Miracle-dz/UniFAR-FTUs huggingface dataset:
Motor control of an insect leg during level and incline walking

ABSTRACT During walking, the leg motor system must continually adjust to changes in mechanical conditions, such as the inclination of the ground. To understand the underlying control, it is important to know how changes in leg muscle activity relate to leg kinematics (movements) and leg dynamics (forces, torques). Here, we studied these parameters in hindlegs of stick insects (Carausius morosus) during level and uphill/downhill (±45 deg) walking, using a combination of electromyography, 3D motion capture and ground reaction force measurements. We find that some kinematic parameters including leg joint angles and body height vary across walking conditions. However, kinematics vary little compared with dynamics: horizontal leg forces and torques at the thorax–coxa joint (leg protraction/retraction) and femur–tibia joint (leg flexion/extension) tend to be stronger during uphill walking and are reversed in sign during downhill walking. At the thorax–coxa joint, the different mechanical demands are met by adjustments in the timing and magnitude of antagonistic muscle activity. Adjustments occur primarily in the first half of stance after the touch-down of the leg. When insects transition from level to incline walking, the characteristic adjustments in muscle activity occur with the first step of the leg on the incline, but not in anticipation. Together, these findings indicate that stick insects adjust leg muscle activity on a step-by-step basis so as to maintain a similar kinematic pattern under different mechanical demands. The underlying control might rely primarily on feedback from leg proprioceptors signaling leg position and movement. Highlighted Article: In stick insect hindlegs, muscle activity is adjusted to different mechanical demands during walking, primarily early in stance. Adjustments strongly affect forces/torques but not kinematics and suggest step-by-step control.
Eligibility for a Shorter Treatment Regimen for Multidrug-resistant Tuberculosis in the United States, 2011-2016.

BACKGROUND In 2016, the World Health Organization (WHO) recommended a shorter (9-12 month) multidrug-resistant tuberculosis (MDR-TB) treatment regimen (as compared to the conventional 18-24 month regimen) for patients without extrapulmonary TB, pregnancy, previous second-line TB medication exposure, or drug resistance to pyrazinamide, ethambutol, kanamycin, moxifloxacin, ethionamide, or clofazimine. The recommendation was based on successful clinical trials conducted in Asia and Africa, but studies, using mainly European data, have shown few patients in higher resource settings would meet WHO eligibility criteria. METHODS We assessed eligibility for the shorter regimen among U.S. MDR-TB cases that had full drug susceptibility testing (DST) results and were reported during 2011-2016 to the U.S. National TB Surveillance System. We estimated costs by applying the eligibility criteria for the shorter regimen, and proportional inpatient/outpatient costs from a previous population-based study to all MDR-TB patients reported to NTSS. RESULTS Of 586 reported MDR cases, 10% (59) were eligible for the shorter regimen. Of 527 ineligible patients, 386 had full DST, of which 246 were resistant to ethambutol and 217 resistant to pyrazinamide. Compared with conventional MDR-TB treatment, implementing the shorter regimen would reduce the U.S. annual societal MDR-TB cost burden by 4%, but the cost burden for eligible individuals would be reduced by 37-46%. CONCLUSIONS Relying on full DST use, our analysis found a minority of U.S. MDR-TB patients would be eligible for the shorter regimen. Cost reductions would be minimal for society, but large for eligible individuals.
Nerve growth factor is expressed and stored in central neurons of adult zebrafish

Nerve growth factor (NGF), a member of the neurotrophin family, was initially described as neuronal survival and growth factor, but successively has emerged as an active mediator in many essential functions in the central nervous system of mammals. NGF is synthesized as a precursor pro‐NGF and is cleaved intracellularly into mature NGF. However, recent evidence demonstrates that pro‐NGF is not a simple inactive precursor, but is also secreted outside the cells and can exert multiple roles. Despite the vast literature present in mammals, studies devoted to NGF in the brain of other vertebrate models are scarce. Zebrafish is a teleost fish widely known for developmental genetic studies and is well established as model for translational neuroscience research. Genomic organization of zebrafish and mouse NGF is highly similar, and zebrafish NGF protein has been reported in mature and two‐precursors forms. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the NGF mRNA and protein distribution in the adult zebrafish brain and to characterize the phenotype of NGF‐positive cells. NGF mRNA was visualized by in situ hybridization on whole‐mount brains. NGF protein distribution was assessed on microtomic sections by using an antiserum against NGF, able to recognize pro‐NGF in adult zebrafish brain as demonstrated also in previous studies. To characterize NGF‐positive cells, anti‐NGF was employed on microtomic slides of aromatase B transgenic zebrafish (where radial glial cells appeared fluorescent) and by means of double‐immunolabeling against NGF/proliferative cell nuclear antigen (PCNA; proliferation marker) and NGF/microtube‐associated protein2 (MAP2; neuronal marker). NGF mRNA and protein were widely distributed in the brain of adult zebrafish, and their pattern of distribution of positive perikaryal was overlapping, both in males and females, with few slight differences. Specifically, the immunoreactivity to the protein was observed in fibers over the entire encephalon. MAP2 immunoreactivity was present in the majority of NGF‐positive cells, throughout the zebrafish brain. PCNA and aromatase B cells were not positive to NGF, but they were closely intermingled with NGF cells. In conclusion, our study demonstrated that mature neurons in the zebrafish brain express NGF mRNA and store pro‐NGF.
PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice

Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self‐renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate the proliferation and differentiation of SMSCs and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes the effects of hypoxia on preferential self‐renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to the tricarboxylic acid (TCA) cycle by producing acetyl coenzyme A from pyruvate. PDH kinase 1, highly expressed under hypoxia, is down‐regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin‐deficient mouse model of Duchenne muscular dystrophy. Thus, the flow from glycolysis to the TCA cycle mediated by PDH plays a pivotal role in the differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration. —Hori, S. , Hiramuki, Y. , Nishimura, D. , Sato, F. , Sehara‐Fujisawa, A. PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. FASEB J. 33, 8094–8109 (2019). www.fasebj. org
Culture of Rectal Swab Specimens for Enteric Bacterial Pathogens Decreases Time to Test Result While Preserving Assay Sensitivity Compared to Bulk Fecal Specimens

Diarrheal illness is a major cause of morbidity and mortality throughout the world, yet the etiologic agent of many cases of gastrointestinal illness remains unspecified, often due to the lack of convenient, timely, and sensitive diagnostic testing. Although bulk fecal specimens remain the recommended specimen type for enteric culture, rectal swabs may be an option preferred by clinicians and patients due to the convenience and timing of collection. ABSTRACT Diarrheal illness is a major cause of morbidity and mortality throughout the world, yet the etiologic agent of many cases of gastrointestinal illness remains unspecified, often due to the lack of convenient, timely, and sensitive diagnostic testing. Although bulk fecal specimens remain the recommended specimen type for enteric culture, rectal swabs may be an option preferred by clinicians and patients due to the convenience and timing of collection. However, the lack of data evaluating the sensitivity of rectal swabs compared to fecal specimens for detection of enteric pathogens precludes this specimen type from being recommended by national guidelines. In this study, we retrospectively reviewed 480 paired rectal swab and fecal specimens submitted for enteric culture to the Barnes-Jewish Hospital and St. Louis Children’s Hospital microbiology laboratories in St. Louis, MO, from 2002 to 2017. We report 32% positivity of paired specimens with an overall agreement of 93% and Cohen's κ of 0.84 (95% confidence interval, 0.78 to 0.89). Additionally, we evaluated the time to result from the time of patient presentation to the health care setting and demonstrate that rectal swabs have a significantly shorter time to an actionable result than bulk fecal specimens (median, 67.4 h versus 78.4 h, respectively; P < 0.001). These findings indicate that rectal swabs facilitate on-demand culture-based testing with a sensitivity comparable to that of fecal specimens and thus should be recommended for enteric bacterial culture when bulk fecal specimens are unavailable.
Human peripheral blood-derived exosomes for microRNA delivery

Exosomes serve important functions in cell-to-cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood-derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR-21 using a human peripheral blood derived-exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL-1 cells, miR-21 expression was successfully regulated by treatment with human peripheral blood derived-exosomes loaded with an miR-21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR-21 mimic- or inhibitor-loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR-21 mimic- or inhibitor-loaded exosomes. Furthermore, miR-21 mimic-loaded exosomes enhanced fibrosis, whereas miR-21 inhibitor-loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA-loaded human peripheral blood derived-exosomes may be used as a therapeutic tool for cardiac diseases.
Re-transmissibility of mouse-adapted ME7 scrapie strain to ovine PrP transgenic mice

Scrapie is a mammalian transmissible spongiform encephalopathy or prion disease that predominantly affects sheep and goats. Scrapie has been shown to overcome the species barrier via experimental infection of other rodents. To confirm the re-transmissibility of the mouse-adapted ME7 scrapie strain to ovine prion protein (PrP) transgenic mice, mice of an ovinized transgenic mouse line carrying the Suffolk sheep PrP gene that contained the A136 R154 Q171/ARQ allele were intracerebrally inoculated with brain homogenates obtained from terminally ill ME7-infected C57BL/6J mice. Herein, we report that the mouse-adapted ME7 scrapie strain was successfully re-transmitted to the transgenic mice expressing ovine PrP. In addition, we observed changes in the incubation period, glycoform profile, and pattern of scrapie PrP (PrPSc) deposition in the affected brains. PrPSc deposition in the hippocampal region of the brain of 2nd-passaged ovine PrP transgenic mice was accompanied by plaque formation. These results reveal that the mouse-adapted ME7 scrapie strain has the capacity to act as a template for the conversion of ovine normal monomeric precursors into a pathogenic form in ovine PrP transgenic mice. The change in glycoform pattern and the deposition of plaques in the hippocampal region of the brain of the 2nd-passaged PrP transgenic mice are most likely cellular PrP species dependent rather than being ME7 scrapie strain encoded.
Risk and Predictors of Esophageal and Stomach Cancers in HIV-Infected Veterans: A Matched Cohort Study.

BACKGROUND To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. SETTING Retrospective cohort study in the Veterans Health Administration. METHODS We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. RESULTS In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). CONCLUSION HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.
Synergistic antitumor effect of anti‐PD‐L1 combined with oxaliplatin on a mouse tumor model

Oxaliplatin (OXP) can change tumor microenvironment from immune‐suppressive toward the immune‐favorable condition. Almost all of the antitumor agents cannot totally cure cancer as monotherapy. So the current focus of cancer research became combining therapy using different treatment regimen, especially chemotherapy with checkpoint blockers. In this study, we assessed the activity of combining regimen using anti‐PD‐L1 with OXP in CT26 tumor‐bearing BALB/c mice. We further analyzed the immune cell phenotypes in tumor site, lymph nodes, and spleen by flow cytometry analysis. Our study showed that combination therapy with OXP and anti‐PD‐L1 significantly increased survival in vivo and inhibited tumor growth of tumor‐bearing mice. Inconsistent with better antitumor activity, our combination therapy led to an increase in tumor‐infiltrating activated CD8+ T cells. In draining lymph nodes and spleen, regulatory T cells decreased significantly. Mice receiving either anti‐PD‐L1 or OXP alone had a larger tumor and lower survival rate in comparison with combination therapy receiving group. The time and order of administration of each component of the combination therapy affected antitumor response.
Long‐Term Outcomes Following Heart Team Revascularization Recommendations in Complex Coronary Artery Disease

Background The Heart Team (HT) comprises integrated interdisciplinary decision making. Current guidelines assign a Class Ic recommendation for an HT approach to complex coronary artery disease (CAD). However, there remains a paucity of data in regard to hard clinical end points. The aim was to determine characteristics and outcomes in patients with complex CAD following HT discussion. Methods and Results This observational study was conducted at St Thomas’ Hospital (London, UK). Case mixture included unprotected left main, 2‐vessel (including proximal left anterior descending artery) CAD, 3‐vessel CAD, or anatomical and/or clinical equipoise. HT strategy was defined as optimal medical therapy (OMT) alone, OMT+percutaneous coronary intervention (PCI), or OMT+coronary artery bypass grafting. From April 2012 to 2013, 51 HT meetings were held and 398 cases were discussed. Patients tended to have multivessel CAD (74.1%), high SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) scores (median, 30; interquartile range, 23–39), and average age 69±11 years. Multinomial logistic regression analysis performed to determine variables associated with HT strategy demonstrated decreased likelihood of undergoing PCI compared with OMT in older patients with chronic kidney disease and peripheral vascular disease. The odds of undergoing coronary artery bypass grafting compared with OMT decreased in the presence of cardiogenic shock and left ventricular dysfunction and increased in younger patients with 3‐vessel CAD. Three‐year survival was 60.8% (84 of 137) in the OMT cohort, 84.3% (107 of 127) in the OMT+PCI cohort, and 90.2% in the OMT+coronary artery bypass grafting cohort (92 of 102). Conclusions In our experience, the HT approach involved a careful selection process resulting in appropriate patient‐specific decision making and good long‐term outcomes in patients with complex CAD.
Treatment of Crohn’s anal fistulas guided by magnetic resonance imaging

Introduction Clinical evaluation of the Crohn’s anal fistulas (CF) closure is inadequate to some extent due to earlier closure of cutaneous openings compared to fistulous tracts. There is a need for a more accurate method of assessment. Aim To compare clinical signs of CF with radiological findings, before and after treatment, to follow complete closure. Material and methods It was a retrospective study of 23 patients suffering from CF admitted to a single specialist centre, who were treated with a combination of surgical and biological therapy. Fistula healing was evaluated with fistula drainage assessment classification (FDA), perianal disease activity index (PDAI), and van Assche magnetic resonance imaging score (MRI) before and 3 months after surgery and induction of the biological treatment. Results Clinical response occurred in 13 (57%) patients 3 months after induction treatment. Complete clinical response was achieved in 8 (35%) patients, whereas partial response occurred in 5 (22%) patients. Persistence of a fistula tract was visualised on MRI in 4 (50%) patients with clinical closure. Conclusions The healing process of CF should be monitored by MRI due to the discrepancy between premature closure of external openings and fistulous tracts. Prolonged biological therapy until complete healing of anal fistulas confirmed on MRI might improve the results of treatment.
Procedure-specific Training for Robot-assisted Distal Pancreatectomy.

MINI: Cohort study (n = 237) describing a training program to teach robot-assisted distal pancreatectomy to surgeons at an academic institution and assess its impact on outcomes. After training, perioperative blood loss and length of stay improved, while complication rates remained unchanged. Propensity-score matching confirmed a 2-day reduction in length of stay after RADP. OBJECTIVE To train practicing surgeons in robot-assisted distal pancreatectomy (RADP) and assess the impact on 5 domains of healthcare quality. BACKGROUND RADP may reduce the treatment burden compared with open distal pancreatectomy (ODP), but studies on institutional training and implementation programs are scarce. METHODS A retrospective, single-center, cohort study evaluating surgical performance during a procedure-specific training program for RADP (January 2006 to September 2017). Baseline and unadjusted outcomes were compared "before training" (ODP only; June 2012). Exclusion criteria were neoadjuvant therapy, vascular- and unrelated organ resection. Run charts evaluated index length of stay (LOS) and 90-day comprehensive complication index. Cumulative sum charts of operating time (OT) assessed institutional learning. Adjusted outcomes after RADP versus ODP were compared using a secondary propensity-score-matched (1:1) analysis to determine clinical efficacy. RESULTS After screening, 237 patients were included in the before-training (133 ODP) and after-training (24 ODP, 80 RADP) groups. After initiation of training, mean perioperative blood loss decreased (-255 mL, P<0.001), OT increased (+65 min, P < 0.001), and median LOS decreased (-1 day, P < 0.001). All other outcomes remained similar (P>0.05). Over time, there were nonrandom (P < 0.05) downward shifts in LOS, while comprehensive complication index was unaffected. We observed 3 learning curve phases in OT: accumulation (<31 cases), optimization (case 31-65), and a steady-state (>65 cases). Propensity-score-matching confirmed reductions in index and 90-day LOS and blood loss with similar morbidity between RADP and ODP. CONCLUSION Supervised procedure-specific training enabled successful implementation of RADP by practicing surgeons with immediate improvements in length of stay, without adverse effects on safety.
Expression of a 1-aminocyclopropane-1-carboxylate (ACC) oxidase gene in peach ( Prunus persica L.) fruit in response to treatment with carbon dioxide and 1-methylcyclopropene: possible role of ethylene

In this study we investigated the effect of exogenous ethylene treatment on ethylene production, 1-aminocyclopropane-1-carboxylate (ACC) oxidase activity and expression of an ACC oxidase (PP-ACO1) gene previously cloned (Mathooko et al., 2001) in peach ( Prunus persica L.) fruit. We also investigated the mode of action of CO 2 and 1-methycyclopropene (1-MCP) in the regulation of ethylene biosynthesis during peach fruit ripening. Fruits were treated with various concentrations of ethylene (0.1, 1, 10, 100, 500, 1000 ppm) and also with CO 2 and 1-MCP in the presence or absence of 500 ppm ethylene. Ethylene stimulated ethylene production at concentrations of 100 ppm and above while ACC oxidase activity was stimulated in a concentration-dependent manner. PP-ACO1 was slightly constitutively expressed and exogenous ethylene stimulated accumulation of its mRNA transcript in a concentration-dependent manner up to 100 ppm after which the level remained constant. CO 2 and 1-MCP inhibited the ethylene-stimulated ethylene production, ACC oxidase activity and accumulation of PP-ACO1 transcripts by about 50%. These results indicate that ethylene plays a key role in the regulation of ethylene production and ACC oxidase activity and its gene expression in peach fruit. Further the results indicate that CO 2 and 1-MCP regulate ethylene biosynthesis in peach fruit during ripening, at least in part, by antagonizing ethylene action. Key Words: ACC oxidase, carbon dioxide, ehylene, 1-methylcyclopropene, peach, Prunus persica . African Journal of Biotechnology Vol.3(10) 2004: 497-502