Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of AT 1 Receptor Blockade on Blood Pressure, Renal Haemodynamics and Hormonal Responses to Intravenous Angiotensin II Infusion in Hypertensive Patients

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean - SEM, 106 - 2 mmHg) was significantly decreased compared with treatment with losartan (110 - 2 mmHg) and valsartan (109 - 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 - 0.4%) significantly more than losartan (1.5 - 0.4%) and valsartan (1.6 - 0.4%) and reduced the increase in aldosterone secretion (17 - 5 pg/ml/) significantly more than losartan (74 - 17 pg/ml/) and valsartan (82 - 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT 1 receptor blockade with candesartan.
Design and implementation of distributed control system for cascaded H-Bridge multilevel STATCOM

Concentrated control system (CCS) has been used for almost all reported cascaded H-Bridge (CHB) multilevel static synchronous compensators (STATCOM's). However, the CCS can not achieve “true” modular implementation. This paper presents a novel distributed control system (DCS), which combines one central controller and several cell controllers. The central controller is responsible for the upper-layer control including dc voltage loop and output current loop. The dc capacitor voltage balancing control and pulse-width modulation (PWM) algorithm are implemented by each cell controller. In DCS, each cell is treated as an independent power unit with its own controller. This makes modularization easier. Moreover, the software in the central controller and dc voltage detecting circuits become very simple compared with the traditional CCS. Some practical issues of the proposed DCS are discussed in detail. A novel dc voltage balancing method which can be implemented independently in each cell controller is proposed. A seven-level CHB STATCOM prototype is built. The validity of the proposed DCS and dc voltage balancing strategy is verified by the experimental results.
Respirometric assessment of substrate binding by antibiotics in peptone biodegradation

The study evaluated the inhibitory impact of antibiotics on the biodegradation of peptone mixture by an acclimated microbial culture under aerobic conditions. A fill and draw reactor fed with the peptone mixture defined in the ISO 8192 procedure and sustained at steady state at a sludge age of 10 days was used as the biomass pool with a well-defined culture history. Acute inhibition experiments involved running six parallel batch reactors seeded with biomass from the fill and draw reactor and the same peptone mixture together with pulse feeding of 50 mg/L and 200 mg/L of Sulfamethoxazole, Erythromycin and Tetracycline. Substrate utilization was evaluated by observing the respective oxygen uptake rate profiles and compared with a control reactor, which was started with no antibiotic addition. While all available external substrate was removed from solution, addition of antibiotics induced a significant decrease in the amount of oxygen consumed, indicating that a varying fraction of peptone mixture was blocked by the antibiotic and did not participate to the on-going microbial growth mechanism. This observation was also compatible with the concept of the uncompetitive inhibition mechanism, which defines a similar substrate blockage through formation of an enzyme- inhibitor complex.
Pneumococcal Surface Protein A Inhibits Complement Activation by Streptococcus pneumoniae

ABSTRACT Pneumococcal surface protein A (PspA) is a surface-exposed protein virulence factor for Streptococcus pneumoniae. In this study, no significant depletion of serum complement was observed for the serum of mice infected with pneumococci that express PspA. In contrast, in mice infected with an isogenic strain of pneumococci lacking PspA, significant activation of serum complement was detected within 30 min after infection. Also, the PspA-deficient strain but not the PspA-expressing strain was cleared from the blood within 6 h. The contribution of PspA to pneumococcal virulence was further investigated by using mice deficient for C5, C3, or factor B. In mice deficient for C3 or factor B, PspA-negative pneumococci became fully virulent. In contrast, in C5-deficient mice as in wild-type mice, PspA-deficient pneumococci were avirulent. These in vivo data suggest that, in nonimmune mice infected with pneumococci, PspA interferes with complement-dependent host defense mechanisms mediated by factor B. Immunoblots of pneumococci opsonized in vitro suggested that more C3b was deposited on PspA-negative than on PspA-positive pneumococci. This was observed with and without anticapsular antibody. Furthermore, processing of the α chain of C3b was reduced in the presence of PspA. We propose that PspA exerts its virulence function by interfering with deposition of C3b onto pneumococci and/or by inhibiting formation of a fully functional alternative pathway C3 convertase. By blocking recruitment of the alternative pathway, PspA reduces the amount of C3b deposited onto pneumococci, thereby reducing the effectiveness of complement receptor-mediated pathways of clearance.
Soil Microbes Trade-Off Biogeochemical Cycling for Stress Tolerance Traits in Response to Year-Round Climate Change

Winter air temperatures are rising faster than summer air temperatures in high-latitude forests, increasing the frequency of soil freeze/thaw events in winter. To determine how climate warming and soil freeze/thaw cycles affect soil microbial communities and the ecosystem processes they drive, we leveraged the Climate Change across Seasons Experiment (CCASE) at the Hubbard Brook Experimental Forest in the northeastern United States, where replicate field plots receive one of three climate treatments: warming (+5°C above ambient in the growing season), warming in the growing season + winter freeze/thaw cycles (+5°C above ambient +4 freeze/thaw cycles during winter), and no treatment. Soil samples were taken from plots at six time points throughout the growing season and subjected to amplicon (rDNA) and metagenome sequencing. We found that soil fungal and bacterial community composition were affected by changes in soil temperature, where the taxonomic composition of microbial communities shifted more with the combination of growing-season warming and increased frequency of soil freeze/thaw cycles in winter than with warming alone. Warming increased the relative abundance of brown rot fungi and plant pathogens but decreased that of arbuscular mycorrhizal fungi, all of which recovered under combined growing-season warming and soil freeze/thaw cycles in winter. The abundance of animal parasites increased significantly under combined warming and freeze/thaw cycles. We also found that warming and soil freeze/thaw cycles suppressed bacterial taxa with the genetic potential for carbon (i.e., cellulose) decomposition and soil nitrogen cycling, such as N fixation and the final steps of denitrification. These new soil communities had higher genetic capacity for stress tolerance and lower genetic capacity to grow or reproduce, relative to the communities exposed to warming in the growing season alone. Our observations suggest that initial suppression of biogeochemical cycling with year-round climate change may be linked to the emergence of taxa that trade-off growth for stress tolerance traits.
Longterm Survival and Associated Risk Factors in Patients with Adult-onset Idiopathic Inflammatory Myopathies and Amyopathic Dermatomyositis: Experience in a Single Institute in Japan

Objective. To analyze clinical characteristics, survival, causes of death, and risk factors associated with mortality in patients with adult-onset idiopathic inflammatory myopathies (IIM) in Japan. Methods. We retrospectively investigated 197 patients diagnosed with adult-onset IIM at our hospital from 1984 to 2009 according to Bohan and Peter criteria for polymyositis (PM)/dermatomyositis (DM) and modified Sontheimer’s criteria for clinically amyopathic DM (ADM). Results. Survival in the whole group at 1, 5, and 10 years was 85%, 75%, and 67%, respectively. Mortality in cancer-associated myositis was the worst (25% at 5 yrs), followed by clinically ADM (61% at 5 yrs) and primary DM (77% at 5 yrs). Primary DM had significantly low survival compared to primary PM (91% at 5 yrs; p = 0.0427). Among the 53 patients who died were 6 patients with ADM (11%) and 20 patients with primary DM (38%). Interstitial lung disease (ILD) was the main cause of death in clinically ADM (71%) and primary DM (60%), most of which occurred within the first few months. Fewer patients died in primary PM (9%) and overlap myositis (13%). Independent risk factors for death were older age (HR 1.031; 95% CI 1.009–1.053) and skin ulcers (HR 3.018; 95% CI 1.340–6.796) in the whole group and ILD with mild serum creatine kinase levels (< 500 IU/l; HR 3.537; 95% CI 1.260–9.928) in primary DM. Conclusion. Survival of clinically ADM and primary DM was low, mainly due to fatal ILD, compared to primary PM. Establishing therapeutic strategy for ILD may improve the survival in our patient population.
Do 21-Gene Recurrence Score Influence Chemotherapy Decisions in T1bN0 Breast Cancer Patients?

Purpose: Hormone receptor (HR)-positive breast cancer patients with tumor size ≤1.0 cm and negative node have favorable outcomes. The 21-gene Recurrence Score (RS) could predict response to chemotherapy for HR+ breast cancer, but its role in T1bN0 disease is challenging. Methods: T1bN0 breast cancer patients diagnosed between January 2014 and June 2019 with RS results were included and categorized as Low- (RS < 18), Intermediate- (RS 18–30), or High-risk (RS > 30) groups. Univariate and multivariate analysis were used to assess factors associated with RS distribution and chemotherapy recommendation. Chemotherapy decisions change and patient adherence after 21-gene RS testing were also evaluated. Results: Among 237 patients with T1bN0 tumors, proportions of Low-, Intermediate-, and High-risk RS were 19.8, 63.3, and 16.9%, respectively. Multivariate analysis found that ER expression (P = 0.011), PR expression (P < 0.001), and Ki-67 index (P = 0.001) were independently associated with RS distribution. Adjuvant chemotherapy was recommended for 31.6% of patients, which was more frequently given to patients with higher tumor grade [Odds ratio (OR) = 2.99 for grade II, OR = 59.19 for grade III, P = 0.006], lymph vascular invasion (OR = 8.22, P = 0.032), Luminal-B subtype (OR = 5.68, P < 0.001), and Intermediate-to High-risk RS (OR = 10.01 for Intermediate-risk, OR = 192.42 for High-risk, P < 0.001). Chemotherapy decision change was found in 18.6% of patients, mainly in those with Intermediate- to High-risk RS tumor with the majority from no-chemotherapy to chemotherapy. The treatment compliance rate after the 21-gene RS testing with MDT was 95.4%. Conclusion: RS category was related to ER, PR, and Ki-67 expression, which was recognized as an independent factor of chemotherapy recommendation in T1bN0 breast cancer. The 21-gene RS testing would lead to a chemotherapy decision change rate of 18.6% as well as a high treatment adherence, which can be applied in T1bN0 patients.
El estilo de enseñanza como determinante del tiempo de compromiso motor en Educación Física

El objetivo de la siguiente investigacion es analizar el tiempo de compromiso motor en dos estilos de ensenanza distintos, el descubrimiento guiado y la asignacion de tareas, en las clases de Educacion Fisica. Para lograrlo se ha tenido en cuenta una muestra de veinticuatro alumnos (n= 24) de 4o curso de Educacion Secundaria Obligatoria. Se ha utilizado la observacion como metodo de investigacion y la linea de tiempo como instrumento. El tratamiento estadistico aplicado ha sido descriptivo y de comparacion entre medias, utilizando el paquete estadistico SPSS 15.0. Los resultados indican que el tiempo de compromiso motor utilizando un estilo de ensenanza de descubrimiento guiado oscila entre un 60% y un 80%. Sin embargo, los porcentajes disminuyen hasta de un 40% a un 59% cuando el estilo de ensenanza es el de asignacion de tareas. Por lo cual, concluimos que cuando el profesor de Educacion Fisica utiliza en sus clases el estilo de ensenanza descubrimiento guiado, el tiempo de compromiso motor que obtiene es bueno. Por el contrario, cuando se usa el estilo de ensenanza asignacion de tareas la valoracion puede estimarse como regular.
Comparative efficacy of behavior therapy, cognitive therapy, and cognitive behavior therapy for chronic insomnia: a randomized controlled trial.

OBJECTIVE To examine the unique contribution of behavior therapy (BT) and cognitive therapy (CT) relative to the full cognitive behavior therapy (CBT) for persistent insomnia. METHOD Participants were 188 adults (117 women; M age = 47.4 years, SD = 12.6) with persistent insomnia (average of 14.5 years duration). They were randomized to 8 weekly, individual sessions consisting of BT (n = 63), CT (n = 65), or CBT (n = 60). RESULTS Full CBT was associated with greatest improvements, the improvements associated with BT were faster but not as sustained and the improvements associated with CT were slower and sustained. The proportion of treatment responders was significantly higher in the CBT (67.3%) and BT (67.4%) relative to CT (42.4%) groups at post treatment, while 6 months later CT made significant further gains (62.3%), BT had significant loss (44.4%), and CBT retained its initial response (67.6%). Remission rates followed a similar trajectory, with higher remission rates at post treatment in CBT (57.3%) relative to CT (30.8%), with BT falling in between (39.4%); CT made further gains from post treatment to follow up (30.9% to 51.6%). All 3 therapies produced improvements of daytime functioning at both post treatment and follow up, with few differential changes across groups. CONCLUSIONS Full CBT is the treatment of choice. Both BT and CT are effective, with a more rapid effect for BT and a delayed action for CT. These different trajectories of changes provide unique insights into the process of behavior change via behavioral versus cognitive routes.
c-Jun and p53 Activity Is Modulated by SUMO-1 Modification*

The ubiquitin-related SUMO-1 molecule has been shown recently to modify covalently a number of cellular proteins including IκBα. SUMO-1 modification was found to antagonize IκBα ubiquitination and protect it from degradation. Here we identify the transcription factors c-Jun and p53, two well known targets of ubiquitin, as new substrates for SUMO-1 both in vitro and in vivo. In contrast to ubiquitin, SUMO-1 preferentially targets a single lysine residue in c-Jun (Lys-229), and the abrogation of SUMO-1 modification does not compromise its ubiquitination. Activation of Jun NH2-terminal kinases, which induces a reduction in c-Jun ubiquitination, similarly decreases SUMO-1 modification. Accordingly, loss of the two major Jun NH2-terminal kinase phosphorylation sites in c-Jun, Ser-63 and Ser-73, greatly enhances conjugation by SUMO-1. A SUMO-1- deficient c-JunK229R mutant shows an increased transactivation potential on an AP-1-containing promoter compared with wild-type c-Jun, suggesting that SUMO-1 negatively regulates c-Jun activity. As with c-Jun, SUMO-1 modification of p53 is abrogated by phosphorylation but remains unaltered upon chemical damage to DNA or Mdm2-mediated ubiquitination. The SUMO-1 attachment site in p53 (Lys-386) resides within a region known to regulate the DNA binding activity of the protein. A p53 mutant, defective for SUMO-1 conjugation, shows unaltered ubiquitination but has a slightly impaired apoptotic activity, indicating that modification by SUMO-1 might be important for the full biological activity of p53. Taken together, these data provide a first link between the SUMO-1 conjugation pathway and the regulation of transcription factors.
Prevention of Allograft Rejection by Use of Regulatory T Cells With an MHC‐Specific Chimeric Antigen Receptor

CD4+CD25highFOXP3+ regulatory T cells (Tregs) are involved in graft‐specific tolerance after solid organ transplantation. However, adoptive transfer of polyspecific Tregs alone is insufficient to prevent graft rejection even in rodent models, indicating that graft‐specific Tregs are required. We developed a highly specific chimeric antigen receptor that recognizes the HLA molecule A*02 (referred to as A2‐CAR). Transduction into natural regulatory T cells (nTregs) changes the specificity of the nTregs without alteration of their regulatory phenotype and epigenetic stability. Activation of nTregs via the A2‐CAR induced proliferation and enhanced the suppressor function of modified nTregs. Compared with nTregs, A2‐CAR Tregs exhibited superior control of strong allospecific immune responses in vitro and in humanized mouse models. A2‐CAR Tregs completely prevented rejection of allogeneic target cells and tissues in immune reconstituted humanized mice in the absence of any immunosuppression. Therefore, these modified cells have great potential for incorporation into clinical trials of Treg‐supported weaning after allogeneic transplantation.
Evidence for reduced Cl‐ and increased Na+ permeability in cystic fibrosis human primary cell cultures.

1. Employing a primary cell culture system and intracellular microelectrodes, we quantitated and compared the Na+ and Cl‐ pathways in apical membranes of normal and cystic fibrosis (CF) human airway epithelia. 2. Like the transepithelial difference (PD) in situ, the PD of CF epithelia in culture (‐27 +/‐ 4 mV, mean +/‐ S.E.M.; n = 28) exceeded the PD of normal epithelia (‐10 +/‐ 1 mV; n = 22). The raised PD principally reflected an increase in the rate of active transport (equivalent short circuit, Ieq) for CF epithelia (61 +/‐ 9 microA cm‐2) as compared with normal epithelia (23 +/‐ 3 microA cm‐2). No significant differences in transepithelial resistance were detected. 3. As indicated by ion replacement studies (gluconate for Cl‐), the apical membrane of normal cells exhibits an apical membrane Cl‐ conductance (GCl) that can be activated by isoprenaline. CF cells do not exhibit an apical membrane GCl, nor can a GCl be activated by isoprenaline. 4. CF cells exhibited a larger amiloride‐sensitive Ieq and amiloride‐sensitive apical membrane conductance (GNa) than normal cells. Further, the amiloride‐sensitive Ieq was increased by isoprenaline in CF but not normal airway epithelia. 5. Equivalent circuit analysis yielded evidence for a more positive electromotive force (EMF) across the apical membrane and a more negative EMF across the basolateral membrane of CF cells as compared with normal cells. Baseline resistances of the apical (Ra) and basolateral (Rb) membranes did not differ for normal and CF cells. 6. Estimates of the resistance of the paracellular path to ion flow (Rs) by equivalent circuit analysis or ion substitution detected no differences in Rs between CF and normal cells. 7. We conclude that abnormalities in both cellular Cl‐ permeability (reduced) and Na+ permeability (increased) are characteristic of the cultured CF respiratory epithelial cell. These data suggest that a defect in the regulation of apical membrane permeabilities is a central feature of this disease.
The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C

ABSTRACT The recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-SCHM) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-SBJ) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SPBJ) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3′ untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTRBJ) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants. IMPORTANCE The recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.
Silymarin treatment of viral hepatitis: a systematic review

Summary. Silymarin from the milk thistle herb (Silybum marianum) is used by many patients with chronic viral hepatitis, but its efficacy remains unknown. We performed a systematic review of silymarin for the treatment of chronic viral hepatitis B and C. An exhaustive search strategy identified 148 papers that studied silymarin compounds in liver disease. Of these, four trials included patients with hepatitis C, one included hepatitis B patients, and two, unspecified chronic viral hepatitis. However, only one trial exclusively studied patients with hepatitis C, and none involved patients with only hepatitis B. Silymarin treatment resulted in a decrease in serum transaminases compared with baseline in four studies, and compared with placebo in only one study. There is no evidence that silymarin affects viral load or improves liver histology in hepatitis B or C. No studies were found that investigated the use of silymarin concomitantly with interferon, nucleoside analogues, or other conventional treatments for hepatitis B or C. In conclusion, silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Nevertheless it may be worthwhile to determine its effects in conjunction with standard antiviral treatment.