Miracle-dz/UniFAR-FTUs huggingface dataset:
Adult-onset Still's disease-associated interstitial lung disease represents severe phenotype of the disease with higher rate of haemophagocytic syndrome and relapse.

OBJECTIVES Adult-onset Still's disease (AOSD) is an inflammatory disorder characterised by sustained fevers, arthritis, and skin involvement. Interstitial lung disease (ILD) is a rare manifestation, and its clinical characteristics have yet to be determined. METHODS We sought to examine the clinical characteristics of AOSD-associated ILD. We retrospectively investigated 78 patients diagnosed as AOSD. ILD was diagnosed based on chest high-resolution computed tomography (HRCT). Clinical characteristics were compared between patients with and without ILD. Relapse was defined as sustained fevers, re-emergence of arthritis, and skin involvement after remission. We further investigated the pathological features of ILD on available samples. RESULTS Patients with ILD, found in 9 of 78 (11.5 %), had older age of onset (mean age 62.6) than those without ILD (mean age 38.8) (p<0.01). The 3-year survival rates were comparable between patients with ILD (92.5%) and those without ILD (88.9%) (p=0.23). Patients with ILD had a higher cumulative rate of haemophagocytic syndrome (HPS) and relapse than those without (p<0.0001 and p=0.009, respectively). Chest HRCT showed marked thickening of the interlobular septa, the bronchovascular bundles, or the visceral pleura in all cases. There was no honeycomb or volume loss. Pulmonary pathological findings revealed marked thickening of the visceral pleura and the interlobular septa. CONCLUSIONS Patients with ILD might have higher risks for HPS and relapse. Careful observation and appropriate therapeutic intervention might be needed.
Semaglutide as a promising antiobesity drug

Semaglutide is a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) with a long elimination half‐life, allowing subcutaneous (sc) administration once per week. Both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) recently approved once‐weekly sc semaglutide for the treatment of type 2 diabetes mellitus (T2DM). The weight loss efficacy of once‐weekly sc semaglutide appears to be superior compared with the other once‐weekly GLP‐1 RAs in patients with T2DM. Semaglutide was recently evaluated as an antiobesity drug in a phase II dose‐finding trial, which demonstrated superior weight loss efficacy of once daily sc semaglutide compared with both placebo and once daily 3.0 mg liraglutide in patients with obesity but without T2DM. The magnitude of semaglutide‐induced weight loss in this study exceeded the criteria of both the EMA and FDA for antiobesity drugs, and there were no safety concerns, indicating the eligibility of once daily sc semaglutide as a future antiobesity drug.
Probability Distortion Depends on Choice Sequence in Rhesus Monkeys

Humans and other primates share many decision biases, among them our subjective distortion of objective probabilities. When making choices between uncertain rewards we typically treat probabilities nonlinearly: overvaluing low probabilities of reward and undervaluing high ones. A growing body of evidence, however, points to a more flexible pattern of distortion than the classical inverse-S one, highlighting the effect of experimental conditions in shifting the weight assigned to probabilities, such as task feedback, learning, and attention. Here we investigated the role of sequence structure (the order in which gambles are presented in a choice task) in shaping the probability distortion patterns of rhesus macaques: we presented 2 male monkeys with binary choice sequences of MIXED or REPEATED gambles against safe rewards. Parametric modeling revealed that choices in each sequence type were guided by significantly different patterns of probability distortion: whereas we elicited the classical inverse-S-shaped probability distortion in pseudorandomly MIXED trial sequences of gamble-safe choices, we found the opposite pattern consisting of S-shaped distortion, with REPEATED sequences. We extended these results to binary choices between two gambles, without a safe option, and confirmed the unique influence of the sequence structure in which the animals make choices. Finally, we showed that the value of gambles experienced in the past had a significant impact on the subjective value of future ones, shaping probability distortion on a trial-by-trial basis. Together, our results suggest that differences in choice sequence are sufficient to reverse the direction of probability distortion. SIGNIFICANCE STATEMENT Our lives are peppered with uncertain, probabilistic choices. Recent studies showed how such probabilities are subjectively distorted. In the present study, we show that probability distortions in macaque monkeys differ significantly between sequences in which single gambles are repeated (S-shaped distortion), as opposed to being pseudorandomly intermixed with other gambles (inverse-S-shaped distortion). Our findings challenge the idea of fixed probability distortions resulting from inflexible computations, and points to a more instantaneous evaluation of probabilistic information. Past trial outcomes appeared to drive the “gap” between probability distortions in different conditions. Our data suggest that, as in most adaptive systems, probability values are slowly but constantly updated from prior experience, driving measures of probability distortion to either side of the S/inverse-S debate.
WARP: A Unique Extracellular Matrix Component of Cartilage, Muscle, and Endothelial Cell Basement Membranes

The von Willebrand factor A‐domain‐related protein (WARP) encoded by the VWA1 gene, is an orphan extracellular matrix protein that is expressed in a subset of ECM structures but whose function is poorly understood. Here, recent advances on understanding VWA1/WARP will be reviewed including analysis of VWA1 reporter and global knock‐out mice, interaction studies, and recent transcriptome analyses. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
An alternative to plaster cast treatment in a pediatric trauma center using the CAD/CAM technology to manufacture customized three-dimensional-printed orthoses in a totally hospital context: a feasibility study

The aim of this study is to implement the clinical use of the three-dimensional (3D) design and printing technology in pediatric pathologies requiring immobilization. We describe the manufacturing process of the 3D device in place of the plaster cast usually applied to a child 48/72 h after the access to the Trauma Center Traumatology Hub. This procedure had already been performed at Level II, Trauma Center, Campania Region, Orthopaedic Division of Santobono Children’s Hospital, Naples, Italy. The operative phase was performed by two 3D printers and a scanner in the bioengineering laboratory of the hospital’s outpatient area. The phase of software elaboration requires close cooperation among physicians and engineers. We decided to use a model with a double-shell design and holes varying in width to ensure complete ventilation and lightness of the device. We chose to treat nondisplaced metaphyseal distal fractures of the radius in 18 patients enrolled from January 2017 to November 2017. The flow chart includes clinical and radiological examinations of every enrolled child, collecting information required by the program and its elaboration by bioengineers, and then transfer of the results to 3D printers. The child, immobilized by a temporary splint, wore his 3D device after 12/24 h. Then, he underwent serial check-ups in which the effectiveness and appropriateness of the treatment were clinically monitored and evaluated using subjective scales: visual analogue scale and patient-rated wrist evaluation. All the fractures consolidated both radiologically and clinically after the treatment, with no complications reported. Only one partial breakage of the device happened because of an accidental fall. The statistical analysis of the visual analogue scale and patient-rated wrist evaluation data shows that children’s activities of everyday life improved during the immobilization thanks to this treatment. This first study shows that using a 3D device instead of a traditional plaster cast can be an effective alternative approach in the treatment of pediatric nondisplaced metaphyseal distal radius fractures, with high overall patient satisfaction. We believe that 3D technology could be extended to the treatment of more complex fractures; this will be the subject of our second study.
Spermidine and Voluntary Activity Exert Differential Effects on Sucrose- Compared with Fat-Induced Systemic Changes in Male Mice.

BACKGROUND Excess dietary fat and sugar are linked to obesity and metabolic syndrome. Polyamines such as spermidine are implicated in fat accumulation and may support activity-induced weight loss. OBJECTIVE This study tested interventional spermidine supplementation and voluntary activity against fat- and sucrose-induced systemic and gut microbiota changes. METHODS A 3-factorial study design (3 × 2 × 2) was used to test the factors diet, activity, and spermidine. Male 6-wk-old C57BL/6N mice were fed a control diet (CD; carbohydrate:protein:fat, 70%:20%:10% of energy; 7% sucrose), a high-fat diet (HFD; carbohydrate:protein:fat, 20%:20%:60% of energy; 7% sucrose), or a high-sucrose diet (HSD; carbohydrate:protein:fat, 70%:20%:10% of energy; 35% sucrose). Diet groups were left untreated (+0) or had unlimited access to running wheels (+A) or were supplemented with 3 mM spermidine via drinking water (+S) or a combination of both (+A+S) for 30 wk (n = 7-10). RESULTS In comparison to the CD, the HFD enhanced body weights (by 36%, P < 0.001), plasma lipids (cholesterol by 24%, P < 0.001; triglycerides by 27%, P = 0.004), and glucose concentrations (by 18%, P < 0.001), whereas the HSD increased weight by 13% (P < 0.001) and fasting glucose by 17% (P < 0.001) but did not increase plasma lipids. Microbiota taxonomic composition changed upon the HFD and HSD (both P < 0.001); however, only the HSD increased microbial diversity (P < 0.001) compared with the CD. Activity influenced microbiota composition (P < 0.01) and reduced glucose concentrations in HSD-fed (P = 0.021) and HFD-fed (P < 0.001) mice compared with nonactive mice. The combination of activity and spermidine affected energy intake (P-interaction = 0.037) and reduced body weights of HSD+A+S mice compared with HSD+0 mice (P = 0.024). CONCLUSIONS In male C57BL/6N mice, dietary sucrose and fat caused diverse metabolic and microbiota changes that were differentially susceptible to physical exercise. Spermidine has the potential to augment activity-induced beneficial effects, particularly for sucrose-induced obesity.
Activation of CD8+ T Cell Responses after Melanoma Antigen Targeting to CD169+ Antigen Presenting Cells in Mice and Humans

The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169+ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans.
Do people improve health behavior after their partner is diagnosed with cancer? A prospective study in the Danish diet, Cancer and Health Cohort

Abstract Background: The cancer diagnosis is regarded as a stressful life event that is thought to trigger a teachable moment to induce health behavior changes among cancer patients. However, this may also hold true for their partners. We assessed if partners of cancer patients make more health behavior changes compared to persons whose partner remained cancer-free. Methods: Lifestyles was assessed in the prospective Danish Diet, Cancer and Health study. Logistic regression analyses were used to assess health behavior change among partners of cancer patients (n = 672) compared to partners of persons who remained cancer-free (n = 5534). Additionally, associations in two subgroups were assessed: bereaved partners and partners of patients who remained alive after cancer. Results: Partners of cancer patients were more likely to decrease their alcohol intake compared to partners of persons who remained cancer free. This finding could mainly be attributed to bereaved partners. Moreover, bereaved partners were also more likely to decrease their BMI. In contrast to our hypothesis, bereaved partners were more likely to decrease fruit intake and increase sugared beverages compared to partners of persons who remained cancer free. In general, men tended to improve their physical activity, while women tended to worsen their physical activity following the cancer diagnosis of their partner. Conclusions: A cancer diagnosis in the partner does seem to improve health behavior change only for alcohol intake. Bereaved partners tend to worsen dietary behaviors after the patient’s death.
Nucleotide Weight Matrices Reveal Ubiquitous Mutational Footprints of AID/APOBEC Deaminases in Human Cancer Genomes

Cancer genomes accumulate nucleotide sequence variations that number in the tens of thousands per genome. A prominent fraction of these mutations is thought to arise as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases. These enzymes, collectively called activation induced deaminase (AID)/APOBECs, deaminate cytosines located within defined DNA sequence contexts. The resulting changes of the original C:G pair in these contexts (mutational signatures) provide indirect evidence for the participation of specific cytosine deaminases in a given cancer type. The conventional method used for the analysis of mutable motifs is the consensus approach. Here, for the first time, we have adopted the frequently used weight matrix (sequence profile) approach for the analysis of mutagenesis and provide evidence for this method being a more precise descriptor of mutations than the sequence consensus approach. We confirm that while mutational footprints of APOBEC1, APOBEC3A, APOBEC3B, and APOBEC3G are prominent in many cancers, mutable motifs characteristic of the action of the humoral immune response somatic hypermutation enzyme, AID, are the most widespread feature of somatic mutation spectra attributable to deaminases in cancer genomes. Overall, the weight matrix approach reveals that somatic mutations are significantly associated with at least one AID/APOBEC mutable motif in all studied cancers.
Aurora borealis and string of pearls in vitreoretinal lymphoma: patterns of vitreous haze

Aims Peculiar retinal signs of vitreoretinal lymphoma (VRL) have been identified. However, limited information on the vitreous features of VRL is available. This study aims to characterise the vitreous involvement in VRL with the help of multimodal imaging. Methods In this retrospective, observational study, we reviewed charts and imaging of all patients with biopsy-proven VRL seen from January 2016 to April 2018 at a single referral centre. These included ultrawide-field imaging, ophthalmic ultrasonography and slit-lamp photography. The main outcome measures were patterns of vitreous haze of VRL, as observed by combining clinical and multimodal imaging information. Results Twenty-six eyes of 13 patients were included. At presentation, vitreous haze was present in 24 eyes (92%) and was the only sign of VRL in 4 eyes (15%). Three patterns of vitreous haze were identified in VRL. An aurora borealis pattern was present in 12 eyes and showed linear opacities with a myriad of cells aligned along the vitreous fibrils. A string of pearls pattern was present in two eyes at baseline and developed in other four eyes after vitrectomy, showing fine fibrils connecting bunches of inflammatory material. A non-specific pattern was observed in 10 eyes. Ophthalmic ultrasound showed corpuscular material correlating with the grading of vitreous haze. Conclusion VRL shows different patterns of vitreous haze. Multimodal imaging, including ultrawide-field imaging and slit-lamp photography, helps in recognising these patterns, raising suspicion for VRL.
Economic evaluation of sunitinib versus pazopanib and best supportive care for the treatment of metastatic renal cell carcinoma in Chile: cost-effectiveness analysis and a mixed treatment comparison

ABSTRACT Background: Sunitinib and Pazopanib are two metastatic renal cell carcinoma (MRCC) treatment alternatives, however the health system in Chile does not consider coverage for any. The cost-effectiveness versus relevant comparator was assessed to support evidence-based decision making. Methods: A four health states Markov model was built: first, second line treatments, BSC and death. Benefits were measured in QALYs, and efficacy estimates were obtained from an indirect treatment comparison. A 10-year time horizon and a 3% undifferentiated discount rate were considered. Deterministic and probabilistic sensitivity analyses were performed. Results: The costs of treating MRCC with Sunitinib were higher than Pazopanib and BSC. When comparing Sunitinib versus Pazopanib, the incremental benefit is small favoring Sunitinib (0.03 QALYs). The base case scenario shows an average ICER of PA versus BSC of US$62,327.11/QALY and of US$85,885/QALY for Sunitinib versus Pazopanib. The ICER was most sensitive to the OS relative to BSC, where evidence was associated to important bias. Conclusions: Sunitinib or Pazopanib can be considered cost-effective if a 3 GDP per-capita threshold is assumed. The decision between SU or PA is highly sensitive to the price of the drugs, rather than the outcomes. Therefore, the decision might be made based on cost-minimization exercise.
A multicenter point prevalence survey of antibiotic use in Punjab, Pakistan: findings and implications

ABSTRACT Objectives: In line with the recent global action plan for antimicrobial resistance, this is the first time such a comprehensive antimicrobial point prevalence survey has been undertaken in Pakistan, the sixth most populous country. Methods: This point prevalence survey (PPS) was conducted in 13 hospitals among 7 different cities of Pakistan. The survey included all inpatients receiving an antibiotic on the day of PPS. A web-based application was used for data entry, validation, and reporting as designed by the University of Antwerp (www.global-pps.com). Results: Out of 1954 patients, 1516 (77.6%) were treated with antibiotics. The top three most reported indications for antibiotic use were prophylaxis for obstetrics or gynaecological indications (16.5%), gastrointestinal indications (12.6%) and lower respiratory tract infections (12.0%). The top three most commonly prescribed antibiotics were ceftriaxone (35.0%), metronidazole (16.0%) and ciprofloxacin (6.0%). Out of the total indications, 34.2% of antibiotics were prescribed for community-acquired infections (CAI), 5.9% for healthcare-associated infections (HAI), and 57.4% for either surgical or medical prophylaxis. Of the total use for surgical prophylaxis, 97.4% of antibiotics were given for more than one day. Conclusions: Unnecessary prophylactic antibiotic use is extremely high, and broad-spectrum prescribing is common among hospitals in Pakistan. There is an urgent need to work on the national action plan of Pakistan on antibiotic resistance to address this.
Behcet’s disease and pregnancy: obstetrical and neonatal outcomes in a population-based cohort of 12 million births

Abstract Background Behcet’s disease (BD) is a rare, multi-systemic inflammatory disorder for which only limited and contradictory data exists in the context of pregnancy. Our objective was to estimate the prevalence of BD in pregnancy and to evaluate maternal and fetal outcomes associated with pregnant women living with BD. Methods Using the 1999–2013 Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from the United States, we performed a population-based retrospective cohort study consisting of pregnancies that occurred during this time period. ICD-9 codes were used to identify delivery admissions to women with or without BD. Multivariate logistic regression was used to estimate the adjusted effects of BD on maternal and fetal outcomes. Results Among the 12,592,676 pregnancies in our cohort, 144 were to women with BD, for an overall prevalence of 1.14 cases/100,000 births between 1999 and 2013. Over the study period, the prevalence of BD rose from 0.5 to 2.4/100,000 births. Women with BD demonstrated a two-fold greater frequency of non-delivery hospital admissions during pregnancy, and were more likely to be Caucasian, have private medical insurance, be of the upper income quartiles, and deliver at an urban teaching hospital. Women with BD were at greater risk for preterm labor and postpartum venous thromboembolism, while their newborns were more likely to be born premature. Conclusion BD-associated pregnancies are increasing in prevalence and are associated with a greater risk for adverse maternal and fetal outcomes in pregnancy. Appropriate thromboprophylaxis during pregnancy should be considered given the increased risk for venous thromboembolism.
Association between depression and overweight in Chinese adolescents: a cross-sectional study

Objective Based on a nationally representative adolescent sample, we examined the association of depression on the prevalence of overweight or obesity and whether this association was moderated by gender. Methods There were 1081 adolescents from the China Family Panel Studies that participated in our study. Depression in adolescents was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Ordered logistic regression model was used to quantify its association with overweight or obesity. Analyses were performed for the total group, and separately for males and females. Results The prevalence of depression in Chinese adolescents was 23.22%. Depression (CES-D ≥16) was significantly associated with overweight or obesity (OR=1.47, 95% CI: 1.14 to 1.91, p=0.004) after adjustment for personal, household and regional confounders. Among four subdimensions of depression, depressed affect and lack of positive affect were significantly associated with increases in the odds of overweight or obesity. In females, only lack of positive affect was significantly associated with overweight or obesity, whereas the estimated associations of all other measures of depression on overweight or obesity were positive in males. Conclusions These findings provide evidence that depression is associated with overweight or obesity among adolescents in China, especially among males.