Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of quorum sensing and biofilm of Gram‐negative bacterial pathogens by Cinnamomum zeylanicum L.

The development of antibiotic resistant microbial pathogens has become a global health threat and a major concern in modern medicine. The problem of antimicrobial resistance (AMR) has majorly arisen due to sub‐judicious use of antibiotics in health care and livestock industry. A slow progress has been made in last two decades in discovery of new antibiotics. A new strategy in combatting AMR is to modulate or disarm the microbes for their virulence and pathogenicity. Plants are considered as promising source for new drugs against AMR pathogens. In this study, fraction‐based screening of the Cinnamomum zeylanicum extract was performed followed by detailed investigation of antiquorum sensing and antibiofilm activities of the most active fraction that is, C. zeylanicum hexane fraction (CZHF). More than 75% reduction in violacein pigment of C. violaceum 12472 was overserved. CZHF successfully modulated the virulence of Pseudomonas aeruginosa PAO1 by 60.46%–78.35%. A similar effect was recorded against Serratia marcescens MTCC 97. A broad‐spectrum inhibition of biofilm development was found in presence of sub‐MICs of CZHF. The colonization of bacteria onto the glass coverslips was remarkably reduced apart from the reduction in exopolymeric substances. Alkaloids and terpenoids were found in CZHF. GC/MS analysis revealed the presence of cinnamaldehyde dimethyl acetal, 2‐propenal, coumarin, and α‐copaene as major phytocompounds. This study provides enough evidence to support potency of C. zeylanicum extract in targeting the virulence of Gram −ve pathogenic bacteria. The plant extract or active compounds can be developed as successful drugs after careful in vivo examination to target microbial infections.
Mental health comorbidity in youth with atopic dermatitis: A narrative review of possible mechanisms

The presence of atopic dermatitis (AD) in youth has been linked to a variety of mental health concerns including disruptive behavior, symptoms of anxiety and depression, and diagnoses of attention deficit/hyperactivity disorder and autism spectrum disorder. However, the factors accounting for these relationships are not well understood. The current review summarizes possible mechanisms identified in previous research and highlights areas for future investigation. Among the primary mechanisms studied to date, child sleep is the only factor that has been characterized in relative detail, with findings generally supporting the mediating role of sleep problems in the relationship between AD and psychological symptoms. There is substantial evidence suggesting a negative impact of child AD on parent mental health and the impact of parent mental health on child psychological functioning, although the latter has not been assessed specifically in populations of children with AD. There is also preliminary support for other mechanisms, including pruritus and pain, atopic comorbidities, social functioning, and systemic antihistamine use, in the development of mental health concerns in pediatric AD. Furthermore, research suggests the presence of bidirectional relationships between AD and psychological functioning via inflammatory responses to stress and impaired treatment adherence. Overall, significant additional research is needed to better characterize the nature and magnitude of the relationships among these multiple mechanisms and various psychosocial outcomes. Nevertheless, the findings to date support routine screening of psychological health in patients with AD as well as screening for potential risk factors, which may also serve as targets of therapeutic intervention.
Clinical Outcomes of Coil Embolization for Unruptured Intracranial Aneurysms Categorized by Region and Hospital Size : A Nationwide Cohort Study in Korea

Objective To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea. Methods The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions. Results In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed. Conclusion The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians’ experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs.
Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation

ABSTRACT Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.
Compact cross‐coupled filters based on isosceles right triangular and equilateral triangular SIW cavities

Two kinds of classical triangular metric resonant cavities including the isosceles right triangular and equilateral triangular metric cavities are investigated carefully. A comprehensive and rigorous derivation process of these two resonant cavities is proposed. Based on this, the mode function and the transverse field components for the modes in the triangular substrate-integrated waveguide (SIW) cavities can be provided. Then the resonant frequency of both kinds of triangular SIW cavities can be calculated. Combined it with the coupling matrix, a fourth-degree filter implemented of isosceles right triangular SIW cavities and a sixth-degree filter formed by equilateral triangular SIW cavities are designed, fabricated and measured in detail. The measured results are in line with the simulated ones. The frequency responses of both filters show a pair of transmission zeroes at each side of the pass band due to the cross-coupling structure. It also verifies the validity of the derivation in this study. Compared with the rectangular and circular resonant ones, the construct of the triangular cavity has the advantage of much more compact. Besides, the proposed filters based on the triangular cavity also have their own advantages of low cost, good selectivity and easy integration with other planar circuits.
Elucidation of binding mechanism, affinity, and complex structure between mWT1 tumor‐associated antigen peptide and HLA‐A*24:02

We have applied our advanced computational and experimental methodologies to investigate the complex structure and binding mechanism of a modified Wilms' Tumor 1 (mWT1) protein epitope to the understudied Asian‐dominant allele HLA‐A*24:02 (HLA‐A24) in aqueous solution. We have applied our developed multicanonical molecular dynamics (McMD)‐based dynamic docking method to analyze the binding pathway and mechanism, which we verified by comparing the highest probability structures from simulation with our experimentally solved x‐ray crystal structure. Subsequent path sampling MD simulations elucidated the atomic details of the binding process and indicated that first an encounter complex is formed between the N‐terminal's positive charge of the 9‐residue mWT1 fragment peptide and a cluster of negative residues on the surface of HLA‐A24, with the major histocompatibility complex (MHC) molecule preferring a predominantly closed conformation. The peptide first binds to this closed MHC conformation, forming an encounter complex, after which the binding site opens due to increased entropy of the binding site, allowing the peptide to bind to form the native complex structure. Further sequence and structure analyses also suggest that although the peptide loading complex would help with stabilizing the MHC molecule, the binding depends in a large part on the intrinsic affinity between the MHC molecule and the antigen peptide. Finally, our computational tools and analyses can be of great benefit to study the binding mechanism of different MHC types to their antigens, where it could also be useful in the development of higher affinity variant peptides and for personalized medicine.
ZEB1 promotes non-homologous end joining double-strand break repair

Abstract Repair of DSB induced by IR is primarily carried out by Non-Homologous End Joining (NHEJ), a pathway in which 53BP1 plays a key role. We have discovered that the EMT-inducing transcriptional repressor ZEB1 (i) interacts with 53BP1 and that this interaction occurs rapidly and is significantly amplified following exposure of cells to IR; (ii) is required for the localization of 53BP1 to a subset of double-stranded breaks, and for physiological DSB repair; (iii) co-localizes with 53BP1 at IR-induced foci (IRIF); (iv) promotes NHEJ and inhibits Homologous Recombination (HR); (v) depletion increases resection at DSBs and (vi) confers PARP inhibitor (PARPi) sensitivity on BRCA1-deficient cells. Lastly, ZEB1’s effects on repair pathway choice, resection, and PARPi sensitivity all rely on its homeodomain. In contrast to the well-characterized therapeutic resistance of high ZEB1-expressing cancer cells, the novel ZEB1-53BP1-shieldin resection axis described here exposes a therapeutic vulnerability: ZEB1 levels in BRCA1-deficient tumors may serve as a predictive biomarker of response to PARPis.
Fuzzy logic in geology

Contributors Foreword Preface Glossary Of Symbols Introduction Fuzzy Logic: A Specialized Tutorial Fuzzy Logic And Earth Science: An Overview Fuzzy Logic In Geological Sciences: A Literature Review Applications of Fuzzy Logic to Stratigraphic Modeling Fuzzy Logic In Hydrology And Water Resources Formal Concept Analysis In Geology Fuzzy Logic and Earthquake Research Fuzzy Transform: Application to the Reef Growth Problem Ancient Sea-Level Estimation Acknowledgments Index
Coleus vettiveroides ethanolic root extract induces cytotoxicity by intrinsic apoptosis in HepG2 cells

Hepatocellular carcinoma (HCC) contributes to more than 80% of all primary cancers globally and ranks fourth in cancer‐related deaths, due to the lack of an effective, definite therapeutic drug. Coleus vettiveroides (CV) has been used in Indian traditional medicine to treat diabetes, liver ailments, skin diseases, leukoderma, and leprosy. This study investigates the anticancer effect of CV ethanolic root extract in HepG2 cells. HepG2 cells were treated with CV extract, and its cytotoxicity was analyzed by MTT assay. AO/EB staining, propidium iodide staining, DCFH‐DA assay, phalloidine staining, flow cytometry, and qPCR studies were performed for ROS expression, apoptosis and cell cycle analysis. The phytochemical analysis confirmed the presence of quercetin and galangin in CV root extract. The results showed that CV inhibited the proliferation of HepG2 cells, with altered cellular and nuclear morphology. CV was also found to increase intracellular ROS levels and oxidative stress markers in HepG2 cells. CV significantly altered the actin microfilament distribution in HepG2 cells and caused cell cycle arrest at the sub G0‐G1 phase. CV also induced mitochondria‐mediated apoptosis, as evidenced by increased expression of p53, Bax, cytochrome C, Apaf‐1, PARP, caspase‐3 and caspase‐9, and downregulated Bcl‐2 expression. Therefore, CV exerts its anticancer effect by inducing mitochondrial dysfunction, oxidative stress, cytoskeletal disorganization, cell cycle arrest, and mitochondria‐mediated apoptosis, and it could be a potent therapeutic option for HCC.
Systematic elucidation of the multi-target pharmacological mechanism of Terminalia arjuna against congestive cardiac failure via network pharmacology and molecular modelling approaches

Abstract Congestive cardiac failure (CCF) is a pathophysiologic state when the heart is not able to maintain its cardiac output to meet the demand of metabolising tissues. CCF is responsible for approximately 2.9 million deaths worldwide. The heterogeneous nature of CCF draws the attention of researchers to find more enthralling and promising diagnostic and treatment options. Terminalia arjuna (Arjuna) is an evergreen, deciduous tree exhibited various astringent, anti-bacterial, and anti-microbial properties. T. arjuna is being used in various regions for anginal pain, hypertension, congestive heart failure, and dyslipidemia. Although previous in vitro studies have demonstrated the therapeutic potential of T. arjuna, the exact molecular mechanism underlying its protective effect on the heart remains unclear. In this study, a network pharmacology technique was used to explore the active ingredients, potential targets in T. arjuna for the treatment of CCF. In the framework of this study, we explored the active ingredient–target–pathway network and figured out that oleanolic acid, arjunolic acid, luteolin, kaempferol, cholesterol, ellagic acid 4-O-xylopyranoside 3,3’-dimethyl ether, and cyclohexyl (2,4-dimethyl phenyl) methanone contributed significantly to the development of CCF by affecting AKT1, MAPK14, TNF, IL6, ESR1, and HSP90AA1 genes. Molecular docking analysis further validated the activities of these compounds against potential targets. To sum up, integrated network pharmacology and docking analysis revealed that T. arjuna exerts its cardioprotective effect by acting on various signalling pathways, including the thyroid hormone, VEGF signalling pathway, AGE-RAGE signalling pathway in diabetic complications, HIF signalling pathway, sphingolipid signalling pathway, and oestrogen signalling pathways. Overall, this study provides valuable insights into the molecular mechanism of T. arjuna in CCF and highlights its potential as a promising preventive treatment for this condition. Graphical Abstract
Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery

BACKGROUND Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time. OBJECTIVE To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery. DESIGN Retrospective cohort study. SETTING U.S. hospitals in the Premier Healthcare Database. PATIENTS 17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018. INTERVENTIONS Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg). MEASUREMENTS The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting. RESULTS The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group. LIMITATION Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment. CONCLUSION These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug. PRIMARY FUNDING SOURCE National Institute on Aging.
Einsatz KI-gestützter Diagnostik von Sprach- und Sprechstörungen bei neurodegenerativen Erkrankungen

ZUSAMMENFASSUNG Gegenstand und Ziel Der Artikel behandelt die Anwendungsmöglichkeiten der KI-gestützten Sprachanalyse bei neurodegenerativen Erkrankungen. Das Ziel besteht darin, einen Überblick über die sprachlichen Auffälligkeiten bei verschiedenen Krankheiten zu geben und zu zeigen, wie KI-basierte Methoden zur Diagnosestellung und Behandlung eingesetzt werden können. Material und Methoden Es werden neurodegenerative Erkrankungen und ihre spezifischen sprachlichen Störungen vorgestellt. Die traditionellen Methoden der Sprachanalyse für neurologische Erkrankungen werden erläutert und Möglichkeiten der KI-gestützten Analyse diskutiert. Ergebnisse Die KI-basierte Sprachanalyse stellt eine vielversprechende Möglichkeit zur Früherkennung und Diagnosestellung von neurologischen Erkrankungen dar. Durch automatische Transkripte und Fehleranalysen können subtile Veränderungen der Sprache und des Sprechens erkannt und objektiviert werden. Die KI-basierte Sprachanalyse ermöglicht eine genaue und quantifizierbare Bewertung von sprachlichen Defiziten und kann Fachpersonal zusätzliche Informationen liefern. Schlussfolgerung Die KI-basierte Sprachanalyse bietet neue Möglichkeiten zur Früherkennung und Überwachung von neurologischen Erkrankungen. Sie kann subtile Veränderungen der Sprache frühzeitig erkennen und eine rechtzeitige Intervention ermöglichen. Dennoch sollte sie als unterstützendes Werkzeug betrachtet werden und nicht als Ersatz für die Expertise von Fachpersonal. Die KI-basierte Sprachanalyse kann Ressourcen schonen, die Genauigkeit der Diagnose verbessern und eine kontinuierliche Verlaufsdiagnostik ermöglichen. Klinische Relevanz Die KI-basierte Sprachanalyse kann dazu beitragen, neurodegenerative Erkrankungen frühzeitig zu erkennen und eine gezielte Behandlung einzuleiten. Sie bietet eine objektivierbare Methode zur Bewertung sprachlicher Defizite und kann die Diagnosestellung unterstützen.
A High-performance RDMA-oriented Learned Key-value Store for Disaggregated Memory Systems

Disaggregated memory systems separate monolithic servers into different components, including compute and memory nodes, to enjoy the benefits of high resource utilization, flexible hardware scalability, and efficient data sharing. By exploiting the high-performance RDMA (Remote Direct Memory Access), the compute nodes directly access the remote memory pool without involving remote CPUs. Hence, the ordered key-value (KV) stores (e.g., B-trees and learned indexes) keep all data sorted to provide range query services via the high-performance network. However, existing ordered KVs fail to work well on the disaggregated memory systems, due to either consuming multiple network roundtrips to search the remote data or heavily relying on the memory nodes equipped with insufficient computing resources to process data modifications. In this article, we propose a scalable RDMA-oriented KV store with learned indexes, called ROLEX, to coalesce the ordered KV store in the disaggregated systems for efficient data storage and retrieval. ROLEX leverages a retraining-decoupled learned index scheme to dissociate the model retraining from data modification operations via adding a bias and some data movement constraints to learned models. Based on the operation decoupling, data modifications are directly executed in compute nodes via one-sided RDMA verbs with high scalability. The model retraining is hence removed from the critical path of data modification and asynchronously executed in memory nodes by using dedicated computing resources. ROLEX efficiently alleviates the fragmentation and garbage collection issues, due to allocating and reclaiming space via fixed-size leaves that are accessed via the atomic-size leaf numbers. Our experimental results on YCSB and real-world workloads demonstrate that ROLEX achieves competitive performance on the static workloads, as well as significantly improving the performance on dynamic workloads by up to 2.2× over state-of-the-art schemes on the disaggregated memory systems. We have released the open-source codes for public use in GitHub.
Jeder BMI Punkt zählt – VOR der Schwangerschaft

Abstrakt Hintergrund LGA-Neugeborene haben ein höheres Risiko für neonatale Komplikationen und leiden später häufiger an Diabetes und Fettleibigkeit. Als Risikofaktoren für die Geburt eines LGA Kindes ist neben der Adipositas der Mutter ein unzureichend behandelter GDM und die übermäßige Gewichtszunahme in der Schwangerschaft beschrieben. Methodik Wir sind in einer Studie der Frage nachgegangen welcher dieser Faktoren in der Schwangerschaft bei adipösen Frauen den größten Einfluss auf das Risiko für die Geburt eines makrosomen Kindes hat. Ergebnisse Im Vergleich zwischen adipösen und nicht-adipösen Schwangeren unterschieden sich in der Gruppe der nicht-adipösen Frauen die LGA-Raten signifikant zwischen GDM- und Nicht-GDM-Frauen (13 vs. 7,3%). Im Gegensatz dazu ergab die Subgruppenanalyse der adipöser Mütter keinen Einfluss des GDM auf die LGA-Rate. Diskussion Für das Outcome der Schwangerschaften adipöser Frauen zählt damit tatsächlich vor allem die BMI Reduktion VOR der Schwangerschaft. Eine adäquate Schwangerschaftsbetreuung kann darüber hinaus den Einfluss von weitern Einflussfaktoren wie GDM und übermäßiger Gewichtszunahme reduzieren helfen.