Miracle-dz/UniFAR-FTUs huggingface dataset:
Controlled-release approaches towards the chemotherapy of tuberculosis

Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization’s 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18–24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.
Exact 3-D Solution for Free Bending Vibration of Thick FG Plates and Homogeneous Plate Coated by a Single FG Layer on Elastic Foundations

This paper presents new exact 3-D (three-dimensional) elasticity closed-form solutions for out-of-plane free vibration of thick rectangular single layered FG (functionally graded) plates and thick rectangular homogeneous plate coated by a functionally graded layer with simply supported boundary conditions. It is assumed that the plate is on a WinklerPasternak elastic foundation and elasticity modulus and mass density of the FG layer vary exponentially through the thickness of the FG layer, whereas Poisson’s ratio is constant. In order to solve the equations of motion, a proposed displacement field is used for each layer. Influences of stiffness of the foundation, inhomogeneity of the FG layer and coating thickness-to-total thickness ratio on the natural frequencies of the plates are discussed. Numerical results presented in this paper can serve as benchmarks for future vibration analyses of single layered FG plates and coated plates on elastic foundations. © 2015 IAU, Arak Branch. All rights reserved.
Central Venous Oxygen Saturation as a Predictor of a Successful Spontaneous Breathing Trial from Mechanical Ventilation: A Prospective, Nested Case-Control Study

Background: Weaning from mechanical ventilation is a key element in the care of critically ill patients, and Spontaneous Breathing Trial (SBT) is a crucial step in this procedure. This nested case-control study aimed to evaluate whether central oxygen saturation (ScvO2) values and their changes could independently predict the SBT outcome among mechanically ventilated patients. Methods: A prospective cohort of patients who were mechanically ventilated for at least 48hours and fulfilled the criteria of readiness to wean constituted the study population. All patients attempted a SBT and were then categorized in SBT success group and SBT failure group, based on a combination of criteria which indicated whether SBT was successful or not. Multivariate binary logistic regression analysis was utilized to indicate the independent predictors of SBT success, while the Receiver Operating Characteristic (ROC) curves were used to demonstrate the diagnostic accuracy of these independent predictors. Results: Seventy-seven patients 69(18-86) years old; 62.3% male) constituted the study population. SBT was successful among 63.6% of them. A decrease in ScvO2 values (ΔScvO2) < 4% between the beginning and the end of the trial independently predicted the successful outcome (OR=18.278; 95% CI=4.017-83.163), along with age, Hemoglobin concentration (Hb) and arterial oxygen saturation (SaO2). Diagnostic accuracy for ΔScvO2 alone (ROC area=0.715) was slightly superior to that of either SaO2 (0.625) or Hb (0.685) to predict SBT success. Conclusion: ScvO2 is an independent predictor of the weaning outcome and its evaluation may further facilitate the accurate categorization among those patients who pass or fail the SBT.
Human Genome Epidemiology ( HuGE ) Review Glutathione S-TransferaseM 1 ( GSTM 1 ) and Glutathione S-Transferase T 1 ( GSTT 1 ) Null Polymorphisms , Smoking , and Their Interaction in Oral Cancer : A HuGE Review and Meta-Analysis

The association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and oral cancer is not consistent across studies, and data on their interaction with smoking in oral cancer are lacking. The authors systematically searched PubMed and SciVerse Scopus for case-control studies examining the association between null genotypes of theGSTM1 andGSTT1 genes and oral cancer. Twenty-eight case-control studies published in English were identified. Summary odds ratios were derived via random-effects models. The summary odds ratio for the GSTM1 null genotype was 1.43 in Asians (95% confidence interval (CI): 1.14, 1.78; P< 0.01, I 1⁄4 73%) and 0.98 in Caucasians (95%CI: 0.76, 1.28; P1⁄4 0.91, I 1⁄4 0%). Case-only analysis of 6 studies (552 cases) showed an inverse multiplicative interaction between GSTM1 null polymorphisms and smoking (ever/high levels of smoking vs. never/low levels) (odds ratio (OR) 1⁄4 0.51, 95% CI: 0.32, 0.82; P 1⁄4 0.01, I 1⁄4 34%). TheGSTT1 null genotypewas not significantly associated with oral cancer in Asians (OR1⁄4 1.07, 95%CI: 0.82, 1.38; P1⁄4 0.63, I 2 1⁄4 65%) or Caucasians (OR1⁄4 1.04, 95%CI: 0.41, 2.65; P1⁄4 0.93, I 2 1⁄4 55%). In conclusion, the GSTM1 null genotype may be associated with a higher risk of oral cancer in Asians but not in Caucasians, and this effect may be modified by smoking status. The GSTT1 null genotype may not be associated with oral cancer.
Magnesium attenuates endothelin‐1‐induced vasoreactivity and enhances vasodilatation in mouse pulmonary arteries: Modulation by chronic hypoxic pulmonary hypertension

What is the central question of this study? The central goal of this study was to elucidate the role of magnesium in the regulation of pulmonary vascular reactivity in relationship to hypoxic pulmonary hypertension. What is the main finding and its importance? We found that magnesium is essential for normal vasoreactivity of the pulmonary artery. Increasing the magnesium concentration attenuates vasoconstriction and improves vasodilatation via release of nitric oxide. Pulmonary hypertension is associated with endothelial dysfunction resulting in the suppression of magnesium modulation of vasodilatation. These results provide evidence that magnesium is important for the modulation of pulmonary vascular function.
Spike sorting: the overlapping spikes challenge

Abstract When recording action potentials (spikes) from many neurons simultaneously via multichannel micro-electrodes the overlapping of spikes from different neurons is a demanding problem for detection and classifi-cation of spikes (spike sorting). Since multichannel electrodes provide better possibilities to separate the superimposed waveforms, we refined an algorithm for separation of overlapping spikes for the use on multichannel recordings and tested it on simulated data with different numbers of signal channels and with several signal parameters. We show that the larger the number of signal channels the better the separation that may be achieved, especially under demanding recording conditions.
Seal strength improvement of valve-regulated lead-acid (VRLA) battery

This research has two objectives. The first objective is to study the effect of assembly process factors on the seal strength of the VRLA battery. The second objective is to find the optimal setting of significant parameters to maximize the seal strength to reduce the defective rate from air leakage defect. This research applied the design of experiment (DOE) technique using the two-level full factorial design to screen out the factors and then used the face-centered central composite design to help find the relationship between the seal strength and the significant factors. It was found that the factors which significantly affect the seal strength were the stopper distance of the case, the stopper distance of the lid, and the melting time. The optimization technique helped determine that the machine setting should be at the stopper distance of the case at 34.97 mm. , the stopper distance of the lid at 77.95 mm. , and the melting time at 3.1 second to maximize the heat seal strength. After improvement, the defective rate from air leakage defect significantly decreased from 0.12% to 0.01%.
Alcohol consumption and risk of lung cancer: a pooled analysis of cohort studies.

BACKGROUND Although smoking is the primary cause of lung cancer, much is unknown about lung cancer etiology, including risk determinants for nonsmokers and modifying factors for smokers. OBJECTIVE We hypothesized that alcohol consumption contributes to lung cancer risk. DESIGN We conducted a pooled analysis using standardized exposure and covariate data from 7 prospective studies with 399,767 participants and 3137 lung cancer cases. Study-specific relative risks (RRs) and CIs were estimated and then combined to calculate pooled multivariate RRs by using a random-effects model. RESULTS We found a slightly greater risk for the consumption of > or = 30 g alcohol/d than for that of 0 g alcohol/d in men (RR: 1.21; 95% CI: 0.91, 1.61; P for trend = 0.03) and in women (RR: 1.16; 95% CI: 0.94, 1.43; P for trend = 0.03). In male never smokers, the RR for consumption of > or = 15 g alcohol/d rather than 0 g alcohol/d was 6.38 (95% CI: 2.74, 14.9; P for trend < 0.001). In women, there were few never-smoking cases and no evidence of greater risk (RR: 1.35; 95% CI: 0.64, 2.87). Because of possible residual confounding by smoking, we performed sensitivity analyses by reclassifying the never smokers in the highest drinking category as former smokers. Resulting associations for alcohol consumption were somewhat attenuated, but P for trend = 0.05 for men, which was near the original P = 0.03. CONCLUSIONS A slightly greater risk of lung cancer was associated with the consumption of > or = 30 g alcohol/d than with no alcohol consumption. Alcohol consumption was strongly associated with greater risk in male never smokers. Residual confounding by smoking may explain part of the observed relation.
Genetic evidence for pax‐3 function in myogenesis in the nematode Pristionchus pacificus

SUMMARY PAX3 is a member of the PAX3/7 subfamily of the paired box proteins. In vertebrates, Pax3 is essential for skeletal myogenesis by activating a cascade of transcriptional events that are necessary and sufficient for skeletal myogenesis. Four related basic helix‐loop‐helix transcription factors, MyoD, Myf5, Mrf4, and Myogenin, are targets of PAX3 and serve as myogenic regulatory factors. Although the role of Pax3 in myogenesis is well studied in vertebrates, little is known about invertebrate PAX‐3 proteins and myogenesis. Here, we took advantage of viable alleles of pax‐3 in the nematode satellite model organism Pristionchus pacificus to investigate the function of PAX‐3 in myogenesis. Two strong reduction‐of‐function alleles of Ppa‐pax‐3 show severe muscle‐derived abnormalities and phalloidin staining indicates a disruption of body wall muscle patterning. Furthermore, we identified a myogenic regulatory factor‐related gene Ppa‐hlh‐1/MyoD and a serum response factor‐related gene Ppa‐unc‐120. Expression of both genes in Ppa‐pax‐3 mutant animals is down regulated suggesting that Ppa‐pax‐3 acts upstream in the regulatory network. Together, our results provide the first genetic evidence for a conserved function of PAX‐3 in myogenesis between vertebrates and nematodes.
Industrial bioprocessing perspectives on managing therapeutic protein charge variant profiles

Controlling the charge profile of therapeutic protein is a critical challenge in the current quality‐by‐design (QbD) paradigm, throughout all phases of biologics process development (PD): cell line development, upstream cell culture, recovery process, downstream purification, and analytical characterization. Charge variant profiles may influence efficacy and/or lead to unintended side‐effects. Thus, maintaining a consistent charge profile is of tremendous importance, and increasingly, researchers have focused efforts toward developing strategies to mitigate variability during cell culture and to improve separation and detection of charge variants. Current understanding of factors affecting charge variant formation during manufacturing remains inadequate, and sometimes, even substantial commitment of resources may still not fully achieve the desired or consistent profiles. As such, this review attempts to provide a comprehensive resource for the biologics community by summarizing the impact of charge variants and CQA management, analytical methods for charge variant detection, as well as strategies in downstream and upstream PD for controlling charge variant profiles.
What Characteristics Confer Proteins the Ability to Induce Allergic Responses? IgE Epitope Mapping and Comparison of the Structure of Soybean 2S Albumins and Ara h 2

Ara h 2, a peanut 2S albumin, is associated with severe allergic reactions, but a homologous protein, soybean 2S albumin, is not recognized as an important allergen. Structural difference between these proteins might explain this clinical discrepancy. Therefore, we mapped sequential epitopes and compared the structure of Ara h 2, Soy Al 1, and Soy Al 3 (Gly m 8) to confirm whether structural differences account for the discrepancy in clinical responses to these two proteins. Commercially synthesized peptides covering the full length of Ara h 2 and two soybean 2S albumins were analyzed by peptide microarray. Sera from 10 patients with peanut and soybean allergies and seven non-atopic controls were examined. The majority of epitopes in Ara h 2 identified by microarray are consistent with those identified previously. Several regions in the 2S albumins are weakly recognized by individual sera from different patients. A comparison of allergenic epitopes on peanut and soybean proteins suggests that loop-helix type secondary structures and some amino acids with a large side chain including lone electron pair, such as arginine, glutamine, and tyrosine, makes the peptides highly recognizable by the immune system. By utilizing the peptide microarray assay, we mapped IgE epitopes of Ara h 2 and two soybean 2S albumins. The use of peptide microarray mapping and analysis of the epitope characteristics may provide critical information to access the allergenicity of food proteins.
URL and Domain Obfuscation Techniques - Prevalence and Trends Observed on Phishing Data

For phishing to be successful, it is necessary to instill confidence and appear legitimate in the eyes of the potential victim, especially when mimicking a known brand. To achieve this, attackers employ various obfuscation techniques. Some are aimed to bypass existing technical (software) protections; others are aimed against the targeted victim (person). On the side of prevention, these techniques are seen as a clear sign of phishing, and many detection algorithms use these characteristics to decide whether to show or block the given webpage. Analysis conducted on 15 years of phishing data (2009-2023) collected from PhishTank and PhishStats websites focused on the prevalence and trends of various obfuscation techniques. These figures would allow validation and weighting of the relevancy of these indicators in phishing web page detection throughout the covered period and also provide a future baseline for creating a robust phishing dataset. Analysis steps required collecting and consolidating the phishing URL data. Due to the nature of the phishing data collection and their potential overlap, it was necessary to cleanse and filter out incorrect and duplicate records. The analysis’s core part summarizes the selected techniques’ prevalence and highlights notable observations. A noteworthy finding is that they occur rarely despite being a powerful indicator of phishing. Any of the techniques reviewed is present in less than ≈3% of the phishing URLs across the entire 15-year period. The most common techniques (in order of prevalence) are the - use of IP addresses, URL shorteners, ports, and Punycode. The remaining ones are extremely rare, with single or maximum double-digit occurrences.
Buying Reputation as a Signal of Quality: Evidence from an Online Marketplace

Seller reputation, generated by buyer feedback, is critical to fostering trust in online marketplaces. Marketplaces or sellers may choose to compensate buyers for providing feedback. Signaling theory predicts that only sellers of high‐quality products will reward buyers for truthful feedback, especially when a product lacks any feedback and when the seller is not established. We confirm these hypotheses using Taobao's reward‐for‐feedback mechanism. High‐quality products, especially without established feedback, are chosen for feedback rewards, which cause sales to increase by 36%. Marketplaces and consumers can therefore benefit from allowing sellers to buy feedback and signal their high‐quality products in the process.
Animal Welfare and Organic Aquaculture in Open Systems Stephanie

The principles of organic farming espouse a holistic approach to agriculture that promotes sustainable and harmonious relationships amongst the natural environment, plants, and animals, as well as regard for animals’ physiological and behavioral needs. However, open aquaculture systems—both organic and conventional—present unresolved and significant challenges to the welfare of farmed and wild fish, as well as other wildlife, and to environmental integrity, due to water quality issues, escapes, parasites, predator control, and feed-source sustainability. Without addressing these issues, it is unlikely that open net-pen aquaculture production can be compatible with the principles inherent to organic farming.
Histamine-releasing factor enhances food allergy

Food allergy occurs due to IgE- and mast cell–dependent intestinal inflammation. Previously, we showed that histamine-releasing factor (HRF), a multifunctional protein secreted during allergy, interacts with a subset of IgE molecules and that the HRF dimer activates mast cells in an HRF-reactive IgE-dependent manner. In this study, we investigated whether HRF plays any role in food allergy. Specifically, we determined that prophylactic and therapeutic administration of HRF inhibitors that block HRF-IgE interactions reduces the incidence of diarrhea and mastocytosis in a murine model of food allergy. Food allergy–associated intestinal inflammation was accompanied by increased secretion of the HRF dimer into the intestine in response to proinflammatory, Th2, and epithelial-derived cytokines and HRF-reactive IgE levels at the elicitation phase. Consistent with these data, patients with egg allergy had higher blood levels of HRF-reactive IgE compared with individuals that were not hypersensitive. Successful oral immunotherapy in egg-allergy patients and food-allergic mice reduced HRF-reactive IgE levels, thereby suggesting a pathological role for HRF in food allergy. Together, these results suggest that antigen and HRF dimer amplify intestinal inflammation by synergistically activating mast cells and indicate that HRF has potential as a therapeutic target in food allergy.
Elevated seawater temperature disrupts the microbiome of an ecologically important bioeroding sponge

Bioeroding sponges break down calcium carbonate substratum, including coral skeleton, and their capacity for reef erosion is expected to increase in warmer and more acidic oceans. However, elevated temperature can disrupt the functionally important microbial symbionts of some sponge species, often with adverse consequences for host health. Here, we provide the first detailed description of the microbial community of the bioeroding sponge Cliona orientalis and assess how the community responds to seawater temperatures incrementally increasing from 23°C to 32°C. The microbiome, identified using 16S rRNA gene sequencing, was dominated by Alphaproteobacteria, including a single operational taxonomic unit (OTU; Rhodothalassium sp.) that represented 21% of all sequences. The “core” microbial community (taxa present in >80% of samples) included putative nitrogen fixers and ammonia oxidizers, suggesting that symbiotic nitrogen metabolism may be a key function of the C. orientalis holobiont. The C. orientalis microbiome was generally stable at temperatures up to 27°C; however, a community shift occurred at 29°C, including changes in the relative abundance and turnover of microbial OTUs. Notably, this microbial shift occurred at a lower temperature than the 32°C threshold that induced sponge bleaching, indicating that changes in the microbiome may play a role in the destabilization of the C. orientalis holobiont. C. orientalis failed to regain Symbiodinium or restore its baseline microbial community following bleaching, suggesting that the sponge has limited ability to recover from extreme thermal exposure, at least under aquarium conditions.