Moxifloxacin Replacement in Contemporary Tuberculosis Drug Regimens Is Ineffective against Persistent Mycobacterium tuberculosis in the Cornell Mouse Model

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a leading killer worldwide, and disease control is hampered by ineffective control of persistent infections. Substitution of moxifloxacin for isoniazid or ethambutol in standard TB regimens reduces treatment duration and relapse rates in animal studies and four-month regimens were not non-inferior in clinical trials. Resuscitation promoting factor (RPF) dependent bacilli have recently been implicated in M. tuberculosis persistence. We aimed to investigate the therapeutic effects of moxifloxacin substitution in the standard drug regimen for eradicating colony forming count (CFU) positive and RPF-dependent persistent M. tuberculosis using the Cornell murine model. M. tuberculosis infected mice were treated with regimens in which either isoniazid or ethambutol were replaced by moxifloxacin to the standard regimen. The efficacy of the regimens was compared to the standard regimen for bacterial CFU count elimination and removal of persistent tubercle bacilli evaluated using culture filtrate (CF) derived from M. tuberculosis strain H37Rv. We also measured disease relapse rates. Moxifloxacin-isoniazid substituted regimen achieved total organ CFU count clearance at 11 weeks post-treatment, faster than standard regimen (14 weeks), and with a 34% lower relapse rate. Moxifloxacin-ethambutol substituted regimen was similar to standard regimens in these regards. Importantly, neither moxifloxacin-substituted regimens nor the standard regimen could remove CF-dependent persistent bacilli. Evaluation of CF-dependent persistent M. tuberculosis requires confirmation in human studies, and has implications in future drug design, testing and clinical applications

Crossover critical behavior of Ga1-xMnxAs

The critical behavior of Ga1-xMnxAs in a close vicinity of the Curie temperature was experimentally studied by using the thermal diffusivity measurements. Taking into account that the inverse of the thermal diffusivity has the same critical behavior as the specific heat, the critical exponent {\alpha} for the samples investigated has been determined. With approaching close to the critical temperature, the crossover from the mean-field-like to the Ising-like critical behavior has been observed. From the crossover behavior the values of the Ginzburg number and the exchange interaction length in Ga1-xMnxAs with different concentrations of Mn were determined.Comment: 17 pages, 5 figure

Primary gastric chorioadenocarcinoma: a needle in a haystack

Primary gastric chorioadenocarcinoma (PGC) is an exceedingly rare neoplasm which is often misdiagnosed as gastric adenocarcinoma at presentation. A markedly elevated serum beta human chorionic gonadotrophin (Beta HCG) level is a characteristic feature of this tumor. A 44 year old white male presented with generalized abdominal pain and fullness, tarry black stools and weight loss of 3 months duration. Medical work-up including imaging with CT scans revealed the presence of a gastric mass and multiple liver metastases. Tumor markers were significant for a Betahuman chorionic gonadotrophin (Beta HCG) of 23717.5 MIU/ML. Scrotal ultrasound did not show the presence of a testicular mass. Upper GI endoscopy with biopsy was positive for a poorly differentiated adenocarcinoma with Beta HCG staining on immunohistochemistry. The patient was diagnosed with metastatic PGC. He received four cycles of chemotherapy with Bleomycin, Etoposide and Cisplatinum. At the end of the fourth cycle, Beta HCG was 23 MIU/ML. CT scan for restaging, however showed an increase in the size of the metastatic lesions. The patient subsequently became profoundly pancytopenic, developed disseminated intravascular coagulation (DIC) and expired 12 months after initial presentation. PGC genetically and morphologically represents an adenocarcinoma and a choriocarcinoma. The significance of an elevated serum Beta HCG is controversial and it may have a role in evaluating response to treatment and tumor recurrence. Curative resection, appropriate chemotherapy and the absence of metastatic lesions is associated with improved survival. Hence, a high index of suspicion must be maintained to diagnose this tumor correctly at presentation and tailor therapy accordingly

Разработка и применение интеллектуальных технологий и оборудования для обработки семян

Seed processing is an important link in the seed industry chain. Crop seed industry is a national strategic and basic core of industry. Drying, cleaning, selecting, grading, coating, packaging and storage of crop seeds are the main measures to realize the precision sowing of crops and the increase of grain yield and income. Continuously improving the intelligence and fi ne level of seed processing equipment is of great signifi cance to ensure the production and supply of excellent seeds and the stability of agricultural production. This paper describes the development status of modern seed processing equipment technology in China, introduces the establishment of seed processing equipment engineering technology research center, taking maize, rice, wheat and cotton seed processing technology and machinery as an example, describes the key technologies and technological process of the breakthrough in the major crop seed processing, analyzes the existing problems of seed processing equipment in China at this stage as well as the development trend in the future, provides a reference for government decision makers in resolving the problem of mechanical damage in the process of seed processing and further improving the intellectualization level of seed processing, promotes the common progress of the global seed processing equipment technology.Обработка семян – важное звено в цепочке семеноводства. Отрасль растениеводства – это национальная стратегическая и базовая отрасль промышленности страны. Сушка, очистка, отбор, сортировка, дражирование, упаковка и хранение семян сельскохозяйственных культур являются основными мерами по обеспечению точного посева сельскохозяйственных культур и увеличения урожайности и доходов зерна. Постоянное повышение интеллектуального уровня оборудования для обработки семян имеет большое значение для получения и поставки отличных семян и обеспечения стабильности сельскохозяйственного производства. В этой работе описывается состояние разработки современного оборудования для обработки семян в Китае, рассказывается о создании центра инженерных технологий оборудования для обработки семян. На примере технологий и оборудования для обработки семян кукурузы, риса, пшеницы и хлопка описываются ключевые технологии и технологический процесс, лежащие в основе технологического прорыва в обработке семян основных сельскохозяйственных культур. Анализируются существующие проблемы, связанные с оборудованием для обработки семян в Китае на данном этапе, а также будущие тенденции развития обработки семян. Статья предоставляет рекомендации для лиц, принимающих правительственные решения в области проблем механических повреждений семян в процессе обработки и решения о дальнейшем повышении уровня интеллектуализации обработки семенного материала. Данная работа способствует дальнейшему развитию глобальных технологий в этой сфере

Atomic-scale images of charge ordering in a mixed-valence manganite

Transition-metal perovskite oxides exhibit a wide range of extraordinary but imperfectly understood phenomena. Charge, spin, orbital, and lattice degrees of freedom all undergo order-disorder transitions in regimes not far from where the best-known of these phenomena, namely high-temperature superconductivity of the copper oxides, and the 'colossal' magnetoresistance of the manganese oxides, occur. Mostly diffraction techniques, sensitive either to the spin or the ionic core, have been used to measure the order. Unfortunately, because they are only weakly sensitive to valence electrons and yield superposition of signals from distinct mesoscopic phases, they cannot directly image mesoscopic phase coexistence and charge ordering, two key features of the manganites. Here we describe the first experiment to image charge ordering and phase separation in real space with atomic-scale resolution in a transition metal oxide. Our scanning tunneling microscopy (STM) data show that charge order is correlated with structural order, as well as with whether the material is locally metallic or insulating, thus giving an atomic-scale basis for descriptions of the manganites as mixtures of electronically and structurally distinct phases.Comment: 8 pages, 4 figures, 19 reference

Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Effects of serum proteins on corrosion behavior of ISO 5832–9 alloy modified by titania coatings

Stainless steel ISO 5832–9 type is often used to perform implants which operate in protein-containing physiological environments. The interaction between proteins and surface of the implant may affect its corrosive properties. The aim of this work was to study the effect of selected serum proteins (albumin and γ-globulins) on the corrosion of ISO 5832–9 alloy (trade name M30NW) which surface was modified by titania coatings. These coatings were obtained by sol– gel method and heated at temperatures of 400 and 800 °C. To evaluate the effect of the proteins, the corrosion tests were performed with and without the addition of proteins with concentration of 1 g L−1 to the physiological saline solution (0.9 % NaCl, pH 7.4) at 37 °C. The tests were carried out within 7 days. The following electrochemical methods were used: open circuit potential, linear polarization resistance, and electrochemical impedance spectroscopy. In addition, surface analysis by optical microscopy and X-ray photoelectron spectroscopy (XPS) method was done at the end of weekly corrosion tests. The results of corrosion tests showed that M30NW alloy both uncoated and modified with titania coatings exhibits a very good corrosion resistance during weekly exposition to corrosion medium. The best corrosion resistance in 0.9 % NaCl solution is shown by alloy samples modified by titania coating annealed at 400 °C. The serumproteins have no significant effect onto corrosion of investigated biomedical steel. The XPS results confirmed the presence of proteins on the alloy surface after 7 days of immersion in proteincontaining solutions.The investigations were supported by the National Science Centre project No. N N507 501339. The authors gratefully acknowledge Dr. Janusz Sobczak and Dr. hab. Wojciech Lisowski from Institute of Physical Chemistry of PAS for XPS surface analyses

Association of NPAC score with survival after acute myocardial infarction

BACKGROUND AND AIMS: Risk stratification in acute myocardial infarction (AMI) is important for guiding clinical management. Current risk scores are mostly derived from clinical trials with stringent patient selection. We aimed to establish and evaluate a composite scoring system to improve short-term mortality classification after index episodes of AMI, independent of electrocardiography (ECG) pattern, in a large real-world cohort. METHODS: Using electronic health records, patients admitted to our regional teaching hospital (derivation cohort, n = 1747) and an independent tertiary care center (validation cohort, n = 1276), with index acute myocardial infarction between January 2013 and December 2017, as confirmed by principal diagnosis and laboratory findings, were identified retrospectively. RESULTS: Univariate logistic regression was used as the primary model to identify potential contributors to mortality. Stepwise forward likelihood ratio logistic regression revealed that neutrophil-to-lymphocyte ratio, peripheral vascular disease, age, and serum creatinine (NPAC) were significant for 90-day mortality (Hosmer- Lemeshow test, p = 0.21). Each component of the NPAC score was weighted by beta-coefficients in multivariate analysis. The C-statistic of the NPAC score was 0.75, which was higher than the conventional Charlson's score (C-statistic = 0.63). Judicious application of a deep learning model to our dataset improved the accuracy of classification with a C-statistic of 0.81. CONCLUSIONS: The NPAC score comprises four items from routine laboratory parameters to basic clinical information and can facilitate early identification of cases at risk of short-term mortality following index myocardial infarction. Deep learning model can serve as a gatekeeper to facilitate clinical decision-making

Territory-Wide Chinese Cohort of Long QT Syndrome: Random Survival Forest and Cox Analyses

Introduction: Congenital long QT syndrome (LQTS) is a cardiac ion channelopathy that predisposes affected individuals to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD). The main aims of the study were to: (1) provide a description of the local epidemiology of LQTS, (2) identify significant risk factors of ventricular arrhythmias in this cohort, and (3) compare the performance of traditional Cox regression with that of random survival forests. / Methods: This was a territory-wide retrospective cohort study of patients diagnosed with congenital LQTS between 1997 and 2019. The primary outcome was spontaneous VT/VF. / Results: This study included 121 patients [median age of initial presentation: 20 (interquartile range: 8–44) years, 62% female] with a median follow-up of 88 (51–143) months. Genetic analysis identified novel mutations in KCNQ1, KCNH2, SCN5A, ANK2, CACNA1C, CAV3, and AKAP9. During follow-up, 23 patients developed VT/VF. Univariate Cox regression analysis revealed that age [hazard ratio (HR): 1.02 (1.01–1.04), P = 0.007; optimum cut-off: 19 years], presentation with syncope [HR: 3.86 (1.43–10.42), P = 0.008] or VT/VF [HR: 3.68 (1.62–8.37), P = 0.002] and the presence of PVCs [HR: 2.89 (1.22–6.83), P = 0.015] were significant predictors of spontaneous VT/VF. Only initial presentation with syncope remained significant after multivariate adjustment [HR: 3.58 (1.32–9.71), P = 0.011]. Random survival forest (RSF) model provided significant improvement in prediction performance over Cox regression (precision: 0.80 vs. 0.69; recall: 0.79 vs. 0.68; AUC: 0.77 vs. 0.68; c-statistic: 0.79 vs. 0.67). Decision rules were generated by RSF model to predict VT/VF post-diagnosis. / Conclusions: Effective risk stratification in congenital LQTS can be achieved by clinical history, electrocardiographic indices, and different investigation results, irrespective of underlying genetic defects. A machine learning approach using RSF can improve risk prediction over traditional Cox regression models

Multi-cancer early detection test sensitivity for cancers with and without current population-level screening options

There are four solid tumors with common screening options in the average-risk population aged 21 to 75 years (breast, cervical, colorectal, and, based on personalized risk assessment, prostate), but many cancers lack recommended population screening and are often detected at advanced stages when mortality is high. Blood-based multi-cancer early detection tests have the potential to improve cancer mortality through additional population screening. Reported here is a post-hoc analysis from the third Circulating Cell-free Genome Atlas substudy to examine multi-cancer early detection test performance in solid tumors with and without population screening recommendations and in hematologic malignancies. Participants with cancer in the third Circulating Cell-free Genome Atlas substudy analysis were split into three subgroups: solid screened tumors (breast, cervical, colorectal, prostate), solid unscreened tumors, and hematologic malignancies. In this post hoc analysis, sensitivity is reported for each subgroup across all ages and those aged ⩾50 years overall, by cancer, and by clinical cancer stage. Aggregate sensitivity in the solid screened, solid unscreened, and hematologic malignancy subgroups was 34%, 66%, and 55% across all cancer stages, respectively; restricting to participants aged ⩾50 years showed similar aggregate sensitivity. Aggregate sensitivity was 27%, 53%, and 60% across stages I to III, respectively. Within the solid unscreened subgroup, aggregate sensitivity was >75% in 8/18 cancers (44%) and >50% in 13/18 (72%). This multi-cancer early detection test detected cancer signals at high (>75%) sensitivity for multiple cancers without existing population screening recommendations, suggesting its potential to complement recommended screening programs. Clinical trial identifier: NCT02889978