Miracle-dz/UniFAR-FTUs huggingface dataset:
Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management

Nosocomial pneumonia (NP), including hospital-acquired pneumonia in non-intubated patients and ventilator-associated pneumonia, is one of the most frequent hospital-acquired infections, especially in the intensive care unit. NP has a significant impact on morbidity, mortality and health care costs, especially when the implicated pathogens are multidrug-resistant ones. This narrative review aims to critically review what is new in the field of NP, specifically, diagnosis and antibiotic treatment. Regarding novel imaging modalities, the current role of lung ultrasound and low radiation computed tomography are discussed, while regarding etiological diagnosis, recent developments in rapid microbiological confirmation, such as syndromic rapid multiplex Polymerase Chain Reaction panels are presented and compared with conventional cultures. Additionally, the volatile compounds/electronic nose, a promising diagnostic tool for the future is briefly presented. With respect to NP management, antibiotics approved for the indication of NP during the last decade are discussed, namely, ceftobiprole medocaril, telavancin, ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam.
Changes in Rumen Microbiota Affect Metabolites, Immune Responses and Antioxidant Enzyme Activities of Sheep under Cold Stimulation

Simple Summary Under a cold environment, the animal’s weight is reduced and even health is affected. As we all know, microbiota is beneficial to animal health. It can produce metabolites to improve animal immunity and avoid damage. Therefore, we aimed to understand the self-protection mechanisms of sheep under cold stress. To investigate this mechanism, we designed two experiments to explore the effects of low temperature and wind speed on sheep phenotypes, rumen microbes, immune cytokines and oxidative stress. Our results identified that the sheep remained healthy in a cold environment. This may be due to the enrichment of Lachnospiraceae in the rumen. A large amount of propionate may enter into the gluconeogenesis reaction, resulting in a decrease in the content of propionate in the rumen, thereby reducing animal’s immunity. In summary, the increase of Lachnospiraceae and propionate in the rumen may help sheep live in a cold environment. Our experiments provide some direction for the healthy feeding of animals in cold environments. Abstract Low-temperature environments can strongly affect the normal growth and health of livestock. In winter, cold weather can be accompanied by strong winds that aggravate the effects of cold on livestock. In this study, two experiments were conducted to investigate the effect of low temperature and/or wind speed on physiological indices, rumen microbiota, immune responses and oxidative stress in sheep. When sheep were exposed to cold temperature and/or stronger wind speeds, the average daily gain (ADG) decreased (p < 0.05), and the abundance of Lachnospiraceae was significantly higher (p < 0.05). The acetate and propionate contents and the proportion of propionate in the rumen also significantly reduced (p < 0.05). The immunoglobulin G (IgG) and TH1-related cytokines in the blood were significantly lower (p < 0.05). However, antioxidant enzyme contents were significantly increased and the concentration of malondialdehyde (MDA) was reduced (p < 0.05). In a cold environment, the abundance of Lachnospiraceae in the rumen of sheep was highly enriched, and the decreasing of propionate might be one of the factors affecting the immunity of the animals, the sheep did not suffer from oxidative damage during the experiment.
Effects on Synchronization and Reproductive Efficiency of Delaying the Removal of the Intravaginal Progesterone Device by 24 h in the 5d Co-Synch Protocol in Heifers

Simple Summary Reproductive biotechnologies in beef farms are key issues, such as artificial insemination, fixed-time artificial insemination (FTAI), embryo transfer, and ovum pick up, among others. Artificial insemination takes the first place with these available tools. Thus, science keeps improving hormonal treatments and procedures to optimize pregnancies after insemination. A synchronization protocol commonly used in beef heifers is the 5d Co-synch protocol, which fits better in terms of ovarian synchronization and resulting conception rate. We propose a modification of this protocol, which consists of delaying by 24 h the removal of the intravaginal progesterone device, to decrease the percentage of heifers showing estrus before the date of FTAI. Moreover, this modification will make easier the workload when inseminating herds with heifers and cows at the same time. Based on our results, the protocol 5d Co-synch with the delayed removal of the intravaginal progesterone device fits as well as the original protocol in terms of synchronization and conception rate. Therefore, it can be implemented in the heifers of beef cattle commercial farms. Abstract In beef herds, increasing animal welfare, improving reproductive performance and easing animal management are key goals in farm economics. We explored whether delaying the removal of the intravaginal progesterone device by 24 h in heifers synchronized with a 5d Co-synch 72-h protocol could improve reproductive efficiency of fixed-time artificial insemination (FTAI). In experiment 1, we examined the total synchronization rate (TSR) in cycling Holstein heifers. Heifers (13.4 ± 0.69 mo.) were randomly assigned to the standard 5d Co-synch 56-h protocol (5dCo56; n = 10), 5d Co-synch 72-h (5dCo72; n = 17), or the modified 5d Co-synch 72-h protocol, in which removal of the progesterone device was delayed by 24 h (6dCo48; n = 19). In experiment 2, 309 cycling beef heifers on 18 commercial farms were subjected to the 5d Co-synch 72-h or 6-d Co-synch 48-h protocol and conception rate (CR) studied. In experiment 1, the three protocols led no differences on TSRs of 80.0% (5dCo56), 88.2% (5dCo72), and 89.5% (6dCo48). In experiment 2, the CR from the beef heifers, observed during two consecutive reproductive seasons did not differ: 59.7% for 5dCo72 and 62.0% for 6dCo48 (p = 0.907). Therefore, delaying removal by 24 h provides satisfactory results without reducing reproductive efficiency of heifers.
An Integrated Approach for the Valorization of Sea Bass (Dicentrarchus labrax) Side Streams: Evaluation of Contaminants and Development of Antioxidant Protein Extracts by Pressurized Liquid Extraction

In this study, the presence of As, Hg, Cd, Pb, and mycotoxins in sea bass side streams (muscle, head, viscera, skin, and tailfin) was evaluated as a preliminary step to assess the effect of an innovative extraction technique (Pressurized Liquid Extraction; PLE) to obtain antioxidant protein extracts. Then, a response surface methodology-central composite design was used to evaluate and optimize the PLE extraction factors (pH, temperature, and extraction time) in terms of total protein content and total antioxidant capacity (TEAC and ORAC). Heavy metals were found in all samples while DON mycotoxin only in viscera, both far below the safe limits established by authorities for fish muscle tissue and fish feed, respectively. The selected optimal PLE extraction conditions were pH 7, 20 °C, 5 min for muscle, pH 4, 60 °C, 15 min for heads, pH 7, 50 °C, 15 min for viscera, pH 7, 55 °C, 5 min for skin, and pH 7, 60 °C, 15 min for tailfins. Optimal PLE conditions allowed increasing protein content (1.2–4.5 fold) and antioxidant capacity (1–5 fold) of sea bass side stream extracts compared to controls (conventional extraction). The highest amount of protein was extracted from muscle while the highest protein recovery percentage was found in viscera. Muscle, head, and viscera extracts showed higher antioxidant capacity than skin and tailfin extracts. Moreover, different SDS-PAGE patterns were observed among samples and a greater quantity of protein fragments of lower molecular weight were found in optimal than control extracts.
Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.
Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.
Community Health Workers as a Strategy to Tackle Psychosocial Suffering Due to Physical Distancing: A Randomized Controlled Trial

Background: During the COVID-19 pandemic, many primary care professionals were overburdened and experienced difficulties reaching vulnerable patients and meeting the increased need for psychosocial support. This randomized controlled trial (RCT) tested whether a primary healthcare (PHC) based community health worker (CHW) intervention could tackle psychosocial suffering due to physical distancing measures in patients with limited social networks. Methods: CHWs provided 8 weeks of tailored psychosocial support to the intervention group. Control group patients received ‘care as usual’. The impact on feelings of emotional support, social isolation, social participation, anxiety and fear of COVID-19 were measured longitudinally using a face-to-face survey to determine their mean change from baseline. Self-rated change in psychosocial health at 8 weeks was determined. Results: We failed to find a significant effect of the intervention on the prespecified psychosocial health measures. However, the intervention did lead to significant improvement in self-rated change in psychosocial health. Conclusions: This study confirms partially the existing evidence on the effectiveness of CHW interventions as a strategy to address mental health in PHC in a COVID context. Further research is needed to elaborate the implementation of CHWs in PHC to reach vulnerable populations during and after health crises.
Hunger for Home Delivery: Cross-Sectional Analysis of the Nutritional Quality of Complete Menus on an Online Food Delivery Platform in Australia

Online food delivery (OFD) platforms have changed how consumers purchase food prepared outside of home by capitalising on convenience and smartphone technology. Independent food outlets encompass a substantial proportion of partnering outlets, but their offerings’ nutritional quality is understudied. Little is also known as to how OFD platforms influence consumer choice. This study evaluated the nutritional quality and marketing attributes of offerings from independent takeaway outlets available on Sydney’s market-leading OFD platform (UberEats®). Complete menus and marketing attributes from 202 popular outlets were collected using web scraping. All 13841 menu items were classified into 38 food and beverage categories based on the Australian Dietary Guidelines. Of complete menus, 80.5% (11,139/13,841) were discretionary and 42.3% (5849/13,841) were discretionary cereal-based mixed meals, the largest of the 38 categories. Discretionary menu items were more likely to be categorised as most popular (OR: 2.5, 95% CI 1.9–3.2), accompanied by an image (OR: 1.3, 95% CI 1.2–1.5) and offered as a value bundle (OR: 6.5, 95% CI 4.8–8.9). Two of the three discretionary food categories were more expensive than their healthier Five Food Group counterparts (p < 0.02). The ubiquity of discretionary choices offered by independent takeaways and the marketing attributes employed by OFD platforms has implications for public health policy. Further research on the contribution of discretionary choices and marketing attributes to nutritional intakes is warranted.
Integration of Data from Liquid–Liquid Phase Separation Databases Highlights Concentration and Dosage Sensitivity of LLPS Drivers

Liquid–liquid phase separation (LLPS) is a molecular process that leads to the formation of membraneless organelles, representing functionally specialized liquid-like cellular condensates formed by proteins and nucleic acids. Integrating the data on LLPS-associated proteins from dedicated databases revealed only modest agreement between them and yielded a high-confidence dataset of 89 human LLPS drivers. Analysis of the supporting evidence for our dataset uncovered a systematic and potentially concerning difference between protein concentrations used in a good fraction of the in vitro LLPS experiments, a key parameter that governs the phase behavior, and the proteomics-derived cellular abundance levels of the corresponding proteins. Closer scrutiny of the underlying experimental data enabled us to offer a sound rationale for this systematic difference, which draws on our current understanding of the cellular organization of the proteome and the LLPS process. In support of this rationale, we find that genes coding for our human LLPS drivers tend to be dosage-sensitive, suggesting that their cellular availability is tightly regulated to preserve their functional role in direct or indirect relation to condensate formation. Our analysis offers guideposts for increasing agreement between in vitro and in vivo studies, probing the roles of proteins in LLPS.
Drying Shrinkage and Rapid Chloride Penetration Resistance of Recycled Aggregate Concretes Using Cement Paste Dissociation Agent

In the present study, a recycled concrete aggregate (RCA) coating treatment using a cement paste dissociation agent (CPDA) with different mixing methods was newly incorporated in RCA concrete mixtures. First, a preliminary test program was conducted to determine the proper dosage of the CPDA solution throughout its RCA concrete test results from compressive strength, flexural strength, and elastic modulus. Then, a series of experimental tests were carried out to investigate the effect of RCA coating treatment, different mixing method such as the equivalent mortar volume (EMV) method and conventional method, and different RCA replacement ratios on durability test results of RCA concrete such as drying shrinkage values and rapid chloride penetration test (RCPT) values. The test results showed that all RCA concretes mixed with the coated RCAs were found to be workable regardless of different mix methods, with the slump and air contents of all the mixes being almost identical. All the concrete specimens, which were mixed with the coated RCAs with CPDA solution, represented lower drying shrinkage and RCPT values than those mixed without RCA coating treatment, regardless of different mix proportioning methods or RCA replacement ratios. This holds for the concrete specimens proportioned with the EMV method, regardless of different RCA replacement ratios.
Modulation of Tubular pH by Acetazolamide in a Ca2+ Transport Deficient Mice Facilitates Calcium Nephrolithiasis

Proximal tubular (PT) acidosis, which alkalinizes the urinary filtrate, together with Ca2+ supersaturation in PT can induce luminal calcium phosphate (CaP) crystal formation. While such CaP crystals are known to act as a nidus for CaP/calcium oxalate (CaOx) mixed stone formation, the regulation of PT luminal Ca2+ concentration ([Ca2+]) under elevated pH and/or high [Ca2+] conditions are unknown. Since we found that transient receptor potential canonical 3 (TRPC3) knockout (KO; -/-) mice could produce mild hypercalciuria with CaP urine crystals, we alkalinized the tubular pH in TRPC3-/- mice by oral acetazolamide (0.08%) to develop mixed urinary crystals akin to clinical signs of calcium nephrolithiasis (CaNL). Our ratiometric (λ340/380) intracellular [Ca2+] measurements reveal that such alkalization not only upsurges Ca2+ influx into PT cells, but the mode of Ca2+ entry switches from receptor-operated to store-operated pathway. Electrophysiological experiments show enhanced bicarbonate related current activity in treated PT cells which may determine the stone-forming phenotypes (CaP or CaP/CaOx). Moreover, such alkalization promotes reactive oxygen species generation, and upregulation of calcification, inflammation, fibrosis, and apoptosis in PT cells, which were exacerbated in absence of TRPC3. Altogether, the pH-induced alteration of the Ca2+ signaling signature in PT cells from TRPC3 ablated mice exacerbated the pathophysiology of mixed urinary stone formation, which may aid in uncovering the downstream mechanism of CaNL.
Foamy Viruses, Bet, and APOBEC3 Restriction

Non-human primates (NHP) are an important source of viruses that can spillover to humans and, after adaptation, spread through the host population. Whereas HIV-1 and HTLV-1 emerged as retroviral pathogens in humans, a unique class of retroviruses called foamy viruses (FV) with zoonotic potential are occasionally detected in bushmeat hunters or zookeepers. Various FVs are endemic in numerous mammalian natural hosts, such as primates, felines, bovines, and equines, and other animals, but not in humans. They are apathogenic, and significant differences exist between the viral life cycles of FV and other retroviruses. Importantly, FVs replicate in the presence of many well-defined retroviral restriction factors such as TRIM5α, BST2 (Tetherin), MX2, and APOBEC3 (A3). While the interaction of A3s with HIV-1 is well studied, the escape mechanisms of FVs from restriction by A3 is much less explored. Here we review the current knowledge of FV biology, host restriction factors, and FV–host interactions with an emphasis on the consequences of FV regulatory protein Bet binding to A3s and outline crucial open questions for future studies.
The Therapeutic Potential of Carnosine/Anserine Supplementation against Cognitive Decline: A Systematic Review with Meta-Analysis

Carnosine is a natural occurring endogenous dipeptide that was proposed as an anti-aging agent more than 20 years ago. Carnosine can be found at low millimolar concentrations at brain level and different preclinical studies have demonstrated its antioxidant, anti-inflammatory, and anti-aggregation activity with neuroprotective effects in animal models of Alzheimer’s disease (AD). A selective deficit of carnosine has also been linked to cognitive decline in AD. Different clinical studies have been conducted to evaluate the impact of carnosine supplementation against cognitive decline in elderly and AD subjects. We conducted a systematic review with meta-analysis, in accordance with the PRISMA guidelines coupled to the PICOS approach, to investigate the therapeutic potential of carnosine against cognitive decline and depressive symptoms in elderly subjects. We found five studies matching the selection criteria. Carnosine/anserine was administered for 12 weeks at a dose of 1 g/day and improved global cognitive function, whereas no effects were detected on depressive symptoms. These data suggest a preliminary evidence of clinical efficacy of carnosine against cognitive decline both in elderly subjects and mild cognitive impairment (MCI) patients, although larger and long-term clinical studies are needed in MCI patients (with or without depression) to confirm the therapeutic potential of carnosine.
Considerations for and Mechanisms of Adjunct Therapy in COPD

Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to COPD. While these therapies have shown to be beneficial when used in the appropriate instances, there are particular considerations that need to be minded when using these therapies. This review article discussed the mechanism of roflumilast, macrolide antibiotics, other chronic antibiotic regimens, vitamin D supplementation, oral corticosteroids, n-acetylcysteine, and nebulized hypertonic saline, the clinical data behind each of these therapies, adverse events associated with therapy, and the expert recommendations for their utilization. Our goal is to provide a brief but informative and clinically useful review of commonly encountered therapies used in advanced COPD.