Miracle-dz/UniFAR-FTUs huggingface dataset:
Adult-onset Still's disease presenting as blotchy and flagellate pigmentation

Indian Journal of Dermatology, Venereology and Leprology | Volume 85 | Issue 6 | November-December 2019 626 et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378‐90. 2. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, et al. Phase II placebo‐controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:2505‐12. 3. Lipworth AD, Robert C, Zhu A ×. Hand‐foot syndrome (hand‐foot skin reaction, palmar‐plantar erythrodysesthesia): Focus on sorafenib and sunitinib. Oncology 2009;77:257‐71. 4. Guerra JR, Suelves AM, Bella A, Lolo D. Hand, foot and scrotal blisters in a patient with cancer receiving oral chemotherapy. BMJ Case Rep 2014;2014. pii: bcr2013202822. 5. Sibaud V, Delord JP, Chevreau C. Sorafenib‐induced hand‐foot skin reaction: A Koebner phenomenon? Target Oncol 2009;4:307‐10.
Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.

BACKGROUND The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 with ECOG PS ≤ 2 and between 71 and 75 with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. PATIENTS AND METHODS Subgroup analyses according to age (<70 versus 70-75 years) and gender were performed for overall response rate (ORR), progression-free survival (PFS) and AE rates. RESULTS Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, p<0.01 and 69% versus 57%, p<0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). CONCLUSIONS The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Effect of cyclosporine a and polymorphisms in CYP2C19 and ABCC2 on the concentration of voriconazole in patients undergoing allogeneic hematopoietic stem cell transplantation

Abstract 1. Voriconazole is known to display highly variable pharmacokinetics affecting treatment efficacy and safety. This study aimed to identify the factors causing the variation of voriconazole concentration in patients with allogeneic hematopoietic stem cell transplantation. 2. The data of patients was collected, including clinical characteristics and voriconazole concentrations. A total of 5 single nucleotide polymorphisms of 3 candidate genes (CYP2C19, ABCC2, ABCG2) related to voriconazole metabolism were genotyped by MassArray method. The correlation between polymorphisms and voriconazole concentration was analyzed. 3. A total of 244 voriconazole concentrations of 43 patients were included in this study. The voriconazole concentration was significantly correlated with patients' total bile acid (p = 0.001) and cyclosporin A (p < 0.001). The median concentration of the CYP2C19 normal metabolizers was remarkably lower than poor metabolizers (0.86 vs 2.27 μg/mL). The median concentration of ABCC2 rs2273697 GG genotype carriers was significantly higher than that of GA genotype carriers (p = 0.026). 4. The variability of voriconazole concentration is partially explained by total bile acid, metabolic types of CYP2C19. The voriconazole concentration of CYP2C19 normal metabolizers is likely to be lower than 1.0 μg/mL and thus at risk of infection due to inadequate treatment.
Degradation of the transcription factors PIF4 and PIF5 under UV‐B promotes UVR8‐mediated inhibition of hypocotyl growth in Arabidopsis

Summary Inhibition of hypocotyl growth is a well‐established UV‐B‐induced photomorphogenic response that is mediated by the UV‐B photoreceptor UV RESISTANCE LOCUS 8 (UVR8). However, the molecular mechanism by which UVR8 signaling triggers inhibition of hypocotyl growth is poorly understood. The bZIP protein ELONGATED HYPOCOTYL 5 (HY5) functions as the main positive regulatory transcription factor in the UVR8 signaling pathway, with HY5‐HOMOLOG (HYH) playing a minor role. However, here we demonstrate that hy5 hyh double mutants maintain significant UVR8‐dependent hypocotyl growth inhibition. We identify UVR8‐dependent inhibition of the activities of bHLH transcription factors PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5 as part of the UVR8 signaling pathway, which results in inhibition of hypocotyl growth. The UVR8‐mediated repression of several hypocotyl elongation‐related genes is independent of HY5 and HYH but largely associated with UVR8‐dependent degradation of PIF4 and PIF5, a process that consequently diminishes PIF4/5 target promoter occupancy. Taken together, our data indicate that UVR8‐mediated inhibition of hypocotyl growth involves degradation of PIF4 and PIF5. These findings contribute to our mechanistic understanding of UVR8‐induced photomorphogenesis and further support the function of PIFs as integrators of different photoreceptor signaling pathways.
Fused Sparse Network Learning for Longitudinal Analysis of Mild Cognitive Impairment

Alzheimer’s disease (AD) is a neurodegenerative disease with an irreversible and progressive process. To understand the brain functions and identify the biomarkers of AD and early stages of the disease [also known as, mild cognitive impairment (MCI)], it is crucial to build the brain functional connectivity network (BFCN) using resting-state functional magnetic resonance imaging (rs-fMRI). Existing methods have been mainly developed using only a single time-point rs-fMRI data for classification. In fact, multiple time-point data is more effective than a single time-point data in diagnosing brain diseases by monitoring the disease progression patterns using longitudinal analysis. In this article, we utilize multiple rs-fMRI time-point to identify early MCI (EMCI) and late MCI (LMCI), by integrating the fused sparse network (FSN) model with parameter-free centralized (PFC) learning. Specifically, we first construct the FSN framework by building multiple time-point BFCNs. The multitask learning via PFC is then leveraged for longitudinal analysis of EMCI and LMCI. Accordingly, we can jointly learn the multiple time-point features constructed from the BFCN model. The proposed PFC method can automatically balance the contributions of different time-point information via learned specific and common features. Finally, the selected multiple time-point features are fused by a similarity network fusion (SNF) method. Our proposed method is evaluated on the public AD neuroimaging initiative phase-2 (ADNI-2) database. The experimental results demonstrate that our method can achieve quite promising performance and outperform the state-of-the-art methods.
Safety of switching from intravenous to subcutaneous rituximab during first‐line treatment of patients with non‐Hodgkin lymphoma: the Spanish population of the MabRella study

Rituximab is a standard treatment for non‐Hodgkin diffuse large B‐cell (DLBCL) and follicular (FL) lymphomas. A subcutaneous formulation was developed to improve the resource use of intravenous rituximab, with comparable efficacy and safety profiles except for increased administration‐related reactions (ARRs). MabRella was a phase IIIb trial to assess the safety of switching from intravenous to subcutaneous administration of rituximab during first‐line induction/maintenance for DLBCL or FL, focusing on ARRs. Efficacy, satisfaction and quality of life were also assessed. Patients received subcutaneous rituximab plus standard induction chemotherapy for DLBCL or FL for 4–7 cycles, and/or every 2 months maintenance monotherapy for FL for 6–12 cycles. The study included 140 patients: DLBCL, n = 29; FL, n = 111. Ninety‐five percent of patients experienced adverse events, reaching grade ≥3 in 38·6% and were serious in 30·0%. AARs occurred in 48·6%, mostly (84·9%) at the injection site, with only 2·1% of patients reaching grade 3. The end‐of‐induction complete/unconfirmed complete response rate was 69·6%. After a median follow‐up of 33·5 months, median disease‐/event‐/progression‐free and overall survivals were not attained. The Rituximab Administration Satisfaction Questionnaire showed improvements in overall satisfaction and the EuroQoL‐5D a good quality‐of‐life perception at induction/maintenance end. Therefore, switching to subcutaneous rituximab showed no new safety issues and maintained efficacy with improved satisfaction and quality of life.
P120 Catenin Isoforms Differentially Associate with Breast Cancer Invasion and Metastasis

Tumor metastasis is the endpoint of tumor progression and depends on the ability of tumor cells to locally invade tissue, transit through the bloodstream and ultimately to colonize secondary organs at distant sites. P120 catenin (p120) has been implicated as an important regulator of metastatic dissemination because of its roles in cell–cell junctional stability, cytoskeletal dynamics, growth and survival. However, conflicting roles for p120 in different tumor models and steps of metastasis have been reported, and the understanding of p120 functions is confounded by the differential expression of p120 isoforms, which differ in N-terminal length, tissue localization and, likely, function. Here, we used in silico exon expression analyses, in vitro invasion assays and both RT-PCR and immunofluorescence of human tumors. We show that alternative exon usage favors expression of short isoform p120-3 in 1098 breast tumors and correlates with poor prognosis. P120-3 is upregulated at the invasive front of breast cancer cells migrating as collective groups in vitro. Furthermore, we demonstrate in histological sections of 54 human breast cancer patients that p120-3 expression is maintained throughout the metastatic cascade, whereas p120-1 is differentially expressed and diminished during invasion and in metastases. These data suggest specific regulation and functions of p120-3 in breast cancer invasion and metastasis.
Function of crzA in Fungal Development and Aflatoxin Production in Aspergillus flavus

The calcineurin pathway is an important signaling cascade for growth, sexual development, stress response, and pathogenicity in fungi. In this study, we investigated the function of CrzA, a key transcription factor of the calcineurin pathway, in an aflatoxin-producing fungus Aspergillus flavus (A. flavus). To examine the role of the crzA gene, crzA deletion mutant strains in A. flavus were constructed and their phenotypes, including fungal growth, spore formation, and sclerotial formation, were examined. Absence of crzA results in decreased colony growth, the number of conidia, and sclerocia production. The crzA-deficient mutant strains were more susceptible to osmotic pressure and cell wall stress than control or complemented strains. Moreover, deletion of crzA results in a reduction in aflatoxin production. Taken together, these results demonstrate that CrzA is important for differentiation and mycotoxin production in A. flavus.
The Power of Recognition: A Qualitative Study of Social Connectedness and Wellbeing through LGBT Sporting, Creative and Social Groups in Ireland

The broad research consensus suggesting substantial vulnerabilities among lesbian, gay, bisexual and transgender (LGBT) communities may fail to recognize the protective factors available to these populations. The sparse literature on mental health promotion highlights the importance of understanding strengths-based community approaches that promote LGBT wellbeing. Informed by the Ottawa Charter for Health Promotion, underpinned by Honneth’s Theory of Recognition, this paper outlines the findings of a qualitative Irish study on LGBT social connectedness through a diverse range of sporting, creative and social interests. Ten in-depth interviews were conducted with 11 people (including one couple) who self-identified as lesbian (5), gay (4), bisexual (1) and transgender (1) aged between 22 and 56 years. A university Research Ethics Committee granted approval. The data were transcribed and coded using thematic analysis, enhanced through a memo-writing approach to reflexivity. The theme of ‘connecting’ emphasized the shared nature of activities, with like-minded others through groups established by, and for, LGBT communities. Messages from the study reinforce the central role of LGBT communities in the promotion of mental health and social wellbeing, with important policy and practice implications. This requires the contextualization of the contribution of LGBT communities within understandings of social justice, identity and recognition.
Sprint start performance: the potential influence of triceps surae electromechanical delay

ABSTRACT In the sprint start, a defined sequence of distinct response delays occurs before the athlete produces a movement response. Excitation of lower limb muscles occurs prior to force production against the blocks, culminating in a movement response. The time delay between muscle excitation and movement, electromechanical delay (EMD), is considered to influence sprint start response time (SSRT). This study examined the delay in sprint start performance from EMD of the triceps surae muscle and examined whether certain sprinters gain an advantage in SSRT. Nineteen experienced sprinters performed sprint starts from blocks, with SSRT measured by an International Association of Athletics Federations (IAAF)-approved starting block system. EMD times were detected during a heel-lift experiment. Using revised SSRT limits, based on concerns over the validity of the IAAF 100 ms false start limit, EMD produced a significant moderate correlation with SSRT (r = 0.572, p = 0.011). Regression analysis determined that together, EMD and signal processing time (the delay between the auditory signal and muscle excitation) accounted for 37% of the variance in SSRT. Initial results suggest EMD is part of the response time process and that certain athletes may gain a performance advantage due to reduced EMD.
Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules

Significance Central to adaptive immunity is the interaction between the αβ T cell antigen receptor (TCR) and peptides presented by the major histocompatibility complex (MHC) molecules. It is fundamental to understand any potential generalities regarding a TCR-pMHC recognition event. Two theories have been proposed to explain how TCR recognition of pMHC is specified: The germline-encoded theory, which proposes an evolutionary “hardwiring” of the TCR for recognition of MHC molecules through germline-encoded motifs, and the selection theory of TCR recognition, which suggests that TCR selection during development imposes the constraint of MHC recognition. Here, we show that TCRs have intrinsic specificity for MHC molecules, inherent to TCRαβ sequences, and enhanced but not determined by coreceptor expression. The repertoire of αβ T cell antigen receptors (TCRs) on mature T cells is selected in the thymus where it is rendered both self-tolerant and restricted to the recognition of major histocompatibility complex molecules presenting peptide antigens (pMHC). It remains unclear whether germline TCR sequences exhibit an inherent bias to interact with pMHC prior to selection. Here, we isolated TCR libraries from unselected thymocytes and upon reexpression of these random TCR repertoires in recipient T cell hybridomas, interrogated their reactivities to antigen-presenting cell lines. While these random TCR combinations could potentially have reacted with any surface molecule on the cell lines, the hybridomas were stimulated most frequently by pMHC ligands. The nature and CDR3 loop composition of the TCRβ chain played a dominant role in determining pMHC-reactivity. Replacing the germline regions of mouse TCRβ chains with those of other jawed vertebrates preserved reactivity to mouse pMHC. Finally, introducing the CD4 coreceptor into the hybridomas increased the proportion of cells that could respond to pMHC ligands. Thus, αβ TCRs display an intrinsic and evolutionary conserved bias for pMHC molecules in the absence of any selective pressure, which is further strengthened in the presence of coreceptors.
Spatiotemporal clustering of malaria in southern-central Ethiopia: A community-based cohort study

Introduction Understanding the spatiotemporal clustering of malaria transmission would help target interventions in settings of low malaria transmission. The aim of this study was to assess whether malaria infections were clustered in areas with long-lasting insecticidal nets (LLINs) alone, indoor residual spraying (IRS) alone, or a combination of LLINs and IRS interventions, and to determine the risk factors for the observed malaria clustering in southern-central Ethiopia. Methods A cohort of 34,548 individuals residing in 6,071 households was followed for 121 weeks, from October 2014 to January 2017. Both active and passive case detection mechanisms were used to identify clinical malaria episodes, and there were no geographic heterogeneity in data collection methods. Using SaTScan software v 9.4. 4, a discrete Poisson model was used to identify high rates of spatial, temporal, and spatiotemporal malaria clustering. A multilevel logistic regression model was fitted to identify predictors of spatial malaria clustering. Results The overall incidence of malaria was 16.5 per 1,000 person-year observations. Spatial, temporal, and spatiotemporal clustering of malaria was detected in all types of malaria infection (P. falciparum, P. vivax, or mixed). Spatial clustering was identified in all study arms: for LLIN + IRS arm, a most likely cluster size of 169 cases in 305 households [relative risk (RR) = 4.54, P<0.001]; for LLIN alone arm a cluster size of 88 cases in 103 households (RR = 5.58, P<0.001); for IRS alone arm a cluster size of 58 cases in 50 households (RR = 7.15, P<0.001), and for control arm a cluster size of 147 cases in 377 households (RR = 2.78, P<0.001). Living 1 km closer to potential vector breeding sites increased the odds of being in spatial clusters by 41.32 fold (adjusted OR = 41.32, 95% CI = 3.79–138.89). Conclusions The risk of malaria infection varied significantly between kebeles, within kebeles, and even among households in areas targeted for different types of malaria control interventions in low malaria transmission setting. The results of this study can be used in planning and implementation of malaria control strategies at micro-geographic scale. Trial registration PACT R2014 11000 882128 (8 September 2014).
To cement or not to cement acetabular cups in total hip arthroplasty: a systematic review and re-evaluation

Introduction: Total Hip Arthroplasty (THA) in the treatment of primary osteoarthritis of the hip has evolved to a very safe and cost-effective intervention with revision rates below 5% after 10 years. To this day, however, controversy remains on whether or not to cement the acetabular cup. Methods: A comprehensive PubMed search of the English literature for studies published between 2007 and 2018 was performed. Studies comparing the clinical (revision rate, functionality), radiological (wear) or economic (cost) differences between cemented (cemented stem with cemented cup) and hybrid (cemented stem with uncemented cup) prostheses for primary osteoarthritis of the hip were identified as eligible. Results: A total of 1032 studies were identified whereof twelve were included for qualitative synthesis. All studies concerning the risk of revision were based on registry data, covering a total of 365,693 cups. Cemented prostheses had a similar or lower risk of revision compared to hybrid prostheses in every study, but performed slightly worse on functionality and quality of life. While cemented prostheses were the cheapest option, hybrids were the most cost-effective. Discussion: The widespread preference for cementless fixation of the acetabulum cannot be explained by a superior survival of cementless or hybrid models. Irrespective of age, cemented fixation of the acetabulum remains the gold standard to which other techniques should be compared.
Evaluation of laboratory parameters and symptoms after parathyroidectomy in dialysis patients with secondary hyperparathyroidism

Abstract Objectives: The aim of the study was to evaluate the laboratory parameters and symptoms after parathyroidectomy (PTX) in dialysis patients with secondary hyperparathyroidism (SHPT), and to briefly analyze the different therapeutic effects of the three surgical methods. Methods: A total of 182 dialysis patients who underwent PTX between February 2012 and January 2018 at the Second Affiliated Hospital of Soochow University were included in this study and followed for 12 months. Laboratory parameters such as calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) were measured before and after operation. According to the follow-up time and type of operation, we calculated the percentage of laboratory indicators reaching the recommended range of the KDIGO guidelines after surgery. We also analyzed the improvement of bone pain and pruritus, as well as surgical complications. Results: After the operation, the levels of iPTH, Ca, and P decreased significantly at each time point. ALP increased at the first postoperative week and gradually decreased to normal range after 3 months. Symptoms, such as bone pain and pruritus, were significantly relieved. According to the follow-up time and three surgical methods (subtotal parathyroidectomy, total parathyroidectomy, total parathyroidectomy plus autologous transplantation), we found that the ratio of each laboratory parameter reaching the recommended range of KDIGO guidelines was significantly different. Conclusion: PTX is a safe and effective therapy for treating SHPT that is refractory to medical therapies and accompanied by related signs and symptoms in dialysis patients. All three operative techniques were effective in controlling SHPT.