration measures in prison is collected through a quantitative survey addressed to the prison authorities.

Discussion
This study protocol presentes a European study which aims to assess drug use among people living in prison and recently released people who use drugs as well as the existing care services in prisons. Hereby, factors related to the prison environment and their needs, both inside and outside prison are taken into account. Importantly, this study protocol describes a methodology which is developed to be executed in different prison settings within different countries simultaneously. Accordingly, for each country the protocol is adjustable to specific national legal requirements, regional differences and distinct local regulations of prison administrations. However, extensive modularity inevitably comes with significant limitations of comparability and generalizability of the results.
Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington’s disease mice
Authors: Caron Nicholas S. , Byrne Lauren M. , Lemarié Fanny L. , Bone Jeffrey N. , Aly Amirah E.-E. , Ko Seunghyun , Anderson Christine , Casal Lorenzo L. , Hill Austin M. , Hawellek David J. , McColgan Peter , Wild Edward J. , Leavitt Blair R. , Hayden Michael R. 
Published: October 2024

Abstract
Background
Therapeutic approaches aimed at lowering toxic mutant huntingtin (mHTT) levels in the brain can reverse disease phenotypes in animal models of Huntington's disease (HD) and are currently being evaluated in clinical trials. Sensitive and dynamic response biomarkers are needed to assess the efficacy of such candidate therapies. Neurofilament light chain (NfL) is a biomarker of neurodegeneration that increases in cerebrospinal fluid (CSF) and blood with progression of HD. However, it remains unknown whether NfL in biofluids could serve as a response biomarker for assessing the efficacy of disease-modifying therapies for HD.

Methods
Longitudinal plasma and cross-sectional CSF samples were collected from the YAC128 transgenic mouse model of HD and wild-type (WT) littermate control mice throughout the natural history of disease. Additionally, biofluids were collected from YAC128 mice following intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting the mutant HTT transgene (HTT ASO), at ages both before and after the onset of disease phenotypes. NfL concentrations in plasma and CSF were quantified using ultrasensitive single-molecule array technology.

Results
Plasma and CSF NfL concentrations were significantly elevated in YAC128 compared to WT littermate control mice from 9 months of age. Treatment of YAC128 mice with either 15 or 50 µg HTT ASO resulted in a dose-dependent, allele-selective reduction of mHTT throughout the brain at a 3-month interval, which was sustained with high-dose HTT ASO treatment for up to 6 months. Lowering of brain mHTT prior to the onset of regional brain atrophy and HD-like motor deficits in this model had minimal effect on plasma NfL at either dose, but led to a dose-dependent reduction of CSF NfL. In contrast, initiating mHTT lowering in the brain after the onset of neuropathological and behavioural phenotypes in YAC128 mice resulted in a dose-dependent stabilization of NfL increases in both plasma and CSF.

Conclusions
Our data provide evidence that the response of NfL in biofluids is influenced by the magnitude of mHTT lowering in the brain and the timing of intervention, suggesting that NfL may serve as a promising exploratory response biomarker for HD.
A process evaluation of a home garden intervention
Authors: Ritter Thea , Mockshell Jonathan , Garrett James , Ogutu Sylvester , Asante-Addo Collins 
Published: October 2024

Abstract
Background
Most reviews of nutrition-sensitive programs assess the evidence base for nutrition outcomes without considering how programs were delivered. Process evaluations can fill this void by exploring how or why impacts were or were not achieved. This mid-term process evaluation examines a home garden intervention implemented in a large-scale, livelihoods improvement program in Odisha, India. The objectives are to understand whether the intervention was operating as planned (fidelity), investigate potential pathways to achieve greater impact, and provide insights to help design future home garden programs.

Methodology
Data collection and analysis for this theory-driven process evaluation are based on a program impact pathway that shows the flow of inputs, processes, outputs, outcomes, and impacts. Quantitative and qualitative data from focus group discussions, semi-structured interviews, and a Process Net-Mapping exercise with beneficiaries, frontline workers, and program management staff.

Results
Despite a mismatch between the design and implementation (low fidelity), the process evaluation identified positive outputs, outcomes, and impacts on home garden production, consumption, income, health and nutritional outcomes, and women’s empowerment. Flexibility led to greater positive outcomes on nutrition, the adoption of sustainable agricultural practices and easy-to-understand nutrition models, and the likelihood of the intervention being sustained after the program ends.

Conclusions
To help food systems in rural settings reduce food insecurity by utilizing more sustainable agricultural practices, we recommend that home garden interventions include instruction on easy-to-understand nutrition models and on how to make natural fertilizer. Finding local solutions like home gardens to help address critical supply issues and food insecurity is paramount.
Dietary supplementation with pterostilbene activates the PI3K-AKT-mTOR signalling pathway to alleviate progressive oxidative stress and promote placental nutrient transport
Authors: Cao Mingming , Bai Liyun , Wei Haoyun , Guo Yantong , Sun Guodong , Sun Haoyang , Shi Baoming 
Published: October 2024

Abstract
Background
Progressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport.

Results
PTE increased the antioxidant capacity and immunoglobulin content in mothers’ blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces.

Conclusions
These findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity.

Graphical Abstract
Flexible sensing probe for the simultaneous monitoring of neurotransmitters imbalance
Authors: Cha Hye Bin , Zhang Yao , Yu Hyun-Yong , Lee Yi Jae 
Published: October 2024

AbstractSimultaneous detection of multiple neurotransmitters and their related activities is crucial for enhancing our understanding of complex neurological mechanisms and disorders. In this study, we developed a flexible, high-sensitivity multi-electrodes array probe capable of concurrent detection of four neurotransmitters: dopamine, serotonin, acetylcholine and glutamate. The probe was fabricated on a polyimide substrate with 16 circular gold-film electrodes. These electrodes were modified with PEDOT/GluOx and PEDOT/ChOx for enzymatic detection of glutamate and acetylcholine, and with rGO/PEDOT/Nafion for the detection of dopamine and serotonin. Our electrochemical sensor achieved sensitivities of 184.21 and 219.29 μA/μM cm2 for glutamate and acetylcholine, respectively, with limits of detection (LOD) of 0.0242 and 0.0351 μM within a concentration range of 0.1–100 μM. For dopamine and serotonin, the sensor showed sensitivities of 195.9 and 181.2 μA/μM cm2, respectively, with LOD of 0.4743 and 0.3568 μM. This research advances the field of neurochemical sensing and provides valuable insights into the balance of neurotransmitters associated with neurological disorders. These insights improve diagnostic and therapeutic strategies.