Miracle-dz/UniFAR-FTUs huggingface dataset:
ERS clinical practice guidelines on treatment of sarcoidosis

Background The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. Methods A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. Results The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. Conclusions There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment. Evidence-based guidelines for the treatment of sarcoidosis are presented. The ERS Task Force committee used the GRADE approach and specific recommendations are made. A major factor in treating patients is the risk of loss of organ function or impairment of quality of life. https://bit.ly/3iAERfY
Clinical expression, epidemiology, and monitoring of Mycoplasma gallisepticum and Mycoplasma synoviae: an update

ABSTRACT Mycoplasma gallisepticum (MG) and Mycoplasma synoviae (MS) are of clinical and economic importance for the global poultry industry. Many countries and integrations are involved in monitoring programmes to control both mycoplasma species. This review provides an extensive historic overview of the last seven decades on the development of the knowledge regarding the factors that influence the clinical expression of the disease, the epidemiology, and monitoring of both MG and MS. This includes the detection of new virulent strains, studies unravelling the transmission routes, survival characteristics, and the role of other avian hosts. Also the role of molecular typing tests in unravelling epidemiology and factors that complicate the interpretation of test results is discussed. The latter includes the presence of heterologous mycoplasma infections, the use of heterologous oil-emulsion vaccines, and the use of antibiotic treatments. Also the occurrence of MG and MS strains with low virulence and the use of live and/or inactivated MS and MS vaccines are discussed.
Effectiveness of blended learning in pharmacy education: A systematic review and meta-analysis

Background & objective Though blended learning (BL), is widely adopted in higher education, evaluating effectiveness of BL is difficult because the components of BL can be extremely heterogeneous. Purpose of this study was to evaluate the effectiveness of BL in improving knowledge and skill in pharmacy education. Methods PubMed/MEDLINE, Scopus and the Cochrane Library were searched to identify published literature. The retrieved studies from databases were screened for its title and abstracts followed by the full-text in accordance with the pre-defined inclusion and exclusion criteria. Methodological quality was appraised by modified Ottawa scale. Random effect model used for statistical modelling. Key findings A total of 26 studies were included for systematic review. Out of which 20 studies with 4525 participants for meta-analysis which employed traditional teaching in control group. Results showed a statistically significant positive effect size on knowledge (standardized mean difference [SMD]: 1.35, 95% confidence interval [CI]: 0.91 to 1.78, p<0.00001) and skill (SMD: 0.68; 95% CI: 0.19 to 1.16; p = 0.006) using a random effect model. Subgroup analysis of cohort studies showed, studies from developed countries had a larger effect size (SMD: 1.54, 95% CI: 1.01 to 2.06), than studies from developing countries(SMD: 0.44, 95% CI: 0.23 to 0.65, studies with MCQ pattern as outcome assessment had larger effect size (SMD: 2.81, 95% CI: 1.76 to 3.85) than non-MCQs (SMD 0.53, 95% CI 0.33 to 0.74), and BL with case studies (SMD 2.72, 95% CI 1.86–3.59) showed better effect size than non-case-based studies (SMD: 0.22, CI: 0.02 to 0.41). Conclusion BL is associated with better academic performance and achievement than didactic teaching in pharmacy education.
Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: A prospective observational study.

BACKGROUND The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value. METHODS A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14+ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR). RESULTS A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively. CONCLUSIONS Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.
Racial Adjustment Adversely Affects Glomerular Filtration Estimates in African Americans Living with HIV.

Background The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Results 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P<0.001) and 91% vs. 88% for eGFRcr-cys (P=0.045). Lean mass was correlated with eGFRcr bias and, in adjusted analyses, lean mass was significantly lower in PLWH compared with HIV-negative AAs compatible with not using the race coefficient. Conclusions We found that the standard, widely used eGFRcr equation overestimate iGFR and has poor accuracy in AAs living with HIV.
First Report of Shot-hole on Flowering Cherry Caused by Burkholderia contaminans and Pseudomonas syringae pv. syringae.

The shot-hole disease (SH) is one of the most common and important diseases affecting the flowering cherry (FC; Prunus × yedoensis Matsumura; 'Somei-yoshino') trees in South Korea every year, resulting in premature defoliation and reduced flowering in the following year. However, pathogens associated with the disease remain unknown, which has rendered disease management challenging. Here, the pathogens associated with SH, their biochemical characteristics, and their host range were elucidated. Detached leaf and in planta assays revealed that two biofilm-forming bacteria, namely Burkholderia contaminans (Bc) and Pseudomonas syringae pv. syringae (Pss), caused SH of FC trees. These pathogens were recorded for the first time as the causes of SH of FC trees in South Korea. Additionally, the two pathogens induced similar disease symptoms in several stone fruits belonging to the genus Prunus, including peach (P. persica), plum (P. salicina), and apricot (P. mume), with peach being the most susceptible. These results indicate that Bc and Pss caused SH on FC trees and presented a broad spectrum of hosts. Furthermore, Xanthomonas arboricola pv. pruni, the causative agent of leaf spot on stone fruits, incited brown spots and shot holes on FC leaves. Therefore, FC trees are susceptible to infections by various pathogenic bacteria, including Bc, Pss, and Xap. These findings will be of great importance as a reference for effective management of SH in the face of possible cross-infection between Prunus species in the future.
Increased risk of shoulder calcific tendinopathy in diabetes mellitus: A nationwide, population‐based, matched cohort study

Calcific tendinopathy of the rotator cuff is a common cause of painful disability in the shoulder with unclear aetiology. Diabetes mellitus (DM) is associated with calcific tendinopathy; however, large epidemiological data are lacking. Thus, we conducted a nationwide population‐based matched cohort study to investigate the risk for calcific tendinopathy of the shoulder in diabetic patients.
Testosterone ameliorates age-related brain mitochondrial dysfunction

Brain mitochondrial dysfunction and reduced testosterone levels are common features of aging in men. Although evidence suggests that the two phenomena are interrelated, it is unclear whether testosterone supplementation ameliorates mitochondrial dysfunction in the aging male brain. Here, we show that testosterone supplementation significantly alleviates exploratory behavioral deficits and oxidative damage in the substantia nigra and hippocampus of aging male rats. These effects were consistent with improved mitochondrial function, reflected by testosterone-induced increases in mitochondrial membrane potential (MMP), antioxidant enzyme (GSH-PX, catalase, and Mn-SOD) expression/activity, and mitochondrial respiratory complex activities in both brain regions. Furthermore, elevated PGC-1α, NRF-1, and TFAM expression (suggestive of enhanced mitochondrial biogenesis), increased citrate synthase activity, mtDNA copy number, and ND1, COX1, and ATP6 expression (indicative of increased mitochondrial content), as well as increased PINK1/Parkin and decreased P62 expression (suggesting mitophagy activation), were detected in the substantial nigra and hippocampus of aged male rats after testosterone supplementation. These findings suggest that testosterone supplementation may be a viable approach to ameliorating brain mitochondrial dysfunction and thus prevent or treat cognitive-behavioral deficits and neurodegenerative conditions associated with aging.
Mechanisms for Mid-Air Reorientation Using Tail Rotation in Gliding Geckos

Abstract Arboreal animals face numerous challenges when negotiating complex three-dimensional terrain. Directed aerial descent or gliding flight allows for rapid traversal of arboreal environments, but presents control challenges. Some animals, such as birds or gliding squirrels, have specialized structures to modulate aerodynamic forces while airborne. However, many arboreal animals do not possess these specializations but still control posture and orientation in mid-air. One of the largest inertial segments in lizards is their tail. Inertial reorientation can be used to attain postures appropriate for controlled aerial descent. Here, we discuss the role of tail inertia in a range of mid-air reorientation behaviors using experimental data from geckos in combination with mathematical and robotic models. Geckos can self-right in mid-air by tail rotation alone. Equilibrium glide behavior of geckos in a vertical wind tunnel show that they can steer toward a visual stimulus by using rapid, circular tail rotations to control pitch and yaw. Multiple coordinated tail responses appear to be required for the most effective terminal velocity gliding. A mathematical model allows us to explore the relationship between morphology and the capacity for inertial reorientation by conducting sensitivity analyses, and testing control approaches. Robotic models further define the limits of performance and generate new control hypotheses. Such comparative analysis allows predictions about the diversity of performance across lizard morphologies, relative limb proportions, and provides insights into the evolution of aerial behaviors.
A contemporary practical approach to the multidisciplinary management of unclassifiable interstitial lung disease

Fibrotic interstitial lung diseases (ILDs) frequently have nonspecific and overlapping clinical and radiological features, resulting in ∼10–20% of patients with ILD lacking a clear diagnosis and thus being labelled with unclassifiable ILD. The objective of this review is to describe how patients with unclassifiable ILD should be evaluated, and what impact specific clinical, radiological and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype. We highlight recent data that have suggested an increasing role for antifibrotic medications in a variety of fibrotic ILDs, but justify the ongoing importance of making an accurate ILD diagnosis given the benefit of immunomodulatory therapies in many patient populations. We provide a practical approach to support management decisions that can be used by clinicians and tested by clinical researchers, and further identify the need for additional research to support a rational and standardised approach to the management of patients with unclassifiable ILD. This review describes how patients with unclassifiable ILD should be evaluated and what impact specific clinical, radiological and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype https://bit.ly/3o43nqr
Consequences of AV blockade omission in flecainide therapy

Flecainide is a well-established and widely used Vaughan-Williams class IC antiarrhythmic agent indicated for the prevention of ventricular arrhythmias, paroxysmal atrial fi brillation/ fl utter, paroxysmal supraventricular tachycardia, and pharmacologic cardioversion. Its effects are exhibited via the blockade of cardiac sodium channels, which slows the conduction of the cardiac action potential. Flecainide is listed as an effective
Polypharmacy and Frailty among Hemodialysis Patients

Background: Both polypharmacy and frailty are highly prevalent among the patients on hemodialysis and associated with adverse outcomes; however, little is known about the association between them. Methods: We examined 337 patients enrolled in the ACTIVE/ADIPOSE dialysis cohort study between 2009 and 2011. The number of prescribed medications and frailty were assessed at baseline, 12, and 24 months. Frailty was defined based upon the Fried’s frailty phenotype. We used logistic regression with generalized estimating equations to model the association of the number of medications and frailty at baseline and over time. A competing-risk regression analysis was also used to assess the association between the number of medications and incidence of frailty. Results: The mean number of medications was 10 ± 5, and 94 patients (28%) were frail at baseline. Patients taking >11 medications showed higher odds for frailty than the patients taking fewer than 8 medications (OR 1.54, 95% CI 1.05–2.26). During the 2-year of follow-up, 87 patients developed frailty among those who were nonfrail at baseline. Compared with the patients taking fewer than 8 medications, the incidence of frailty was approximately 2-fold in those taking >11 medications (sub-distribution hazard ratio 2.15, 95% CI 1.32–3.48). Conclusions: Using a higher number of medications was associated with frailty and the incidence of frailty among hemodialysis patients. Minimizing polypharmacy may reduce the incidence and prevalence of frailty among dialysis patients.
Microstructural design for mechanical–optical multifunctionality in the exoskeleton of the flower beetle Torynorrhina flammea

Significance In the design of multifunctional materials, harnessing structural and compositional synergies while avoiding unnecessary trade-offs is critical in achieving high performance of all required functions. Biological material systems like the cuticles of many arthropods often fulfill multifunctionality through the intricate design of material structures, simultaneously achieving mechanical, optical, sensory, and other vital functionalities. A better understanding of the structural basis for multifunctionality and the functional synergies and trade-offs in biological materials could thus provide important insights for the design of bioinspired multifunctional materials. In this study, we demonstrate a concerted experimental, theoretical, and computational approach that uncovers the structure–mechanics–optics relationship of the beetle’s cuticle, opening avenues to investigate biological materials and design photonic materials with robust mechanical performance. Biological systems have a remarkable capability of synthesizing multifunctional materials that are adapted for specific physiological and ecological needs. When exploring structure–function relationships related to multifunctionality in nature, it can be a challenging task to address performance synergies, trade-offs, and the relative importance of different functions in biological materials, which, in turn, can hinder our ability to successfully develop their synthetic bioinspired counterparts. Here, we investigate such relationships between the mechanical and optical properties in a multifunctional biological material found in the highly protective yet conspicuously colored exoskeleton of the flower beetle, Torynorrhina flammea. Combining experimental, computational, and theoretical approaches, we demonstrate that a micropillar-reinforced photonic multilayer in the beetle’s exoskeleton simultaneously enhances mechanical robustness and optical appearance, giving rise to optical damage tolerance. Compared with plain multilayer structures, stiffer vertical micropillars increase stiffness and elastic recovery, restrain the formation of shear bands, and enhance delamination resistance. The micropillars also scatter the reflected light at larger polar angles, enhancing the first optical diffraction order, which makes the reflected color visible from a wider range of viewing angles. The synergistic effect of the improved angular reflectivity and damage localization capability contributes to the optical damage tolerance. Our systematic structural analysis of T. flammea’s different color polymorphs and parametric optical and mechanical modeling further suggest that the beetle’s microarchitecture is optimized toward maximizing the first-order optical diffraction rather than its mechanical stiffness. These findings shed light on material-level design strategies utilized in biological systems for achieving multifunctionality and could thus inform bioinspired material innovations.
G-quadruplex binders as cytostatic modulators of innate immune genes in cancer cells

Abstract G-quadruplexes (G4s) are non-canonical nucleic acid structures involved in fundamental biological processes. As G4s are promising anticancer targets, in past decades the search for effective anticancer G4 binders aimed at the discovery of more cytotoxic ligands interfering with specific G4 structures at oncogenes or telomeres. Here, we have instead observed a significant activation of innate immune genes by two unrelated ligands at non-cytotoxic concentrations. The studied G4 binders (pyridostatin and PhenDC3) can induce an increase of micronuclei triggering the activation of the cytoplasmic STING (stimulator of interferon response cGAMP interactor 1) signaling pathway in human and murine cancer cells. Ligand activity can then lead to type I interferon production and innate immune gene activation. Moreover, specific gene expression patterns mediated by a G4 binder in cancer cells correlate with immunological hot features and better survival in human TCGA (The Cancer Genome Atlas) breast tumors. The findings open to the development of cytostatic G4 binders as effective immunomodulators for combination immunotherapies in unresponsive tumors.
Transcriptional analysis of sweet corn hybrids in response to crowding stress

Crop tolerance to crowding stress, specifically plant population density, is an important target to improve productivity in processing sweet corn. Due to limited knowledge of biological mechanisms involved in crowding stress in sweet corn, a study was conducted to 1) investigate phenotypic and transcriptional response of sweet corn hybrids under different plant densties, 2) compare the crowding stress response mechanisms between hybrids and 3) identify candidate biological mechanisms involved in crowding stress response. Yield per hectare of a tolerant hybrid (DMC21-84) increased with plant density. Yield per hectare of a sensitive hybrid (GSS2259P) declined with plant density. Transcriptional analysis found 694, 537, 359 and 483 crowding stress differentially expressed genes (DEGs) for GSS2259P at the Fruit Farm and Vegetable Farm and for DMC21-84 at the Fruit Farm and Vegetable Farm, respectively. Strong transcriptional change due to hybrid was observed. Functional analyses of DEGs involved in crowding stress also revealed that protein folding and photosynthetic processes were common response mechanisms for both hybrids. However, DEGs related to starch biosynthetic, carbohydrate metabolism, and ABA related processes were significant only for DMC21-84, suggesting the genes have closer relationship to plant productivity under stress than other processes. These results collectively provide initial insight into potential crowding stress response mechanisms in sweet corn.