bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic and antagonistic drug interactions are prevalent but not conserved across acute myeloid leukemia cell lines
Authors: Toprak Erdal , Kalkan Fatma Neslihan , Yildiz M. , Wood N. Ezgi , Farid Michael , McCoy Melissa , Lin Milo , Zhang Cheng Cheng , Posner Bruce , Chung Stephen 
Published: August 2024

Abstract

Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults. Its heterogeneity, both between patients and within the same patient, is often a factor contributing to poor treatment outcomes. Despite advancements in AML biology and medicine in general, the standard AML treatment, the combination of cytarabine and daunorubicin, has remained the same for decades. Combination drug therapies are proven effective in achieving targeted efficacy while minimizing drug dosage and unintended side effects, a common problem for older AML patients. However, a systematic survey of the synergistic potential of drug-drug interactions in the context of AML pathology is lacking. Here, we examine the interactions between 15 commonly used cancer drugs across distinct AML cell lines and demonstrate that synergistic and antagonistic drug-drug interactions are widespread but not conserved across these cell lines. Notably, enasidenib and venetoclax, recently approved anticancer agents, exhibited the highest counts of synergistic interactions and the fewest antagonistic ones. In contrast, 6-Thioguanine, a purine analog, was involved in the highest number of antagonistic interactions. The interactions we report here cannot be attributed solely to the inherent natures of these three drugs, as each drug we examined was involved in several synergistic or antagonistic interactions in the cell lines we tested. Importantly, these drug-drug interactions are not conserved across cell lines, suggesting that the success of combination therapies might vary significantly depending on AML genotypes. For instance, we found that a single mutation in the TF1 cell line could dramatically alter drug-drug interactions, even turning synergistic interactions into antagonistic ones. Our findings provide a preclinical survey of drug-drug interactions, revealing the complexity of the problem.
Impact of Breast Milk Microbiota on the Neonatal Intestinal Microbiota according to Delivery type and Circumstance, a cross-sectional study
Authors: kamel iman H. , Ali Walaa H. , mahmoud walaa S. , kamhawy Alyaa H. , Armaneous Ayman F. , Hammad Doaa Y. , Yousef Walaa , Basha Walaa A. , Mostafa Mohammed I. , Allayeh Abdou K. , El-Hariri Hazem M. , Nayra Mehanna Sh. , Ahmed Wafaa O. 
Published: August 2024

Abstract

Background: A mother's microbiota, including that in her gut, vagina, and breast milk, plays a big role in her baby's health. Imbalances in this microbiota can lead to problems during pregnancy. Several things affect how this microbiota gets passed down to a newborn.
Objective:investigating the factors affecting passage of microbiota from the mother to the baby, and to see how breast milk bacteria and breastfeeding influence the types of bacteria in a newborn's gut.
Methods: This is a cross sectional study that aimed to assess the impact of breast milk microbiota on the neonatal intestinal Microbiota. The study was carried out on a total of 40 mother-infant pairs. 8 had normal vaginal delivery and 32 had caesarean section delivery.
All study participants met our collection criteria. Ethical considerations, history taking, and examination were done. Mother's breast milk samples were collected in sterile units and preserved at minus 18 celsius (oC) freezer. Neonatal stool samples were collected using the stool collection protocol using sterile containers. Stool samples that were not analyzed immediately were stored in minus 80 oC freezer.
All specimens including mothers breast milk and neonatal stool were subjected to Deoxyribonucleic acid (DNA) extraction and real time polymerase chain reaction (PCR) to assess the microbiota.
Results and conclusion:
most of the participated neonates were males. Most of the mothers were obese, had good hygiene, and lived in urban places. Cesarean section was the most frequent (80.0%) mode of delivery. Bifido bacteria was the most abundant type found in both neonates’ stool and breast milk followed by Strept. and Staph. Neonates with positive stool Bifido had significantly higher gestational age. A significant association between the presence of stool Bifido and type of feeding was found. The antibiotics administration, either in infants or their mothers, was negatively associated with the presence of stool Bifido bacteria. Our results indicated that neonatal age, weight, sex and mode of delivery showed no significant association with any of the three types of bacteria either in the stool or milk.
New and De Novo Biallelic Variant Associated With Owren's Disease: Precision Medicine in Blooding Disorders
Authors: Jimenes Michel Alejandra Ewonds , Giraldo² Lina Johanna Moreno 
Published: August 2024

Abstract

Introduction
Autosomal recessive coagulation factor V deficiency (1)causes moderate to severe bleeding (2). Currently, 450 clinically significant variants have been identified of the 3942 described.(2)
Materials and methods
10-year-old female with 3 hospitalizations for dental extraction, ileo-psoas hematoma and knee hemarthrosis. Non-consanguineous parents, without altered paraclinical related family history. Performing complete F5 gene NGS + CNV sequencing for phenotype- endotype -genotype correlation.
Results
A probably pathogenic variant was identified, homozygous gene F5, consisting of the deletion of the thymine nucleotide at position 2.809 of the cDNA exon 13, (c.2809del) that at the protein level produces a frameshift change that leads to a premature stop codon. at amino acid 958 (p.Ser 937ValfsTer22) in a protein of 2224 amino acids.
Discussion – Conclusion
It is a single nucleotide deletion that occurs within the coding sequence of the F5 gene, leading to a frameshift variant. Which results in a non-functional truncated protein due to loss of critical C-terminal amino acid sequences.
This variant is not reported in the databases HGMD-ClinVar-LOVD-dbSNP-gnomADv.4 - InternationalSocietyonThrombosisandhemostasismutation - InternationalRegistryofRBDsinMilan -theFVMutation. In silico predictors (autoPVS1yMutationTaster) report as deleterious. Artificial intelligence assistants (GenAI-VarChat-Alphafold-Mastermind) the variant was not reported, but was related to pathogenicity.
Uniprot, Alliance of Genome Resources, BioCyc, MetaCyc-G66-30677, RefSeq, Ensembl, gene interaction networks and according to interpretation standards it is classified as pathogenic IA: PM1-PS1-PVS1-PM2.
HPO, NCBIGene:2153 relate other phenotypes: Thrombophilia due to deficiency deficiency of activated protein C cofactor (AD); Budd -Chiari syndrome (AR); pregnancy loss recurrent (AD), Ischemic stroke (multifactorial).
The genotypic and phenotypic heterogeneity of the gene, the presence of new and de novo variants as the case requires genomic, bioinformatics, algorithms, molecular, ontological studies, and artificial intelligence for specific diagnosis and treatment, correlation, monitoring, genetic counseling, generate knowledge in fields of medicine 7P.
Cost effectiveness analysis of colorectal cancer screening modalities in Kuwait: Comparison of Three Alternative Screening Strategies
Authors: Nur Amrizal Muhammad , Aljunid Syed Mohamed , Tolma Eleni L. , Annaka Mahmoud , Alwotayan Rihab , Elbasmi Amani , Alali Walid Q. 
Published: August 2024

Abstract

Colorectal cancer (CRC) poses a significant health challenge in Kuwait, ranking as the second most common cancer with a 2019 incidence rate of 13.2 cases per 100,000 people. This study evaluates the cost-effectiveness (CEA) of CRC screening methods from the perspective of Kuwait's healthcare providers. Using a Decision Tree Analysis Model, the study compared three screening modalities: Fecal Occult Blood Test (FOBT) followed by colonoscopy or sigmoidoscopy, colonoscopy alone, sigmoidoscopy alone and alongside no screening. Over a 10-year period post-diagnosis, the model tracked costs and outcomes based on CRC patients' life expectancy, expressing results using Incremental Cost Effectiveness Ratios (ICERs). Result: FOBT followed by colonoscopy or sigmoidoscopy emerged as the most cost-effective option, costing USD 3,573.00 and yielding 7.7 Quality-Adjusted Life Years (QALYs). In comparison, no screening resulted in 7.2 QALYs at USD 4,084.00, while sigmoidoscopy and colonoscopy alone provided 6.8 QALYs each, costing USD 4,905.00 and USD 5,002.00, respectively. Sensitivity analyses explored uncertainties in cost and outcome estimates. Conclusion: FOBT followed by colonoscopy or sigmoidoscopy could efficiently utilize healthcare resources compared to other modalities or no screening. This approach offers critical guidance for healthcare policymakers in Kuwait, advocating for the adoption of combined FOBT and colonoscopy or sigmoidoscopy strategies to enhance CRC screening effectiveness and economic efficiency.
Successful Corneal Endothelium Preservation in the Management of Epithelial Downgrowth with 5-Fluorouracil injections and membranectomy
Authors: Kam Ka Wai , Ma Andre , Ng Joanna , Choi Paul , Yip Wilson Wai Kuen , Young Alvin L. 
Published: August 2024

Abstract

A 74-year-old Chinese man underwent extracapsular cataract extraction in his right eye and developed a translucent iris membrane 4 months later. He was treated with two intracameral 5-FU injections and membranectomy at 2 weeks apart. At one year following the second membranectomy, the patient maintained a clear cornea without residual or recurrent membrane, an endothelial cell density of 1072 cell/mm2, a visual acuity of 20/50 and a normal intraocular pressure. Our technique of using dispersive and cohesive viscoelastics in protecting the corneal endothelium from intracameral 5-FU, helped preserve corneal endothelial cells and maintain corneal clarity at two years after surgery.
Contemporaneous changes in cytokines and cognitive function during chemotherapy in patients with breast cancer- a prospective follow up study
Authors: Wu Shu-I , Chen Vincent Chin-Hung , Hsu Yen-Hsuan , Tzang Bor-Show , Stewart Robert , Lin Chin-Kuo 
Published: August 2024

Abstract

Background
This study investigated fluctuations in levels of chosen cytokines among patients with breast cancer before to after chemotherapy. Contemporaneous changes in cognitive function were examined.
Methods
Adult patients with breast cancer stages I to III without brain metastasis were invited to participate in this longitudinal follow up study. A multidimensional neuropsychological examination was administered at two timepoints evaluating multiple subjective and objective cognitive domains, depression, anxiety, or fatigue before and at least 3 months after chemotherapy, and baseline demographic information. Cytokine levels were taken at the same times. Stepwise multivariate Generalized Linear Mixed Model was used to examine changes in cytokines and associations with changes in cognitive function.
Results
Over a mean interval of 10.46 months, Event-based prospective memory (p < 0.001), Word list immediate (p < 0.001) or delayed recall (p = 0.024), and self- perceived cognitive impairment (p = 0.026) were significantly improved following chemotherapy. Higher levels of IFNγ and worse performance on the Color Trails Test Part 1, inverse associations of IFNγ or IL-12p70 with Block Design, and TNFα with Digit Symbol Substitution were found, but no significant time effects were noted. However, significant group and time effects were only observed in IL-2 and IL-12p70 with improvements in Event-based prospective memory. That is, from baseline to follow up, each increase in log values of IL-12p70 and IL-2 were associated with 2.18 (SE = 0.65, p = 0.001) and 2.16 (0.68, p = 0.002) points of increase in Event-based prospective memory. No significant effects were detected for other cytokines or cognitive tests.
Conclusion
Improvements in Event-based prospective memory were positively associated with contemporaneous changes in IL-2 and IL-12p70. Our finding may not only reduce BC patients’ concerns about chemotherapy-related cognitive adverse effects, but also demonstrates the possible needs for further replications and investigations on interactions of systemic cytokines, inflammation, and cognitive functions associated with cancer and chemotherapy.
Association of Type 1 Stiff-person Syndrome and Insulinoma: a Case Report and Narrative Review
Authors: Sibilla Michela , Beccuti Guglielmo , Belcastro Sara , Mortara Umberto , Parisi Simone , Campra Donata , Piovesan Alessandro , Ferrero Bruno , Maccario Mauro , Papotti Mauro , Berton Alessandro Maria 
Published: August 2024

Abstract

Introduction
Stiff-person syndrome (SPS) is a rare neurological disorder that causes progressive muscle rigidity, gait disturbances and functional impairment; type 1 is autoimmune, with postitive anti-GAD antibodies (Ab) while type 2 is paraneoplastic, associated with anti-amphiphysin Ab.
Case presentation
A 41-year-old man with silent medical history presented with stiffness and functional impairment; after numerous rheumatological and neurological investigations he was diagnosed with SPS, with evidence of high titer anti-GAD Ab. After treatment with benzodiazepines was started, the patient began to experience episodes of confusion, which persisted even after reducing the dosage. During one of these episodes, he was admitted to the emergency department and a glucose level of 26 mg/dL was found. Differential diagnosis led to an insulin secreting neuroendocrine tumor of the pancreas, thus a paraneoplastic origin of SPS was hypothesized. However, anti- amphiphysin Ab were negative, anti-GAD were persistently elevated and symptoms only transiently improved after removal of the tumor.
Conclusion
This is the first case, to our knowledge, of association between type 1 SPS and insulinoma, with partial and transient improvement of neurological symptoms after resolution of the associated hypoglycemic syndrome.
Non-communicable diseases among people living with HIV, Victoria Chitepo provincial hospital: A retrospective cohort study, a secondary data analysis (2013-2023)
Authors: Chokuona Kudzai Fortunate Vongai , Mukuzunga Munyaradzi , Chadambuka Addmore , Juru Tsitsi Patience , Gombe Notion Tafara , Shambira Gerald , Tshimanga Mufuta 
Published: August 2024

Abstract

Background
Non-communicable diseases (NCDs) associated with human immunodeficiency virus (HIV) are emerging as the leading cause of death globally. An in depth analysis of the burden of NCDs in Manicaland province has not been done. We analyzed the NCDs/HIV data at Victoria Chitepo provincial hospital.
Methods
We conducted a retrospective cohort study from October 2013 to September 2023 using secondary data. Five major groups of NCDs were selected which were hypertension (HPT), diabetes mellitus (DM), chronic kidney injury (CKD), cancers and chronic respiratory illness. Kaplan Meier analysis and Cox proportional hazard analysis were performed. Risk ratios and hazard ratios with 95% confidence intervals were generated.
Results
A total of 974 patient records were reviewed with a median age of 43 (Q1=35; Q3 = 51) years. Number of years on antiretroviral therapy (ART) (HR = 5.99, 95% CI: p < 0.001), age (HR = 4.78, 95%CI: p < 0.001) and DM/HIV comorbidity (HR = 4.63, 95% CI: p < 0.001) were hazards to HPT while being on efavirenz based regimen had a lower risk (HR = 0.47, 95% CI: p = 0.01) of developing HPT. Number of years on ART (HR = 9.89, 95% CI: p < 0.001), being on PI based regimen (HR = 4.66, 95% CI: p < 0.001), age (HR = 3.86, 95% CI, p < 0.001) and being on WHO stage 3 or 4 (HR = 3.75, 95% CI: p < 0.001) were hazards to DM. In 2022, the prevalence rate was 12 per 1000 people per year.
Conclusion
HPT and DM are the common NCDs among people living with HIV in this cohort. To minimize complications related to NCD/HIV comorbidities, we recommend routine screening of NCDs at monthly basis for early diagnosis and treatment.
Predicting Falls Using Electronic Health Records: A Time Series Approach
Authors: Hoover Peter , Blumke Terri , Ware Anna , Pillai Malvika , Veigulis Zachary , Curtin Catherine , Osborne Thomas 
Published: August 2024

Abstract

Background and Aims:
Inpatient falls are a major cause of injury within hospitals and are known to delay recovery and increase patient length of stay. The Morse Fall Scale is a commonly utilized tool to assess fall-risk and is broadly implemented, particularly within Veterans Health Administration. Yet, this scale has limited accuracy. A more precise risk assessment tool is urgently needed to identify those at risk and to ensure targeted fall-risk mitigating interventions. The goal of this work was to develop a more accurate fall prediction model within the Veterans Health Administration.
Methods
The cohort included Veterans admitted to a Veterans Health Administration acute care setting from July 1st, 2020, to June 30th, 2022, with a length of stay between one and seven days. Demographic and clinical data were obtained through VHA electronic health records. Veterans were identified as having a documented fall through clinical progress notes. A transformer model was used to obtain features of this data, which was then used to train a Light Gradient-Boosting Machine for classification and prediction. Area under the precision-recall curve assisted in model tuning, with geometric mean used to define an optimal classification threshold.
Results
Among 242,844 Veterans assessed, 5,965 (2.5%) experienced a fall during their acute inpatient stay. Employing a transformer model with a Light Gradient-Boosting Machine resulted in an area under the curve of 0.851 and an area under the precision-recall curve of 0.285. With an accuracy of 76.3%, the model resulted in a specificity of 76.2% and a sensitivity of 77.3%.
Conclusion
The classification model exhibited a performance greater than the Morse Fall Scale and other risk-assessment tools for predicting risk of fall. Incorporating this type of risk model, which can be automatically calculated from existing data, could provide more efficient and accurate method for identifying at-risk patients.
Gallic acid alleviates ferroptosis by negatively regulating APOC3 and improves nerve function deficit caused by traumatic brain injury
Authors: Liu Yu , Fu Xiaojia , Ji Huanhuan , Guo Jianqiang , Zhao Zongren , Zheng Jinyu 
Published: August 2024

Abstract

Background: Traumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. A variety of secondary brain injuries occur after TBI, including ferroptosis characterized by iron-dependent lipid peroxidation. Gallic acid is a kind of traditional Chinese medicine, which has many biological effects such as anti-inflammatory and antioxidant. We further investigated whether Gallic acid can improve the neurological impairment caused by ferroptosis after TBI by targeting APOC3.
Method: Weighted gene coexpression network analyses (WGCNA) and 3 kinds of machine-learning algorithms were used to find the potential biomarkers. Then the HERB database was used to select the Chinese herb that acted on the target gene APOC3. Finally, we selected Gallic acid as a drug targeting APOC3 and verified by Western blotting. The effect of Gallic acid on the improvement of neurological function was studied by Nissl staining and FJB staining. Finally, the effect of Gallic acid on the cognitive ability of TBI mice was explored through behavioral experiments.
Results: Gallic acid can inhibit the expression level of APOC3 and thus inhibit the level of ferroptosis after TBI. It can also reduce the degeneration of nerve tissue by inhibiting ferroptosis and improve the neurological function deficit. The behavioral experiment proved that Gallic acid can alleviate the behavioral cognitive impairment caused by TBI.
Conclusion: Gallic acid can reduce ferroptosis by inhibiting APOC3, and then alleviate neurological impairment after TBI.
Nitrogen Fixing Bacteria Reduces Drought Stress and Improve Molecular and Biochemical Response in the Garden Thyme
Authors: Goshasbi Farideh , Sabbagh Seyed Kazem , Heydari Mostfa 
Published: August 2024

Abstract

Abiotic stresses such as water-deficient are the most important factor that could impress the agricultural process causing a reduction of crop yield. Use of Bio-fertilizers could improve growth condition of drought stressed plant to reduce the damage of water deficit. The objective of this work is to assay comparative effect of some organic and non-organic fertilizers on the flowering branches essential and some antioxidant activity (APX, PO, CAT), then expression analysis of two thymus and carvacrol bio-synthesis related genes(CYP171 d178 and CYP171D180 ) in Thymus vulgaris under water deficit stress in a field trial was investigated using qRT-PCR method. The treatments were arranged in a completely randomized design with a total of 42 experimental separate blocks. The highest and lowest yield of flowering branches was observed in NPK and mycorrhizae treatments Approximately, Azospirillum bio-fertilizer showed high effect on enzyme activity in treated plants. Unlike, chemical fertilizer showed minimum efficiency on enzyme activity. A high expression level (approximately, 6-fold change) of both genes was observed in treated plants with Azospirillum bio-fertilizer while the lowest expression level (1.3-fold change) was observed in chemical fertilizer application when compared to other fertilizers. According to the obtained results of this work, we conclude that yearly fertilizer application could have a significant effect on molecular and biochemical traits and resulted in increase of yield component via decrease of drought stress.