Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer

Purpose: VEGFR2-directed therapy is commonly used to treat metastatic esophagogastric cancer, but disease progresses in most patients within months. Therapeutic resistance is likely mediated in part by co-occurring amplifications of the genes for multiple oncogenic receptor tyrosine kinases (RTK). We therefore tested the efficacy of combined inhibition of VEGFR1-3, PDGFα/β, and FGFR1-3 using nintedanib. Patients and Methods: Patients with metastatic esophagogastric adenocarcinoma and disease progression on first-line chemotherapy were treated with nintedanib 200 mg twice daily. The primary endpoint was progression-free survival (PFS) at 6 months; secondary endpoints included tumor response and safety. Tumor biopsies were profiled by targeted capture next-generation sequencing (NGS) to identify molecular predictors of drug response. Results: The study achieved its primary endpoint; 6 of 32 patients (19%) were progression-free at 6 months. With a median follow-up of 14.5 months among survivors, median overall survival (OS) was 14.2 months [95% confidence interval (CI), 10.8 months–NR]. Nintedanib was well tolerated; grade ≥ 3 toxicities were uncommon and included grade 3 hypertension (15%) and liver enzyme elevation (4%). FGFR2 alterations were identified in 18% of patients but were not predictive of clinical outcome on nintedanib therapy. Alterations in cell-cycle pathway genes were associated with worse median PFS (1.61 months for patients with cell-cycle pathway alterations vs. 2.66 months for patients without, P = 0.019). Conclusions: Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell-cycle pathway genes and increased global copy-number alteration (CNA) burden warrant further study as prognostic or predictive biomarkers.
Safety Evaluation of Autologous Tissue Vaccine Cancer Immunotherapy in a Canine Model

Background/Aim: Previous work in rodent models showed that an autologous tissue vaccine is both a safe and effective approach for treating cancer; however, as a translational step, safety must first be evaluated in a more clinically-relevant model. Materials and Methods: An autologous immunotherapy produced from resected tumors, was evaluated in a clinically-relevant canine model to assess safety. Ninety-three dogs with spontaneously occurring tumors received vaccination with inactivated autologous tumor tissue combined with an adjuvant of particulate porcine small intestinal submucosa extracellular matrix (SIS-ECM). Patients were followed to assess the occurrence of adverse events, overall survival, and tumor recurrence and/or metastasis. Results: A small number (12%) of patients experienced limited, mild pyrexia, injection site swelling, or lethargy, all resolving without clinical intervention. Conclusion: Autologous whole cell cancer immunotherapy can be used safely in the canine model of cancer and represents a safe approach for the treatment for cancer.
Spectrally Similar Graph Pooling

We consider the problem of learning compositional hierarchies of graphs. Even though structural characteristics of graphs can be learned by Graph Neural Networks (GNNs), it is difficult to find an overall compositional hierarchy using such flat operators. In this paper, we propose a new graph pooling algorithm, Spectrally Similar Graph Pooling (SSGPool), to learn hierarchical representations of graphs. The main idea of the proposed SSGPool algorithm is to learn a coarsening matrix which maps nodes from an original graph to a smaller number of nodes in a coarsened graph. The coarsening matrix is trained to coarsen the nodes based on their feature vectors while keeping the spectral characteristics of the original graph in the coarsened one. Experiments on various graph benchmarks show the advantage of our method compared to strong baselines. To further investigate the effectiveness of our proposed method, we evaluate our approach on a real-world problem, image retrieval with visual scene graphs. Quantitative and qualitative analyses on the retrieval problem confirm that the proposed method efficiently captures the hierarchical semantic structure of scene graphs.
Prediction of Bone Metastasis in Inflammatory Breast Cancer Using a Markov Chain Model.

BACKGROUND Inflammatory breast cancer (IBC) is a rare yet aggressive variant of breast cancer with a high recurrence rate. We hypothesized that patterns of metastasis differ between IBC and non-IBC. We focused on the patterns of bone metastasis throughout disease progression to determine statistical differences that can lead to clinically relevant outcomes. Our primary outcome of this study is to quantify and describe this difference with a view to applying the findings to clinically relevant outcomes for patients. SUBJECTS, MATERIALS, AND METHODS We retrospectively collected data of patients with nonmetastatic IBC (n = 299) and non-IBC (n = 3,436). Probabilities of future site-specific metastases were calculated. Spread patterns were visualized to quantify the most probable metastatic pathways of progression and to categorize spread pattern based on their propensity to subsequent dissemination of cancer. RESULTS In patients with IBC, the probabilities of developing bone metastasis after chest wall, lung, or liver metastasis as the first site of progression were high: 28%, 21%, and 21%, respectively. For patients with non-IBC, the probability of developing bone metastasis was fairly consistent regardless of initial metastasis site. CONCLUSION Metastatic patterns of spread differ between patients with IBC and non-IBC. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis. IMPLICATIONS FOR PRACTICE This study demonstrated that the patterns of metastasis leading to and following bone metastasis differ significantly between patients with inflammatory breast cancer (IBC) and those with non-IBC. Patients with IBC had a progression pattern that tended toward the development of bone metastasis if they had previously developed metastases in the liver, chest wall, and lung, rather than in other sites. Selection of patients with IBC with known liver, chest wall, and/or lung metastasis would create a population in whom to investigate effective methods for preventing future bone metastasis.
Rethinking false spring risk

Temperate plants are at risk of being exposed to late spring freezes. These freeze events—often called false springs—are one of the strongest factors determining temperate plants species range limits and can impose high ecological and economic damage. As climate change may alter the prevalence and severity of false springs, our ability to forecast such events has become more critical, and it has led to a growing body of research. Many false spring studies largely simplify the myriad complexities involved in assessing false spring risks and damage. While these studies have helped advance the field and may provide useful estimates at large scales, studies at the individual to community levels must integrate more complexity for accurate predictions of plant damage from late spring freezes. Here, we review current metrics of false spring, and how, when, and where plants are most at risk of freeze damage. We highlight how life stage, functional group, species differences in morphology and phenology, and regional climatic differences contribute to the damage potential of false springs. More studies aimed at understanding relationships among species tolerance and avoidance strategies, climatic regimes, and the environmental cues that underlie spring phenology would improve predictions at all biological levels. An integrated approach to assessing past and future spring freeze damage would provide novel insights into fundamental plant biology and offer more robust predictions as climate change progresses, which are essential for mitigating the adverse ecological and economic effects of false springs.
The Otubain YOD1 Suppresses Aggregation and Activation of the Signaling Adaptor MAVS through Lys63-Linked Deubiquitination

Key points The otubain YOD1 fine-tunes MAVS-RLR pathway–mediated antiviral immunity. YOD1 interacts with MAVS on mitochondria. YOD1 deubiquitinates MAVS and abrogates aggregation of MAVS. MAVS is a critical adaptor required for activating an innate antiviral immune response against viral infection. The activation of MAVS requires modification of the Lys63-linked ubiquitination and formation of prion-like aggregates. However, the molecular mechanisms regulating MAVS activity remain largely obscured. In this study, we identified a deubiquitinase YOD1, also known as a member of the ovarian tumor family, as a negative regulator of MAVS activation in both human and murine cells. YOD1 was recruited to mitochondria to interact with MAVS through its UBX and Znf domains after viral infection. Subsequently, YOD1 cleaved the K63-linked ubiquitination and abrogated the formation of prion-like aggregates of MAVS, which led to attenuation of IRF3, P65 activation, and IFN-β production. Knockdown of YOD1 potentiated IRF3 and P65 activation, IFN-β production, and antiviral innate immune response to RNA virus. Our findings thus provided, to our knowledge, novel insights into the regulatory cascade of the cellular antiviral response through YOD1-mediated K63-linked deubiquitination and aggregation of MAVS. Visual Abstract
EVALUASI PENERAPAN SISTEM INFORMASI MANAJEMEN KEIMIGRASIAN (SIMKIM) KANTOR IMIGRASI KELAS I YOGYAKARTA : PENDEKATAN KUALITATIF

Penelitian ini menginvestigasi penerapan sistem informasi manajemen keimigrasian (SIMKIM) di Kantor Imigrasi Kelas I Yogyakarta. Penelitian ini menjadi penting karena SIMKIM sudah diterapkan lebih dari lima tahun sehingga diperlukan evaluasi. Dalam konteks ini, evaluasi penerapan SIMKIM pada penelitian ini menggunakan model Delone dan Mclean dengan Information system continuence. Penelitian ini menggunakan pendekatan kualitatif dengan metode studi kasus (case study) melalui pengumpulan data dokumentasi, observasi dan wawancara. Teknik penentuan informan yang digunakan dalam penelitian ini ialah purposive sampling. Hasil analisis dari model Delone dan Mclean dengan Information system continuence menunjukan bahwa secara keseluruhan penerapan SIMKIM di Kantor Imigrasi Kelas I Yogyakarta telah membantu operasional manajemen dalam melaksanakan fungsi keimigrasian. Namun, pada penerapan SIMKIM masih belum optimal hal ini disebabkan oleh masih terdapat kendala dari sistem itu tersendiri seperti kecepatan akses dan faktor eksternal seperti data kependudukan yang belum tersedia.
How C-terminal additions to insulin B-chain fragments create superagonists for T cells in mouse and human type 1 diabetes

In type 1 diabetes, mouse and human CD4+ T cells recognize mutated and chimeric superagonist insulin B-chain epitopes similarly. Superagonist diabetogenic peptides Type 1 diabetes is an autoimmune disease triggered, in part, by activation of CD4+ T cells specific for insulin-derived autoantigens. Wang et al. prepared ternary complexes of diabetogenic T cell receptors attached to ligands formed by binding of insulin B-chain peptides to mouse or human MHC class II proteins known to be associated with genetic susceptibility to diabetes. Structural and functional analyses revealed that fusion peptides featuring covalent linkage of the C terminus of an insulin B-chain peptide to specific fragments of insulin C-peptide were highly potent ligands, enabling avid binding of both mouse and human TCRs. These findings point to transpeptidation reactions in lysosomes as a potential source of superagonist chimeric insulin peptides with an important driver role in autoimmune diabetes. In type 1 diabetes (T1D), proinsulin is a major autoantigen and the insulin B:9-23 peptide contains epitopes for CD4+ T cells in both mice and humans. This peptide requires carboxyl-terminal mutations for uniform binding in the proper position within the mouse IAg7 or human DQ8 major histocompatibility complex (MHC) class II (MHCII) peptide grooves and for strong CD4+ T cell stimulation. Here, we present crystal structures showing how these mutations control CD4+ T cell receptor (TCR) binding to these MHCII-peptide complexes. Our data reveal stricking similarities between mouse and human CD4+ TCRs in their interactions with these ligands. We also show how fusions between fragments of B:9-23 and of proinsulin C-peptide create chimeric peptides with activities as strong or stronger than the mutated insulin peptides. We propose transpeptidation in the lysosome as a mechanism that could accomplish these fusions in vivo, similar to the creation of fused peptide epitopes for MHCI presentation shown to occur by transpeptidation in the proteasome. Were this mechanism limited to the pancreas and absent in the thymus, it could provide an explanation for how diabetogenic T cells escape negative selection during development but find their modified target antigens in the pancreas to cause T1D.
PRECAUCIONES DEL ORTODONCISTA EN LA ATENCIÓN DE PACIENTES CON AFECCIONES PERIODONTALES

1 Intern Student, Specialization in Orthodontics and Dentofacial Orthopedics. School of Dentistry, Universidad de La Frontera, Temuco, Chile. ORCID: 0000-0002-3922-1789 2 Professor, Specialization in Orthodontics and Dentofacial Orthopedics. School of Dentistry, Universidad de La Frontera, Temuco, Chile. ORCID: 0000-0002-0241-2637 3 Professor, Specialization in Orthodontics and Dentofacial Orthopedics. School of Dentistry, Universidad de La Frontera, Temuco, Chile. ORCID: 0000-0002-5975-2237 4 Prof. Mg, Head of the Specialization in Orthodontics and Dentofacial Orthopedics. School of Dentistry, Universidad de La Frontera, Temuco, Chile. ORCID: 0000-0003-3084-0142
Family history of prostate cancer and age‐related trend of testosterone levels among US males: NHANES 2003–2004

Studies have suggested that rapid age‐related declines of testosterone (T) level may play a critical role in the development of prostate cancer (PCa), and family history of PCa is another well‐established risk factor of PCa, which have been reported to be associated with androgen metabolism‐related genes. However, few studies have ever investigated whether a family history of PCa influences the risk of PCa via regulating the age‐related trend of T level among males over the life course.
Location, location, location: Tissue resident memory T cells in mice and humans

This review summarizes key studies that have shaped our understanding of tissue resident memory T cells in mice and humans. The discovery of T cells resident in diverse tissues has altered our understanding of adaptive immunity to encompass site-specific responses mediated by tissue-adapted memory T cells throughout the body. Here, we discuss the key phenotypic, transcriptional, and functional features of these tissue-resident memory T cells (TRM) as established in mouse models of infection and translated to humans by novel tissue sampling approaches. Integration of findings from mouse and human studies may hold the key to unlocking the potential of TRM for promoting tissue immunity and preventing infection.
Predictors of Functional Outcome After Treatment of Acute Ischemic Stroke

Background: Acute ischemic stroke (AIS) is a common condition with significant consequences. Advances in treatment modified outcome and prognosis. Aim: The present study aimed to discuss the predictors of functional outcome of AIS after the first three months. Patients and Methods: All the studied 131 patients had careful history taking, thorough clinical examination, and non-contrast brain CT scans. The initial severity of the stroke and evolution after thrombolysis was evaluated using the National Instituted of Health Stroke Scale (NIHSS). Patients were treated with low molecular weight heparin (LMWH) or rt-PA. Functional status at three months was evaluated using the modified Rankin Scale. Results: The present study included 131 patients with AIS. Favorable functional outcome was achieved in 52 patients (39.7 %) while the remainder 79 patients had a poor outcome. Using logistic regression analysis, significant predictors of poor outcome on univariate analysis included age ≥ 60 years (OR:3.2, CI: 1.3-7.9,p=0.014), presence of atheromatous plaques (OR: 16.8, CI: 4.8-58.3, p < 0.001), late initiation of treatment (OR: 10.6, CI: 3.4-32.1,p < 0.001) and persistent occlusion (OR: 7.8, CI: 3.2-18.8, p < 0.001). However, on multivariate analysis, variable predictive of poor outcome included age ≥ 60 years (OR: 32.5, CI: 5.4-196.5, p < 0.001), presence of atheromatous plaques (OR: 9.4, CI: 1.7-51.2, p= 0.01), late initiation of treatment (OR: 10.0, CI: 1.5-67.1,p= 0.018) and persistent occlusion (OR:25.7, CI: 6.9-95.8,p < 0.001). Conclusions: Independent predictors of poor outcome in AIS patients include age ≥ 60 years, presence of atheromatous plaques, late initiation of treatment, and persistent occlusion.
Effect of Conventional and Acid-modified Casein Phosphopeptide-Amorphous Calcium Phosphate Crèmes on Dentin Permeability Before and After Acid Challenge.

This study investigated the effect of conventional and acidified casein phosphopeptide-amorphous calcium phosphate-containing crèmes (CPP-ACP and ACPP-ACP) on dentin permeability (DP) before and after acid challenge, using a fluid-flow measuring device and scanning electron microscopic (SEM) examination. Fifty dentin discs were prepared from intact human third molars. Each tooth was sectioned 3 mm above and below the cementoenamel junction. The smear layer was removed to expose the dentin and dentinal tubules. For fluid-flow measurement, 20 specimens were used and divided into two groups: (a) CPP-ACP (pH=7) and (b) ACPP-ACP (pH=2). The dentin surfaces were treated with the crème for five minutes daily for two weeks, and then an acid challenge was performed using 6% citric acid. Under simulated pulpal pressure, DP was measured at baseline, five minutes, two weeks, and after acid challenge. The remaining specimens were prepared and examined using SEM to investigate dentinal tubule occlusion. DP was not significantly different between the two CPP-ACP-containing crèmes at any test period ( p≥0.05). DP after two weeks or acid challenge was significantly lower than that at five minutes ( p<0.05). The results were consistent with the SEM micrographs that presented patent dentinal tubules after a five-minute application and partial blockage of dentinal tubules after the two-week application. The dentinal tubules remained partially occluded after acid challenge. Using conventional and acid-modified CPP-ACP-containing crèmes for two weeks decreased DP and partially occluded the dentinal tubules, which resisted acid challenge.
HEALTH SERVICES QUALITY BETWEEN HYPERTENSION AND DIABETES MELLITUS PATIENTS IN COMMUNITY HEALTH SERVICES IN THE SLEMAN DISTRICT, YOGYAKARTA, INDONESIA

The implementation of the Chronic Disease Management Program or PROLANIS has been adopted in Indonesia by National Social Security Implementation on Health Agency (BPJS-K) since 2015. The program focuses on hypertension (HT) and diabetes mellitus (DM). However, since the first time the program was implemented, there was no comprehensive evaluation of it. The aim of this study was to analyze health service quality among HT and DM patients based on five dimensions of quality in 25 community health services (CHSs) in the Sleman district, Yogyakarta, Indonesia. This is a cross-sectional study with a simple random sampling technique that included 230 respondents from 25 CHSs. The instrument was SERVQUAL that consisted of 35 items of a questionnaire. The data were analyzed by a gap analysis, Customer Satisfaction Index (CSI) and Importance Performance Analysis (IPA); meanwhile, a Man–Whitney test was proposed to determine differences in health services quality in the PROLANIS program. Based on the gap analysis, it was found that whole dimensions were below 0-point; the CSI analysis obtained 74.45 for HT and 75.15 for DM; and the IPA analysis found that the distribution of respondents’ answers in the questionnaire were in quadrants 1 and 2. The Man–Whitney analysis was used to get the assurance aspect correlated with health service quality in DM and HT patients (p = 0.001). Health service quality in the PROLANIS program was based on five dimensions of quality was low, unless assurance dimension. The government should improve health services quality in aspects of tangibility, responsiveness, empathy, and reliability to get satisfaction among HT and DM patients in the PROLANIS program.
“Epidemiology and aetiology of influenza-like illness among households in metropolitan Vientiane, Lao PDR”: A prospective, community-based cohort study

Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4–11.9) episodes per 100 person-years. ILI was significantly associated with age group (p<0.001), sex (p<0.001), and number of bedrooms (p = 0.04) in multivariate analysis. In 548 nasopharyngeal swabs, the most commonly detected potential pathogens were Streptococcus pneumoniae (17.0%), Staphylococcus aureus (11.3%), influenza A (11.1%; mostly subtype H3N2), rhinovirus (7.5%), and influenza B (8.0%). Streptococci were isolated from 42 (8.6%) of 536 throat swabs, most (27) of which were Lancefield Group G. Co-infections were observed in 132 (24.1%) of the 548 ILI episodes. Our study generated valuable data on respiratory disease burden and patterns of etiologies associated with community-acquired acute respiratory illness Laos. Establishment of a surveillance strategy in Laos to monitor trends in the epidemiology and burden of acute respiratory infections is required to minimize their impact on human health.