Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistent diarrhea: a persistent infection with enteropathogens or a gut commensal dysbiosis?

In children from developing countries 5-10% of acute diarrhea (AD) episodes develop into persistent diarrhea (PD) defined by > 14 days of diarrhea duration. PD represents a major health burden leading to growth faltering. It is also associated with half of all diarrhea mortality. A rational intervention is thus crucial, but depends on an understanding of the pathogenesis of PD, which is still lacking. Many surveys were conducted in Latin America and in South Asia; they differ, however, with respect to enteropathogens associated with PD. Enteroaggregative strains of Escherichia coli (EAEC) were identified by several studies, but they may reflect selection by the frequent antibiotic use during the preceding AD episode. Epidemiologists have in fact identified antibiotic misuse as a major risk factor for PD. Together with the effectiveness of empirical treatment based on nutritional interventions with lactose-reduced and lactose-free diets and particularly complex plant polysaccharides from green banana, one might suspect a role of commensal gut microbiota dysbiosis instead of a persistent infection with enteropathogens in many PD cases. An analysis of the commensal gut microbiota development in persistent diarrhea during nutritional interventions is likely to increase our understanding of PD pathogenesis.
Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment Week 144 Results

Abstract: In 2 double-blind phase 3 trials, 1733 antiretroviral-naive adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95% confidence interval: 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P < 0.001), with no cases of proximal tubulopathy for TAF vs 4 for TDF. There were greater increases in lipids with TAF vs TDF, with no difference in the total cholesterol to high-density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.
Metabolic characteristics of programmed cell death‐ligand 1‐expressing lung cancer on 18F‐fluorodeoxyglucose positron emission tomography/computed tomography

Programmed cell death‐1 (PD‐1) and programmed cell death‐ligand 1 (PD‐L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) with regard to PD‐L1 protein expression. PD‐L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD‐L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative 18F‐FDG PET/CT. The cut‐off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD‐L1 protein expression compared with those without PD‐L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD‐L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD‐L1 positivity. PD‐L1‐expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative 18F‐FDG PET/CT was a predictor of PD‐L1 protein expression in patients with NSCLC.
Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus

Cerebellar malformations cause changes to the sleep-wake cycle, resulting in sleep disturbance. However, it is unclear how the cerebellum contributes to the sleep-wake cycle. To examine the neural connections between the cerebellum and the nuclei involved in the sleep-wake cycle, we investigated the axonal projections of Purkinje cells in the mouse posterior vermis by using an adeno-associated virus (AAV) vector (serotype rh10) as an anterograde tracer. When an AAV vector expressing humanized renilla green fluorescent protein was injected into the cerebellar lobule IX, hrGFP and synaptophysin double-positive axonal terminals were observed in the region of medial parabrachial nucleus (MPB). The MPB is involved in the phase transition from rapid eye movement (REM) sleep to Non-REM sleep and vice versa, and the cardiovascular and respiratory responses. The hrGFP-positive axons from lobule IX went through the ventral spinocerebellar tract and finally reached the MPB. By contrast, when the AAV vector was injected into cerebellar lobule VI, no hrGFP-positive axons were observed in the MPB. To examine neurons projecting to the MPB, we unilaterally injected Fast Blue and AAV vector (retrograde serotype, rAAV2-retro) as retrograde tracers into the MPB. The cerebellar Purkinje cells in lobules VIII–X on the ipsilateral side of the Fast Blue-injected MPB were retrogradely labeled by Fast Blue and AAV vector (retrograde serotype), but no retrograde-labeled Purkinje cells were observed in lobules VI–VII and the cerebellar hemispheres. These results indicated that Purkinje cells in lobules VIII–X directly project their axons to the ipsilateral MPB but not lobules VI–VII. The direct connection between lobules VIII–X and the MPB suggests that the cerebellum participates in the neural network controlling the sleep-wake cycle, and cardiovascular and respiratory responses, by modulating the physiological function of the MPB.
Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non‐fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid‐condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard‐tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage.
A Compressive Sensing-Based CMOS Image Sensor With Second-Order $\Sigma \Delta$ ADCs

This paper presents a new analog-to-digital conversion scheme for a second-order <inline-formula> <tex-math notation="LaTeX">$\Sigma \Delta $ </tex-math></inline-formula> incremental analog to digital converter (ADC) that can be employed in a compressive sensing (CS)-based CMOS image sensor (CIS) as a column-parallel ADC. The conversion scheme removes image distortion from a reconstructed image by making the ADC output codes represent an average of the ADC inputs. In addition, a new multiplexing scheme implementing a compressive sensing matrix helps to reduce hardware complexity and control compression ratio without hardware modifications. A <inline-formula> <tex-math notation="LaTeX">$160\times 160$ </tex-math></inline-formula> pixel CS-based CIS fabricated in <inline-formula> <tex-math notation="LaTeX">$0.11~\mu \text{m}$ </tex-math></inline-formula> CIS process successfully demonstrates the proposed schemes.
Mold and Endotoxin Levels in the Aftermath of Hurricane Katrina: A Pilot Project of Homes in New Orleans Undergoing Renovation

Background After Hurricane Katrina, many New Orleans homes remained flooded for weeks, promoting heavy microbial growth. Objectives A small demonstration project was conducted November 2005–January 2006 aiming to recommend safe remediation techniques and safe levels of worker protection, and to characterize airborne mold and endotoxin throughout cleanup. Methods Three houses with floodwater lines between 0.3 and 2 m underwent intervention, including disposal of damaged furnishings and drywall, cleaning surfaces, drying remaining structure, and treatment with a biostatic agent. We measured indoor and outdoor bioaerosols before, during, and after intervention. Samples were analyzed for fungi [culture, spore analysis, polymerase chain reaction (PCR)] and endotoxin. In one house, real-time particle counts were also assessed, and respirator-efficiency testing was performed to establish workplace protection factors (WPF). Results At baseline, culturable mold ranged from 22,000 to 515,000 colony-forming units/m3, spore counts ranged from 82,000 to 630,000 spores/m3, and endotoxin ranged from 17 to 139 endotoxin units/m3. Culture, spore analysis, and PCR indicated that Penicillium, Aspergillus, and Paecilomyces predominated. After intervention, levels of mold and endotoxin were generally lower (sometimes, orders of magnitude). The average WPF against fungal spores for elastomeric respirators was higher than for the N-95 respirators. Conclusions During baseline and intervention, mold and endotoxin levels were similar to those found in agricultural environments. We strongly recommend that those entering, cleaning, and repairing flood-damaged homes wear respirators at least as protective as elastomeric respirators. Recommendations based on this demonstration will benefit those involved in the current cleanup activities and will inform efforts to respond to future disasters.
Discontinuity Detection in the Shield Metal Arc Welding Process

This work proposes a new methodology for the detection of discontinuities in the weld bead applied in Shielded Metal Arc Welding (SMAW) processes. The detection system is based on two sensors—a microphone and piezoelectric—that acquire acoustic emissions generated during the welding. The feature vectors extracted from the sensor dataset are used to construct classifier models. The approaches based on Artificial Neural Network (ANN) and Support Vector Machine (SVM) classifiers are able to identify with a high accuracy the three proposed weld bead classes: desirable weld bead, shrinkage cavity and burn through discontinuities. Experimental results illustrate the system’s high accuracy, greater than 90% for each class. A novel Hierarchical Support Vector Machine (HSVM) structure is proposed to make feasible the use of this system in industrial environments. This approach presented 96.6% overall accuracy. Given the simplicity of the equipment involved, this system can be applied in the metal transformation industries.
High-Density Silicon Photomultipliers: Performance and Linearity Evaluation for High Efficiency and Dynamic-Range Applications

Silicon photomultipliers (SiPM) are photodetectors that have obtained a growing attention in the last years. They have single photon sensitivity, but also a high dynamic range: the output current signal is proportional to the number of detected photons and it is possible to distinguish up to tens of photon per each light pulse. In Fondazione Bruno Kessler (Trento, Italy) we developed the so called high-density SiPMs, with narrow trenches to isolate the cells (i.e. single-photon avalanche diodes) and with high fill factor. These detectors feature high photon detection efficiency and high dynamic range. Moreover, the reduction of the cell size reduces the correlated noise (i.e. lower crosstalk between cells and lower afterpulsing probability) and it makes the single-cell response faster, increasing the maximum counting rate. These characteristics can be very important in applications like light detection and ranging, spectroscopy, and physics experiments. In this paper, we present the structure of high-density SiPMs and their performance. In particular, the photon detection efficiency, the photon number resolving capabilities, the linearity versus photon flux, and the single-photon time resolution, investigating how these parameters change with the cell pitch.
A qualitative analysis of the barriers to antiretroviral therapy initiation among children 2 to 18 months of age in Swaziland

HIV/AIDS remains one of the leading causes of death among children under 5 years old in Swaziland. Although studies have shown that early initiation of infants and children diagnosed with HIV on antiretroviral therapy (ART) significantly reduces mortality, many children do not initiate ART until the later stages of disease. This study was designed to collect qualitative data from mothers and caregivers of HIV-positive children to identify the barriers to ART initiation. Focus group discussion (FGD) sessions were conducted in siSwati between July and September 2014 among caregivers of aged children 2–18 months in Swaziland who did or did not initiate ART between January 2011 and December 2012 after HIV DNA PCR-positive diagnosis of the infants. Denial, guilt, lack of knowledge, tuberculosis (TB)/HIV co-infection, HIV-related stigma, lack of money, and distance to clinics were reported by the participants as barriers to ART initiation. The findings further revealed that non-initiation on ART was not linked to a negative perception of the treatment. Findings suggest a need to improve sensitivity among healthcare workers as well as education and counselling services that will facilitate the ART initiation process.
Passive smoking and expired carbon monoxide concentrations in healthy and asthmatic children.

BACKGROUND Carbon monoxide (CO) in expired air has been reported to be an indirect measurement for the quantity of passive smoking. Since endogen CO is produced in inflammatory processes and inflammation is the main pathogenetic mechanism of asthma, it was aimed to investigate the relationship between the intensity of passive smoking and CO concentration in expired air of healthy and asthmatic children. METHODS AND RESULTS The study was performed in the outpatient pediatrics clinics and day care centers. Knowledge about indoor smoking habits were obtained from parents. The exhaled CO concentrations were measured by a portable device in 235 healthy (mean age, 4.4 +/- 2.3 years) and 54 asthmatic (mean age, 4.5 +/- 1.7 years) children. Children with no smoking parents had the lowest exhaled CO concentrations. Significant relationships were found between the number of smoking cigarettes in the house and exhaled CO concentrations in both healthy (p = 0.003) and asthmatic (p = 0.01) children. Carbon monoxide concentrations were higher in asthmatic children than healthy ones (mean +/- SD, 1.32 +/- 1.50 ppm and 0.86 +/- 1.35 ppm, respectively, p = 0.028) if their parental smoking habits were not taken into account. Asthmatic children of non-smoking parents had higher CO concentrations than healthy subjects of non-smoking parents (1.05 +/- 1.55 ppm vs 0.37 +/- 0.53 ppm, p = 0.01). On the other hand, asthmatic children who has no smoking parents and did not receive inhaled steroids had significantly higher CO concentrations (1.75 +/- 1.45 ppm) than those who received steroids (0.58 +/- 0.65 ppm, p = 0.024). CONCLUSIONS Exhaled CO can be used as an indicator of passive smoking in children. Higher expired CO of asthmatic children may reflect inflammation of the lung in asthma.
Real-world affected upper limb activity in chronic stroke: an examination of potential modifying factors

Abstract Background: Despite improvement in motor function after intervention, adults with chronic stroke experience disability in everyday activity. Factors other than motor function may influence affected upper limb (UL) activity. Objective: To characterize affected UL activity and examine potential modifying factors of affected UL activity in community-dwelling adults with chronic stroke. Methods: Forty-six adults with chronic stroke wore accelerometers on both ULs for 25 hours and provided information about potential modifying factors [time spent in sedentary activity, cognitive impairment, depressive symptomatology, number of comorbidities, motor dysfunction of the affected UL, age, activities of daily living (ADL) status, and living arrangement]. Accelerometry was used to quantify duration of affected and unaffected UL activity. The ratio of affected-to-unaffected UL activity was also calculated. Associations within and between accelerometry-derived variables and potential modifying factors were examined. Results: Mean hours of affected and unaffected UL activity were 5.0 ± 2.2 and 7.6 ± 2.1 hours respectively. The ratio of affected-to-unaffected UL activity was 0.64 ± 0.19, and hours of affected and unaffected UL activity were strongly correlated (r = 0.78). Increased severity of motor dysfunction and dependence in ADLs were associated with decreased affected UL activity. No other factors were associated with affected UL activity. Conclusions: Severity of motor dysfunction and ADL status should be taken into consideration when setting goals for UL activity in people with chronic stroke. Given the strong, positive correlation between affected and unaffected UL activity, encouragement to increase activity of the unaffected UL may increase affected UL activity.
Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer

Significance Cells require specific molecular entities to regulate biological processes, which are often out of balance in diseases. Once identified, their activities may be modulated by specific ligands. DPP4 protein is an example of a target to successfully treat type II diabetes by small molecule ligands. Besides DPP4, other members of this protein family, DPP8 and DPP9 are similarly interesting and relevant in immune response and cancer. It is crucial to understand their structures and enzymatic mechanism to enable structure-based drug development. Here we unveil the crystallographic structures of DPP8 and DPP9, whereby we observe a different active site architecture and substrate binding mechanism in this family. These discoveries open new options for drug development targeting DPP8 and DPP9. Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 Å) and DPP9 (3.0 Å) unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively. Similar to DPP4, DPP8 and DPP9 molecules consist of one β-propeller and α/β hydrolase domain, forming a functional homodimer. However, they differ extensively in the ligand binding site structure. In intriguing contrast to DPP4, where liganded and unliganded forms are closely similar, ligand binding to DPP8/9 induces an extensive rearrangement at the active site through a disorder-order transition of a 26-residue loop segment, which partially folds into an α-helix (R-helix), including R160/133, a key residue for substrate binding. As vestiges of this helix are also seen in one of the copies of the unliganded form, conformational selection may contributes to ligand binding. Molecular dynamics simulations support increased flexibility of the R-helix in the unliganded state. Consistently, enzyme kinetics assays reveal a cooperative allosteric mechanism. DPP8 and DPP9 are closely similar and display few opportunities for targeted ligand design. However, extensive differences from DPP4 provide multiple cues for specific inhibitor design and development of the DPP family members as therapeutic targets or antitargets.
Comparison and Evaluation of Annual NDVI Time Series in China Derived from the NOAA AVHRR LTDR and Terra MODIS MOD13C1 Products

Time series of Normalized Difference Vegetation Index (NDVI) derived from multiple satellite sensors are crucial data to study vegetation dynamics. The Land Long Term Data Record Version 4 (LTDR V4) NDVI dataset was recently released at a 0.05 × 0.05° spatial resolution and daily temporal resolution. In this study, annual NDVI time series that are composited by the LTDR V4 and Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI datasets (MOD13C1) are compared and evaluated for the period from 2001 to 2014 in China. The spatial patterns of the NDVI generally match between the LTDR V4 and MOD13C1 datasets. The transitional zone between high and low NDVI values generally matches the boundary of semi-arid and sub-humid regions. A significant and high coefficient of determination is found between the two datasets according to a pixel-based correlation analysis. The spatially averaged NDVI of LTDR V4 is characterized by a much weaker positive regression slope relative to that of the spatially averaged NDVI of the MOD13C1 dataset because of changes in NOAA AVHRR sensors between 2005 and 2006. The measured NDVI values of LTDR V4 were always higher than that of MOD13C1 in western China due to the relatively lower atmospheric water vapor content in western China, and opposite observation appeared in eastern China. In total, 18.54% of the LTDR V4 NDVI pixels exhibit significant trends, whereas 35.79% of the MOD13C1 NDVI pixels show significant trends. Good agreement is observed between the significant trends of the two datasets in the Northeast Plain, Bohai Economic Rim, Loess Plateau, and Yangtze River Delta. By contrast, the datasets contrasted in northwestern desert regions and southern China. A trend analysis of the regression slope values according to the vegetation type shows good agreement between the LTDR V4 and MOD13C1 datasets. This study demonstrates the spatial and temporal consistencies and discrepancies between the AVHRR LTDR and MODIS MOD13C1 NDVI products in China, which could provide useful information for the choice of NDVI products in subsequent studies of vegetation dynamics.