bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysing the six-year malaria trends at Metehara Health Centre in Central Ethiopia: the impact of resurgence on the 2030 elimination goals
Authors: Mandefro Aynalem , Tadele Geletta , Mekonen Bacha , Golassa Lemu 
Published: January 2024

Abstract
Background
Despite Ethiopia’s concerted efforts to eliminate malaria by 2030, the disease continues to pose a significant public health and socioeconomic challenge in the country. The year 2021 witnessed 2.78 million malaria cases and 8041 associated deaths, emphasizing the persistent threat. Monitoring the prevalence trend of malaria is crucial for devising effective control and elimination strategies. This study aims to assess the trend of malaria prevalence at the Metehara Health Centre in the East Shoa Zone, Ethiopia.

Methods
A retrospective study, spanning from February to September 2023, utilized malaria registration laboratory logbooks at Metehara Health Centre to evaluate the prevalence of malaria from 2017/18 to 2022/23. Malaria and related data were collected using a pre-designed data collection sheet. Descriptive statistics were employed for data summarization, presented through graphs and tables.

Results
Out of 59,250 examined blood films, 17.4% confirmed the presence of Plasmodium infections. Among the confirmed cases, 74.3%, 23.8%, and 1.84% were attributed to Plasmodium falciparum, Plasmodium vivax, and mixed infections, respectively. The trend of malaria exhibited a steady decline from 2017/18 to 2021/22, reaching 9.8% prevalence. However, an abrupt increase to 26.5% was observed in 2022/23. Males accounted for a higher proportion (66%) of cases compared to females (34%). The age group 15–24 years experienced the highest malaria incidence at 42%. Notably, malaria cases peaked during autumn (September to November) at 43% and reached the lowest percentage during spring (March to May) at 13%.

Conclusion
Malaria persists as a significant health challenge in and around Metehara, central Ethiopia, predominantly driven by Plasmodium falciparum. The five-year declining trend was interrupted by a notable upsurge in 2022/23, indicating a resurgence of malaria in the study area. It is imperative to adopt a reverse strategy to sustain the progress achieved by the national malaria control plan.
What our children lost and gained at the time of school closure during the Covid-19 pandemic: a study on psychological distress, behavioural concerns and protective factors of resilience among preschool children in Kerala, India
Authors: Vincent Jose , Santhakumari Resmi Madhusoodanan , Nalinakumari Kesavan Nair Anjana , Sharahudeen Anisha , K.P Asvini , Suresh Meenu Maheswari , Valamparampil Mathew J. , A.V Gayathri , Sujatha Chintha , Thekkumkara Surendran Anish 
Published: January 2024

Abstract
Background
The pandemic has put at risk the social and emotional development of children on account of the paucity of arenas for social interaction. This study from Kerala, India was conducted to assess the resilience factors, behavioural concerns, psychological distress symptoms among the children aged 3 to 5 years. We also tried to look into the lost opportunities that could have aided the social and emotional development of children like peer interaction, child care hours.

Methods
The cross-sectional study was conducted among the children aged 3 to 5 years. A total of 535 children attending the immunisation clinics were enrolled by consecutive sampling. Devereux Early Childhood Assessment P2 (DECA P2) questionnaire was used to assess the levels of resilient factors and behavioural concerns in the study population.

Results
We observed a high proportion of children in the area of need category of protective factors under DECA P2. The proportion of children falling under area of concern was 64.5%, 49%, 68.4% for attachment/relationship, self-regulation, and initiative respectively. 24.9% study subjects have a behavioural concern score that puts them in the area of need category. The logistic regression model we created identified ‘Male Gender,’ ‘Mothers could spend only less time for child care’ and ‘electronic devices used as pacifier’ as significant predictors for belonging to Area of need Behavioural Concerns T score category.

Conclusion
A large proportion of children aged between 3 to 5 years with reported behavioural concerns and lack of protective factors for socioemotional development. This can be attributed partly to the ongoing pandemic and its associated restrictions. The increased child care hours invested by parents or grandparents could have sized down the full impact that the pandemic would have had on the socio emotional development of the child. Increased time spent using electronic devices coupled with dwindled opportunities for interaction with peers have been notable challenges.
Time-series analysis of temperature variability and cardiovascular emergency department visits in Atlanta over a 27-year period
Authors: Lane Morgan , Ebelt Stefanie , Wu Zhen , Scovronick Noah , D’Souza Rohan R. , Chang Howard H. 
Published: January 2024

Abstract
Background
Short-term temperature variability, defined as the temperature range occurring within a short time span at a given location, appears to be increasing with climate change. Such variation in temperature may influence acute health outcomes, especially cardiovascular diseases (CVD). Most research on temperature variability has focused on the impact of within-day diurnal temperature range, but temperature variability over a period of a few days may also be health-relevant through its impact on thermoregulation and autonomic cardiac functioning. To address this research gap, this study utilized a database of emergency department (ED) visits for a variety of cardiovascular health outcomes over a 27-year period to investigate the influence of three-day temperature variability on CVD.

Methods
For the period of 1993–2019, we analyzed over 12 million CVD ED visits in Atlanta using a Poisson log-linear model with overdispersion. Temperature variability was defined as the standard deviation of the minimum and maximum temperatures during the current day and the previous two days. We controlled for mean temperature, dew point temperature, long-term time trends, federal holidays, and day of week. We stratified the analysis by age group, season, and decade.

Results
All cardiovascular outcomes assessed, except for hypertension, were positively associated with increasing temperature variability, with the strongest effects observed for stroke and peripheral vascular disease. In stratified analyses, adverse associations with temperature variability were consistently highest in the moderate-temperature season (October and March-May) and in the 65 + age group for all outcomes.

Conclusions
Our results suggest that CVD morbidity is impacted by short-term temperature variability, and that patients aged 65 and older are at increased risk. These effects were more pronounced in the moderate-temperature season and are likely driven by the Spring season in Atlanta. Public health practitioners and patient care providers can use this knowledge to better prepare patients during seasons with high temperature variability or ahead of large shifts in temperature.
The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway
Authors: Karakostis Konstantinos , Malbert-Colas Laurence , Thermou Aikaterini , Vojtesek Borek , Fåhraeus Robin 
Published: January 2024

Abstract
Background
The ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating the MDM2 protein, which develops an affinity for the p53 mRNA secondary structure. Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein—p53 mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the p53 mRNA in the DNA damage sensing mechanism, are still highly anticipated.

Methods
The proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein—mRNA and protein–protein interactions. ELISA and co-immunoprecipitation confirmed the interactions in vitro and in cells.

Results
This study provides a novel mechanism whereby the p53 mRNA interacts with the ATM kinase enzyme and shows that the L22L synonymous mutant, known to alter the secondary structure of the p53 mRNA, prevents the interaction. The relevant mechanistic roles in the DNA Damage Sensing pathway, which is linked to downstream DNA damage response, are explored. Following DNA damage (double-stranded DNA breaks activating ATM), activated MDMX protein competes the ATM—p53 mRNA interaction and prevents the association of the p53 mRNA with NBS1 (MRN complex). These data also reveal the binding domains and the phosphorylation events on ATM that regulate the interaction and the trafficking of the complex to the cytoplasm.

Conclusion
The presented model shows a novel interaction of ATM with the p53 mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous mutations altering secondary mRNA structures.
Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study
Authors: Kuo Chin-Sung , Kuo Nai-Rong , Yeh Yun-Kai , Lee Yau-Jiunn , Chuang Lee-Ming , Chen Hua-Fen , Chen Ching-Chu , Lee Chun-Chuan , Hsu Chih-Cheng , Li Hung-Yuan , Ou Horng-Yih , Hwu Chii-Min 
Published: January 2024

Abstract
Background
The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event.

Methods
Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined.

Results
The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure.

Conclusion
This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.
Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England
Authors: Harris Magdalena , Scott Jenny , Hope Vivian , Busza Joanna , Sweeney Sedona , Preston Andrew , Southwell Mat , Eastwood Niamh , Vuckovic Cedomir , McGaff Caitlynne , Yoon Ian , Wilkins Louise , Ram Shoba , Lord Catherine , Bonnet Philippe , Furlong Peter , Simpson Natasha , Slater Holly , Platt Lucy 
Published: January 2024

Abstract
Background
Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact.

Methods
The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms.

Anticipated impact
SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally.

Conclusion
People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform.
Trial registration: ISRCTN12541454 https://doi.org/10.1186/ISRCTN12541454
Inhibitor of PD-1/PD-L1: a new approach may be beneficial for the treatment of idiopathic pulmonary fibrosis
Authors: Tan Jie , Xue Qianfei , Hu Xiao , Yang Junling 
Published: January 2024

AbstractIdiopathic pulmonary fibrosis (IPF) is a globally prevalent, progressive disease with limited treatment options and poor prognosis. Because of its irreversible disease progression, IPF affects the quality and length of life of patients and imposes a significant burden on their families and social healthcare services. The use of the antifibrotic drugs pirfenidone and nintedanib can slow the progression of the disease to some extent, but it does not have a reverse effect on the prognosis. The option of lung transplantion is also limited owing to contraindications to transplantation, possible complications after transplantation, and the risk of death. Therefore, the discovery of new, effective treatment methods is an urgent need. Over recent years, various studies have been undertaken to investigate the relationship between interstitial pneumonia and lung cancer, suggesting that some immune checkpoints in IPF are similar to those in tumors. Immune checkpoints are a class of immunosuppressive molecules that are essential for maintaining autoimmune tolerance and regulating the duration and magnitude of immune responses in peripheral tissues. They can prevent normal tissues from being damaged and destroyed by the immune response. While current studies have focused on PD-1/PD-L1 and CTLA-4, PD-1/PD-L1 may be the only effective immune checkpoint IPF treatment. This review discusses the application of PD-1/PD-L1 checkpoint in IPF, with the aim of finding a new direction for IPF treatment.
Causal relationship between gut microbiota and gastrointestinal diseases: a mendelian randomization study
Authors: Wu Kaiwen , Luo Qiang , Liu Ye , Li Aoshuang , Xia Demeng , Sun Xiaobin 
Published: January 2024

Abstract
Background
Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases.

Methods
Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed.

Results
The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results.

Conclusions
The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.
Rheumatological complaints in H syndrome: from inflammatory profiling to target treatment in a case study
Authors: Tesser Alessandra , Valencic Erica , Boz Valentina , Tornese Gianluca , Pastore Serena , Zanatta Manuela , Tommasini Alberto 
Published: January 2024

Abstract
Background
H Syndrome is a rare genetic condition caused by biallelic pathogenic variants in the SLC29A3 gene. It is characterized by a wide range of clinical manifestations, many of which are related to the immune-rheumatological field. These include scleroderma-like skin changes, deforming arthritis, and enlarged lymph nodes. The condition also features cardiac and endocrine defects, as well as hearing loss, for which the immune pathogenesis appears less clear. Immunomodulatory medications have been shown to improve many symptoms in recent experiences.

Case presentation
A 21-year-old girl was referred to our institute after being diagnosed with H syndrome. Her medical history was characterized by the development of finger and toe deformities, which developed since the first years of life and progressively worsened with clinodactyly. At 6 years of age, she was diagnosed with diabetes mellitus without typical autoantibodies and with bilateral sensorineural hearing loss. She also complained of frequent episodes of lymphadenopathy, sometimes with colliquation and growth retardation due to pancreatic insufficiency. It wasn’t until the genetic diagnosis of H syndrome that the continual increase in acute phase reactants was noticed, suggesting that an immunological pathogenesis may be the source of her problems. During her visit to our institute, she reported serious pain in both feet and hands and difficulty walking due to knee arthritis and muscle contractures. Conventional therapy with steroid injection in affected joints and methotrexate only led to partial improvement. After a thorough assessment of her inflammatory profile showing a high interferon score, the girl received treatment with baricitinib. Furthermore, based on recent data showing that SLC29A3 deficiency results in interferon production because of Toll-like Receptor 7 activation in lysosomes, hydroxychloroquine was also added. The combination of the two drugs resulted for the first time in a rapid and persistent normalization of inflammatory markers, paralleled by a dramatic improvement in symptoms.

Conclusions
We describe the results of inhibiting IFN inflammation in H syndrome and discuss how JAK inhibitors and antimalarials might represent a mechanistically based treatment for this orphan drug disorder.
Synergistic effect of sildenafil combined with controlled hypothermia to alleviate microglial activation after neonatal hypoxia–ischemia in rats
Authors: Julien Pansiot , Zinni Manuela , Bonnel Natacha , El Kamouh Marina , Odorcyk Felipe , Peters Lea , Gautier Emilie-Fleur , Leduc Marjorie , Broussard Cédric , Baud Olivier 
Published: January 2024

Abstract
Background and purpose
The only validated treatment to prevent brain damage associated with hypoxia–ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective drug candidates include sildenafil citrate, a phosphodiesterase-type 5 inhibitor. The main objective of this preclinical study is to assess its ability to reduce HI-induced neuroinflammation, in particular through its potential effect on microglial activation.

Methods
HI was induced in P10 Sprague–Dawley rats by unilateral carotid permanent artery occlusion and hypoxia (HI) and treated by either hypothermia (HT) alone, Sildenafil (Sild) alone or combined treatment (SildHT). Lesion size and glial activation were analyzed by immunohistochemistry, qRT-PCR, and proteomic analyses performed at P13.

Results
None of the treatments was associated with a significant early reduction in lesion size 72h after HI, despite significant changes in tissue loss distribution. Significant reductions in both Iba1 + (within the ipsilateral hemisphere) and GFAP + cells (within the ipsilateral hippocampus) were observed in SildHT group, but not in the other treatment groups. In microglia-sorted cells, pro-inflammatory markers, i.e. Il1b, Il6, Nos2, and CD86 were significantly downregulated in SildHT treatment group only. These changes were restricted to the ipsilateral hemisphere, were not evidenced in sorted astrocytes, and were not sex dependent. Proteomic analyses in sorted microglia refined the pro-inflammatory effect of HI and confirmed a biologically relevant impact of SildHT on specific molecular pathways including genes related to neutrophilic functions.

Conclusions
Our findings suggest that Sildenafil combined with controlled hypothermia produces maximum effect in mitigating microglial activation induced by HI through complex proteomic regulation. The reduction of neuroinflammation induced by Sildenafil may represent an interesting therapeutic strategy for neonatal neuroprotection.