Miracle-dz/UniFAR-FTUs huggingface dataset:
Aerosol Detection and Transmission of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): What Is the Evidence, and What Are the Knowledge Gaps?

In human and veterinary medicine, there have been multiple reports of pathogens being airborne under experimental and field conditions, highlighting the importance of this transmission route. These studies shed light on different aspects related to airborne transmission such as the capability of pathogens becoming airborne, the ability of pathogens to remain infectious while airborne, the role played by environmental conditions in pathogen dissemination, and pathogen strain as an interfering factor in airborne transmission. Data showing that airborne pathogens originating from an infectious individual or population can infect susceptible hosts are scarce, especially under field conditions. Furthermore, even though disease outbreak investigations have generated important information identifying potential ports of entry of pathogens into populations, these investigations do not necessarily yield clear answers on mechanisms by which pathogens have been introduced into populations. In swine, the aerosol transmission route gained popularity during the late 1990’s as suspicions of airborne transmission of porcine reproductive and respiratory syndrome virus (PRRSV) were growing. Several studies were conducted within the last 15 years contributing to the understanding of this transmission route; however, questions still remain. This paper reviews the current knowledge and identifies knowledge gaps related to PRRSV airborne transmission.
Respiratory syncytial virus (RSV): a scourge from infancy to old age

Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.
Pregnant Smokers’ Experiences and Opinions of Techniques Aimed to Address Barriers and Facilitators to Smoking Cessation: A Qualitative Study

Pregnant women experience certain barriers and facilitators (B&Fs) when trying to quit smoking. This study aimed to elicit women’s views on techniques that could help overcome or enhance these. Semi-structured interviews were conducted with 12 pregnant women who had experience of smoking during pregnancy. Participants were prompted to discuss experiences of B&Fs and give suggestions of techniques that could address these appropriately. A thematic analysis was conducted using the one sheet of paper method. Four themes relating to suggested techniques were identified: accessing professional help, nicotine replacement therapy (NRT), distraction, and social interactions. Experiences of accessing professional help were generally positive, especially if there was a good rapport with, and easy access to a practitioner. Most women were aware of NRT, those who had used it reported both negative and positive experiences. Praise and encouragement from others towards cessation attempts appeared motivating; peer support groups were deemed useful. Women reported experiencing B&Fs which fell under four themes: influence of others, internal motivation, cues to smoke, and health. Overall, accessing professional support generated positive changes in smoking habits. Establishing ways of how to encourage more women to seek help and raising awareness of different types of support available would seem beneficial.
Trends in aggressivity and driver risk for cars, SUVs, and pickups: Vehicle incompatibility from 1989 to 2016

Abstract Objective: When 2 vehicles of different sizes collide, the occupants of the smaller vehicle are more likely to be injured than the occupants of the larger vehicle. The larger vehicle is both more protective of its own occupants and more aggressive toward occupants of the other vehicle. However, larger, heavier vehicles tend to be designed in ways that amplify their incompatibility with smaller, lighter vehicles (by having a higher ride height, for example). A 2012 study by the Insurance Institute for Highway Safety (IIHS) concluded that fatalities caused by design incompatibility have decreased in recent years. The current study was conducted to update the 2012 IIHS analysis and to explore trends in vehicle incompatibility over time. Methods: Analyses examined deaths in crashes involving 1- to 4-year-old passenger vehicles from 1989 to 2016 collected from the Fatality Analysis Reporting System (FARS). Trends in driver risk were examined by comparing driver death rates per million registered vehicle years across vehicle type and size. Trends in aggressivity were examined by comparing partner driver death rates across vehicle type and size. Results: Cars and SUVs have continued their trend toward reduced incompatibility. In 1989–1992, SUVs were 132% more likely to kill the driver in a partner car compared with when a car crashed with another car. By 2013–2016, this value had dropped to 28%. Pickups and cars remain just as incompatible in 2013–2016 as they were in 1989–1992, however (159% vs. 158%). Remaining pickup incompatibility may be largely due to excess curb weight rather than to shape or design features, because light pickups were just 23% more likely to kill the driver in a partner car compared with when a car crashed with another car. Conclusions: The trend toward reduced fleet incompatibility has continued in the latest crash data, particularly for cars and SUVs. Although pickup–car incompatibility has also decreased over time, pickups remain disproportionately aggressive toward other vehicles, possibly due to their greater average curb weight. Reducing the weight of some of the heaviest vehicles and making crash avoidance technology fitment more widespread may be promising means to reduce remaining fleet incompatibility. Identifying the source of remaining incompatibility will be important for safety improvements going forward.
Molecular Energetics of Doxorubicin Pumping by Human P-Glycoprotein

The pumping of anti-tumor drugs by P-glycoprotein (P-gp) causes multidrug resistance (MDR) and consequent failure of chemotherapy. However, the understanding on the molecular mechanism of P-gp for transporting substrates is still far from adequate. Herein, the transport of a typical anti-tumor drug, doxorubicin, by P-gp is investigated using targeted molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The MM-PBSA analysis identifies the driving forces for the transport of doxorubicin towards the extracellular space as electrostatic repulsions in the initial stage, which are contributed by positively charged residues (R148, K181, K189, K285, K291, K734, R789, K826, K934 and K1000), and then hydrophobic interactions provided by hydrophobic residues (L65, M69, F336, I340, F343, Y953, V982, F983 and M986). The contributions of these residues are further validated by targeted MD simulations, which shows blocked pumping after the mutation of these important residues to glycine. The MM-PBSA and minimum distance analyses of each residue during the transport reveal that the positively charged residues promote the transport of doxorubicin through long range electrostatic repulsions and the hydrophobic residues provide a pathway through continuous hydrophobic interactions to maintain the transport. The results have thus provided molecular insights into the function of P-gp and would be beneficial in the design of potent P-gp inhibitors against MDR in the medication of cancers.
Flow Patterns of Viscoelastic Fracture Fluids in Porous Media: Influence of Pore-Throat Structures

Viscoelastic surfactant (VES) fluid and hydrolyzed polyacryamide (HPAM) solution are two of the most common fracturing fluids used in the hydraulic fracturing development of unconventional reservoirs. The filtration of fracturing fluids in porous media is mainly determined by the flow patterns in pore-throat structures. In this paper, three different microdevices analogue of porous media allow access to a large range of Deborah number (De) and concomitantly low Reynolds number (Re). Continuous pore-throat structures were applied to study the feedback effect of downstream structure on upstream flow of VES fluid and HPAM solution with Deborah (De) number from 1.11 to 146.4. In the infinite straight channel, flow patterns between VES fluids and HPAM solution were similar. However, as pore length shortened to 800 μm, flow field of VES fluid exhibited the triangle shape with double-peaks velocity patterns. The flow field of HPAM solution presented stable and centralized streamlines when Re was larger than 4.29 × 10−2. Additionally, when the pore length was further shortened to 400 μm, double-peaks velocity patterns were vanished for VES fluid and the stable convergent flow characteristic of HPAM solution was observed with all flow rates.
Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

Summary The use of antimicrobials in human and veterinary medicine has coincided with a rise in antimicrobial resistance (AMR) in the food‐borne pathogens Campylobacter jejuni and Campylobacter coli. Faecal contamination from the main reservoir hosts (livestock, especially poultry) is the principal route of human infection but little is known about the spread of AMR among source and sink populations. In particular, questions remain about how Campylobacter resistomes interact between species and hosts, and the potential role of sewage as a conduit for the spread of AMR. Here, we investigate the genomic variation associated with AMR in 168 C. jejuni and 92 C. coli strains isolated from humans, livestock and urban effluents in Spain. AMR was tested in vitro and isolate genomes were sequenced and screened for putative AMR genes and alleles. Genes associated with resistance to multiple drug classes were observed in both species and were commonly present in multidrug‐resistant genomic islands (GIs), often located on plasmids or mobile elements. In many cases, these loci had alleles that were shared among C. jejuni and C. coli consistent with horizontal transfer. Our results suggest that specific antibiotic resistance genes have spread among Campylobacter isolated from humans, animals and the environment.
Essential tremor: diagnosis and management

ABSTRACT Essential tremor is one of the most common movement disorders in adults and can affect both children and adults. An updated consensus statement in 2018 redefined essential tremor as an isolated action tremor present in bilateral upper extremities for at least three years. Tremor may also be present in other locations, commonly the neck or the vocal cords. Patients with additional neurologic symptoms are now categorized as “essential tremor plus. ” Additional clinical features associated with the condition include but are not limited to cognitive impairment, psychiatric disorders, and hearing loss. When treatment is needed, propranolol and primidone are considered first line treatments. Patients who are severely affected are often offered deep brain stimulation. Although the ventral intermediate nucleus of the thalamus is the traditional surgical target, the caudal zona incerta is also being studied as a possible superior alternative. Magnetic resonance imaging guided high intensity focused ultrasound is a newer surgical alternative that may be ideal for patients with substantial medical comorbidities. Current research explores novel oral treatments, chemodenervation, and noninvasive neuromodulation for treatment of essential tremor.
WQ-3810 exerts high inhibitory effect on quinolone-resistant DNA gyrase of Salmonella Typhimurium

ABSTRACT The inhibitory effect of WQ-3810 on DNA gyrase was assayed to evaluate the potential of WQ-3810 as a candidate drug for the treatment of quinolone resistant Salmonella Typhymurium infection. The inhibitory effect of WQ-3810, ciprofloxacin and nalidixic acid was compared by accessing the drug concentration that halves the enzyme activity (IC50) of purified S. Typhimurium wildtype and mutant DNA gyrase with amino acid substitution at position 83 or/and 87 in subunit A (GyrA) causing quinolone resistance. As a result, WQ-3810 reduced the enzyme activity of both wildtype and mutant DNA gyrase at a lower concentration than ciprofloxacin and nalidixic acid. Remarkably, WQ-3810 showed a higher inhibitory effect on DNA gyrase with amino acid substitutions at position 87 than with that at position 83 in GyrA. This study revealed that WQ-3810 could be an effective therapeutic agent, especially against quinolone resistant Salmonella enterica having amino acid substitution at position 87. Graphical abstract WQ-3810 shows high inhibitory activity against quinolone resistant DNA gyrase.
Are we doing enough to manage financial conflicts of interest?

An underappreciated provision of the 2010 Affordable Care Act requires that the Centers for Medicare and Medicaid Services collect and disclose payments made to physicians and institutions from medical manufacturers and related entities. This Open Payments (OP) database contains general payments (non-research-related), research payments, and physician ownership interests. Total value of payments from industry to all medical specialties during 2013–2016 was about $30 billion.
Assessing Major Bleeding Risk in Atrial Fibrillation Patients Concurrently Taking Non-Vitamin K Antagonist Oral Anticoagulants and Antiepileptic Drugs.

AIMS This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin-K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. METHODS AND RESULTS We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from June 1, 2012, to December 31, 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104319 patients (age 75.0±10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone (difference 98.43, 95% CI 82.37-114.49); 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14-102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47-95.30). CONCLUSIONS For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding.
Normal variations in brain oxygen extraction fraction are partly attributed to differences in end-tidal CO2

Cerebral oxygen extraction fraction is an important physiological index of the brain’s oxygen consumption and supply and has been suggested to be a potential biomarker for a number of diseases such as stroke, Alzheimer’s disease, multiple sclerosis, sickle cell disease, and metabolic disorders. However, in order for oxygen extraction fraction to be a sensitive biomarker for personalized disease diagnosis, inter-subject variations in normal subjects must be minimized or accounted for, which will otherwise obscure its interpretation. Therefore, it is essential to investigate the physiological underpinnings of normal differences in oxygen extraction fraction. This work used two studies, one discovery study and one verification study, to examine the extent to which an individual’s end-tidal CO2 can explain variations in oxygen extraction fraction. It was found that, across normal subjects, oxygen extraction fraction is inversely correlated with end-tidal CO2. Approximately 50% of the inter-subject variations in oxygen extraction fraction can be attributed to end-tidal CO2 differences. In addition, oxygen extraction fraction was found to be positively associated with age and systolic blood pressure. By accounting for end-tidal CO2, age, and systolic blood pressure of the subjects, normal variations in oxygen extraction fraction can be reduced by 73%, which is expected to substantially enhance the utility of oxygen extraction fraction as a disease biomarker.
Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

The intestinal microbiota has been reported to affect depression, a common mental condition with severe health‐related consequences. However, what mediates the effect of the intestinal microbiota on depression has not been well elucidated. We summarize the roles of the mitochondria in eliciting beneficial effects on the gut microbiota to ameliorate symptoms of depression. It is well known that mitochondria play a key role in depression. An important pathogenic factor, namely inflammatory response, may adversely impact mitochondrial functionality to maintain cellular homeostasis. Dysfunction of mitochondria not only affects neuronal function but also reduces neuron cell numbers. We posit that the intestinal microbiota could affect neuronal mitochondrial function through short‐chain fatty acids such as butyrate. Brain inflammatory processes could also be affected through the modulation of gut permeability and blood lipopolysaccharide levels. Aberrant mitochondria functionality coupled to adverse cellular homeostasis could be a key mediator for the effect of the intestinal microbiota on the progression of depression.
Late relapse in patients with diffuse large B‐cell lymphoma: impact of rituximab on their incidence and outcome

Diffuse large B‐cell lymphoma (DLBCL) constitutes 25–35% of all non‐Hodgkin lymphomas in Western countries. Approximately two thirds of the patients can be cured with standard immuno‐chemotherapy. Most relapses occur within 1–2 years from diagnosis, however, the occurrence of relapses after 5 years or more has been described. We aimed at defining the incidence and clinical features of late relapses. Data of 1113 DLBCL patients were analysed. Among the 196 patients relapsing after a first complete remission, 36 (18% of relapses and 3% of all DLBCLs) experienced a recurrence more than 5 years from diagnosis. Late relapsing patients, in comparison with those relapsing earlier, showed a more favourable risk profile at presentation: normal lactate dehydrogenase levels (P = 0·002), early Ann Arbor stage (P = 0·006) and low International Prognostic Index (P = 0·003). The risk of late relapse was lowered by the introduction of rituximab as part of the front‐line treatment (P < 0·001). Cause‐specific survival (CSS) from the time of relapse was significantly better for late relapsing patients compared to those relapsing early: 5‐year CSS rates were 53% and 31%, respectively (P = 0·033). A trend toward a better overall survival was also observed, with 5‐year rates after relapse of 47% and 25%, respectively (P = 0·054).
Role of Selenium and Selenoproteins in Male Reproductive Function: A Review of Past and Present Evidences

Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction. In this review, we highlight the implications of selenoproteins in male fertility and reproduction followed by the characteristic biological functions of Se and selenoproteins associated with overall male reproductive function. It is evident from observations of past studies (both animal and human) that Se is essentially required for spermatogenesis and male fertility, presumably because of its vital role in modulation of antioxidant defense mechanisms and other essential biological pathways and redox sensitive transcription factors. However, bearing in mind the evidences from mainstream literature, it is also advisable to perform more studies focusing on the elucidation of additional roles played by the peculiar and canonical selenoproteins i.e., glutathione peroxidase 4 (GPX4) and selenoprotein P (SELENOP) in the male reproductive functions. Nevertheless, search for the elucidation of additional putative mechanisms potentially modulated by other biologically relevant selenoproteins should also be included in the scope of future studies. However, as for the implication of Se in fertility and reproduction in men, though a few clinical trials explore the effects of Se supplementation on male fertility, due to inconsistencies in the recruitment of subjects and heterogeneity of designs, the comparison of such studies is still complicated and less clear. Therefore, further research focused on the roles of Se and selenoproteins is awaited for validating the evidences at hand and outlining any therapeutic schemes intended for improving male fertility. As such, new dimensions could be added to the subject of male fertility and Se supplementation.