Miracle-dz/UniFAR-FTUs huggingface dataset:
A systematic review of the efficacy of antibiotics for the prevention of swine respiratory disease

Abstract Prevention and control of respiratory disease is a major contributor to antibiotic use in swine. A systematic review was conducted to address the question, ‘What is the comparative efficacy of antimicrobials for the prevention of swine respiratory disease? ’ Eligible studies were controlled trials published in English evaluating prophylactic antibiotics in swine, where clinical morbidity, mortality, or total antibiotic use was assessed. Four databases and the gray literature were searched for relevant articles. Two reviewers working independently screened titles and abstracts for eligibility followed by full-text articles, and then extracted data and evaluated risk of bias for eligible trials. There were 44 eligible trials from 36 publications. Clinical morbidity was evaluated in eight trials where antibiotics were used in nursery pigs and 10 trials where antibiotics were used in grower pigs. Mortality was measured in 22 trials in nursery pigs and 12 trials in grower pigs. There was heterogeneity in the antibiotic interventions and comparisons published in the literature; thus, there was insufficient evidence to allow quantification of the efficacy, or relative efficacy, of antibiotic interventions. Concerns related to statistical non-independence and quality of reporting were noted in the included trials.
Hepatic Carbohydrate Response Element Binding Protein Activation Limits Nonalcoholic Fatty Liver Disease Development in a Mouse Model for Glycogen Storage Disease Type 1a

Glycogen storage disease (GSD) type 1a is an inborn error of metabolism caused by defective glucose‐6‐phosphatase catalytic subunit (G6PC) activity. Patients with GSD 1a exhibit severe hepatomegaly due to glycogen and triglyceride (TG) accumulation in the liver. We have shown that the activity of carbohydrate response element binding protein (ChREBP), a key regulator of glycolysis and de novo lipogenesis, is increased in GSD 1a. In the current study, we assessed the contribution of ChREBP to nonalcoholic fatty liver disease (NAFLD) development in a mouse model for hepatic GSD 1a.
Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: A retrospective cohort study

Background There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong between 2002 and 2015. Methods and findings The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes [n = 2,426]: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes [n = 559,596]: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged <20 years, incidence of both type 1 and type 2 diabetes increased. For type 1 diabetes, the incidence increased from 3.5 (95% CI 2.2–4.9) to 5.3 (95% CI 3.4–7.1) per 100,000 person-years (average annual percentage change [AAPC] 3.6% [95% CI 0.2–7.1], p < 0.05) in boys and from 4.3 (95% CI 2.7–5.8) to 6.4 (95% CI 4.3–8.4) per 100,000 person-years (AAPC 4.7% [95% CI 1.7–7.7], p < 0.05] in girls; for type 2 diabetes, the incidence increased from 4.6 (95% CI 3.2–6.0) to 7.5 (95% CI 5.5–9.6) per 100,000 person-years (AAPC 5.9% [95% CI 3.4–8.5], p < 0.05) in boys and from 5.9 (95% CI 4.3–7.6) to 8.5 (95% CI 6.2–10.8) per 100,000 person-years (AAPC 4.8% [95% CI 2.7–7.0], p < 0.05) in girls. In people aged 20 to <40 years, incidence of type 1 diabetes remained stable, but incidence of type 2 diabetes increased over time from 75.4 (95% CI 70.1–80.7) to 110.8 (95% CI 104.1–117.5) per 100,000 person-years (AAPC 4.2% [95% CI 3.1–5.3], p < 0.05) in men and from 45.0 (95% CI 41.4–48.6) to 62.1 (95% CI 57.8–66.3) per 100,000 person-years (AAPC 3.3% [95% CI 2.3–4.2], p < 0.05) in women. In people aged 40 to <60 years, incidence of type 2 diabetes increased until 2011/2012 and then flattened. In people aged ≥60 years, incidence was stable in men and declined in women after 2011. No trend was identified in the incidence of type 1 diabetes in people aged ≥20 years. The present study is limited by its reliance on electronic medical records for identification of people with diabetes, which may result in incomplete capture of diabetes cases. The differentiation of type 1 and type 2 diabetes was based on an algorithm subject to potential misclassification. Conclusions There was an increase in incidence of type 2 diabetes in people aged <40 years and stabilisation in people aged ≥40 years. Incidence of type 1 diabetes continued to climb in people aged <20 years but remained constant in other age groups.
β2-microglobulin is an independent indicator of acute kidney injury and outcomes in patients with intracerebral hemorrhage

Abstract Acute kidney injury (AKI), a serious complication in critically ill patients, is associated with poor clinical outcomes. We explored the hypothesis that β2-microglobulin (β2-MG) is an independent indicator of AKI development and outcomes in patients with intracerebral hemorrhage (ICH) in the neurosurgical intensive care unit (NICU). Patients with ICH (n = 403) admitted to the NICU of Zhongnan Hospital, Wuhan University, between January 1, 2015 and December 31, 2016 were prospectively enrolled in this single-center, observational study. The primary outcome was the incidence of AKI, secondary outcomes were in-hospital mortality and 1-year mortality (from time of admission). The overall AKI incidence, in hospital, was 35.2%; patients were diagnosed with stage 1 (22.1%), 2 (5.7%), and 3 (7.4%) AKI. β2-MG levels predicted AKI with an area under the curve of 0.712 (95% confidence interval [CI], 0.652–0.772) and a cut-off of 2026.85 μg/L (sensitivity, 57.5%; specificity, 79.4%). Compared with the group having lower β2-MG values, the group with higher values (β2-MG >2123.50 μg/L) had significantly higher risks of AKI (odds ratio, 2.606; 95% CI, 1.315–5.166), in-hospital mortality (hazard ratio [HR], 2.548; 95% CI, 1.318–4.924), and 1-year mortality (HR, 3.161; 95% CI, 1.781–5.611) in adjusted analyses. β2-MG levels predict AKI development and outcomes in patients with ICH in the NICU.
Vasomotor symptoms and accelerated epigenetic aging in the Women's Health Initiative (WHI).

PURPOSE The hallmark menopausal symptom, vasomotor symptoms (VMS), has been linked to adverse health indicators. However, the relationship between VMS and biological aging has not been tested. We examined associations between menopausal VMS and biological aging as assessed by two DNA methylation-based epigenetic aging indicators previously linked to poor health outcomes. METHODS Participants were members of the Women's Health Initiative Observational Study (WHI-OS) integrative genomics sub-study (N = 1,206) who had both ovaries and were not taking hormone therapy. Relationships between VMS at enrollment (presence, severity) or VMS timing groups (no VMS: not at menopause onset nor at study enrollment; early VMS: at menopause onset but not at enrollment; persistent VMS: at menopause onset and study enrollment; and late VMS: at enrollment but not at menopause onset) and epigenetic clock indicators predictive of physical aging and early death (DNAm PhenoAge, DNAm GrimAge) were tested in linear regression models adjusting for age, race/ethnicity, hysterectomy, education, body mass index, smoking, and in additional models, sleep disturbance. RESULTS Women were on average 65 years of age at enrollment. Severe hot flashes at enrollment were associated with higher DNAm PhenoAge [relative to no hot flashes: B(SE)=2.79(1.27), p=. 028, multivariable]. Further, late-occurring VMS were associated with both higher DNAm PhenoAge [B(SE)=2.15 (.84), p=. 011] and DNAm GrimAge [B(SE)=1.09 (.42), p=. 010, multivariable] relative to no VMS. MAIN CONCLUSIONS Among postmenopausal women, severe or late-occurring VMS was associated with accelerated epigenetic age, controlling for chronological age. Postmenopausal women with severe or late-occurring VMS may have greater underlying epigenetic aging.
Intracytoplasmic sperm injection and fetal origins of autism spectrum disorder: an intriguing, though controversial association

Abstract Latest knowledge assigns the origins of autism spectrum disorder (ASD)-currently affecting 1% of children- to intrauterine life, when fetal brain develops. Besides genetics, environmental factors, responsible for epigenetic changes contributed to its rising incidence. In vitro fertilization (IVF) and the most widely used intracytoplasmic sperm injection (ICSI) are implicated in epigenetic changes. A series of studies examined the impact of ICSI on ASD in the offspring. Results are usually conflicting, due to inherent problems of study design and power, mixed IVF/ICSI cases and not exclusively ASD diagnoses included. Furthermore, preterm birth, low birthweight infants, advanced parental age, hormonal disturbances, all associated with ICSI, are known factors affecting ASD. While solid data supporting ICSI contribution to currently alarming ASD increase are lacking, exploration of underlying molecular mechanisms would strengthen possible associations. In the meanwhile, ICSI use should be restricted to male-factor infertility cases.
Viral Load Kinetics of SARS-CoV-2 Infection in First Two Patients in Korea

As of February 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak started in China in December 2019 has been spreading in many countries in the world. With the numbers of confirmed cases are increasing, information on the epidemiologic investigation and clinical manifestation have been accumulated. However, data on viral load kinetics in confirmed cases are lacking. Here, we present the viral load kinetics of the first two confirmed patients with mild to moderate illnesses in Korea in whom distinct viral load kinetics are shown. This report suggests that viral load kinetics of SARS-CoV-2 may be different from that of previously reported other coronavirus infections such as SARS-CoV.
Effect of acetazolamide on susceptibility to central sleep apnea in chronic spinal cord injury.

Spinal cord injury (SCI) is an established risk factor for central sleep apnea (CSA). Acetazolamide (ACZ), a carbonic anhydrase inhibitor, has been shown to decrease the frequency of CSA by inducing mild metabolic acidosis. We hypothesized that ACZ would decrease the propensity to develop hypocapnic CSA. We randomized 16 participants with sleep-disordered breathing (8 SCI, 8 able-bodied controls) to receive ACZ (500 mg bid x 3 days) or placebo with a one-week washout before crossing over to the other drug arm. Study nights included polysomnography and determination of the hypocapnic apneic threshold and CO2 reserve using noninvasive ventilation. For participants with spontaneous CSA, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal PCO2 (PETCO2) before and after. Steady-state plant gain (PG) was calculated from PETCO2 and VE ratio during stable sleep. Treatment with ACZ for three days resulted in increased CO2 reserve (-4.0±1.2 vs -3.0±0.7 mmHg for able-bodied, -3.4±1.9 vs -2.2±2.2 mmHg for SCI, p<0.0001 ). ACZ significantly reduced PG when compared to placebo (4.1±1.7 vs 5.4±1.8 mmHg L-1 min for able-bodied, 4.1±2.0 vs 5.1±1.7 mmHg L-1 min for SCI, p<0.01). ACZ decreased apnea-hypopnea index (28.8±22.9 vs 39.3±24.1 events/h, p=0.05), central apnea index (0.6±1.5 vs 6.3±13.1 events/h, p=0.05) and oxyhemoglobin desaturation index (7.5±8.3 vs 19.2±15.2 events/h, p=0.01) compared to placebo. Our results suggest that treatment with ACZ decreases susceptibility to hypocapnic CSA due to decreased PG. Acetazolamide may attenuate CSA but its clinical utility requires further investigation.
Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats

Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.
A Novel Neorickettsial Infection in 3 Dogs in the Pacific Northwest

The genus Neorickettsia includes obligate, intracellular bacteria responsible for diseases including Potomac horse fever caused by Neorickettsia risticii and salmon poisoning disease (SPD) caused by Neorickettsia helminthoeca. The Stellanchasmus falcatus (SF) agent is a member of this genus previously associated only with mild clinical signs in dogs. Between 2013 and 2016, 3 dogs in Washington State (USA) presented with disease suggestive of SPD, but N. helminthoeca was not detected by molecular techniques. Clinical signs included depression, anorexia, and diarrhea. Cytologic examination of aspirates supported a diagnosis of granulomatous lymphadenitis with organisms suggestive of Neorickettsia. Dogs either died or were humanely euthanized due to poor response to therapy. Necropsy findings included lymphadenomegaly and hepatomegaly. Histopathology identified granulomatous and lymphoplasmacytic splenitis, lymphadenitis, enteritis, and hepatitis with extensive necrosis. Neorickettsia DNA was detected using genus-specific primers and direct sequencing showed 100% sequence identity to the SF agent in all 3 dogs. This is the first clinicopathologic description of severe disease in dogs attributed to the SF agent. These findings may suggest the emergence of a novel neorickettsial disease in the Pacific Northwest.
Arp2/3 nucleates F-actin coating of fusing insulin granules in pancreatic β cells to control insulin secretion

ABSTRACT F-actin dynamics are known to control insulin secretion, but the point of intersection with the stimulus-secretion cascade is unknown. Here, using multiphoton imaging of β cells isolated from Lifeact-GFP transgenic mice, we show that glucose stimulation does not cause global changes in subcortical F-actin. Instead, we observe spatially discrete and transient F-actin changes around each fusing granule. This F-actin remodelling is dependent on actin nucleation and is observed for granule fusion induced by either glucose or high potassium stimulation. Using GFP-labelled proteins, we identify local enrichment of Arp3, dynamin 2 and clathrin, all occurring after granule fusion, suggesting early recruitment of an endocytic complex to the fusing granules. Block of Arp2/3 activity with drugs or shRNA inhibits F-actin coating, traps granules at the cell membrane and reduces insulin secretion. Block of formin-mediated actin nucleation also blocks F-actin coating, but has no effect on insulin secretion. We conclude that local Arp2/3-dependent actin nucleation at the sites of granule fusion plays an important role in post-fusion granule dynamics and in the regulation of insulin secretion. Highlighted Article: F-actin nucleation with Arp2/3 is triggered locally at each fusing insulin granule and controls granule dynamics and insulin secretion.
Chrysin Reduces Oxidative Stress but Does Not Affect Polyol Pathway in the Lenses of Type 1 Diabetic Rats

Prolonged hyperglycemia is one of the main causes of reactive oxygen species and free radicals generation in diabetes which may affect various organs, including the eye. Oxidative damage to proteins and lipids in the eye lens could lead to cataract formation. To cope with oxidative stress, the endogenous antioxidative system may be supported by the supplementation of exogenous antioxidants. The aim of this study was to evaluate the effect of chrysin, a natural flavonoid, on oxidative stress and polyol pathway-related markers in the lenses of streptozotocin-induced type 1 male diabetic rats. Chrysin at doses of 50 and 100 mg/kg was administered by gavage for 28 days. This treatment resulted in a decrease in antioxidative enzymes activity and oxidative stress index. Moreover, chrysin administration elevated the reduced glutathione level in the lenses. A decrease in the markers linked to oxidative damage to proteins and lipids in the lenses was noted, especially after treatment with 50 mg/kg of chrysin. Neither of the chrysin doses affected glycemia-related markers in the serum or altered parameters related to the polyol pathway and advanced glycation end-products level in the lenses of diabetic rats. Upon obtaining results, it can be concluded that chrysin reveals antioxidative activity in the lenses but shows no antihyperglycemic or antiglycation properties.
YEARS Algorithm Versus Wells’ Score: Predictive Accuracies in Pulmonary Embolism Based on the Gold Standard CT Pulmonary Angiography*

Supplemental Digital Content is available in the text. Objectives: This study retrospectively applied Wells’ score and YEARS algorithm to the same sample of patients to evaluate the predictive performance of each when compared with the gold standard CT pulmonary angiography. Design: Retrospective analytical study. Setting: A tertiary University Hospital in Ireland. Patients: Data from 794 patients who underwent CT pulmonary angiography to rule out pulmonary embolism. Interventions: Patients were analyzed using retrospective application of both Wells’ score and YEARS algorithm. Sensitivity, specificity, and diagnostic odds ratio were calculated and compared. Measurements and Main Results: Of 794 scans, 78 (9.8%) were positive for pulmonary embolism. The YEARS algorithm was more sensitive than the Wells’ score (97.44% vs 74.36%) but was less specific (13.97% vs 33.94%). Furthermore, the diagnostic odds ratio of YEARS was higher than Wells’ score (6.27 vs 1.48). YEARS provides better negative predictive value (98% vs 92.4%), and both scores have poor positive predictive value (10.9%). Conclusions: Both scores successfully exclude pulmonary embolism, although YEARS has a better negative predictive value. Both exhibit poor positive predictive value.
Atlas‐based GABA mapping with 3D MEGA‐MRSI: Cross‐correlation to single‐voxel MRS

The purpose of this work is to develop and validate a new atlas‐based metabolite quantification pipeline for edited magnetic resonance spectroscopic imaging (MEGA‐MRSI) that enables group comparisons of brain structure‐specific GABA levels. By using brain structure masks segmented from high‐resolution MPRAGE images and coregistering these to MEGA‐LASER 3D MRSI data, an automated regional quantification of neurochemical levels is demonstrated for the example of the thalamus. Thalamic gamma‐aminobutyric acid + coedited macromolecules (GABA+) levels from 21 healthy subjects scanned at 3 T were cross‐validated both against a single‐voxel MEGA‐PRESS acquisition in the same subjects and same scan sessions, as well as alternative MRSI processing techniques (ROI approach, four‐voxel approach) using Pearson correlation analysis. In addition, reproducibility was compared across the MRSI processing techniques in test–retest data from 14 subjects. The atlas‐based approach showed a significant correlation with SV MEGA‐PRESS (correlation coefficient r [GABA+] = 0.63, P < 0.0001). However, the actual values for GABA+, NAA, tCr, GABA+/tCr and tNAA/tCr obtained from the atlas‐based approach showed an offset to SV MEGA‐PRESS levels, likely due to the fact that on average the thalamus mask used for the atlas‐based approach only occupied 30% of the SVS volume, ie, somewhat different anatomies were sampled. Furthermore, the new atlas‐based approach showed highly reproducible GABA+/tCr values with a low median coefficient of variance of 6.3%. In conclusion, the atlas‐based metabolite quantification approach enables a more brain structure‐specific comparison of GABA+ and other neurochemical levels across populations, even when using an MRSI technique with only cm‐level resolution. This approach was successfully cross‐validated against the typically used SVS technique as well as other different MRSI analysis methods, indicating the robustness of this quantification approach.
Industry Payment to Vascular Neurologists

Supplemental Digital Content is available in the text. Background and Purpose— Industry payments to physicians raise concerns regarding conflicts of interest that could impact patient care. We explored nonresearch and nonownership payments from industry to vascular neurologists to identify trends in compensation. Methods— Using Centers for Medicare and Medicaid Services and American Board of Psychiatry and Neurology data, we explored financial relationships between industry and US vascular neurologists from 2013 to 2018. We analyzed payment characteristics, including payment categories, payment distribution among physicians, regional trends, and biomedical manufacturers. Furthermore, we analyzed the top 1% (by compensation) of vascular neurologists with detailed payment categories, their position, and their contribution to stroke guidelines. Results— The number of board certified vascular neurologist increased from 1169 in 2013 to 1746 in 2018. The total payments to vascular neurologist increased from $99 749 in 2013 to $1 032 302 in 2018. During the study period, 16% to 17% of vascular neurologists received industry payments. Total payments from industry and mean physician payments increased yearly over this period, with consulting fee (31.1%) and compensation for services other than consulting (30.7%) being the highest paid categories. The top 10 manufacturers made the majority of the payments, and the top 10 products changed from drug or biological products to devices. Physicians from south region of the United States received the highest total payment (38.72%), which steadily increased. Payments to top 1% vascular neurologists increased from 64% to 79% over the period as payments became less evenly distributed. Among the top 1%, 42% specialized in neuro intervention, 11% contributed to American Heart Association/American Stroke Association guidelines, and around 75% were key leaders in the field. Conclusions— A small proportion of US vascular neurologists consistently received the majority of industry payments, the value of which grew over the study period. Only 11% of the top 1% receiving industry payments have authored American Heart Association/American Stroke Association guidelines, but ≈75% seem to be key leaders in the field. Whether this influences clinical practice and behavior requires further investigation.