Miracle-dz/UniFAR-FTUs huggingface dataset:
The human central nervous system transmits common synaptic inputs to distinct motor neuron pools during non‐synergistic digit actions

Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi‐muscle EMG recordings. We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un‐matched forces in different directions. We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control. The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire.
The use of the orbitofrontal H‐sulcus as a reference frame for value signals

Understanding the factors that drive organization and function of the brain is an enduring question in neuroscience. Using functional magnetic resonance imaging (fMRI), structure and function have been mapped in primary sensory cortices based on knowledge of the organizational principles that likely drive a given region (e.g., aspects of visual form in primary visual cortex and sound frequency in primary auditory cortex) and knowledge of underlying cytoarchitecture. The organizing principles of higher‐order brain areas that encode more complex signals, such as the orbitofrontal cortex (OFC), are less well understood. One fundamental component that underlies the many functions of the OFC is the ability to compute the reward or value of a given object. There is evidence of variability in the spatial location of responses to specific categories of objects (or value of said objects) within the OFC, and several reference frames have been proposed to explain this variability, including topographic spatial gradients that correspond to axes of primary versus secondary rewards and positive versus negative reinforcers. One potentially useful structural morphometric reference frame in the OFC is the “H‐sulcus,” a pattern formed by medial orbital, lateral orbital and transverse orbital sulci. In 48 human subjects, we use a structural morphometric tracing procedure to localize functional activation along the H‐sulcus for face and food stimuli. We report the novel finding that food‐selective responses are consistently found within the caudal portion of the medial orbital sulcus, but no consistency within the H‐sulcus for response to face stimuli. These results suggest that sulcogyral anatomy of the H‐sulcus may be an important morphological metric that contributes to the organizing principles of the OFC response to certain stimulus categories, including food.
Berberine attenuates olanzapine induced-metabolic syndrome.

Objective To elucidate the protective effect of berberine on olanzapine induced-metabolic syndrome. Methods This prospective experimental study involved thirty Sprague-Dawley male rats which were divided into three groups. Group A (n=10): Rats treated with distilled water, Group B (n=10): Rats treated with olanzapine, Group C (n=10): Rats treated with olanzapine plus berberine. The duration of the study was 8 weeks, baseline and follow up data were evaluated. Fasting blood glucose(FBG) total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL), Low density lipoprotein (LDL), atherogenic index of plasma (AI), fasting serum insulin level, insulin resistance, β- cell function and insulin sensitivity were evaluated.SPSS 20. Results Olanzepine led to significant deterioration in gluco-metabolic profile compared with control P<0.01. Olanzapine plus berberine improved body weight, FBG, FSI, HOMA-IR and QUICKI compared with olanzapine P=0.0001. Conclusions Berberine attenuates olanzapine induced-metabolic via amelioration of gluco-lipid disturbances.
Trends in the Incidence of Activities of Daily Living Disability Among Chinese Elderly from 2002-2014.

BACKGROUND Evidence of the trend of the incidence of activities of daily living (ADL) disability among Chinese older people is limited. We aimed to investigate the time trends and potential risk factors for the incidence of ADL disability among Chinese elderly (65+ years). METHODS We established two consecutive and non-overlapping cohorts (6,857 participants in the 2002 cohort and 5,589 participants in the 2008 cohort) from the Chinese Longitudinal Healthy Longevity Survey. ADL disability was defined as the need for assistance with at least one essential activity (dressing, bathing, toileting, eating, indoor activities, and continence). Cox proportional hazards models were used to identify factors associated with the trend in the incidence of ADL disability from 2002 to 2014. RESULTS The incidence (per 1,000 person-years) of ADL disability decreased significantly from 64.2 in the 2002 cohort to 46.6 in the 2008 cohort (P <0.001), and decreasing trends in the incidence of ADL disability were observed for all sex, age and residence subgroups (all P < 0.001), even after adjusting for multiple potential confounding factors. Moreover, we found that adjustment for sociodemographic, lifestyle information, and cardiovascular risk factors (hypertension, diabetes, heart disease and stroke) explained less of the decline in ADL disability during the period from 2002 to 2014. CONCLUSION The incidence of ADL disability among the elderly in China appears to have decreased during the study period, and this finding cannot be explained by existing sociodemographic and lifestyle information and cardiovascular risk factors.
A psychoacoustic application for the adjustment of electrical hearing thresholds in cochlear implant patients

Objective Fitting cochlear implants, especially the precise determination of electrical hearing thresholds, is a time-consuming and complex task for patients as well as audiologists. Aim of the study was to develop a method that enables cochlear implant (CI) patients to determine their electrical hearing thresholds precisely and independently. Applicability and impact of this method on speech perception in noise at soft speech levels were evaluated. Method An adaptive psychoacoustic procedure for precise hearing threshold determination (precT) was implemented using MatLab (MathWorks) and a graphical user interface was created. Sound signals were calibrated with a CIC4-Implant-Decoder. Study design: A prospective study including 15 experienced adult cochlear implant users was conducted. Electrical hearing thresholds were determined using the automated precT procedure (auto-precT). Speech perception in noise at 50 dB SPL presentation levels was measured for three conditions: (P1) T-levels kept at the previously established T-levels; (P2) T-levels set to the hearing thresholds determined using auto-precT application; (P3) T-levels set 10 cu below the values determined with auto-precT. Results All subjects were able to perform the auto-precT application independently. T-levels were altered on average by an absolute value of 10.5 cu using auto-precT. Median speech reception thresholds were significantly improved from 2.5 dB SNR (P1) to 1.6 dB SNR (P2, p = 0.02). Speech perception was lowest using the globally lowered T-levels, median 2.9 dB SNR (P3, not significant compared to P1 and P2). Conclusion The applicability of the developed auto-precT application was confirmed in the present clinical study. Patients benefited from adjusting previously established T-levels to the threshold levels determined by the auto-precT application. The integration of the application in the clinical fitting routine as well as a remote fitting software approach is recommended. Furthermore, future possibilities of auto-precT include the implementation of the application on tablets or smart phones.
Cardiac reinnervation affects cardiorespiratory adaptations to exercise training in individuals with heart transplantation

Purpose The purpose of this study was to investigate the hemodynamic and cardiorespiratory adaptations to exercise in individuals with heart transplantation with evidence of cardiac reinnervation (cardiac reinnervation group) versus without evidence of cardiac reinnervation (no cardiac reinnervation group). Methods Sedentary individuals with heart transplantation (age = 45.5 ± 2.2 years; time elapsed since surgery = 6.7 ± 0.7 years) were divided into the cardiac reinnervation (n = 16) and no cardiac reinnervation (n = 17) groups according to their heart rate response to cardiopulmonary exercise testing. The 24-hour ambulatory blood pressure, carotid-femoral pulse wave velocity, and cardiorespiratory fitness were assessed before and after 12 weeks of a thrice-weekly exercise program (five minutes of warm-up, 30 min of endurance exercise, one set of 10–15 reps in five resistance exercises, and five minutes of cool-down). Results The cardiac reinnervation group had reduced (p < 0.01) 24-hour systolic/diastolic blood pressure (7/9 mm Hg), daytime systolic/diastolic blood pressure (9/10 mm Hg) and nighttime diastolic blood pressure (6 mm Hg) after training. The no cardiac reinnervation group reduced (p < 0.05) only 24-hour (5 mm Hg), daytime (5 mm Hg) and nighttime (6 mm Hg) diastolic blood pressure after training. Hourly analysis showed that the cardiac reinnervation group reduced systolic/diastolic blood pressure for 10/21 h, while the no cardiac reinnervation group reduced systolic/diastolic blood pressure for only 3/11 h. The cardiac reinnervation group also improved both maximal oxygen consumption (10.8%) and exercise tolerance (13.4%) after training, but the no cardiac reinnervation group improved only exercise tolerance (9.9%). Pulse wave velocity did not change in both groups. Conclusion There were greater improvements in ambulatory blood pressure and maximal oxygen consumption in the cardiac reinnervation than the no cardiac reinnervation group. These results suggest that cardiac reinnervation associates with hemodynamic and cardiorespiratory adaptations to exercise training in individuals with heart transplantation.
A multiscale agent-based model of ductal carcinoma in situ

Objective: we present a multiscale agent-based model of Ductal Carcinoma in Situ (DCIS) in order to gain a detailed understanding of the cell-scale population dynamics, phenotypic distributions, and the associated interplay of important molecular signaling pathways that are involved in DCIS ductal invasion into the duct cavity (a process we refer to as duct advance rate here). Methods: DCIS is modeled mathematically through a hybridized discrete cell-scale model and a continuum molecular scale model, which are explicitly linked through a bidirectional feedback mechanism. Results: we find that duct advance rates occur in two distinct phases, characterized by an early exponential population expansion, followed by a long-term steady linear phase of population expansion, a result that is consistent with other modeling work. We further found that the rates were influenced most strongly by endocrine and paracrine signaling intensity, as well as by the effects of cell density induced quiescence within the DCIS population. Conclusion: our model analysis identified a complex interplay between phenotypic diversity that may provide a tumor adaptation mechanism to overcome proliferation limiting conditions, allowing for dynamic shifts in phenotypic populations in response to variation in molecular signaling intensity. Further, sensitivity analysis determined DCIS axial advance rates and calcification rates were most sensitive to cell cycle time variation. Significance: this model may serve as a useful tool to study the cell-scale dynamics involved in DCIS initiation and intraductal invasion, and may provide insights into promising areas of future experimental research.
A mutant KRAS‐induced factor REG4 promotes cancer stem cell properties via Wnt/β‐catenin signaling

Mutant KRAS provides a driving force for enhancement of cancer stem cells (CSCs) characteristics contributing transformation of colorectal cancer (CRC) cells harboring adenomatous polyposis coli (APC) mutations. Here, we identified the factors mediating the promotion of CSCs properties induced by KRAS mutation through microarray analyses of genes specifically induced in CRC spheroids harboring both KRAS and APC mutations. Among them, REG4 was identified as a key factor since CRISPR/Cas9‐mediated knockout of REG4 most significantly affected the stem cell characteristics in which CSCs markers were effectively suppressed. We show that REG4 mediates promotion of CSCs properties via Wnt/β‐catenin signaling in various in vitro studies including tumor organoid systems. Furthermore, expression patterns of CSCs markers and REG4 correlated in intestinal tumors from Apcmin/+/KrasG12DLA2 mice and in CRC patient tissues harboring both KRAS and APC mutations. The role of REG4 in the tumor‐initiating capacity accompanied by enhancement of CSCs characteristics was also revealed by NSG mice xenograft system. Collectively, our study highlights the importance of REG4 in promoting CSCs properties induced by KRAS mutation, and provides a new therapeutic strategy for CRC harboring both APC and KRAS mutations.
Collagenous Ultrastructure of the Torn Medial Meniscus Posterior Root: A Transmission Electron Microscopy Study

Background: The collagen ultrastructure of torn medial meniscus posterior roots (MMPRs) has not been precisely defined. Purpose: To investigate the ultrastructure of torn MMPRs, focusing on their collagen fibers, and to compare the collagen net architecture between intact and torn MMPRs using the Collagen Meniscal Architecture (CMA) scoring system. Study Design: Descriptive laboratory study. Methods: Forty-three human meniscal specimens were obtained from 32 patients with osteoarthritis during total knee arthroplasty between January 2018 and November 2018. There were 23 specimens taken from patients with an MMPR tear and 20 taken from patients without an MMPR tear served as a control group. The presence of an MMPR tear was defined as a complete radial tear within 9 mm of the posterior root attachment. The collagen ultrastructure of the meniscal specimens was assessed with transmission electron microscopy using the CMA scoring system. Patient demographics included sex, age, and body mass index, and radiographic assessments included the Kellgren-Lawrence (K-L) grading system and the mechanical axis angle. Results: The median CMA score was significantly higher in torn MMPRs (5.5 [interquartile range, 3.5-6.0]) than in intact MMPRs (2.0 [interquartile range, 1.5-3.8]) (P < .001). When the CMA scores were converted to CMA grading, 23 torn MMPRs had 1 grade I, 9 grade II, and 13 grade III menisci. In 20 intact MMPRs, there were 12 grade I, 7 grade II, and 1 grade III menisci. No significant differences in sex, age, body mass index, K-L grade, or mechanical axis angle were found between groups. Conclusion: This study showed that torn MMPRs had decreased numbers and disorganized courses of collagen fibers. The structural problem of torn MMPRs can negatively affect meniscal healing, function, and long-term survival after root repair. Clinical Relevance: These results might provide a histopathological reason for the low healing rate after MMPR repair.
RRM adjacent TARDBP mutations disrupt RNA binding and enhance TDP-43 proteinopathy

TDP-43 is a DNA/RNA binding protein, but whether its interactions with RNA are relevant to inclusion formation in ALS is unclear. Chen et al. report that mutated forms of TDP-43 that are unable to bind RNA have an increased tendency to aggregate, and can mediate toxicity by sequestering wild-type TDP-43.
Antimicrobial resistance genotypes and phenotypes of Campylobacter jejuni isolated in Italy from humans, birds from wild and urban habitats, and poultry

Campylobacter jejuni, a common foodborne zoonotic pathogen, causes gastroenteritis worldwide and is increasingly resistant to antibiotics. We aimed to investigate the antimicrobial resistance (AMR) genotypes of C. jejuni isolated from humans, poultry and birds from wild and urban Italian habitats to identify correlations between phenotypic and genotypic AMR in the isolates. Altogether, 644 C. jejuni isolates from humans (51), poultry (526) and wild- and urban-habitat birds (67) were analysed. The resistance phenotypes of the isolates were determined using the microdilution method with EUCAST breakpoints, and AMR-associated genes and single nucleotide polymorphisms were obtained from a publicly available database. Antimicrobial susceptibility testing showed that C. jejuni isolates from poultry and humans were highly resistant to ciprofloxacin (85.55% and 76.47%, respectively), nalidixic acid (75.48% and 74.51%, respectively) and tetracycline (67.87% and 49.02%, respectively). Fewer isolates from the wild- and urban-habitat birds were resistant to tetracycline (19.40%), fluoroquinolones (13.43%), and quinolone and streptomycin (10.45%). We retrieved seven AMR genes (tet (O), cmeA, cmeB, cmeC, cmeR, blaOXA-61 and blaOXA-184) and gyrA-associated point mutations. Two major B-lactam genes called blaOXA-61 and blaOXA-184 were prevalent at 62.93% and 82.08% in the poultry and the other bird groups, respectively. Strong correlations between genotypic and phenotypic resistance were found for fluoroquinolones and tetracycline. Compared with the farmed chickens, the incidence of AMR in the C. jejuni isolates from the other bird groups was low, confirming that the food-production birds are much more exposed to antimicrobials. The improper and overuse of antibiotics in the human population and in animal husbandry has resulted in an increase in antibiotic-resistant infections, particularly fluoroquinolone resistant ones. Better understanding of the AMR mechanisms in C. jejuni is necessary to develop new strategies for improving AMR programs and provide the most appropriate therapies to human and veterinary populations.
A Dual-Modal Attention-Enhanced Deep Learning Network for Quantification of Parkinson’s Disease Characteristics

It is well known that most patients with Parkinson’s disease (PD) have different degree of movement disorders, such as shuffling, festination and akinetic episodes, which could degenerate the life quality of PD patients. Therefore, it is very useful to develop a computerized tool to provide an objective evaluation of PD patients’ gait. In this study, we implemented a novel gait evaluating approach to provide not only a binary classification of PD gaits and normal walking, but also a quantification of the PD gaits to relate them to the PD severity level. The proposed system is a dual-modal deep-learning-based model, where left and right gait is modeled separately by a convolutional neural network (CNN) followed by an attention-enhanced long short-term memory (LSTM) network. The left and right samples for model training and testing were segmented sequentially from multiple 1D vertical ground reaction force (VGRF) signals according to the detected gait cycle. Experimental results indicate that our model can provide state-of-the-art performance in terms of classification accuracy. It is expected that the proposed model can be a useful gait assistance to provide a quantitative evaluation of PD gaits with high confidence and accuracy if trained suitably.
The role of 99mTc-HMPAO-labelled white blood cell scintigraphy in the diagnosis of cardiac device-related infective endocarditis.

AIMS The hybrid technique of single-photon emission tomography and computed tomography with technetium99m-hexamethylpropyleneamine oxime-labelled leucocytes (99mTc-HMPAO-SPECT/CT) is an emerging diagnostic technique in patients with cardiac device-related infective endocarditis (CDRIE). This prospective study assessed the 99mTc-HMPAO-SPECT/CT diagnostic profile and its added value to the modified Duke criteria (mDuke) in CDRIE diagnostic work-up. METHODS AND RESULTS The study examined 103 consecutive patients with suspected CDRIE, who underwent 99mTc-HMPAO-SPECT/CT. Diagnostic accuracy was calculated based on a final clinical CDRIE diagnosis, including microbiology, echocardiography, and a 6-month follow-up. Subsequently, we compared the diagnostic value of the initial mDuke classification with a classification including 99mTc-HMPAO-SPECT/CT positive results as an additional major CDRIE criterion: mDuke-SPECT/CT.Overall, CDRIE was diagnosed in 31 (31%) patients, whereas 35 (34%) 99mTc-HMPAO-SPECT/CT were positive. 99mTc-HMPAO-SPECT/CT was characterized by 86% accuracy, 0.69 Cohen's kappa coefficient, 84% sensitivity, 88% specificity, 93% negative, and 74% positive predictive values. The original mDuke displayed 83% accuracy, 0.52 kappa, whereas mDuke-SPECT/CT had 88% accuracy, and 0.73 kappa. Compared with mDuke, mDuke-SPECT/CT showed significantly higher sensitivity (87% vs. 48%, P < 0.001). According to mDuke, 49.5% of patients had possible CDRIE, and after reclassification, that figure dropped to 37%. Furthermore, having assessed the diagnosis categorization improvement following the incorporation of 99mTc-HMPAO-SPECT/CT, the net reclassification index value was found to be 31.4%. CONCLUSION In patients with CDRIE, 99mTc-HMPAO-SPECT/CT provides high diagnostic accuracy, whereas a negative scan excludes CDRIE with high probability. Inclusion of 99mTc-HMPAO-SPECT/CT into mDuke diagnostic criteria yields significantly higher sensitivity and a reduction in possible CDRIE diagnoses.
Downregulation of the inflammatory network in senescent fibroblasts and aging tissues of the long‐lived and cancer‐resistant subterranean wild rodent, Spalax

The blind mole rat (Spalax) is a wild, long‐lived rodent that has evolved mechanisms to tolerate hypoxia and resist cancer. Previously, we demonstrated high DNA repair capacity and low DNA damage in Spalax fibroblasts following genotoxic stress compared with rats. Since the acquisition of senescence‐associated secretory phenotype (SASP) is a consequence of persistent DNA damage, we investigated whether cellular senescence in Spalax is accompanied by an inflammatory response. Spalax fibroblasts undergo replicative senescence (RS) and etoposide‐induced senescence (EIS), evidenced by an increased activity of senescence‐associated beta‐galactosidase (SA‐β‐Gal), growth arrest, and overexpression of p21, p16, and p53 mRNAs. Yet, unlike mouse and human fibroblasts, RS and EIS Spalax cells showed undetectable or decreased expression of the well‐known SASP factors: interleukin‐6 (IL6), IL8, IL1α, growth‐related oncogene alpha (GROα), SerpinB2, and intercellular adhesion molecule (ICAM‐1). Apparently, due to the efficient DNA repair in Spalax, senescent cells did not accumulate the DNA damage necessary for SASP activation. Conversely, Spalax can maintain DNA integrity during replicative or moderate genotoxic stress and limit pro‐inflammatory secretion. However, exposure to the conditioned medium of breast cancer cells MDA‐MB‐231 resulted in an increase in DNA damage, activation of the nuclear factor κB (NF‐κB) through nuclear translocation, and expression of inflammatory mediators in RS Spalax cells. Evaluation of SASP in aging Spalax brain and intestine confirmed downregulation of inflammatory‐related genes. These findings suggest a natural mechanism for alleviating the inflammatory response during cellular senescence and aging in Spalax, which can prevent age‐related chronic inflammation supporting healthy aging and longevity.