ChemTextMiner: An open source tool kit for mining medical literature abstracts

Text mining involves recognizing patterns from a wealth of information hidden latent in unstructured text and deducing explicit relationships among data entities by using data mining tools. Text mining of Biomedical literature is essential for building biological network connecting genes, proteins, drugs, therapeutic categories, side effects etc. related to diseases of interest. We present an approach for textmining biomedical literature mostly in terms of not so obvious hidden relationships and build biological network applied for the textmining of important human diseases like MTB, Malaria, Alzheimer and Diabetes. The methods, tools and data used for building biological networks using a distributed computing environment previously used for ChemXtreme[1] and ChemStar[2] applications are also described

Jais and Jais-chat: Arabic-Centric Foundation and Instruction-Tuned Open Generative Large Language Models

We introduce Jais and Jais-chat, new state-of-the-art Arabic-centric foundation and instruction-tuned open generative large language models (LLMs). The models are based on the GPT-3 decoder-only architecture and are pretrained on a mixture of Arabic and English texts, including source code in various programming languages. With 13 billion parameters, they demonstrate better knowledge and reasoning capabilities in Arabic than any existing open Arabic and multilingual models by a sizable margin, based on extensive evaluation. Moreover, the models are competitive in English compared to English-centric open models of similar size, despite being trained on much less English data. We provide a detailed description of the training, the tuning, the safety alignment, and the evaluation of the models. We release two open versions of the model -- the foundation Jais model, and an instruction-tuned Jais-chat variant -- with the aim of promoting research on Arabic LLMs. Available at https://huggingface.co/inception-mbzuai/jais-13b-chatComment: Arabic-centric, foundation model, large-language model, LLM, generative model, instruction-tuned, Jais, Jais-cha

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Influence of fumed silica nanofiller and stacking sequence on interlaminar fracture behaviour of bidirectional jute-kevlar hybrid nanocomposite

The present study aims to examine the influence of nanofiller content and stacking sequence on the interlaminar fracture properties of Jute-Kevlar hybrid nanocomposite. Mode I and Mode II interlaminar fracture properties are characterized by double cantilever beam (DCB) and end notch flexure (ENF) test samples. Bidirectional jute (J) and kevlar (K) fabrics are used as reinforcement. Nanoscaled fumed silica is used as filler reinforcement. Thirteen different types of composites are prepared with varying stacking sequences (i.e., Jute-Jute-Jute-Jute [JJJJ], Jute-Kevlar-Kevlar-Jute [JKKJ], Kevlar-Jute-Jute-Kevlar [KJJK], and Kevlar-Kevlar-Kevlar-Kevlar [KKKK]) and four nanofiller weight fraction (i.e., 0%, 1.5%, 3%, and 4.5%). It is noticed that interlaminar fiber bridging and interlaminar friction are the key factors influencing Mode I and Mode II fracture toughness, respectively. The presence of nanofiller plays a significant role in enhancing the key factors influencing the fracture toughness of the composites. A noticeable improvement in Mode II fracture toughness is found. The composite stacking sequence JKKJ with 3% fumed silica (JKKJ-3) possess maximum Mode II fracture toughness (951 J/m2), which is 37% more than kevlar fiber-reinforced composite (694 J/m2) (KKKK-0). The evidence of matrix tearing as a result of fiber pull-out, toughened matrix region, and nanofiller wrapping over the fiber are noticed from the optical microscope image of the fractured surface

Performance Evaluation of Mechanical Properties of Nanofiller Reinforced Jute-Kevlar Hybrid Composite

The present study deals with the effect of nanofiller (fumed silica) content and layer sequence of bidirectional woven fabrics on the physical and mechanical properties of Jute (J)–Kevlar (K)-Fumed silica epoxy-based hybrid composite. Jute fibers are treated with alkali to improve surface properties. Twenty number of composite samples are prepared to have five different layer sequences (i.e., Jute-Jute-Jute-Jute [JJJJ], Jute-Kevlar-Kevlar-Jute [JKKJ], Kevlar-Jute-Jute-Kevlar [KJJK], Jute-Kevlar-Jute-Kevlar [JKJK] and Kevlar-Kevlar-Kevlar-Kevlar [KKKK]) and four nanofiller contents (i.e., 0%, 1.5%, 3%, and 4.5%). The mechanical properties of the composites like tensile strength, flexural strength, inter-laminar shear strength, and density have been evaluated. From the result, it is observed that the mechanical properties of the composites are significantly influenced by layer sequence and filler content. The study has also attempted to find out optimum layer sequence and filler content for obtaining the best mechanical performance of the composites using TOPSIS multi-criteria decision-making approach. It is found that Jute-Kevlar-Jute-Kevlar (JKJK) with 1.5% filler, i.e., composite with alternate layers of jute and kevlar with 1.5% fumed silica filler has superior properties than other composites

Mannosylated Polyethyleneimine-Hyaluronan Nanohybrids for Targeted Gene Delivery to Macrophage-Like Cell Lines

Journal articleNonviral gene delivery systems have a number of limitations including low transfection efficiency, specificity, and cytotoxicity, especially when the target cells are macrophages. To address these issues, the hypothesis tested in this study was that mannose functionalized nanohybrids composed of synthetic and natural polymers will improve transfection efficiency, cell viability, and cell specificity in macrophages. Robust nanohybrids were designed from hyaluronic acid (HA) and branched polyethyleneimine (bPEI) using carbodiimide chemistry. The reaction product, i.e., branched polyethyleneimine-hyaluronic acid (bPEI-HA) copolymer was subsequently functionalized with mannose at the terminal end of the copolymer to obtain mannosylated-bPEI-HA (Man-bPEI-HA) copolymer. UV spectroscopy and gel retardation studies confirmed the formation of polyplexes at polymer to DNA weight ratio >= 2. Alamar Blue and MTT assay revealed that the cytotoxicity of the developed nanohybrids were significantly (P < 0.05) lower than that of unmodified bPEI. Mannose functionalization of these nanohybrids showed specificity for both murine and human macrophage-like cell lines RAW 264.7 and human acute monocytic leukemia cell line (THP1), respectively, with a significant level (P < 0.05) of expression of gaussia luciferase (GLuc) and green fluorescent reporter plasmids. Internalization studies indicate that a mannose mediated endocytic pathway is responsible for this higher transfection rate. These results suggest that hyaluronan-based mannosylated nanohybrids could be used as efficient carriers for targeted gene delivery to macrophages

Bacterial siderophore mimicking iron complexes as DNA targeting antimicrobials

Microbial secretion of siderophores for iron uptake can be employed as an efficient strategy to smuggle in bactericidal agents by conjugation to iron. Three iron complexes: complex 1Fe(L1)(2)] Cl-2 L1 = 3-(pyridin-2-yl)dipyrido3,2-a:2',3'-c]phenazine (pydppz or ligand 1), complex 2 Fe(BHA)(L2)Cl]Cl center dot H2O (BHA = benzohydroxamate) L2 = pyrenyl-dipicolylamine (pydpa or ligand 2) and complex 3 Fe(BHA)(L3)Cl]Cl center dot H2O L3 = phenyl-dipicolylamine (phdpa or ligand 3) were synthesized. The ligands were docked for binding to DNA and DNA polymerase I. The antibacterial efficacy of the iron complexes were evaluated against three pathogenic bacteria - Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa as well as cytotoxicity assessed in C2C12 mouse myoblast cells. In silico docking and molecular dynamic simulations of the ligands revealed stable and non-specific binding to DNA and DNA polymerase I, in the order: L1 > L2 > L3. The bactericidal effect of the iron complexes against MRSA predominantly occurred by bacterial DNA fragmentation as analyzed from gel electrophoresis and comet assay. The extent of DNA damage followed the order: complex 1 > complex 2 > complex 3, in commensurate with docking. Siderophore production elicited preferential bactericidal action of the iron complexes against MRSA. Both, complex 1 and complex 2 were 5-10 fold less toxic in C2C12 cells compared to MRSA. Taken together, a combination of DNA targeting and siderophore mimicking ligands conjugated to iron can be deployed as Trojan horse for the entry of antimicrobials into pathogenic bacteria. Thus, DNA targeting antimicrobials offer a promising solution to persistent bacterial infections. Their selectivity towards microbes can be promoted via siderophore uptake pathways