Miracle-dz/UniFAR-FTUs huggingface dataset:
Second-Order Spectral Transform Block for 3D Shape Classification and Retrieval

In this paper, we propose a novel network block, dubbed as second-order spectral transform block, for 3D shape retrieval and classification. This network block generalizes the second-order pooling to 3D surface by designing a learnable non-linear transform on the spectrum of the pooled descriptor. The proposed block consists of following two components. First, the second-order average (SO-Avr) and max-pooling (SO-Max) operations are designed on 3D surface to aggregate local descriptors, which are shown to be more discriminative than the popular average-pooling or max-pooling. Second, a learnable spectral transform parameterized by mixture of power function is proposed to perform non-linear feature mapping in the space of pooled descriptors, i.e., manifold of symmetric positive definite matrix for SO-Avr, and space of symmetric matrix for SO-Max. The proposed block can be plugged into existing network architectures to aggregate local shape descriptors for boosting their performance. We apply it to a shallow network for non-rigid 3D shape analysis and to existing networks for rigid shape analysis, where it improves the first-tier retrieval accuracy by 7.2% on SHREC’14 Real dataset and achieves state-of-the-art classification accuracy on ModelNet40. As an extension, we apply our block to 2D image classification, showing its superiority compared with traditional second-order pooling methods. We also provide theoretical and experimental analysis on stability of the proposed second-order spectral transform block.
Triglyceride-containing lipoprotein sub-fractions and risk of coronary heart disease and stroke: A prospective analysis in 11,560 adults

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.
Plasma levels of dopamine metabolite correlate with mismatch negativity in patients with schizophrenia

Mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, and primarily reflects deficient functioning of the N‐methyl‐D‐aspartate (NMDA) receptor system. Although the dopamine receptor is known not to modulate MMN over the short term, it is unclear whether the dopamine system affects MMN in the long term.
A bivalent B-cell epitope dendrimer peptide can confer long lasting immunity in swine against foot-and-mouth disease.

Foot-and-mouth disease virus (FMDV) causes a widely extended contagious disease of livestock. We have previously reported that a synthetic dendrimeric peptide, termed B2 T(mal), consisting of two copies of a B-cell epitope [VP1(140-158)] linked through maleimide groups to a T-cell epitope [3A(21-35)] of FMDV, elicits potent B- and T-cell specific responses and confers solid protection in pigs to type O FMDV challenge. Longer duration of the protective response as well as the possibility of inducing protection after a single dose are important requirements for an efficient FMD vaccine. Herein, we show that administration of two doses of B2 T(mal) elicited high levels of specific total IgGs and neutralizing antibodies that lasted 4-5 months after the peptide boost. Additionally, concomitant levels of IFN-γ producing specific T-cells were observed. Immunization with two doses of B2 T(mal) conferred a long-lasting reduced susceptibility to FMDV infection, up to 136 days (19/20 weeks) post-boost. Remarkably, a similar duration of the protective response was achieved by a single dose of B2 T(mal). The effect on the B2 T(mal) vaccine of RNA transcripts derived from non-coding regions in the FMDV genome, known to enhance the immune response and protection induced by a conventional inactivated vaccine, was also analyzed. The contribution of our results to the development of FMD dendrimeric vaccines is discussed.
Curcumin-Loaded Solid Lipid Nanoparticles Bypass P-Glycoprotein Mediated Doxorubicin Resistance in Triple Negative Breast Cancer Cells

Multidrug resistance (MDR) is a critical hindrance to the success of cancer chemotherapy. The main thing responsible for MDR phenotypes are plasma-membranes associated with adenosine triphosphate (ATP) Binding Cassette (ABC) drug efflux transporters, such as the P-glycoprotein (Pgp) transporter that has the broadest spectrum of substrates. Curcumin (CURC) is a Pgp inhibitor, but it is poorly soluble and bioavailable. To overcome these limitations, we validated the efficacy and safety of CURC, loaded in biocompatible solid lipid nanoparticles (SLNs), with or without chitosan coating, with the goal of increasing the stability, homogeneous water dispersibility, and cellular uptake. Both CURC-loaded SLNs were 5–10-fold more effective than free CURC in increasing the intracellular retention and toxicity of doxorubicin in Pgp-expressing triple negative breast cancer (TNBC). The effect was due to the decrease of intracellular reactive oxygen species, consequent inhibition of the Akt/IKKα-β/NF-kB axis, and reduced transcriptional activation of the Pgp promoter by p65/p50 NF-kB. CURC-loaded SLNs also effectively rescued the sensitivity to doxorubicin against drug-resistant TNBC tumors, without signs of systemic toxicity. These results suggest that the combination therapy, based on CURC-loaded SLNs and doxorubicin, is an effective and safe approach to overcome the Pgp-mediated chemoresistance in TNBC.
The impact of inpatient capsule endoscopy on the need for therapeutic interventions in patients with obscure gastrointestinal bleeding

Background/Aim: There are limited data evaluating the impact of inpatient video capsule endoscopy (VCE) on the need for therapeutic interventions in hospitalized patients with obscure gastrointestinal bleeding (OGIB). The objective of this study was to determine the impact of inpatient VCE on the need for therapeutic interventions and rehospitalization for recurrent bleeding. Patients and Methods: Hospitalized patients who underwent VCE for OGIB indication were retrospectively included. Clinical data were collected including therapeutic interventions performed after VCE. Specific therapeutic interventions were defined as the medical, endoscopic, or surgical treatment directly targeting the cause of OGIB. Patients were followed up to determine the rate of rehospitalization. Results: A total of 48 inpatient VCE were identified, of which 43 VCE were performed for OGIB indication and were included for analysis. The completion rate and the diagnostic yield were 78.5% and 55.8%, respectively. Subsequent specific therapeutic interventions were performed in 65.2% and 5.8% of patients with positive and negative VCE, respectively (P < 0.001). After a median follow up of 30 months (minimum 12, maximum 58), rehospitalization for recurrent bleeding occurred in 30.4% and 17% of patients with positive and negative VCE, respectively. Patients with angiodysplasia on VCE were significantly more likely to be readmitted (P = 0.02). Throughout the course of the follow-up, only 2 (11.7%) patients with negative VCE underwent specific therapeutic interventions. Conclusion: Inpatient VCE is an effective tool to identify patients who need specific therapeutic interventions. Patients with negative VCE are unlikely to be readmitted or require specific therapeutic interventions in the index admission.
Lung Toxicity Analysis of Nano-Sized Kaolin and Bentonite: Missing Indications for a Common Grouping

Kaolin and bentonite (nanoclay NM-600) are nanostructured aluminosilicates that share a similar chemical composition, platelet-like morphology, and high binding capacity for biomolecules. To investigate if these material-based criteria allow for a common grouping, we prepared particle suspensions of kaolin and bentonite with a similar hydrodynamic diameter and administered them to NR8383 alveolar macrophages in vitro and also to a rat lung using quartz DQ12 as a reference material. Bentonite was far more bioactive in vitro, indicated by a lower threshold for the release of enzymes, tumor necrosis factor α, and H2O2. In addition, in the lung, the early effects of bentonite exceeded those of kaolin and even those of quartz, due to strongly increased numbers of inflammatory cells, and elevated concentrations of total protein and fibronectin within the bronchoalveolar lavage fluid. The pro-inflammatory effects of bentonite decreased over time, although assemblies of particle-laden alveolar macrophages (CD68 positive), numerous type-2 epithelial cells (immunopositive for pro-surfactant protein C), and hypertrophic lung epithelia persisted until day 21. At this point in time, kaolin-treated lungs were completely recovered, whereas quartz DQ12 had induced a progressive inflammation. We conclude that bentonite is far more bioactive than equally sized kaolin. This argues against a common grouping of aluminosilicates, previously suggested for different kaolin qualities.
Remethylation of Dnmt3a−/− hematopoietic cells is associated with partial correction of gene dysregulation and reduced myeloid skewing

Significance Mutations that reduce the function of the de novo DNA methyltransferase, DNMT3A, are very common in patients with clonal hematopoiesis and hematopoietic malignancies. Restoring the function of DNMT3A in mouse hematopoietic cells deficient for this protein corrects the DNA methylation defect in an ordered fashion, and partially restores abnormalities in gene expression and myeloid population skewing. These data may be relevant for therapeutic strategies designed to restore DNMT3A activity in patients with diseases caused by mutations in this gene. Mutations in the DNA methyltransferase 3A (DNMT3A) gene are the most common cause of age-related clonal hematopoiesis (ARCH) in older individuals, and are among the most common initiating events for acute myeloid leukemia (AML). The most frequent DNMT3A mutation in AML patients (R882H) encodes a dominant-negative protein that reduces methyltransferase activity by ∼80% in cells with heterozygous mutations, causing a focal, canonical DNA hypomethylation phenotype; this phenotype is partially recapitulated in murine Dnmt3a−/− bone marrow cells. To determine whether the hypomethylation phenotype of Dnmt3a−/− hematopoietic cells is reversible, we developed an inducible transgene to restore expression of DNMT3A in transplanted bone marrow cells from Dnmt3a−/− mice. Partial remethylation was detected within 1 wk, but near-complete remethylation required 6 mo. Remethylation was accurate, dynamic, and highly ordered, suggesting that differentially methylated regions have unique properties that may be relevant for their functions. Importantly, 22 wk of DNMT3A addback partially corrected dysregulated gene expression, and mitigated the expansion of myeloid cells. These data show that restoring DNMT3A expression can alter the epigenetic “state” created by loss of Dnmt3a activity; this genetic proof-of-concept experiment suggests that this approach could be relevant for patients with ARCH or AML caused by loss-of-function DNMT3A mutations.
Adaptation of Lactobacillus plantarum to Ampicillin Involves Mechanisms That Maintain Protein Homeostasis

Antibiotic resistance acquired by adaptation to certain antibiotics has led to growing public concerns. Here, a long-term evolution experiment was used together with proteomic analysis to identify genes/proteins responsible for the adaptive phenotype. This work has provided novel insights into the biosafety of new probiotics with high tolerance to antibiotics. ABSTRACT The widespread use of antibiotics has caused great concern in the biosafety of probiotics. In this study, we conducted a 12-month adaptive laboratory evolution (ALE) experiment to select for antibiotics-adapted Lactobacillus plantarum P-8, a dairy-originated probiotic bacterium. During the ALE process, the ampicillin MIC for the parental L. plantarum P-8 strain increased gradually and reached the maximum level of bacterial fitness. To elucidate the molecular mechanisms underlying the ampicillin-resistant phenotype, we comparatively analyzed the genomes and proteomes of the parental strain (L. plantarum P-8) and two adapted lines (L. plantarum 400g and L. plantarum 1600g). The adapted lines showed alterations in their carbon, amino acid, and cell surface-associated metabolic pathways. Then, gene disruption mutants were created to determine the role of six highly expressed genes in contributing to the enhanced ampicillin resistance. Inactivation of an ATP-dependent Clp protease/the ATP-binding subunit ClpL, a small heat shock protein, or a hypothetical protein resulted in partial but significant phenotypic reversion, confirming their necessary roles in the bacterial adaptation to ampicillin. Genomic analysis confirmed that none of the ampicillin-specific differential expressed genes were flanked by any mobile genetic elements; thus, even though long-term exposure to ampicillin upregulated their expression, there is low risk of spread of these genes and adapted drug resistance to other bacteria via horizontal gene transfer. Our study has provided evidence of the biosafety of probiotics even when used in the presence of antibiotics. IMPORTANCE Antibiotic resistance acquired by adaptation to certain antibiotics has led to growing public concerns. Here, a long-term evolution experiment was used together with proteomic analysis to identify genes/proteins responsible for the adaptive phenotype. This work has provided novel insights into the biosafety of new probiotics with high tolerance to antibiotics.
Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86)

Purpose: The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. Patients and Methods: PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. Results: A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand–foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic CTNNB1 mutation [four partial responses (PRs) in 10 patients, median PFS 7.6 months] and concurrent KRAS and PTEN/PIK3CA mutations (three PRs in 12 patients, median PFS 5.9 months). Conclusions: Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
Improving HIV medical care engagement by attending to status disclosure and social support

ABSTRACT Expeditious linkage and consistent engagement in medical care is important for people with HIV’s (PWH) health. One theory on fostering linkage and engagement involves HIV status disclosure to mobilize social support. To assess disclosure and social support’s association with linkage and engagement, we conducted a qualitative study sampling black and Latino men who have sex with men (MSM of color) in the U.S. Participants' narratives presented mixed results. For instance, several participants who reported delaying, inconsistent access, or detachment from care also reported disclosing for support purposes, yet sporadic engagement suggests that their disclosure or any subsequent social support have not assisted. The findings contribute to the literature that questions disclosure and social support’s influence on care engagement, especially when decontextualized from circumstances and intentions. Our findings suggest the mechanics of disclosure and social support require planned implementation if intending to affect outcomes, especially among MSM of color. From the findings, we explore steps that may bolster interventions seeking to anchor medical care engagement.
Pomace Olive Oil Concentrated in Triterpenic Acids Restores Vascular Function, Glucose Tolerance and Obesity Progression in Mice

Pomace olive oil, an olive oil sub-product, is a promising source of bioactive triterpenoids such as oleanolic acid and maslinic acid. Considering the vascular actions of pomace olive oil and the potential effects of the isolated oleanolic acid on metabolic complications of obesity, this study investigates for the first time the dietary intervention with a pomace olive oil with high concentrations of the triterpenic acids (POCTA), oleanolic and maslinic acid, during diet-induced obesity in mice. The results demonstrate that obese mice, when switched to a POCTA-diet for 10 weeks, show a substantial reduction of body weight, insulin resistance, adipose tissue inflammation, and particularly, improvement of vascular function despite high caloric intake. This study reveals the potential of a functional food based on pomace olive oil and its triterpenic fraction against obesity progression. Our data also contribute to understanding the health-promoting effects attributable to the Mediterranean diet.
Trends in occupational diseases in the Italian agricultural sector, 2004–2017

Objective To estimate the incidence of, trends in and effect of change in reporting rules on occupational diseases (ODs) in the Italian agricultural sector. Methods Over a 14-year period (2004–2017), ODs among Italian agricultural workers were diagnosed by physicians and reported to the National Institute for Insurance against Workplace Accidents and Occupational Diseases. OD was defined as a disease with a specific clinical diagnosis (International Classification of Diseases) and was predominantly caused by work-related factors. Trends in incidence and effects of changed eligibility criteria for reporting occupational musculoskeletal disorders (MSDs) and noise-induced hearing loss (NIHL) were estimated using a Poisson regression model. Results In 2017, the incidence of all ODs was 1295 per 100 000 agricultural workers. MSDs (961 per 100 000 workers) were the most frequently occurring ODs. MSDs and NIHL showed statistically significant increasing time trends, 26% and 7% annual increase, respectively, during the 2004–2017 period. There was no statistically significant change in the incidence of occupational respiratory, skin and cancer diseases during the 14-year period. After changes in reporting rules, the incidence of MSDs showed an immediate increased effect, with an incidence rate ratio (IRR) of 2.9 (95% CI 2.65 to 3.14) and a significant annual decreasing trend of −9% (95% CI −6% to −12%) over the years after the changed reporting rules (from 2008 to 2017), and an immediate effect on NIHL with an IRR of 1.3 (95% CI 1.13 to 1.53). Conclusion In total, 1.3% of the Italian agricultural workers were diagnosed in 2017 as having an OD. Over a 14-year period, the annual incidence of ODs showed a considerable increasing trend consistent with changed eligibility reporting criteria for occupational MSDs and to a lesser extent for NIHL.
General practitioners' provision of end-of-life care and associations with dying at home: a registry-based longitudinal study

Abstract Background General practitioners (GPs) may play an important role in providing end-of-life care to community-dwelling people. Objective To investigate patients' contacts with GPs, GPs' interdisciplinary collaboration, out-of-hours services and hospitalizations in the last 13 weeks of life and associations with dying at home. Second, investigate whether GP contacts were associated with fewer out-of-hours contacts or days hospitalized. Methods Individually linked data from the Norwegian Cause of Death Registry, Norwegian Patient Registry, Statistics Norway and Control and Payment of Reimbursement to Health Service Providers database for all 80 813 deceased people in Norway within 2012–13. Outcomes were analyzed with logistic regression and negative binomial multilevel mixed-effect models. Results Overall, 1% of people received GP home visits in Week 13 and 4.6% in the last week before death. During the last 4 weeks of life, 9.2% received one or more GP home visits. Altogether, 6.6% received one or more home visits when the GP had one or more interdisciplinary collaborations during the last 4 weeks, of which <3% died at home. GP office consultations decreased towards the end of life. The likelihood of home death versus another location increased in relation to GP home visits [one home visit odds ratio (OR) 1.92, confidence interval (CI) 1.71–2.15; two or more OR 3.49, CI 3.08–3.96] and GP interdisciplinary collaboration (one contact OR 1.76, CI 1.59–1.96; two or more OR 2.52, CI 2.32–2.74). Conclusions GPs play a role in enabling people to die at home by performing home visits and collaborating with other health care personnel. Only a minority received such services in Norway.