Miracle-dz/UniFAR-FTUs huggingface dataset:
IL‐10 produced by CD4+ and CD8+ T cells emerge as a putative immunoregulatory mechanism to counterbalance the monocyte‐derived TNF‐α and guarantee asymptomatic clinical status during chronic HTLV‐I infection

Although it is believed widely that distinct patterns of the host immune response are associated with the outcome of chronic human T cell lymphotropic virus type 1 (HTLV‐I) infection toward asymptomatic or symptomatic neurodegenerative myelopathy (HAM/TSP), the exact mechanism underlying these immunological events still remains unknown. In this study, we have evaluated the cytokine pattern [interleukin (IL)‐12, interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α, IL‐4 and IL‐10] of innate and adaptive immunity cells present at the peripheral blood from non‐infected (NI) and HTLV‐I infected individuals [asymptomatic (AS), oligosymptomatic (OL) and HAM/TSP‐HT], following in vitro short‐term incubation in the absence/presence of phorbol myristate acetate (PMA) pan‐leucocyte stimulation. In the absence of PMA stimulation, our data demonstrate that despite the overall immunological profile of AS mimicry that observed for NI, the high frequency of IL‐12+ neutrophils and TNF‐α+ monocytes are also a hallmark of this group of individuals. However, the outstanding positive correlation between the high frequency of TNF‐α+ monocytes and high levels CD4+ IL‐10+ and CD8+ IL‐10+ T cells suggests the establishment of immunoregulatory mechanisms that guarantee their asymptomatic clinical status. On the other hand, OL and HT did not present any association between the high frequency and TNF‐α+ neutrophils and monocytes and this immunoregulatory profile at their adaptive immunity cells. Upon PMA‐index analysis, high levels of type 1 CD4+ T cells, as well as higher IFN‐γ/IL‐10 and TNF‐α/IL‐10 ratios, were observed in HT, and re‐emphasize the role of Th1‐cytokines from CD4+ cells to HTLV‐I immunity and disease. Moreover, increasing frequency of CD8+ IFN‐γ+ and CD8+ TNF‐α+ cells were observed in the HT, which corroborates the marked inflammatory profile underlying this pathological condition and the role of CD8+ T cells in the pathogenesis of HAM/TSP.
Suivi de la consommation des antibiotiques pour la promotion de leur bon usage et la maîtrise de la résistance bactérienne dans les hôpitaux de soins aigus: mise en place et exemples d'utilisation

Le suivi de la consommation des antibiotiques est un element essentiel dans la promotion de leur bon usage et la maitrise des resistances bacteriennes. En Suisse, les donnees de consommation d’antibiotiques n’avaient encore jamais ete recueillies au niveau national dans une etude longitudinale. Le but de ce travail a ete de mettre en place un suivi de la consommation dans les hopitaux de soins aigus et de valoriser les donnees. La premiere etude a observe les differences de consommation entre les regions linguistiques et a compare les resultats avec ceux des etudes europeennes. La deuxieme etude a aborde la problematique des ruptures d’approvisionnement des antibiotiques en montrant leur impact sur l’utilisation et les couts des autres antibiotiques a tres large spectre, et les resistances des Pseudomonas aeruginosa. La troisieme etude a evalue la relation entre les taux de resistances des P. aeruginosa aux carbapenemes et la diversite d’utilisation des antibiotiques.
The substrate specificity profile of human granzyme A

Abstract The exact biological function of granzyme A, a granule-associated serine protease belonging to the tryptase family of proteases, is still a matter of debate because conflicting roles have been suggested, such as initiation of caspase-independent apoptosis-like cell death and endogenous modulation of inflammatory processes. In contrast to its well-studied family member, granzyme B, far less is known about the physiological targets of granzyme A. Using an N-terminal peptide-centric proteomics technology, the substrate specificity of human granzyme A was extensively characterized at the level of macromolecular protein substrates. Overall, more than 260 cleavage sites, almost exclusively favoring basic residues at the P1 position, in approximately 200 unique protein substrates, including the well-known in vitro substrates APEX-endonuclease 1 and different histones, were identified. Further substrate characterization was used to delineate physical properties in the substrate specificity profiles, which further highlights important aspects in protease/substrate biology.
Human breast lesions: characterization with proton MR spectroscopy.

PURPOSE To assess the clinical usefulness of spatially localized hydrogen-1 magnetic resonance (MR) spectroscopy in distinguishing benign from malignant lesions on the basis of total choline levels. MATERIALS AND METHODS These studies were performed at 1.5 T with a four-channel multicoil that compresses the breast sagittally. Contrast material-enhanced MR imaging and single-voxel H-1 MR spectroscopy were performed in 17 patients (age range, 25-68 years) who had nonspecific mammographic findings. Histopathologic correlations were made from biopsy or surgical specimens. Ten patients had various malignant breast lesions 1-4 cm in diameter, and seven patients had benign processes. RESULTS Most studies were performed with nominal voxel sizes (< 2 cm3). Spectra obtained with an echo time of 31 msec showed resonances from water and mobile fatty acids and, in some cases, the N-trimethyl resonance of choline-containing compounds (Cho) at 3.2 ppm. The absolute concentration of Cho in each lesion was determined with a phantom containing 1 mmol/L Cho as an external reference. On the basis of reference measurements, the least detectable level of Cho was 0.2 mmol/L. With this threshold, seven of 10 malignant lesions showed detectable levels of Cho. In contrast, Cho was seen in only one patient with an extremely rare benign process, a tubular adenoma. The remaining six patients with benign processes demonstrated no detectable Cho levels. CONCLUSION Spatially localized H-1 MR spectroscopy can provide sufficient sensitivity and spectral resolution at 1.5 T to demonstrate Cho in human breast lesions with a spectroscopic protocol that provides up to 1-cm3 resolution. Determining the presence of Cho may provide a useful test for malignancy.
Fat‐suppressed T2‐weighted MRI of the liver: Comparison of respiratory‐triggered fast spin‐echo, breath‐hold single‐shot fast spin‐echo, and breath‐hold fast‐recovery fast spin‐echo sequences

The purpose of our study was to compare the value of respiratory‐triggered fast spin‐echo, breath‐hold single‐shot fast spin‐echo, and breath‐hold fast‐recovery fast spin‐echo sequences in detecting hepatic lesions. Fat‐suppressed T2‐weighted magnetic resonance (MR) images obtained with the three sequences in 36 patients with 138 lesions and nine patients without lesions were prospectively analyzed. Quantitative and qualitative analyses, including receiver operating characteristic (ROC) analyses, were performed. The mean lesion‐to‐liver contrast‐to‐noise ratio (CNR) for hepatic lesions was highest with the respiratory‐triggered fast spin‐echo sequence. On the basis of receiver‐operating characteristic analyses, tumor detection rates were higher with the breath‐hold fast‐recovery fast spin‐echo sequence (Az = 0.94) than with the respiratory‐triggered fast spin‐echo sequence (AZ = 0.80, P < 0.0001) or the single‐shot fast spin‐echo sequence (Az = 0.77, P < 0.0001). The image quality with the breath‐hold fast‐recovery fast spin‐echo sequence was acceptable in all patients. The breath‐hold fast‐recovery fast spin‐echo sequence provided the highest tumor detection in a short imaging time, although the mean lesion‐to‐liver CNRs were inferior to those of the respiratory‐triggered fast spin‐echo and the breath‐hold single‐shot fast spin‐echo sequences. J. Magn. Reson. Imaging 2001;14:439–449. © 2001 Wiley‐Liss, Inc.
Resonance Raman and Raman Spectroscopy for Breast Cancer Detection

Raman spectroscopy is a sensitive method to detect early changes of molecular composition and structure that occur in lesions during carcinogenesis. The Raman spectra of normal, benign and cancerous breast tissues were investigated in vitro using a near-infrared (NIR) Raman system of 785 nm excitation and confocal micro resonance Raman system of 532 nm excitation. A total number of 491 Raman spectra were acquired from normal, benign and cancerous breast tissues taken from 15 patients. When the 785 nm excitation was used, the dominant peaks in the spectra were characteristic of the vibrations of proteins and lipids. The differences between the normal and cancerous breast tissues were observed in both the peak positions and the intensity ratios of the characteristic Raman peaks in the spectral region of 700–1800 cm−1. With 532 nm excitation, the resonance Raman (RR) spectra exhibited a robust pattern of peaks within the region of 500–4000 cm−1. The intensities of four distinct peaks at 1156, 1521, 2854 and 3013 cm−1 detected in the spectra collected from normal breast tissue were found to be stronger in comparison with those collected from cancerous breast tissue. The twelve dramatically enhanced characteristic peaks, including the enhanced amide II peak at 1548 cm−1 in the spectra collected from cancerous breast tissue, distinguished the cancerous tissue from the normal tissue. Principal component analysis (PCA) combined with support vector machine (SVM) analysis of the Raman and RR spectral data yielded a high performance in the classification of cancerous and benign lesions from normal breast tissue.
Phylogeography and Evolutionary History of Reassortant H9N2 Viruses with Potential Human Health Implications

ABSTRACT Avian influenza viruses of the H9N2 subtype have seriously affected the poultry industry of the Far and Middle East since the mid-1990s and are considered one of the most likely candidates to cause a new influenza pandemic in humans. To understand the genesis and epidemiology of these viruses, we investigated the spatial and evolutionary dynamics of complete genome sequences of H9N2 viruses circulating in nine Middle Eastern and Central Asian countries from 1998 to 2010. We identified four distinct and cocirculating groups (A, B, C, and D), each of which has undergone widespread inter- and intrasubtype reassortments, leading to the generation of viruses with unknown biological properties. Our analysis also suggested that eastern Asia served as the major source for H9N2 gene segments in the Middle East and Central Asia and that in this geographic region within-country evolution played a more important role in shaping viral genetic diversity than migration between countries. The genetic variability identified among the H9N2 viruses was associated with specific amino acid substitutions that are believed to result in increased transmissibility in mammals, as well as resistance to antiviral drugs. Our study highlights the need to constantly monitor the evolution of H9N2 viruses in poultry to better understand the potential risk to human health posed by these viruses.
Predictors of Patient Treatment Preferences and Spouse Substituted Judgments: The Case of Dialysis Continuation

Objectives. To examine the factors predicting preferences for continued hemodialysis treatment among patients with endstage renal disease (ESRD) and to compare these factors to those predicting their spouses’ predictions of patients’ preferences (substituted judgments). Design. Descriptive, crosssectional. Participants. Total of 291 hemodialysis patients, aged 55 years and older, and their spouses. Measurement. Hypothetical scenarios were designed to elicit preferences for dialysis continuation under various health conditions. Other measures included the Philadelphia Geriatric Center Negative Affect Scale, Kidney Disease Symptoms Scale, Brief Multidimensional Measure of Religiousness, single-item global subjective health and quality-of-life measures, 2-item fear of end-of-life suffering measure, and selected demographics. Results. Patients’ preferences and spouses’ judgments were only moderately correlated (r = 0.33). Multiple regression analyses revealed that patients’ preferences to continue dialysis were positively related to education, subjective quality of life, and religious participation and negatively related to months of ESRD treatment and fear of end-of-life suffering (R2 = 0.15). Spouses ’ substituted judgments regarding patients’ dialysis continuation preferences were positively related to African American race and spouses’ perceptions of patients ’ quality of life and negatively related to months of ESRD treatment, spouses’ perception of patients’ negative affect, and spouses’ own fear of end-of-life suffering. Conclusion. Patients and surrogates used different criteria in formulating judgments about continuation of life-sustaining treatment and had different perceptions about the patients’ condition. Furthermore, the substituted judgments of spouses were influenced by their own characteristics. These processes may explain inaccurate substituted judgments.
The Power of the Like in Adolescence

We investigated a unique way in which adolescent peer influence occurs on social media. We developed a novel functional MRI (fMRI) paradigm to simulate Instagram, a popular social photo-sharing tool, and measured adolescents’ behavioral and neural responses to likes, a quantifiable form of social endorsement and potential source of peer influence. Adolescents underwent fMRI while viewing photos ostensibly submitted to Instagram. They were more likely to like photos depicted with many likes than photos with few likes; this finding showed the influence of virtual peer endorsement and held for both neutral photos and photos of risky behaviors (e.g., drinking, smoking). Viewing photos with many (compared with few) likes was associated with greater activity in neural regions implicated in reward processing, social cognition, imitation, and attention. Furthermore, when adolescents viewed risky photos (as opposed to neutral photos), activation in the cognitive-control network decreased. These findings highlight possible mechanisms underlying peer influence during adolescence.
Crystal Structure of a Bacterial Unsaturated Glucuronyl Hydrolase with Specificity for Heparin*

Background: Bacterial unsaturated glucuronyl hydrolase (UGL) is essential for complete degradation of host glycosaminoglycans. Results: Crystal structure of Pedobacter heparinus UGL, Phep_2830 specific for heparin degradation, was determined. Conclusion: The pocket-like structure and lid loop of Phep_2830 are involved in heparin disaccharide recognition. Significance: This work contributes to understanding the bacterial degradation of host extracellular matrix components. Extracellular matrix molecules such as glycosaminoglycans (GAGs) are typical targets for some pathogenic bacteria, which allow adherence to host cells. Bacterial polysaccharide lyases depolymerize GAGs in β-elimination reactions, and the resulting unsaturated disaccharides are subsequently degraded to constituent monosaccharides by unsaturated glucuronyl hydrolases (UGLs). UGL substrates are classified as 1,3- and 1,4-types based on the glycoside bonds. Unsaturated chondroitin and heparin disaccharides are typical members of 1,3- and 1,4-types, respectively. Here we show the reaction modes of bacterial UGLs with unsaturated heparin disaccharides by x-ray crystallography, docking simulation, and site-directed mutagenesis. Although streptococcal and Bacillus UGLs were active on unsaturated heparin disaccharides, those preferred 1,3- rather than 1,4-type substrates. The genome of GAG-degrading Pedobacter heparinus encodes 13 UGLs. Of these, Phep_2830 is known to be specific for unsaturated heparin disaccharides. The crystal structure of Phep_2830 was determined at 1.35-Å resolution. In comparison with structures of streptococcal and Bacillus UGLs, a pocket-like structure and lid loop at subsite +1 are characteristic of Phep_2830. Docking simulations of Phep_2830 with unsaturated heparin disaccharides demonstrated that the direction of substrate pyranose rings differs from that in unsaturated chondroitin disaccharides. Acetyl groups of unsaturated heparin disaccharides are well accommodated in the pocket at subsite +1, and aromatic residues of the lid loop are required for stacking interactions with substrates. Thus, site-directed mutations of the pocket and lid loop led to significantly reduced enzyme activity, suggesting that the pocket-like structure and lid loop are involved in the recognition of 1,4-type substrates by UGLs.
Clarificación de aguas de alta turbidez empleando el Mucílago de Opuntia wentiana (Britton & Rose) / (Cactaceae)

El proceso de coagulacion del agua causa la coalescencia de material suspendido, lo cual generalmente se logra adicionando sustancias quimicas a la misma. Sin embargo, dado que algunas de estas sustancias se han asociado a problemas de salud, diversos investigadores estudian como alternativa la utilizacion de coagulantes naturales obtenidos de especies vegetales. Por esta razon, se evaluo la efectividad de un coagulante extraido de la tuna Opuntia wentiana (Britton & Rose) en la clarificacion del agua. Para ello, se recolectaron muestras de agua cruda natural en la planta de tratamiento Pueblo Viejo (Estado Zulia, Venezuela) y a partir de estas se prepararon aguas diluidas con turbiedades iniciales de 100, 120, 160, 180 y 200 UNT. Estas aguas fueron tratadas con diferentes dosis (300, 400, 500, 600 y 700 ppm) del coagulante natural. Se evaluaron los parametros pH, turbidez, color y alcalinidad en las aguas crudas y en las tratadas. Despues de aplicar las dosis optimas del coagulante (600 y 700 ppm), los porcentajes de remocion de turbidez oscilaron entre 85,25 y 94,84% antes de la simulacion de la filtracion y entre 91,82 y 98,34% luego de ello. Estos resultados demostraron la efectividad del coagulante extraido de Opuntia wentiana (Britton & Rose) en la clarificacion del agua.
Acute Appendicitis from Metastatic Small Cell Lung Cancer

A 62-year-old female presented to the emergency department (ED) with right lower quadrant pain for 3 days. Past medical history was notable for small cell lung cancer (SCLC) with brain metastases. A staging positron emission tomography (PET) performed 10 days prior to presentation showed fludeoxyglucose uptake in the proximal appendix without surrounding inflammation (Figure 1). Figure 1 Positron emission tomography performed 10 days prior to presentation showing fludeoxyglucose uptake in the proximal appendix without surrounding inflammation consistent with appendiceal metastasis (arrow). In the ED, her physical exam was notable only for right lower quadrant tenderness to palpation, without rebound or guarding. Vital signs were within normal limits. Laboratory results were notable for a white blood count of 22 K/uL with 94% neutrophils (<5% bands). Contrast-enhanced abdominal computed tomography (CT) was performed in the ED showing a dilated appendix with enhancing wall and surrounding fat stranding suggestive of acute appendicitis (Figure 2). She was taken to the operating room emergently for a laproscopic appendectomy, which revealed a perforated appendix. The patient did well and 1 week postoperatively resumed treatment for her SCLC. Figure 2 Contrast-enhanced abdominal computed tomography of the abdomen performed in the emergency department showing a dilated appendix with enhancing wall and surrounding fat stranding (arrow) suggestive of acute appendicitis. Pathology of the appendiceal specimen demonstrated oval cells and nuclear molding consistent with small cell carcinoma involving the musclaris propria. Malignancies are a rare but known cause of appendiceal obstruction and inflammation, most commonly primary tumors, such as carcinoid or adenocarcinoma. This case of appendicitis from metastatic SCLC is exceedingly more rare, with only 7 prior case reports documented.1,2 Interestingly, this patient also had a staging PET CT that detected the metastasis prior to appendiceal obstruction and symptom onset. Other case reports have described screening PET CT incidentally diagnosing acute appendicitis.3,4 While metastases are an uncommon cause of appendiceal obstruction and inflammation, they should be considered as part of the differential diagnosis when a patient with known malignancy presents with symptoms consistent with appendicitis.
Relation of bronchial responsiveness to body mass index in the ECRHS

Background: There is substantial evidence for an association between symptoms of asthma and overweight or obesity. However, a study that reported no association between bronchial responsiveness (BHR) and body mass index (BMI) suggested that the relation of symptoms to obesity was due to increased diagnosis of asthma. The relation of BHR to BMI was therefore investigated in a large multicentre study. Methods: Data were obtained for 11 277 participants in stage II of the European Community Respiratory Health Survey (ECRHS). BHR to methacholine was analysed in relation to BMI adjusted for a number of factors known to be associated with BHR, including baseline lung function and allergen sensitisation, and combined across 34 centres using random effects meta-analysis. Results: BHR increased with increasing BMI in men (ECRHS slope changed by –0.027 for each unit increase in BMI, 95% confidence interval –0.044 to –0.010, p=0.002), but the relation in women was weak (–0.014, 95% CI –0.033 to 0.005, p=0.14). There was no evidence for an interaction of sex with BMI (p=0.41). Conclusions: BHR is related to BMI in the ECRHS. This suggests that the association is not due to greater diagnosis or perception of symptoms in obese people compared with those of normal weight. The data do not support the finding by some studies of a relation between asthma and obesity in women but not in men.
SAS-4 Protein in Trypanosoma brucei Controls Life Cycle Transitions by Modulating the Length of the Flagellum Attachment Zone Filament*

The evolutionarily conserved centriole/basal body protein SAS-4 regulates centriole duplication in metazoa and basal body duplication in flagellated and ciliated organisms. Here, we report that the SAS-4 homolog in the flagellated protozoan Trypanosoma brucei, TbSAS-4, plays an unusual role in controlling life cycle transitions by regulating the length of the flagellum attachment zone (FAZ) filament, a specialized cytoskeletal structure required for flagellum adhesion and cell morphogenesis. TbSAS-4 is concentrated at the distal tip of the FAZ filament, and depletion of TbSAS-4 in the trypomastigote form disrupts the elongation of the new FAZ filament, generating cells with a shorter FAZ associated with a longer unattached flagellum and repositioned kinetoplast and basal body, reminiscent of epimastigote-like morphology. Further, we show that TbSAS-4 associates with six additional FAZ tip proteins, and depletion of TbSAS-4 disrupts the enrichment of these FAZ tip proteins at the new FAZ tip, suggesting a role of TbSAS-4 in maintaining the integrity of this FAZ tip protein complex. Together, these results uncover a novel function of TbSAS-4 in regulating the length of the FAZ filament to control basal body positioning and life cycle transitions in T. brucei.
Routine detection of acute HIV infection through RNA pooling: survey of current practice in the United States.

Acute human immunodeﬁciency virus (HIV) infection is ahighly infectious and infrequently diagnosed stage of HIV infec-tion that holds promising opportunities for clinical and publichealth intervention. Several state and local public health agenciesare now employing quantitative nucleic acid ampliﬁcation tests(NAATs) to screen pooled specimens for acute HIV infection.