Miracle-dz/UniFAR-FTUs huggingface dataset:
Combining Co-Amorphous-Based Spray Drying with Inert Carriers to Achieve Improved Bioavailability and Excellent Downstream Manufacturability

It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.
RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication

Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.
Consumers’ Implicit and Explicit Recall, Understanding and Perceptions of Products with Nutrition-Related Messages: An Online Survey

This study aimed to assess consumers’ implicit and explicit recall, understanding and perceptions of products with a nutrition claim and a symbol depicting ‘health,’ and to determine whether these perceptions differed among Nutrition Facts table (NFt) users vs. nonusers. In an online survey, participants (n = 1997) were randomized to one of eight conditions in a 2 × 2 × 2 factorial design, consisting of a label with a claim (present/absent) a heart-shaped symbol depicting ‘health’ (present/absent) for a healthier or less healthy soup. Participants were shown a label for 10 s and asked whether they recalled seeing a claim. If participants answered yes, they were then asked to describe their response using open-ended questions. Participants also rated the product’s perceived nutritional quality and purchase intentions using seven-point Likert scales. In the claim condition, most participants (75%) were able to recall the presence of a claim, while 12% incorrectly mentioned the presence of a claim when there was none. Claims likely attracted consumers’ attention and increased perceived nutritional quality, although with limited influence among NFt users (23%). The symbol depicting ‘health’ did not enhance perceived nutritional quality or purchase intentions. Although most participants (77%) made their decisions implicitly using the front of labels, those who used the NFt had a better understanding of the nutritional quality of products.
Type I interferon remodels lysosome function and modifies intestinal epithelial defense

Significance Here, a genome-scale CRISPR/Cas9 screen in epithelial cells using Salmonella, a prototypical intracellular pathogen, led to the discovery of a new role for IFN-I signaling. We found that this canonical antiviral signaling pathway controls the subcellular localization, protein content, pH, and protease activity of lysosomes. IFN-I signaling-dependent lysosomal acidification was associated with heightened Salmonella virulence gene expression and escape into the cytosol, and in vivo studies confirmed a role for epithelial IFN-I signaling in promoting Salmonella systemic infection. We propose that IFN-I signaling-mediated control of lysosome function contributes to host responses to diverse intracellular pathogens and viruses. Investigating how cytokine signaling modifies organelle function will deepen understanding of the cell biology of innate defense. Organelle remodeling is critical for cellular homeostasis, but host factors that control organelle function during microbial infection remain largely uncharacterized. Here, a genome-scale CRISPR/Cas9 screen in intestinal epithelial cells with the prototypical intracellular bacterial pathogen Salmonella led us to discover that type I IFN (IFN-I) remodels lysosomes. Even in the absence of infection, IFN-I signaling modified the localization, acidification, protease activity, and proteomic profile of lysosomes. Proteomic and genetic analyses revealed that multiple IFN-I–stimulated genes including IFITM3, SLC15A3, and CNP contribute to lysosome acidification. IFN-I–dependent lysosome acidification was associated with elevated intracellular Salmonella virulence gene expression, rupture of the Salmonella-containing vacuole, and host cell death. Moreover, IFN-I signaling promoted in vivo Salmonella pathogenesis in the intestinal epithelium where Salmonella initiates infection, indicating that IFN-I signaling can modify innate defense in the epithelial compartment. We propose that IFN-I control of lysosome function broadly impacts host defense against diverse viral and microbial pathogens.
Trends in beekeeping and honey bee colony losses in Latin America

Over the past decade, several countries have carried out monitoring programs of managed honey bee colonies, which suggest beekeeping difficulties, with high colony loss rates all over the world. Although Latin America plays a major role in the global honey supply, information about trends in beekeeping activities and honey bee colony losses are lacking. Using the Food and Agriculture Organization of the United Nations (FAO) dataset and a synthesis of unpublished data of colony losses survey carried out over the last 7 years, we reveal a worrying situation of the beekeeping in this region. The Latin American trends in honey production and beehive numbers are drifting from the global pattern, and several high colony loss rates were registered in this region. These results reveal the presence of beekeeping difficulties in Latin America. However, the variability in methods of colony loss survey across initiatives prevent proper conclusion on loss rates. Efforts are needed to adapt, centralize and standardize methods to monitor honey bee health and colony losses across countries in Latin America, the main objective of the “colony losses” working group at the Latin-American Society for Bee Research, SOLATINA, a large-scale platform created in 2017 to coordinate bee research programs in Latin America.
Elucidating the Efficacy of Vaccination against Vibriosis in Lates calcarifer Using Two Recombinant Protein Vaccines Containing the Outer Membrane Protein K (r-OmpK) of Vibrio alginolyticus and the DNA Chaperone J (r-DnaJ) of Vibrio harveyi

Recombinant cell vaccines expressing the OmpK and DnaJ of Vibrio were developed and subsequently, a vaccination efficacy trial was carried out on juvenile seabass (~5 cm; ~20 g). The fish were divided into 5 groups of 50 fish per group, kept in triplicate. Groups 1 and 2 were injected with 107 CFU/mL of the inactivated recombinant cells vaccines, the pET-32/LIC-OmpK and pET-32/LIC-DnaJ, respectively. Group 3 was similarly injected with 107 CFU/mL of inactivated E. coli BL21 (DE3), Group 4 with 107 CFU/mL of formalin killed whole cells V. harveyi, and Group 5 with PBS solution. Serum, mucus, and gut lavage were used to determine the antibody levels before all fish were challenged with V. harveyi, V. alginolyticus, and V. parahemolyticus, respectively on day 15 post-vaccination. There was significant increase in the serum and gut lavage antibody titers in the juvenile seabass vaccinated with r-OmpK vaccine. In addition, there was an up-regulation for TLR2, MyD88, and MHCI genes in the kidney and intestinal tissues of r-OmpK vaccinated fish. At the same time, r-OmpK triggered higher expression level of interleukin IL-10, IL-8, IL-1ß in the spleen, intestine, and kidney compared to r-DnaJ. Overall, r-OmpK and r-DnaJ triggered protection by curbing inflammation and strengthening the adaptive immune response. Vaccinated fish also demonstrated strong cross protection against heterologous of Vibrio isolates, the V. harveyi, V. alginolyticus, and V. parahaemolyticus. The fish vaccinated with r-OmpK protein were completely protected with a relative per cent of survival (RPS) of 90 percent against V. harveyi and 100 percent against V. alginolyticus and V. parahaemolyticus. A semi-quantitative PCR detection of Vibrio spp. from the seawater containing the seabass also revealed that vaccination resulted in reduction of pathogen shedding. In conclusion, our results suggest r-OmpK as a candidate vaccine molecule against multiple Vibrio strain to prevent vibriosis in marine fish.
Use of roof as roost of Eumops perotis (Molossidae: Chiroptera) in southeast Brazil

ABSTRACT The bat Eumops perotis (Schinz, 1821) is broadly distributed in the Americas. Studies on its biology are still scarce and the few studies available are relatively outdated. In the present study, we describe the biology of Eumops perotis in an artificial roost in the municipality of Pindorama, State of São Paulo, southeastern Brazil, which was monitored for 12 months. We captured 50 individuals; 43 adults (34 males and 9 females) and seven juveniles (three males and four females). Nineteen adults were recaptured throughout the year (15 males and four females) during samplings. Males were ~33% heavier than females. Males remained in the roost throughout the year, while females were absent in June, July, and August. The presence of males with scrotal testes and pregnant females from July to November and the presence of pregnant females and pups from February to April suggest monoestry for this colony. Inside the roost, the behavior of E. perotis was similar to other molossid bats (e.g. contact posture, formation of groups, and presence of isolated males). During winter, the individuals of this colony consumed mostly coleopterans, but their diet also included orthopterans and lepidopterans, mainly in the summer. Therefore, this study contributes to increase the knowledge of the natural history of this species in the Neotropical region.
Trajectories of Depressive Symptoms Experienced by Older People: Effects of Time, Hurricane Sandy, and the Great Recession.

OBJECTIVES To examine depressive symptom trajectories as a function of time and exposure to Hurricane Sandy, accounting for the effects of the Great Recession. METHODS We analyzed 6 waves of data from a 12-year panel using latent class growth models and multinomial logistic regression. RESULTS We identified four groups of people experiencing different trajectories of depressive symptoms. The groups differed on baseline characteristics (gender, age, education, income, race), history of diagnosed depression, and initial level of depressive symptoms. The group with the highest levels of depressive symptoms reported greater levels of peri-traumatic stress exposure to Hurricane Sandy. DISCUSSION Depressive symptoms increased as a function of the Great Recession, but exposure to Hurricane Sandy was not associated with subsequent increases in depressive symptoms for any of the four groups. People who consistently experienced high levels of depressive symptoms over time reported the highest levels of peri-traumatic stress during Hurricane Sandy. Findings highlight the importance of accounting for historical trends when studying the effects of disaster, identify people likely to be at risk during a disaster, and provide novel information about the causal relationship between exposure to disaster and depressive symptoms.
Adaptive venom evolution and toxicity in octopods is driven by extensive novel gene formation, expansion, and loss

Abstract Background Cephalopods represent a rich system for investigating the genetic basis underlying organismal novelties. This diverse group of specialized predators has evolved many adaptations including proteinaceous venom. Of particular interest is the blue-ringed octopus genus (Hapalochlaena), which are the only octopods known to store large quantities of the potent neurotoxin, tetrodotoxin, within their tissues and venom gland. Findings To reveal genomic correlates of organismal novelties, we conducted a comparative study of 3 octopod genomes, including the Southern blue-ringed octopus (Hapalochlaena maculosa). We present the genome of this species and reveal highly dynamic evolutionary patterns at both non-coding and coding organizational levels. Gene family expansions previously reported in Octopus bimaculoides (e.g., zinc finger and cadherins, both associated with neural functions), as well as formation of novel gene families, dominate the genomic landscape in all octopods. Examination of tissue-specific genes in the posterior salivary gland revealed that expression was dominated by serine proteases in non–tetrodotoxin-bearing octopods, while this family was a minor component in H. maculosa. Moreover, voltage-gated sodium channels in H. maculosa contain a resistance mutation found in pufferfish and garter snakes, which is exclusive to the genus. Analysis of the posterior salivary gland microbiome revealed a diverse array of bacterial species, including genera that can produce tetrodotoxin, suggestive of a possible production source. Conclusions We present the first tetrodotoxin-bearing octopod genome H. maculosa, which displays lineage-specific adaptations to tetrodotoxin acquisition. This genome, along with other recently published cephalopod genomes, represents a valuable resource from which future work could advance our understanding of the evolution of genomic novelty in this family.
Closed Incision Negative Pressure Therapy: Indications and Adherence to Protocol

Background Complications associated with wound management not only increase the morbidity and mortality of surgical interventions but they also increase the cost and decrease the quality of care. Closed incision negative pressure therapy (CINPT) has been proposed as a superior method of wound care compared to the more traditional wound management methods. Since the Food and Drug Administration indications for using CINPT are broad and generally nonspecific, it is unclear whether patients are appropriately screened for and receive this treatment modality. Material and Methods To identify common clinical indications for CINPT, we conducted a literature review to define a consensus for CINPT candidates and used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to indicate if certain patient demographics impact decision-making. Results Based on the literature review, encompassing 57 articles, and the National Surgical Quality Improvement Program (NSQIP) database, over 11,000 patients received CINPT. Both the NSQIP data and the literature review commonly reported BMI >30 (47.1% and 39.6%), smoking (22.7% and 29.2%), and diabetes mellitus (22.7% and 47.9) as the most common clinical indications for using CINPT. Discussion The most common indications for using CINPT according to the literature review and the NSQIP database are BMI > 30, smoking status, and diabetes mellitus. Besides identifying patients who potentially benefit the most from CINPT, the results of this study suggest clinical adherence to the practice guidelines reported in the literature regarding wound management using this treatment modality.
Characteristics and Antioxidant Potential of Cold-Pressed Oils—Possible Strategies to Improve Oil Stability

The relations of the antiradical capacity to oxidative stability parameters and the contents of fatty acids, sterols, tocopherols, phenols, flavonoids, chlorophyll, Cu, and Fe were assessed in 33 cold-pressed seed oils: Walnut (7 brands of oils), rosehip (3), camelina (6), milk thistle (5), flax (6), and pumpkin (6). The antiradical capacity of oils depended strongly on tocopherol contents with a synergistic effect with polyphenols. The efficacy of tocopherols in cold-pressed oils was accompanied by a negative correlation of their antioxidant capacity with the peroxide value increase after 3 months of shelf life. This study also showed a positive correlation between the content of phytosterols and the antiradical capacity in the lipophilic fraction of cold-pressed oils rich in n-3 polyunsaturated fatty acids (PUFAs). Multiple regression analysis identified groups of antioxidants naturally occurring in cold-pressed oils in relation to their fatty acid composition, which added to the cold-pressed oils could provide possible strategies to improve their stability. Achieving high stability is primarily a result of high phytosterol content exceeding the molar ratio of 1:100 for total phytosterols to α-linolenic acid. However, the molar ratios of tocopherols to linoleic acid below 1:2000 and polyphenols to linoleic acid below 1:3000 does not prevent oxidation in oils with the predominance of linoleic acid.
Effects of consuming later evening meal v. earlier evening meal on weight loss during a weight loss diet: a randomised clinical trial

Abstract Previous evidence confirms a relationship between the timing of food intake and weight loss. We aimed to evaluate the effect of late v. early evening meal (EEM) consumption on weight loss and cardiometabolic risk factors in women during a weight loss programme. Eighty-two healthy women (BMI 27−35 kg/m2; age 18−45 years) were randomly assigned to two groups: EEM group (eating at 19.00−19.30 hours) or late evening meal (LEM) group (eating at 22.30−23.00 hours), for 12 weeks. Compared with the LEM group, the EEM group had a greater mean reduction in weight (EEM: −6·74 (sd 1·92) kg; LEM: −4·81 (sd 2·22) kg; P < 0·001), BMI (EEM: −2·60 (sd 0·71) kg/m2; LEM: −1·87 (sd 0·85) kg/m2; P < 0·001), waist circumference (EEM: −8 (sd 3·25) cm; LEM: −6 (sd 3·05) cm, P = 0·007), total cholesterol (EEM: −0·51 (sd 0·19) mmol/l, LEM: −0·43 (sd 0·19) mmol/l, P = 0·038), TAG (EEM: −0·28 (sd 0·10) mmol/l, LEM: −0·19 (sd 0·10) mmol/l, P < 0·001) and homoeostasis model assessment of insulin resistance (EEM: −0·83 (sd 0·37); LEM: −0·55 (sd 0·28), P < 0·001) after 12 weeks. In conclusion, eating an earlier evening meal resulted in favourable changes in weight loss and plasma cardiometabolic risk markers during a weight loss programme.
The Burden of Associated Comorbidities in Patients with Obstructive Sleep Apnea—Regional Differences in Two Central–Eastern European Sleep Centers

Background: Obstructive sleep apnea (OSA) is usually associated with cardiovascular and cerebrovascular disease, metabolic syndrome and depression. Data on relevant OSA-associated comorbidities in Central–European populations are scarce. The aim of this study was to compare the prevalence of comorbidities in two OSA cohorts from Hungary and Romania. Methods: Data from 588 (282 from Hungary, 306 from Romania) untreated patients with OSA were retrospectively analyzed. The prevalence rates of hypertension, diabetes, dyslipidemia, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), osteoporosis, cerebrovascular and cardiovascular disease, arrhythmia and depression were compared between the two populations following adjustment for demographics, body mass index, smoking history, comorbidities and sleep parameters. Results: The prevalence rates of hypertension, arrhythmia, cerebrovascular and cardiovascular disease, diabetes and COPD in the whole study population were directly related to the severity of OSA. We found an inverse correlation between the prevalence of osteoporosis and OSA severity (all p < 0.05). Following adjustment, the prevalence of dyslipidemia was higher in the Hungarian cohort, whilst the prevalence of asthma, cardiovascular and cerebrovascular diseases was higher in the Romanian cohort (all p < 0.05). Conclusions: There was no difference in the prevalence rate of most comorbidities in patients with OSA from the two cohorts, except for dyslipidemia, asthma, cardiovascular and cerebrovascular disease.
Investigating the Adoption of Telemedicine Services: An Empirical Study of Factors Influencing Physicians’ Perspective in Pakistan

Telemedicine services are increasingly becoming an integral part of health care system of many countries around the globe. However, despite its emergent proliferation its acceptance hasn’t been strikingly popular in clinical settings of developing countries, where shortage of practicing medical professionals is prevalent. The objective of this research study is to develop a theoretical model based on Technology Acceptance Model (TAM) and then empirically testing it for determining the key factors influencing doctors’ intention to adopt and use Telemedicine Services in clinical settings of a developing country. The partial least square model obtained from data of 220 doctors reflects that Perceived Usefulness (β = 0.30) and Perceived Ease of Use (β = 0.26), are the most significant drivers for doctors to use Telemedicine services in their practice, confirming the validity of original TAM constructs. In addition, new predictive constructs including Legal and Ethical Concerns ((β = -0.23) and Response Cost (β = -0.15) are found to have significant negative effects on usage intention of doctors. The survey findings reflect that telemedicine services are still in its infancy in Pakistan. Rigorous awareness and training programs are required to increase its acceptance among medical professionals. Effective financial and legal solutions also need to be devised leading physicians to uptake the adoption of telemedicine service.
The Influence of Ball Burnishing on Friction in Lubricated Sliding

Ball burnishing treatment, using the Ecoroll system, of steel samples was conducted. In the experiment, the burnishing pressure was changed. After the treatments, measurements of the surface topographies of disc samples were conducted using a white light interferometer Talysurf CCI Lite. Tribological tests were carried out in a ball-on-disc configuration. After these tests, measurements of surface topographies of disc samples were repeated. Worn surfaces were also analyzed with a scanning electron microscope. It was found that as the result of burnishing, surface topography height of tested samples decreased. Ball burnishing led to a reduction in the frictional resistance. The highest friction reduction of more than 40% was achieved with a burnishing pressure of 20 MPa.