FAMIN Is a Multifunctional Purine Enzyme Enabling the Purine Nucleotide Cycle.

Mutations in FAMIN cause arthritis and inflammatory bowel disease in early childhood, and a common genetic variant increases the risk for Crohn's disease and leprosy. We developed an unbiased liquid chromatography-mass spectrometry screen for enzymatic activity of this orphan protein. We report that FAMIN phosphorolytically cleaves adenosine into adenine and ribose-1-phosphate. Such activity was considered absent from eukaryotic metabolism. FAMIN and its prokaryotic orthologs additionally have adenosine deaminase, purine nucleoside phosphorylase, and S-methyl-5'-thioadenosine phosphorylase activity, hence, combine activities of the namesake enzymes of central purine metabolism. FAMIN enables in macrophages a purine nucleotide cycle (PNC) between adenosine and inosine monophosphate and adenylosuccinate, which consumes aspartate and releases fumarate in a manner involving fatty acid oxidation and ATP-citrate lyase activity. This macrophage PNC synchronizes mitochondrial activity with glycolysis by balancing electron transfer to mitochondria, thereby supporting glycolytic activity and promoting oxidative phosphorylation and mitochondrial H+ and phosphate recycling.

DNA-MP: a generalized DNA modifications predictor for multiple species based on powerful sequence encoding method.

Accurate prediction of deoxyribonucleic acid (DNA) modifications is essential to explore and discern the process of cell differentiation, gene expression and epigenetic regulation. Several computational approaches have been proposed for particular type-specific DNA modification prediction. Two recent generalized computational predictors are capable of detecting three different types of DNA modifications; however, type-specific and generalized modifications predictors produce limited performance across multiple species mainly due to the use of ineffective sequence encoding methods. The paper in hand presents a generalized computational approach "DNA-MP" that is competent to more precisely predict three different DNA modifications across multiple species. Proposed DNA-MP approach makes use of a powerful encoding method "position specific nucleotides occurrence based 117 on modification and non-modification class densities normalized difference" (POCD-ND) to generate the statistical representations of DNA sequences and a deep forest classifier for modifications prediction. POCD-ND encoder generates statistical representations by extracting position specific distributional information of nucleotides in the DNA sequences. We perform a comprehensive intrinsic and extrinsic evaluation of the proposed encoder and compare its performance with 32 most widely used encoding methods on $17$ benchmark DNA modifications prediction datasets of $12$ different species using $10$ different machine learning classifiers. Overall, with all classifiers, the proposed POCD-ND encoder outperforms existing $32$ different encoders. Furthermore, combinedly over 5-fold cross validation benchmark datasets and independent test sets, proposed DNA-MP predictor outperforms state-of-the-art type-specific and generalized modifications predictors by an average accuracy of 7% across 4mc datasets, 1.35% across 5hmc datasets and 10% for 6ma datasets. To facilitate the scientific community, the DNA-MP web application is available at https://sds_genetic_analysis.opendfki.de/DNA_Modifications/.

Multidrug resistance among uropathogenic clonal group A E. Coli isolates from Pakistani women with uncomplicated urinary tract infections.

OBJECTIVE: Multi-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis. RESULTS: Phylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms. CONCLUSIONS: Our research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

Changes in immunoglobulin levels during clozapine treatment in schizophrenia.

BACKGROUND AND HYPOTHESIS: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. DESIGN: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). RESULTS: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: ß = -32.66, 95% CI = -62.38, -2.93, p = 0.03; IgG: ß = -63.96, 95% CI = -118.00, -9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: ß = -23.48, 95% CI = -39.56, -7.42, p = 0.004; 24 weeks: ß = -33.12, 95 %CI = -50.30, -15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). CONCLUSIONS: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets.

Urinary tract infections (UTIs) are among the most prevalent bacterial infections affecting people in inpatient and outpatient settings. The current study aimed to sequence the genome of uropathogenic Escherichia coli strain CUI-B1 resourced from a woman having uncomplicated cystitis and pyelonephritis. Followed by deductive genomics towards potential drug targets using E. coli strain CUI-B1, strain O25b: H4-ST131, Proteus mirabilis strain HI4320, Klebsiella pneumoniae strain 1721, and Staphylococcus saprophyticus strain ATCC 15305 uropathogenic strains. Comparative genome analysis revealed that genes related to the survival of E. coli, P. mirabilis, K. pneumoniae, and S. saprophyticus, such as genes of metal-requiring proteins, defense-associated genes, and genes associated with general physiology, were found to be highly conserved in the genomes including strain CUI-B1. However, the genes responsible for virulence and drug resistance, mainly those that are involved in bacterial secretion, fimbriae, adherence, and colonization, were found in various genomic regions and varied from one species to another or within the same species. Based on the genome sequence, virulence, and antimicrobial-resistant gene dataset, the subtractive proteomics approach revealed 22 proteins mapped to the pathogen's unique pathways and among them, entB, clbH, chuV, and ybtS were supposed to be potential drug targets and the single drug could be utilized for all above-mentioned strains. These results may provide the foundation for the optimal target for future discovery of drugs for E. coli-, P. mirabilis-, K. pneumoniae-, and S. saprophyticus-based infections and could be investigated further to employ in personalized drug development.

Long-term Risk of Stroke After New-Onset Atrial Fibrillation in Sepsis Survivors: A 2-Year Follow-Up Study.

BACKGROUND: Cardiovascular complications such as new-onset atrial fibrillation (NOAF) are common in sepsis and are known to increase the risk of in-hospital mortality and stroke. However, only a handful of studies have evaluated the long-term risk of stroke after NOAF in sepsis survivors. As part of our efforts to address this issue, we conducted the first-ever follow-up study in a developing country evaluating the long-term risk of stroke for sepsis survivors following NOAF. Methods: This retrospective study evaluated all adult patients admitted at the Aga Khan University Hospital between July 2019 and December 2019 with the diagnosis of sepsis. Data was collected from medical records of the included patients. Outcome measures included in-hospital mortality and ischemic stroke within 2 years. Results: Seven hundred thirty patients were included in the study; 415 (57%) were males and 315 (43%) females; mean age was 59.4 ± 18 years. 59 (8%) patients developed NOAF. The risk of stroke within 2 years in sepsis survivors was 3.5%. Six out of 30 (20%) patients in the atrial fibrillation (AF) group developed stroke, whereas 11 out of 448 (2%) patients in the non-AF group developed stroke. NOAF was associated with an increased risk of ischemic stroke within 2 years (OR = 6.6; 95% CI, 2.3-12.8; P = <.001). Conclusion: We conclude that AF occurred frequently in sepsis patients and was also associated with a 6-fold increase in the risk of ischemic stroke within 2 years. Reliable interventions for identifying high-risk patients for ischemic stroke are still poorly characterized, and this study may serve as a basis for more extensive multicenter studies to identify patients at high risk for ischemic stroke in the aftermath of septic AF and develop precise interventions for preventing it.

Synthesis, biochemical and computational evaluations of novel bis-acylhydrazones of 2,2'-(1,1'-biphenyl)-4,4'-diylbis(oxy))di(acetohydrazide) as dual cholinesterase inhibitors.

A series of twenty-seven bis(acylhydrazones) were successfully synthesized with high yields through a multistep process, which entailed the esterification of hydroxyl groups, hydrazination with an excess of hydrazine hydrate, and subsequent reactions with various carbonyl moieties (aldehydes). In the final stage of synthesis, different chemical species including aromatic, heterocyclic, and aliphatic compounds were integrated into the framework. The resulting compounds were characterized using several spectroscopic techniques (1H NMR, 13C NMR, and mass spectrometry). Their anticholinesterase activities were assessed in vitro by examining their interactions with two cholinesterase enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among the synthesized hits, compounds 3, 5, 6, 9-12, and 14 exhibited good to moderate inhibition of AChE. Specifically, 10 (IC50 = 26.3 ± 0.4 µM) and 11 (IC50 = 28.4 ± 0.5 µM) showed good inhibitory activity against AChE, while 9, 12, 3, and 6 exhibited significant inhibition potential against AChE with IC50 values ranging from 35.2 ± 1.1 µM to 64.4 ± 0.3 µM. On the other hand, 5 (IC50 = 22.0 ± 1.1 µM) and 27 (IC50 = 31.3 ± 1.3 µM) displayed significant, and 19 (IC50 = 92.6 ± 0.4 µM) showed moderate inhibitory potential for BChE. Notably, 5 and 27 exhibited dual inhibition of AChE and BChE, with greater potency than the standard drug galantamine. The binding patterns of these molecules within the binding cavities of AChE and BChE were anticipated by molecular docking which showed good correlation with our in vitro findings. Further structural optimization of these molecules may yield more potent AChE and BChE inhibitors.

Knowledge, risk perception and uptake of COVID-19 vaccination among internally displaced persons in complex humanitarian emergency setting, Northeast Nigeria.

BACKGROUND: Owing to crowded and unsanitary conditions, internally displaced persons (IDPs) have an increased risk of COVID-19 infection. Adoption of COVID-19 preventive measures among this population is premised on accurate information, adequate knowledge, and risk perception. We assessed COVID-19 knowledge and risk perception and investigated the association between risk perception and COVID-19 preventive measures, including vaccination among IDPs in Northeast Nigeria. METHODS: We conducted a cross-sectional study during July-December 2022 and sampled 2,175 IDPs using stratified sampling. We utilized a 12-point assessment tool to evaluate COVID-19 knowledge. Participants who scored ≥ 6 points were considered to have adequate knowledge. We used a 30-item Risk Behavior Diagnosis Scale to assess COVID-19 risk perception and evaluated each item on a 5-point Likert scale. Participants were divided into risk perception categories by the median of Likert scale scores. We performed weighted logistic regression analysis to identify factors associated with risk perception. Pearson's chi-squared with Rao-Scott adjustment was used to determine the relationship between risk perception and COVID-19 preventive measures. RESULTS: Of 2,175 participants, 55.7% were 18-39 years old, 70.9% were females, and 81.7% had no formal education. Among the IDPs, 32.0% (95% CI: 28.8 - 35.0) were considered to have adequate COVID-19 knowledge, and 51.3% (95% CI: 47.8 - 54.8) perceived COVID-19 risk as high. Moreover, 46.3% (95% CI: 42.8 - 50.0) had received one dose of COVID-19 vaccine, and 33.1% (95% CI: 29.8 - 36.0) received two doses. Adequate knowledge (Adjusted Odds Ratio (AOR) = 2.10, [95% CI: 1.46 - 3.03]) and post-primary education (AOR = 3.20, [95% CI: 1.59 - 6.46]) were associated with risk perception. Furthermore, high risk perception was significantly associated with wearing face masks (χ2 = 106.32, p-value < .001), practicing hand hygiene (χ2 = 162.24, p-value < .001), physical distancing (χ2 = 60.84, p-value < .001) and vaccination uptake (χ2 = 46.85, p-value < .001). CONCLUSIONS: This study revealed gaps in COVID-19 knowledge, risk perception, and vaccination uptake but demonstrated a significant relationship between risk perception and COVID-19 preventive practices. Health education and risk communication should be intensified to improve knowledge, elicit stronger risk perception, and enhance COVID-19 preventive practices.

Strengthening neurosurgical training programs in Sub-saharan Africa: a medical student's perspective.

This article provides a nuanced exploration of the state and exigencies of neurosurgical training in sub-Saharan Africa (SSA), viewed through the discerning lens of a medical student. The region has a pronounced scarcity of neurosurgical services, further compounded by sociocultural intricacies and infrastructural inadequacies, resulting in elevated mortality and morbidity rates. The insufficiency of neurosurgeons, facilities, and training centers, particularly in remote areas, exacerbates this predicament. The imperative to fortify neurosurgical training programs is underscored, necessitating a multifaceted approach inclusive of international collaborations and innovative strategies. The challenges impeding neurosurgical training program implementation range from constrained infrastructure to faculty shortages and financial constraints. Recommendations encompass infrastructural investments, faculty development initiatives, and augmented community engagement. An exploration of neurosurgical training programs across diverse African regions reveals commendable strides and imminent deficits, warranting heightened international collaboration. Furthermore, technological innovations, including virtual reality, robotics, and artificial intelligence, are posited as transformative conduits for augmenting neurosurgical training in SSA. The article concludes with a sagacious compendium of recommendations, encompassing standardized curricula, mentorship paradigms, and stringent evaluation mechanisms, all combining efficaciously fortifying neurosurgical insight in SSA and producing transformative improvements in healthcare outcomes.

Thermal stratification and mixing processes response to meteorological factors in a monomictic reservoir.

Formation and extinction of thermal stratifications impact the reservoir ecosystems and have been closely influenced by meteorological and hydrological factors. However, quantifying the relative importance of these crucial environmental factors and mechanisms in reservoir regions characterized by various depths remain comparatively uninvestigated. Tianbao Reservoir is a typical monomictic warm and drinking water source reservoir in Southwest China. This study supplemented field observations with a three-dimensional numerical simulation model to quantitatively analyze mixing and turnover events. Air temperature and wind were two important meteorological factors resulting in hydrodynamics during stratification and mixing processes. Air temperature led to variations in stratification strength and wind-induced fluctuations of thermocline depth. A 10% rise in air temperature increased stratification strength by 18%, and a 3 m/s rise in wind speed induced the deepening of the thermocline by 2.09 m. Two hydrodynamics involved penetrative convection caused by temperature plummets and wind-induced mixing during winter turnover events were identified. Penetrative convection was the main driving force, and wind shear mixed the upper 21% of the mixed layer, which was contributed by convection. Response of water temperature to air temperature in shallow regions was faster (58 d), and the mixing depth caused by the wind was smaller than that in deep regions. Research on physical processes during stratification and mixing processes can provide support for further study on water quality deterioration distributions.

Gender, culture, and migration: A qualitative study of the socioeconomic challenges facing Afghan women refugees in Khyber Pakhtunkhwa, Pakistan.

The research explores Afghan refugee women's challenges in accessing education, employment, and legal rights in Khyber Pakhtunkhwa, Pakistan. It seeks to inform policy changes to improve their socioeconomic circumstances and mitigate these hardships. The study employs qualitative methodologies, utilizing interviews, observation, and document analysis to capture rich, in-depth narratives from three Afghan refugee women. Each narrative provides unique insights into the women's struggles with education, employment, and securing legal rights. The research highlights challenges from forced migration, gender inequality, cultural norms, and socioeconomic marginalization, causing a holistic crisis for Afghan refugee women in Khyber Pakhtunkhwa, Pakistan. These issues hinder access to education, employment, financial vulnerabilities, and legal uncertainties. The study suggests a comprehensive, multi-pronged approach to policy changes, including education reform for refugee girls, gender-responsive recruitment practices, and legal reforms to secure refugees' rights. It emphasizes gender-responsive support services and involves Afghan refugee women in policy development processes, leveraging their experiences for more effective and inclusive policies.

La recherche explore les difficultés rencontrées par les femmes réfugiées afghanes pour accéder à l'éducation, à l'emploi et aux droits légaux à Khyber Pakhtunkhwa, au Pakistan. Il cherche à éclairer les changements politiques pour améliorer leur situation socio-économique et atténuer ces difficultés. L'étude utilise des méthodologies qualitatives, utilisant des entretiens, des observations et des analyses de documents pour recueillir des récits riches et approfondis de trois femmes réfugiées afghanes. Chaque récit fournit un aperçu unique des luttes des femmes en matière d'éducation, d'emploi et d'obtention de leurs droits légaux. La recherche met en évidence les défis liés à la migration forcée, à l'inégalité entre les sexes, aux normes culturelles et à la marginalisation socio-économique, provoquant une crise holistique pour les femmes réfugiées afghanes à Khyber Pakhtunkhwa, au Pakistan. Ces problèmes entravent l'accès à l'éducation, à l'emploi, souffrent de vulnérabilités financières et d'incertitudes juridiques. L'étude suggère une approche globale et multidimensionnelle des changements politiques, y compris une réforme de l'éducation pour les filles réfugiées, des pratiques de recrutement sensibles au genre et des réformes juridiques pour garantir les droits des réfugiés. Il met l'accent sur les services de soutien sensibles au genre et implique les femmes réfugiées afghanes dans les processus d'élaboration des politiques, en tirant parti de leurs expériences pour des politiques plus efficaces et inclusives.

Language-adaptive artificial intelligence: assessing CHATGPT'S answer to frequently asked questions on total hip arthroplasty questions.

ChatGPT is reported to be an acceptable tool to answer a majority of frequently asked patient questions. ChatGPT also converses in other languages including Urdu, which offers immense potential for the education of Pakistani patients. Therefore, this study evaluated ChatGPT's Urdu answers to the ten most frequently asked questions on Total Hip Arthroplasty, which were then rated by an expert. Out of 10 answers in English, 9 (90%) were satisfactory requiring minimal clarification and 1 (10%) was satisfactory requiring moderate clarification. In both Roman and Nastaliq script Urdu, 1 (10%) answer was satisfactory requiring moderate clarification, while 9 (90%) were unsatisfactory requiring substantial clarification. In conclusion, as opposed to ChatGPT English responses, Urdu responses were much less rigorous, generic, and lacked scientific rigor. We have a long way to go before Pakistani patients with limited English language skills could benefit from AI chatbots like ChatGPT.

Significance of serum ferritin and De Ritis ratio in non-alcoholic fatty liver disease as diagnostic markers.

Objectives: To ascertain the significance of serum ferritin and De Ritis ratio as diagnostic markers in patients of nonalcoholic fatty liver disease with and without type 2 diabetes mellitus. METHODS: The comparative cross-sectional study was conducted from February to October 2022 at the Radiology Department of Combined Military Hospital, Rawalpindi, Pakistan, and comprised individuals aged 30-65 who were divided into 3 groups. Healthy controls formed group I, non-alcoholic fatty liver disease patients without type 2 diabetes mellitus formed group II and non-alcoholic fatty liver disease patients with type 2 diabetes mellitus were in group III. Blood 5ml was withdrawn and assessed for alkaline phosphatase, aspartate transaminase, alanine transaminase and ferritin. De Ritis ratio was calculated and subjected to intergroup comparison. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 110(52.4%) were males and 100(47.6%) were females, with 70(33.3%) in each of the three groups. Group I had 38(54.3%) females and 32(45.7%) males with mean age 37.50±4.513. In group II, there were 27(38.6%) females and 43(61.4%) males with mean age 45.86±9.646, while in group III there were 35(50%) females and 35(50%) males with mean age 54.01±9.243 years. Serum ferritin levels were significantly increased in patient groups II and III compared to control group I (p<0.05). De Ritis ratio was markedly raised in groups II and III compared to group I (p<0.05). Ferritin was significantly correlated to age, weight, height, fasting blood glucose, haemoglobin, alkaline phosphatase, aspartate aminotransferase, alanine transaminase and bilirubin (p<0.05). De Ritis ratio had a significant correlation with body mass index and fasting blood glucose (p<0.05). CONCLUSIONS: Serum ferritin and De Ritis ratio were found to be useful diagnostic indicators for non-alcoholic fatty liver disease, highlighting their importance in improving disease screening.

Prevalence, predictors, and consequences of workplace violence among female healthcare workers in tertiary care hospitals: A cross-sectional study in Pakistan.

OBJECTIVE: To determine the prevalence, predictors and perpetrators of violence, and its impact on the mental health of female healthcare workers. METHODS: The cross-sectional study was conducted from June to October 2022 at three tertiary care hospitals after approval from the ethics review board of Rawalpindi Medical University, Rawalpindi, Pakistan, and comprised female healthcare workers, including doctors, nurses and paramedical staff. Data was collected regarding workplace violence using a structured questionnaire adopted from literature. The incidence of verbal, physical and sexual violence in the preceding 12 months was noted, and predictors were analysed. Data was analysed using SPSS 25. RESULTS: Of the 140 subjects with an age range of 16-60 years, verbal violence was experienced by 102(72.9%) and physical violence by 26(18.6%), while verbal and physical forms of sexual violence were reported by 33(23.6%) and 13(9.3%), respectively. Those in the Medicine department had significantly lower odds of experiencing verbal violence compared to those from the Surgery department (adjusted odds ratio=0.223; 95% confidence interval: 0.078-0.036; p=0.005). Those in the Emergency department had significantly greater odds of experiencing physical violence compared to those in Surgery (adjusted odds ratio=8.716; 95% confidence interval: 1.693-44.87; p=0.01). Violence had a significant detrimental impact on the mental health of female healthcare workers (p<0.05). CONCLUSIONS: Violence was found to be prevalent in the healthcare sector, specifically in stressful and critical-care departments, like Emergency and Surgery.

A comprehensive exploration of artificial intelligence in orthopaedics within lower-middle-income countries: a narrative review.

Integrating Artificial Intelligence (AI) in orthopaedic within lower-middle-income countries (LMICs) promises landmark improvement in patient care. Delving into specific use cases-fracture detection, spine imaging, bone tumour classification, and joint surgery optimisation-the review illuminates the areas where AI can significantly enhance orthopaedic practices. AI could play a pivotal role in improving diagnoses, enabling early detection, and ultimately enhancing patient outcomes- crucial in regions with constrained healthcare services. Challenges to the integration of AI include financial constraints, shortage of skilled professionals, data limitations, and cultural and ethical considerations. Emphasising AI's collaborative role, it can act as a complementary tool working in tandem with physicians, aiming to address gaps in healthcare access and education. We need continued research and a conscientious approach, envisioning AI as a catalyst for equitable, efficient, and accessible orthopaedic healthcare for patients in LMICs.

Identification and genome-wide analysis provide insights into the genetic diversity and biotechnological potentials of novel cold-adapted Acinetobacter strain.

Extreme cold environments, such as polar regions or high-altitude mountains, are known for their challenging conditions including low temperatures, high salinity, and limited nutrient availability. Microbes that thrive in these environments have evolved specialized strategies to survive and function under such harsh conditions. The study aims to identify, sequence the genome, perform genome assembly, and conduct a comparative genome-wide analysis of Acinetobacter sp. strain P1, which was isolated from the Batura glacier regions of Pakistan. A basic local alignment search tool of NCBI using 16 s RNA gene sequence confirmed the strain Acinetobacter following phylogenetic analysis revealed that strain P1 clustered with Acinetobacter sp. strain AcBz01. The high-throughput Genome sequencing was done by the NovaSeq 6000 sequencing system following de novo genome assembly reported 23 contigs, a genome size of 3,732,502 bp containing approximately 3489 genes and 63 RNAs (60 tRNA, 3 rRNA). The comparative genome analysis revealed that Acinetobacter sp. strain P1 exhibited the highest homology with the Acinetobacter baumannii ATCC 17978 genome and encompassed 1668 indispensable genes, 1280 conserved genes 1821 specific genes suggesting high genomic plasticity and evolutionary diversity. The genes with functional assignments include exopolysaccharide phosphotransferase enzyme, cold-shock proteins, T6SS, membrane modifications, antibiotic resistance, and set of genes related to a wide range of metabolic characteristics such as exopolysaccharides were also present. Moreover, the structural prediction analysis of EPS proteins reveals that structural flexibility allows for conformational modifications during catalysis, which boosts or increases the catalytic effectiveness at lower temperatures. Overall, the identification of Acinetobacter, a cold-adapted bacterium, offers promising applications in bioremediation, enzyme production, food preservation, pharmaceutical development, and astrobiology. Further research and exploration of these microorganisms can unlock their full biotechnological potential and contribute to various industries and scientific endeavors.

COPD exacerbations and patient-reported outcomes according to post-bronchodilator FEV1 - a post-hoc analysis of pooled data.

BACKGROUND: Management strategies of chronic obstructive pulmonary disease (COPD) need to be tailored to the forced expiratory volume in one second (FEV1), exacerbations, and patient-reported outcomes (PROs) of individual patients. In this study, we analyzed the association and correlation between the FEV1, exacerbations, and PROs of patients with stable COPD. METHODS: This was a post-hoc analysis of pooled data from two cross-sectional studies that were previously conducted in Malaysia from 2017 to 2019, the results of which had been published separately. The parameters measured included post-bronchodilator FEV1 (PB-FEV1), exacerbations, and scores of modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). Descriptive, association, and correlation statistics were used. RESULTS: Three hundred seventy-four patients were included in the analysis. The PB-FEV1 predicted was < 30% in 85 (22.7%), 30-49% in 142 (38.0%), 50-79% in 111 (29.7%), and ≥ 80% in 36 (9.6%) patients. Patients with PB-FEV1 < 30% predicted had significantly more COPD exacerbations than those with PB-FEV1 30-49% predicted (p < 0.001), 50-79% predicted (p < 0.001), and ≥ 80% predicted (p = 0.002). The scores of mMRC, CAT, and SGRQ-c were not significantly higher in patients with more severe airflow limitation based on PB-FEV1 (p = 0.121-0.271). The PB-FEV1 predicted had significant weak negative correlations with exacerbations (r = - 0.182, p < 0.001), mMRC (r = - 0.121, p = 0.020), and SGRQ-c scores (r = - 0.114, p = 0.028). There was a moderate positive correlation between COPD exacerbations and scores of mMRC, CAT, and SGRQ-c (r = 0.407-0.482, all p < 0.001). There were significant strong positive correlations between mMRC score with CAT (r = 0.727) and SGRQ-c scores (r = 0.847), and CAT score with SGRQ-c score (r = 0.851) (all p < 0.001). CONCLUSIONS: In COPD patients, different severity of airflow limitation was not associated with significant differences in the mMRC, CAT, and SGRQ-c scores. Exacerbations were significantly more frequent in patients with very severe airflow limitation only. The correlation between airflow limitation with exacerbations, mMRC, and SGRQ-c was weak.

Machine learning based efficient prediction of positive cases of waterborne diseases.

BACKGROUND: Water quality has been compromised and endangered by different contaminants due to Pakistan's rapid population development, which has resulted in a dramatic rise in waterborne infections and afflicted many regions of Pakistan. Because of this, modeling and predicting waterborne diseases has become a hot topic for researchers and is very important for controlling waterborne disease pollution. METHODS: In our study, first, we collected typhoid and malaria patient data for the years 2017-2020 from Ayub Medical Hospital. The collected data set has seven important input features. In the current study, different ML models were first trained and tested on the current study dataset using the tenfold cross-validation method. Second, we investigated the importance of input features in waterborne disease-positive case detection. The experiment results showed that Random Forest correctly predicted malaria-positive cases 60% of the time and typhoid-positive cases 77% of the time, which is better than other machine-learning models. In this research, we have also investigated the input features that are more important in the prediction and will help analyze positive cases of waterborne disease. The random forest feature selection technique has been used, and experimental results have shown that age, history, and test results play an important role in predicting waterborne disease-positive cases. In the end, we concluded that this interesting study could help health departments in different areas reduce the number of people who get sick from the water.

Is there an ideal method of reconstruction for proximal humerus osteosarcoma? A review of different reconstruction techniques.

Osteosarcoma is the commonest primary bone malignancy occurring in patients aged <20, and humerus is the third most common site affected by it. In the past, ablative surgery with poor functional outcomes was the only option, but due to advances in chemotherapy, medical imaging and surgical techniques, patient survivorship and the rate of limb salvage surgery has increased significantly. Over the decades many treatment options have been proposed for the reconstruction of the defect following extirpation of the tumour in the proximal humerus, with every procedure having its merits and demerits. However, there is no agreement on the preferred treatment even in similar age groups, and the best way to reconstruct the proximal humerus remains debatable because the restoration of the function of the shoulder girdle remains primarily dependant on the extent of muscle-loss during tumour resection, available surgical expertise and financial constraints in different health systems. The current narrative review was planned to discuss the various reconstruction techniques with their advantages and disadvantages, and a present general review of the relevant literature.