Evaluating the Threshold Score for Classification of Systemic Lupus Erythematosus Using the EULAR/ACR Criteria.

OBJECTIVE: To evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE. METHODS: We conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (-LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and -LRs < 0.1 provide evidence to rule in or rule out SLE. RESULTS: A total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a -LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; -LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the -LR (threshold score 10: -LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: -LR 0.05, 95% CI 0.04-0.06). CONCLUSION: The EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Machine learning enables noninvasive prediction of atrial fibrillation driver location and acute pulmonary vein ablation success using the 12-lead ECG.

BACKGROUND: Atrial fibrillation (AF) is the most common supraventricular arrhythmia, characterized by disorganized atrial electrical activity, maintained by localized arrhythmogenic atrial drivers. Pulmonary vein isolation (PVI) allows to exclude PV-related drivers. However, PVI is less effective in patients with additional extra-PV arrhythmogenic drivers. OBJECTIVES: To discriminate whether AF drivers are located near the PVs vs extra-PV regions using the noninvasive 12-lead electrocardiogram (ECG) in a computational and clinical framework, and to computationally predict the acute success of PVI in these cohorts of data. METHODS: AF drivers were induced in 2 computerized atrial models and combined with 8 torso models, resulting in 1128 12-lead ECGs (80 ECGs with AF drivers located in the PVs and 1048 in extra-PV areas). A total of 103 features were extracted from the signals. Binary decision tree classifier was trained on the simulated data and evaluated using hold-out cross-validation. The PVs were subsequently isolated in the models to assess PVI success. Finally, the classifier was tested on a clinical dataset (46 patients: 23 PV-dependent AF and 23 with additional extra-PV sources). RESULTS: The classifier yielded 82.6% specificity and 73.9% sensitivity for detecting PV drivers on the clinical data. Consistency analysis on the 46 patients resulted in 93.5% results match. Applying PVI on the simulated AF cases terminated AF in 100% of the cases in the PV class. CONCLUSION: Machine learning-based classification of 12-lead-ECG allows discrimination between patients with PV drivers vs those with extra-PV drivers of AF. The novel algorithm may aid to identify patients with high acute success rates to PVI.

The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers.

The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.

Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials.

PURPOSE: To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT). METHODS: We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia. RESULTS: Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified. CONCLUSIONS: Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required.

Validation of the iPhone app using the force platform to estimate vertical jump height.

BACKGROUND: Vertical jump performance has been evaluated with several devices: force platforms, contact mats, Vertec, accelerometers, infrared cameras and high-velocity cameras; however, the force platform is considered the gold standard for measuring vertical jump height. The purpose of this study was to validate an iPhone app called My Jump, that measures vertical jump height by comparing it with other methods that use the force platform to estimate vertical jump height, namely, vertical velocity at take-off and time in the air. METHODS: A total of 40 sport sciences students (age 21.4±1.9 years) completed five countermovement jumps (CMJs) over a force platform. Thus, 200 CMJ heights were evaluated from the vertical velocity at take-off and the time in the air using the force platform, and from the time in the air with the My Jump mobile application. The height obtained was compared using the intraclass correlation coefficient (ICC). RESULTS: Correlation between APP and force platform using the time in the air was perfect (ICC=1.000, P<0.001). Correlation between APP and force platform using the vertical velocity at take-off was also very high (ICC=0.996, P<0.001), with an error margin of 0.78%. CONCLUSIONS: Therefore, these results showed that application, My Jump, is an appropriate method to evaluate the vertical jump performance; however, vertical jump height is slightly overestimated compared with that of the force platform.

Effect of the percentage of Bos taurus inheritance on the fertility of Holstein×Zebu and Brown Swiss×Zebu cows in the Mexican tropics

Background: No dairy breed or crossbreed has superior overall performance in all environments; therefore, it is necessary to determine which crossbreed is the most suitable for the Mexican tropic and what proportion of European breed is optimum for reproduction. Objective: To assess the effect of the proportion of Bos taurus (Bt) genes on reproductive performance of Holstein×Zebu (HZ) and Brown Swiss×Zebu (BZ) cows, and compare reproductive performance of these genotypes in a dual- purpose production system. Methods: Cows were maintained in a rotational grazing system on African star grass (Cynodon plectostachyus) in Veracruz, Mexico. Cows were milked twice daily. Calves were kept tied to the side of their dams while the cows were milked. Results: The percentage of Bt genes did not affect (p>0.05) fertility traits (age at first calving, days to first service after calving, services per conception, conception rate at first service, days open until conception, gestation length, and calving interval) of BZ cows. In contrast, HZ cows with less than 75% Holstein (H) genes were 0.3 years younger (p<0.05) at first calving and had 39.8 fewer days open (p<0.05) than HZ cows with 75% H genes or more. In addition, the calving interval of HZ cows with less than 75% H genes was 44.8 days shorter (p<0.05) than that of HZ cows with 75% H genes or more. The HZ cows had five fewer days pregnant and were 22.8 kg heavier at calving (p<0.05) than BZ cows. Conclusions: The effect of the percentage of Bt genes on cow fertility depends on the dairy breed used. In general, BZ and HZ cows present similar reproductive performance.

Antecedentes: Ninguna raza lechera o cruce tiene un desempeño general superior en todos los ambientes; por lo tanto, es necesario determinar cuál cruce lechero es más apropiado en el trópico mexicano y qué proporción de raza europea es óptima para la reproducción. Objetivo: Evaluar el efecto de la proporción de genes Bos taurus (Bt) en el desempeño reproductivo de vacas cruzadas Holstein×Cebú (HC) y Pardo Suizo×Cebú (PC), y comparar el desempeño reproductivo de estos dos genotipos en un sistema de producción doble propósito. Métodos: Las vacas se mantuvieron en un sistema de pastoreo rotacional en zacate Estrella de África (Cynodon plectostachyus) en Veracruz, México. Las vacas se ordeñaron dos veces al día. Los becerros se mantuvieron atados, a un costado de sus madres mientras éstas se ordeñaron. Resultados: El porcentaje de genes Bt no afectó (p>0,05) ninguna característica de fertilidad (edad a primer parto, días a primer servicio después del parto, servicios por concepción, tasa de preñez a primer servicio, días abiertos a la concepción, duración de la gestación, e intervalo entre partos) de las vacas PC. En contraste, las vacas HC con menos de 75% de genes Holstein (H) fueron 0,3 años más jóvenes (p<0,05) al primer parto y tuvieron 39,8 días abiertos menos (p<0,05) que las vacas HC con 75% de genes H o más. Además, el intervalo entre partos de las vacas HC con menos de 75% de genes H fue 44,8 días más corto (p<0,05) que el de las vacas HC con 75% de genes H o más. Las vacas HC tuvieron cinco días de gestación menos y fueron 22,8 kg más pesadas al parto (p<0,05) que las PC. Conclusiones: El efecto del porcentaje de genes Bt sobre la fertilidad de la vaca depende de la raza lechera usada. En general, las vacas PC y HC tienen similar desempeño reproductivo.

Antecedentes: Nenhuma raça ou cruza leiteira tem desempenho geral superior em todos os ambientes; portanto, é necessário determinar qual cruza leiteira é mais apropriada no trópico mexicano e qual proporção da raça europeia é ideal para a reprodução das vacas. Objetivo: Avaliar o efeito da proporção de genes Bos taurus (Bt) no desempenho reprodutivo de vacas Holandês×Zebu (HZ) e Pardo Suíço×Zebu (PZ), e comparar o desempenho reprodutivo desses dois genótipos em sistema de produção de dupla aptidão. Métodos: As vacas foram mantidas em sistema de pastoreio rotacional em capim Estrela de África (Cynodon plectostachyus) em Veracruz, México. As vacas foram ordenhadas duas vezes por dia. Os bezerros foram mantidos ao lado de suas mães enquanto eram ordenhadas. Resultados: A porcentagem dos genes Bt não afetou (p>0,05) nenhuma característica de fertilidade (idade ao primeiro parto, número de dias para o primeiro serviço pós-parto, serviços por concepção, taxa de prenhes no primeiro serviço, dias abertos, período de gestação e intervalo entre partos) das vacas PZ. Em contraste, vacas HC com menos de 75% dos genes Holandês (H) eram 0,3 anos mais jovens (p<0,05) no primeiro parto e tiveram 39,8 dias abertos a menos (p<0,05) do que as vacas HZ com 75% ou mais dos genes H. Além disso, o intervalo de parto das vacas HZ com menos de 75% dos genes H foram 44,8 dias mais curtos (p<0,05) do que as vacas HZ com 75% ou mais de genes H. As vacas HZ tiveram cinco dias de gestação a menos e foram 22,8 kg mais pesadas no parto (p<0,05) do que as PZ. Conclusões: O efeito da porcentagem de genes Bt na fertilidade da vaca dependeu da raça leiteira utilizada. Em geral, as vacas PZ e HZ tiveram desempenho reprodutivo semelhante.

Accuracy of QT measurement in the EASI-derived 12-lead ECG.

The purpose of this study is to assess QT interval measurements from the EASI 12-lead ECG as compared to the standard 12-lead ECG. The QT interval was automatically measured in simultaneously recorded standard and EASI 12-lead ECGs, using a validated wavelet-based delineator. The agreement between the two sets of measurements was quantified both on a lead-by-lead basis and a multilead basis. The results show an acceptable agreement between QT measurements in the two lead systems, with correlation coefficients (CC) 0.91-0.98 depending on the lead. Standard deviations range from 9.2 ms to 26.4 ms depending on the selected lead. In a few patients large inter-system differences were found, mainly due to different T wave morphologies. Using a multilead delineation, QT intervals were considerably more stable than single-lead measurements and resulted in a much better agreement between the two lead systems (CC: 0.98, QT difference: 1.1 ms +/- 9.8 ms). Thus, EASI-derived 12-lead ECG may be used for reliable QT monitoring when the multilead delineation approach is adopted.

Differential adaptation of two varieties of common bean to abiotic stress: I. Effects of drought on yield and photosynthesis.

The yield of 24 commercial varieties and accessions of common bean (Phaseolus vulgaris) has been determined at different sites in Chile and Bolivia. Statistical analysis was performed in order to characterize whether a particular variety was more or less stable in yield under different environmental conditions. Amongst these, two varieties have been identified for more detailed study: one variety has a higher than average yield under unstressed conditions but is strongly affected by stress, and another has a reduced yield under unstressed conditions but is less affected by stress. The contrasting rate of abscission of the reproductive organs under drought stress was clearly consistent with these differences. The more tolerant genotype shows a great deal of plasticity at the biochemical and cellular level when exposed to drought stress, in terms of stomatal conductance, photosynthetic rate, abscisic acid synthesis, and resistance to photoinhibition. By contrast, the former lacks such plasticity, but shows an enhanced tendency for a morphological response, the movement of leaves, which appears to be its principal response to drought stress.