Miracle-dz/UniFAR-FTUs huggingface dataset:
Using cytometric bead arrays to detect cytokines in the serum of patients with different types of pulmonary tuberculosis

Cytokines play a crucial role in mediating immune responses to tuberculosis (TB). The aim of this study was to evaluate the levels of cytokines in patients with different forms of pulmonary tuberculosis (PTB) and identify valuable cytokine biomarkers for the diagnosis of PTB. We measured the levels of six cytokines (interleukin (IL-2, IL-4, IL-6, and IL-10), tumor necrosis factor (TNF-α), and interferon-γ (IFN-γ)) in the serum of healthy donors (n = 30). Patients with active PTB (n = 46) and those with latent tuberculosis infection (LTBI, n = 38) were examined using cytometric bead arrays. The levels of the six cytokines in the serum samples were measured promptly, sensitively, and simultaneously. The levels of IL-2, IL-6, IL-10, and IFN-γ were significantly higher in the PTB group compared with those reported in the healthy donors (P < 0.01 or P < 0.05). In addition, significantly higher levels of IL-2, IL-6, IL-10, and IFN-γ were found in the active PTB group compared with those observed in the LTBI group (P < 0.01 or P < 0.05). However, the levels of IL-4 and TNF-α in the sera of patients from the PTB group did not show a significant correlation with those measured in the healthy donor group. Our data demonstrated that IL-2, IL-6, IL-10, and IFN-γ may be useful in the auxiliary diagnosis of tuberculosis and as biomarkers for distinguishing LTBI from TB.
Tachykinins modulate nociceptive responsiveness and sensitization: In vivo electrical characterization of primary sensory neurons in tachykinin knockout (Tac1 KO) mice

Since the failure of specific substance P antagonists to induce analgesia, the role of tachykinins in the development of neuropathic pain states has been discounted. This conclusion was reached without studies on the role of tachykinins in normal patterns of primary afferents response and sensitization or the consequences of their absence on the modulation of primary mechanonociceptive afferents after injury. Nociceptive afferents from animals lacking tachykinins (Tac1 knockout) showed a disrupted pattern of activation to tonic suprathreshold mechanical stimulation. These nociceptors failed to encode the duration and magnitude of natural pronociceptive stimuli or to develop mechanical sensitization as consequence of this stimulation. Moreover, paw edema, hypersensitivity, and weight bearing were also reduced in Tac1 knockout mice 24 h after paw incision surgery. At this time, nociceptive afferents from these animals did not show the normal sensitization to mechanical stimulation or altered membrane electrical hyperexcitability as observed in wild-type animals. These changes occurred despite a similar increase in calcitonin gene-related peptide immunoreactivity in sensory neurons in Tac1 knockout and normal mice. Based on these observations, we conclude that tachykinins are critical modulators of primary nociceptive afferents, with a preeminent role in the electrical control of their excitability with sustained activation or injury.
Domains of planning for future long‐term care of adults with intellectual and developmental disabilities: Parent and sibling perspectives

Abstract Background Research shows that adults with intellectual and developmental disabilities (IDD) increasingly outlive caregivers, who often struggle to plan for the future and have little support and knowledge surrounding long‐term care planning. Methods The study team conducted interviews with parents and siblings of adults with IDD and performed qualitative coding using a modified grounded theory to explore domains of future planning and identify barriers and facilitators. Results Themes from the interviews revealed seven major domains of future planning that should be considered by caregivers of adults with IDD. These domains are housing, legal planning, identification of primary caregiver(s), financial planning, day‐to‐day care, medical management and transportation. Approaches to planning within each domain varied greatly. Conclusions The study team dentified the domain of “identification of primary caregiver(s)” as potentially the most important step for caregivers when planning for the future, but also observed that the domains identified are significantly interrelated and should be considered together.
Theoretical Predictions for Ion Composition in the High-Latitude Winter F-Region for Solar Minimum and Low Magnetic Activity

We combined a simple plasma convection model with an ionospheric-atmospheric density model in order to study the ion composition in the high-latitude winter F-region at solar minimum for low geomagnetic activity. Our numerical study produced time-dependent, 3-dimensional, ion density distributions for the ions NO+, O2+, N2+, O+, N+, and He+. We covered the high-latitude ionosphere above 54°N magnetic latitude and at altitudes between 160 and 800 km for a time period of 1 complete day. From our study we found the following (1) The ion composition exhibits a significant variation with latitude, local time, altitude, and universal time. (2) The variations of the ion composition with latitude and local time are in good agreement with the Atmosphere Explorer measurements both quantitatively and qualitatively. (3) At times and at certain locations the molecular ion density can be comparable to the O+ density at 300 km, and at 200 km the O+ density can be comparable to the molecular ion density. These results have important implications for the interpretation of incoherent scatter radar spectra obtained at high-latitudes. (4) Different ground-based observation sites should measure different diurnal variations in ion composition even if these sites are approximately at the same magnetic latitude owing to the UT response of the high-latitude ionosphere. (5) A satellite in a 300 km circular polar orbit should measure large orbit to orbit variations in both electron density and ion composition, again owing to the UT response of the polar ionosphere. (6) Erroneous conclusions can be drawn about ion density scale heights if the variations along the track of a satellite in a highly elliptical polar orbit are assumed to be only due to altitude variations.
Suspicion of malignant degeneration of decidualized endometriosis : imaging pattern and treatment issues ‘ Deciduosis ’ from decidualized endometriosis

Umberto Leone Roberti Maggiore1, Simone Ferrero2,3,, Giorgia Mangili1, Alice Bergamini1, Annalisa Inversetti1, Veronica Giorgione1, Paola Viganò4, and Massimo Candiani5 Obstetrics and Gynecology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milano, Italy Academic Unit of Obstetrics and Gynaecology, IRCCS AOU San Martino IST, Largo R. Benzi 10, 16132 Genova, Italy Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genova, Genova, Italy Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy Obstetrics and Gynecology Unit, Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Via Olgettina 58, 20132 Milano, Italy
Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle

Skeletal muscle adapts to external stimuli such as increased work. Muscle progenitors (MPs) control muscle repair due to severe damage, but the role of MP fusion and associated myonuclear accretion during exercise are unclear. While we previously demonstrated that MP fusion is required for growth using a supra-physiological model (Goh and Millay, 2017), questions remained about the need for myonuclear accrual during muscle adaptation in a physiological setting. Here, we developed an 8 week high-intensity interval training (HIIT) protocol and assessed the importance of MP fusion. In 8 month-old mice, HIIT led to progressive myonuclear accretion throughout the protocol, and functional muscle hypertrophy. Abrogation of MP fusion at the onset of HIIT resulted in exercise intolerance and fibrosis. In contrast, ablation of MP fusion 4 weeks into HIIT, preserved exercise tolerance but attenuated hypertrophy. We conclude that myonuclear accretion is required for different facets of exercise-induced adaptive responses, impacting both muscle repair and hypertrophic growth.
Serum drug concentrations to optimize switching from adalimumab to etanercept in rheumatoid arthritis

Objectives: Inadequate response to adalimumab can be caused by insufficient blockade of the target tumour necrosis factor (TNF) at low serum concentrations. In such cases, patients may respond to another TNF inhibitor. We investigated whether the serum adalimumab concentration is related to the efficacy of a second TNF inhibitor, etanercept, in rheumatoid arthritis (RA). Methods: Patients with RA starting etanercept treatment were prospectively observed in the Reade Rheumatology Registry. In patients previously on adalimumab, serum concentrations were determined before treatment discontinuation. According to this concentration, three subgroups were formed: < 0.5 μg/mL, 0.5–5.0 μg/mL, and ≥ 5.0 μg/mL. The European League Against Rheumatism (EULAR) good/moderate response rate after 52 weeks of etanercept was compared between the switcher subgroups and biologic-naive patients. Results: In total, 449 consecutive patients were included, of whom 69 switched from adalimumab (15%) and 380 were biologic naive (85%). EULAR good or moderate response was achieved by 74% of the biologic-naive patients and by 72%, 50%, and 52% of switchers with adalimumab concentration < 0.5 μg/mL, 0.5–5.0 μg/mL, and ≥ 5.0 μg/mL, respectively (p = 0.15). Patients with an adalimumab concentration ≥ 0.5 μg/mL were significantly less likely to achieve EULAR good/moderate response on etanercept compared to biologic-naive patients, whereas patients with a concentration < 0.5 μg/mL did not significantly differ from patients starting etanercept without prior biologic treatment. Conclusion: RA patients with an inadequate response to adalimumab, in the presence of sufficient drug concentrations, benefit less from switching to another TNF inhibitor, etanercept.
Is it the moon? Effects of the lunar cycle on psychiatric admissions, discharges and length of stay.

BACKGROUND There is an ongoing debate concerning the connection between lunar cycle and psychiatric illness. AIMS OF THE STUDY The purpose of the present study was to evaluate the rates of admission to and discharge from psychiatric inpatient treatment, as well as the length of stay, in relation to the lunar cycle, including 20 different categories of phases of the moon. METHODS The data of 17,966 cases of people treated in an inpatient setting were analysed. Routine clinical data and data about admission and discharge were used. The lunar calendar was obtained from the website of the US Naval Observatory and was used to calculate the dates of the full moon according to the geographic location of the clinics. The clinics are located in the Canton Grisons in Switzerland. The following phases of the moon throughout the lunar cycle were defined: (a) full moon, (b) quarter waxing moon, (c) new moon, and (d) quarter waning moon. In addition, we coded one day and two days preceding every lunar phase as well as the two days following the respective phases of the moon. RESULTS The lunar cycles showed no connection with either admission or discharge rates of psychiatric inpatients, nor was there a relationship with the length of stay. CONCLUSIONS Despite the widespread belief that the moon impacts peoples’ mental health and subsequently psychiatric treatment, this study provides no evidence that our celestial neighbour influences our mental well-being.
Phase 1/2 study of fractionated dose lutetium‐177–labeled anti–prostate‐specific membrane antigen monoclonal antibody J591 (177Lu‐J591) for metastatic castration‐resistant prostate cancer

Prostate cancer is radiosensitive. Prostate‐specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration‐resistant tumors. Lutetium‐177–labeled anti‐PSMA monoclonal antibody J591 (177Lu‐J591) targets prostate cancer with efficacy and dose‐response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely.
Factors associated with prolonged length of stay following robotic-assisted partial nephrectomy.

INTRODUCTION To prospectively analyze the association of clinical and operative variables on patient length of hospital stay (LOS) following robotic-assisted partial nephrectomy (RAPN) and develop an accurate clinical-based scoring system to predict prolonged LOS following RAPN. MATERIALS AND METHODS We analyzed 304 consecutive RAPNs performed by a single surgeon. Prolonged LOS was defined as greater than 3 days of hospitalization postoperatively. Preoperative clinical factors and operative variables were analyzed for association with LOS. After adjusting for multiple testing, p ≤ 0.004 was considered statistically significant. RESULTS LOS was 1 day in 17 (5.6%) patients, 2 days in 136 (44.7%) patients, 3 days in 89 (29.3%) patients, and more than 3 days in 62 (20.4%) patients. Lower preoperative hemoglobin (p = 0.004), total operative time (p < 0.001), estimated blood loss (EBL) (p < 0.001), intraoperative complications or conversion (p < 0.001), and renal mass size (p < 0.001) were associated with prolonged LOS. EBL and total operative time were most predictive of prolonged LOS and were used to create the BLOT (blood loss and operative time) predictive scoring system. Blot scores ranged from 0 to 5, to predict prolonged LOS. We observed prolonged LOS in 4.3%, 9.6%, 25.6%, 47.1%, 50.0%, and 100% of patients with scores of 0, 1, 2, 3, 4, and 5, respectively. CONCLUSIONS Operative time and estimated blood loss are most predictive of prolonged LOS following RAPN. Using these variables, the BLOT score accurately predicts prolonged LOS following RAPN.
Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart‐beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30′), 70 minutes (DCD70′), and 120 minutes (DCD120′) of warm ischemia were studied. The HBD, DCD30′, and DCD70′‐groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120′‐group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120′‐group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold‐urea increase was significantly lower in the DCD120′‐group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120′‐group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120′‐group (≤1) (P < .01). Three hours after transplantation, the DCD120′‐group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time‐points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.
Longitudinal effect of deactivating stimulation sites based on low-rate thresholds on speech recognition in cochlear implant users

Abstract Objective: The objective of the current study was to examine the longitudinal effect of deactivating stimulation sites estimated to produce broad neural excitation on speech recognition. Design: Spatial patterns of neural excitation were estimated based on a previously established psychophysical measure, that is, detection threshold for low-rate pulse trains. Stimulation sites with relatively poor thresholds were deactivated in an experimental map. The acute effect was evaluated, in quiet and in noise, immediately after the experimental map was created (baseline), after the subjects practiced with the experimental map for two months (treatment), and after the subjects’ daily map was switched back again to the clinical map for another two months (withdrawal). Study sample: Eight Cochlear Nucleus device users participated in the study. Results: For both listening in noise and in quiet, the greatest effect of deactivation was observed after the subjects were given time to adapt to the new frequency allocations. The effect was comparable for listening in fluctuating and steady-state noises. All subjects benefited from deactivation for listening in noise, but subjects with greater variability in thresholds were more likely to benefit from deactivation for listening in quiet. Conclusion: The benefit of electrode deactivation for speech recognition can increase with practice.
Trajectories of grief: Comparing symptoms from the DSM‐5 and ICD‐11 diagnoses

Diagnostic criteria for prolonged grief have appeared in the Diagnostic and Statistical Manual of Mental Disorders ( DSM‐5; persistent complex bereavement disorder, PCBD) and in the ICD‐11 (prolonged grief disorder, PGD), and the question of which diagnosis is most clinically useful has been hotly debated. This study provides the first longitudinal comparison of PCBD and PGD in their ability to capture symptom change over time and their relation to long‐term outcomes.
*The efficacy of the attachment-based SAFE® prevention program: a randomized control trial including mothers and fathers

ABSTRACT SAFE® is a primary prevention program to promote secure infant-parent attachment. SAFE explicitly addresses mothers and fathers. In this current first study, efficacy was assessed in a low-risk German sample using a randomized control trial with an active control intervention. A high rate of fathers’ participation was achieved: in SAFE 84.6% and in the control group intervention 73.9% of the fathers participated. Infant-parent attachment was assessed at the end of the year-long programs. There was a significant difference between groups in terms of secure infant-father attachment, but not of infant-mother attachment. In SAFE, 84.6% of the infants were securely attached to their father (n = 39), in comparison to 65.8% in the control group (n = 38). The proportion of secure infant-mother attachment was 66.7% in the SAFE group (n = 54) and 64.0% in the control group (n = 50). The program was successful in promoting infant-father attachment security.
Generated Loss, Augmented Training, and Multiscale VAE

The variational autoencoder (VAE) framework remains a popular option for training unsupervised generative models, especially for discrete data where generative adversarial networks (GANs) require workaround to create gradient for the generator. In our work modeling US postal addresses, we show that our discrete VAE with tree recursive architecture demonstrates limited capability of capturing field correlations within structured data, even after overcoming the challenge of posterior collapse with scheduled sampling and tuning of the KL-divergence weight $\beta$. Worse, VAE seems to have difficulty mapping its generated samples to the latent space, as their VAE loss lags behind or even increases during the training process. Motivated by this observation, we show that augmenting training data with generated variants (augmented training) and training a VAE with multiple values of $\beta$ simultaneously (multiscale VAE) both improve the generation quality of VAE. Despite their differences in motivation and emphasis, we show that augmented training and multiscale VAE are actually connected and have similar effects on the model.
Associations between breastfeeding rates and infant disease: A survey of 2338 Czech children.

AIM Evidence has demonstrated that breastfeeding is the optimal nutrition for infants. The present study aims to report possible associations of the duration of full or partial breastfeeding with selected health outcomes during infancy. METHODS Data from 2304 mothers were obtained by online mother-reported questionnaires at the age of 1 year of the child, providing information on full and partial breastfeeding durations, the frequency of infant upper respiratory tract infections and possible antibiotics use, and the occurrence of allergic diseases. RESULTS Overall breastfeeding initiation rates (i.e. including both partial and full breastfeeding rates counted together) were 97.8%, declined to 95.1% at the age of 3 months, and remained as high as 90.0% at 6 months. At 1 year, 74.7% of children were still partially breastfed. There was no significant benefit of either full or partial breastfeeding over formula feeding for upper respiratory tract infection rates. Fully breastfed children had a significantly lower risk of early exposure to antibiotics when compared with either partially breastfed (odds ratio, OR: 0.74; 95% CI: 0.56, 1.00, P = 0.048) or formula-fed (OR: 0.67; 95% CI: 0.46, 1.0, P = 0.047) children. We found a neutral effect of breastfeeding on the development of allergies. CONCLUSIONS Although no significant association between either full or partial breastfeeding versus formula feeding and the occurrence of respiratory infections during infancy was found, we demonstrated a significantly lower risk of early exposure to antibiotics in fully breastfed children when compared with those either partially breastfed or formula-fed.
Diabetes: Is There a Future for Pharmacogenomics Guided Treatment?

Diabetes is a disease defined on the basis of hyperglycemia. There are monogenic forms of diabetes where defining the genetic cause has a dramatic impact on treatment—with patients being able to transition from insulin to sulfonylureas. However, the majority of diabetes is type 2 diabetes. This review outlines the robust evidence accrued to date for pharmacogenetics of metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase‐4 inhibitors but highlights that these variants will only be of clinical utility when the genotype is already known at the point of prescribing. The future of pharmacogenetics in diabetes and other common complex disease relies on a paradigm shift—that of preemptive panel genotyping and use of clinical decision support tools to assimilate this genetic information with other clinical phenotypic data and to present this information simply to the prescriber. Given the recent dramatic fall in genotyping costs, this future is not far off.