Miracle-dz/UniFAR-FTUs huggingface dataset:
Apixaban to Prevent Venous Thromboembolism in Patients with Cancer

BACKGROUND Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS We conducted a randomized, placebo‐controlled, double‐blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate‐to‐high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow‐up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS Of the 574 patients who underwent randomization, 563 were included in the modified intention‐to‐treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention‐to‐treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P=0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate‐to‐high‐risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol‐Myers Squibb–Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.)
Recent Advances on Nitrofluorene Derivatives: Versatile Electron Acceptors to Create Dyes Absorbing from the Visible to the Near and Far Infrared Region

Push–pull dyes absorbing in the visible range have been extensively studied so that a variety of structures have already been synthesized and reported in the literature. Conversely, dyes absorbing in the near and far infrared region are more scarce and this particularity relies on the following points: difficulty of purification, presence of side-reaction during synthesis, low availability of starting materials, and low reaction yields. Over the years, several strategies such as the elongation of the π-conjugated spacer or the improvement of the electron-donating and accepting ability of both donors and acceptors connected via a conjugated or an aliphatic spacer have been examined to red-shift the absorption spectra of well-established visible dyes. However, this strategy is not sufficient, and the shift often remains limited. A promising alternative consists in identifying a molecule further used as an electron-accepting group and already presenting an absorption band in the near infrared region and to capitalize on its absorption to design near and far infrared absorbing dyes. This is the case with poly(nitro)fluorenes that already exhibit such a contribution in the near infrared region. In this review, an overview of the different dyes elaborated with poly(nitro)fluorenes is presented. The different applications where these different dyes have been used are also detailed.
Precut tissue for descemet stripping automated endothelial keratoplasty: complications are from technique, not tissue.

Endothelial keratoplasty (EK) has evolved dramatically over the past 8 years and one of the major advances has been the introduction of donor tissue, which has been processed by the distributing eye bank before the scheduled transplant surgery. The major advantage of using precut tissue is that the donor posterior lenticule can be examined and measured immediately after the resection of the anterior cap. Specular microscopy quantifying central endothelial cell density and slit lamp biomicroscopy evaluating tissue quality yield useful information that is available to the surgeon using precut tissue but not available when the surgeon cuts the tissue in the operating room. As a practical matter, using precut tissue should also offer the advantage of decreasing the workload, time, and risk the surgeons, otherwise, experience in preparing the tissue themselves. The disadvantage of precut tissue is that the surgeon passes control of this critical step of surgery to the eye bank technician and does not have the opportunity personally to observe any complications that may have occurred during donor processing. In addition, concerns have been raised as to the possibility of adverse tissue changes that may occur between the now extended time when the tissue is precut and the time it is transplanted.
The Effects of Load Stability and Visual Access During Asymmetric Lifting Tasks on Back and Upper Extremity Biomechanical Responses

Objective: To explore the change of muscular and biomechanical responses in different load stability and visual access conditions during an asymmetric lifting task. Background: Previous studies found that lifting unstable loads resulted in changes to the biomechanical loads experienced by the spine and upper extremities. However, researchers have not extensively investigated behaviors when people lift potentially unstable loads. It was hypothesized that lifting a potentially unstable load can lead to changes in lifting behavior, which may be mitigated by visual access to the load. Method: Fourteen volunteers lifted either a stable load or a potentially unstable load that could move within the container during the lifting task. In half of the lifting conditions, the box was covered to restrict visual access when lifting. Spine kinematic and kinetic measures and surface electromyographic (EMG) signals from back, shoulder, and arm muscles were obtained. Results: Lifts of the stable load were faster and generally had higher peak muscle activations than lifts of the potentially unstable load. Participants had less spine flexion when handling the potentially unstable load without visual access. Conclusion: When lifting and moving a potentially unstable load that could lead to a perturbation, people tended to lift the container more slowly comparing with lifting a stable load, which in turn reduced the peak muscle activities. Application: In industry, there are many work situations where workers need to lift or carry unstable loads that can shift during transport. Providing visual access to the load may help mitigate some of these effects.
Autonomic Tone Variations Before the Onset of Paroxysmal Atrial Fibrillation

Background—Mechanisms favoring the occurrence of paroxysmal atrial fibrillation (PAF) are complex and poorly defined. This study was designed to analyze dynamic changes in autonomic tone preceding the onset of PAF in a large group of patients. Methods and Results—Holter tapes from 77 unselected consecutive patients (63 men and 14 women aged 58±12 years) with PAF were analyzed. A total of 147 episodes of sustained AF (>30 minutes) were recorded and submitted to time-domain and frequency-domain heart rate variability analyses; 6 periods were studied using repeated measures ANOVA: the 24-hour period, the hour preceding PAF, and the 20 minutes before PAF divided into four 5-minute periods. In the time-domain analyses, a linear decrease in mean RR interval from 925±16 to 906±16 ms (P <0.0002) was observed before the onset of PAF, together with a significant increase in the standard deviation of NN intervals from 65±4 to 70±4 ms (P <0.02). In the frequency-domain analyses, a significant increase in high-frequency (HF, HF-NU) components was observed before PAF (P <0.001 and P <0.0001, respectively), together with a progressive decrease in low-frequency components (LF, LF-NU) (P <0.0001 and P <0.004, respectively). The low/high frequency ratio showed a linear increase until 10 minutes before PAF, followed by a sharp decrease immediately before PAF, suggesting a primary increase in adrenergic tone followed by a marked modulation toward vagal predominance. No difference was observed in these heart rate variability changes between patients with “lone” PAF and patients with structural heart disease. Conclusions—The occurrence of PAF greatly depends on variations of the autonomic tone, with a primary increase in adrenergic tone followed by an abrupt shift toward vagal predominance.
ELECTRON MICROSCOPIC STUDIES ON STREPTOCOCCI

The presence of M antigens on group A streptococci is associated with hairlike fimbriae that cover the surface of the streptococcal cell wall and are demonstrable by electron microscopy. These fimbriae also may be associated with R antigen. Like M protein, the surface fimbriae are destroyed by trypsin treatment and reappear when "trypsinized" streptococci are reincubated in fresh, trypsin-free broth. Ferritin-conjugated, type-specific antibodies localize on homologous M+ cells in a pattern suggestive of several M antigenic sites along the length of individual surface fimbria. The M-associated fimbriae remain on the residual cell wall after removal of the bulk of group-specific polysaccharide through nitrous acid extraction. This suggests attachment of the fimbriae to the mucopeptide and minor polysaccharide components remaining in the nitrous acid-extracted wall. The pattern of localization of ferritin-conjugated antibodies on homologous streptococci before and after trypsin exposure and upon reincubation of the trypsinized cells in fresh medium suggests the following hypothesis: M antigen is secreted by the cell, is partially excreted through the otherwise intact cell wall, and is bound by the wall so that M protein occupies a peripheral, exposed position on the surfaces of the streptococcal cell wall.
Downregulation of the Central Noradrenergic System by Toxoplasma gondii Infection

Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. ABSTRACT Toxoplasma gondii is associated with physiological effects in the host. Dysregulation of catecholamines in the central nervous system has previously been observed in chronically infected animals. In the study described here, the noradrenergic system was found to be suppressed with decreased levels of norepinephrine (NE) in brains of infected animals and in infected human and rat neural cells in vitro. The mechanism responsible for the NE suppression was found to be downregulation of dopamine β-hydroxylase (DBH) gene expression, encoding the enzyme that synthesizes norepinephrine from dopamine, with downregulation observed in vitro and in infected brain tissue, particularly in the dorsal locus coeruleus/pons region. The downregulation was sex specific, with males expressing reduced DBH mRNA levels whereas females were unchanged. Rather, DBH expression correlated with estrogen receptor in the female rat brains for this estrogen-regulated gene. DBH silencing was not a general response of neurons to infection, as human cytomegalovirus did not downregulate DBH expression. The noradrenergic-linked behaviors of sociability and arousal were altered in chronically infected animals, with a high correlation between DBH expression and infection intensity. A decrease in DBH expression in noradrenergic neurons can elevate dopamine levels, which provides a possible explanation for mixed observations of changes in this neurotransmitter with infection. Decreased NE is consistent with the loss of coordination and motor impairments associated with toxoplasmosis. Further, the altered norepinephrine synthesis observed here may, in part, explain behavioral effects of infection and associations with mental illness.
Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases

Purpose: The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. Experimental Design: The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Results: Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of ≥85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had ≥2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 ± 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had ≥2 CTCs. Detection of ≥2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. Conclusions: The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
Prolonged action potential duration and dynamic transmural action potential duration heterogeneity underlie vulnerability to ventricular tachycardia in patients undergoing ventricular tachycardia ablation

Abstract Aims Differences of action potential duration (APD) in regions of myocardial scar and their borderzones are poorly defined in the intact human heart. Heterogeneities in APD may play an important role in the generation of ventricular tachycardia (VT) by creating regions of functional block. We aimed to investigate the transmural and planar differences of APD in patients admitted for VT ablation. Methods and results Six patients (median age 53 years, five male); (median ejection fraction 35%), were studied. Endocardial (Endo) and epicardial (Epi) 3D electroanatomic mapping was performed. A bipolar voltage of <0.5 mV was defined as dense scar, 0.5–1.5 mV as scar borderzone, and >1.5 mV as normal. Decapolar catheters were positioned transmurally across the scar borderzone to assess differences of APD and repolarization time (RT) during restitution pacing from Endo and Epi. Epi APD was 173 ms in normal tissue vs. 187 ms at scar borderzone and 210 ms in dense scar (P < 0.001). Endocardial APD was 210 ms in normal tissue vs. 222 ms in the scar borderzone and 238 ms in dense scar (P < 0.01). This resulted in significant transmural RT dispersion (ΔRT 22 ms across dense transmural scar vs. 5 ms in normal transmural tissue, P < 0.001), dependent on the scar characteristics in the Endo and Epi, and the pacing site. Conclusion Areas of myocardial scar have prolonged APD compared with normal tissue. Heterogeneity of regional transmural and planar APD result in localized dispersion of repolarization, which may play an important role in initiating VT.
A SUMOylation-dependent switch of RAB7 governs intracellular life and pathogenesis of Salmonella Typhimurium

ABSTRACT Salmonella Typhimurium is an intracellular pathogen that causes gastroenteritis in humans. Aided by a battery of effector proteins, S. Typhimurium resides intracellularly in a specialized vesicle, called the Salmonella-containing vacuole (SCV) that utilizes the host endocytic vesicular transport pathway (VTP). Here, we probed the possible role of SUMOylation, a post-translation modification pathway, in SCV biology. Proteome analysis by complex mass-spectrometry (MS/MS) revealed a dramatically altered SUMO-proteome (SUMOylome) in S. Typhimurium-infected cells. RAB7, a component of VTP, was key among several crucial proteins identified in our study. Detailed MS/MS assays, in vitro SUMOylation assays and structural docking analysis revealed SUMOylation of RAB7 (RAB7A) specifically at lysine 175. A SUMOylation-deficient RAB7 mutant (RAB7K175R) displayed longer half-life, was beneficial to SCV dynamics and functionally deficient. Collectively, the data revealed that RAB7 SUMOylation blockade by S. Typhimurium ensures availability of long-lived but functionally compromised RAB7, which was beneficial to the pathogen. Overall, this SUMOylation-dependent switch of RAB7 controlled by S. Typhimurium is an unexpected mode of VTP pathway regulation, and unveils a mechanism of broad interest well beyond Salmonella–host crosstalk. This article has an associated First Person interview with the first author of the paper. Summary: Manipulation of host SUMOylation by Salmonella Typhimurium governs the function of master regulator RAB7, a phenomenon with implications in intracellular pathogenesis and inflammatory diseases of the gut.
Teaching a Point-of-Care Ultrasound Curriculum to Anesthesiology Trainees With Traditional Didactic Lectures or an Online E-Learning Platform: A Pilot Study.

Background Point-of-care ultrasonography (PoCUS) provides real-time, dynamic clinical evidence for providers to make potentially lifesaving medical decisions; however, these tools cannot be used effectively without appropriate training. Although there is always the option of traditional didactic methods, there has been a recent trend toward a "reverse classroom" web-based model using online e-learning modules. Our objective was to collect pilot data that would justify a future randomized controlled trial, comparing traditional didactics to an e-learning PoCUS curriculum for lung ultrasonography (LUS) and the focused assessment with sonography in trauma (FAST) exam. Methods Anesthesiology interns, residents (CA 1-3), and fellow trainees enrolled in a LUS and FAST exam course and were randomized to receive didactic lectures or e-learning. Trainees completed knowledge pre- and posttests. Surveys were administered to gauge learning satisfaction. All trainees completed a hands-on-training (HOT) workshop. Image acquisition was assessed through practical tests before HOT, immediately after HOT, and 5 months later. Results Eighteen trainees completed the study. There was no evidence of a difference in change in LUS knowledge test score from baseline to posttest between the e-learning and didactic groups (difference in median percentage point change [95 % CI]: 6.6 [-10.0, 23.2]; P = .411). There was no evidence of a difference in LUS knowledge posttest scores (difference in median percentage points [95% CI]: -0.9 [-4.8, 3.0]; P = .629), FAST knowledge posttest score (0 [incalculable]; P = .999), or post-HOT practical test score (-4.2 [-24.6, 16.3]; P = .672) between groups. There was no evidence of a difference in degree of satisfaction with learning experience between groups (odds ratios [95% CI]: 1.75 [0.31, 9.94]; P = .528). Conclusions There was no evidence of a difference between the e-learning and traditional didactic groups in learning or satisfaction outcomes. These results justify establishing an adequately powered, randomized controlled trial assessing the noninferiority of e-learning to traditional didactics for teaching LUS and FAST.
Administration of Momordica charantia Enhances the Neuroprotection and Reduces the Side Effects of LiCl in the Treatment of Alzheimer’s Disease

Recently, the use of natural food supplements to reduce the side effects of chemical compounds used for the treatment of various diseases has become popular. Lithium chloride (LiCl) has some protective effects in neurological diseases, including Alzheimer’s disease (AD). However, its toxic effects on various systems and some relevant interactions with other drugs limit its broader use in clinical practice. In this study, we investigated the in vitro and in vivo pharmacological functions of LiCl combined with Momordica charantia (MC) in the treatment of AD. The in vitro results show that the order of the neuroprotective effect is MC5, MC3, MC2, and MC5523 under hyperglycemia or tau hyperphosphorylation. Therefore, MC5523 (80 mg/kg; oral gavage) and/or LiCl (141.3 mg/kg; intraperitoneal injection) were applied to ovariectomized (OVX) 3×Tg-AD female and C57BL/6J (B6) male mice that received intracerebroventricular injections of streptozotocin (icv-STZ, 3 mg/kg) for 28 days. We found that the combined treatment not only increased the survival rate by reducing hepatotoxicity but also increased neuroprotection associated with anti-gliosis in the icv-STZ OVX 3×Tg-AD mice. Furthermore, the cotreatment with MC5523 and LiCl prevented memory deficits associated with reduced neuronal loss, gliosis, oligomeric Aβ level, and tau hyperphosphorylation and increased the expression levels of synaptic-related protein and pS9-GSK3β (inactive form) in the icv-STZ B6 mice. Therefore, MC5523 combined with LiCl could be a potential strategy for the treatment of AD.
The relationship between maternal anemia during pregnancy with preterm birth: a systematic review and meta-analysis

Abstract Objective: Iron deficiency anemia is the most common cause of anemia during pregnancy. Other causes of anemia include parasitic diseases, micronutrient deficiencies, and genetic hemoglobin apathies. Maternal anemia during pregnancy is the most important public health problem. Since the relationship between maternal anemia by the months of pregnancy and premature birth has been reported differently in various studies; thus, this study aims to determine the relationship between maternal anemia during pregnancy and premature birth. Methods: This systematic review and meta-analysis article was designed based on the recommendations of PRISMA. This study was performed from 1990 to 2018. Articles extracted using related keywords such as maternal, anemia, premature birth, and pregnancy in databases, including Cochrane, Medline, Medlib, Web of Science, PubMed, Scopus, Springer, Science Direct, Embase, Google Scholar, Sid, Irandoc, Iranmedex, and Magiran. Relative risk and its confidence interval were extracted from each of the studies. The random effects model was used to combine study results and heterogeneity among the studies measured using I2 index and the data were analyzed based by using STATA software version 3.2. Results: Overall 18 studies with sample sizes of 932 090 were entered into the meta-analysis. The overall relationship between maternal anemia during pregnancy and premature birth was significant (1.56 [95% CI: 1.25–1.95]). Maternal anemia in the first trimester increases the risk of premature birth (relative risk, 1.65 [95% CI: 1.31–2.08]). But, this relationship was not significant in the second (relative risk, 1.45 [95% CI: 0.79–2.65]) and third trimester (relative risk, 1.43 [95% CI: 0.82–2.51]). Conclusion: Maternal anemia during pregnancy can be considered as a risk factor for premature birth.