Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical, histopathologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma

In this retrospective descriptive study, we characterized the clinical, histologic, and immunohistochemical features of 13 cases of canine gallbladder neuroendocrine carcinoma (GB-NEC). Immunohistochemical stains for neuroendocrine (neuron-specific enolase [NSE], chromogranin A, synaptophysin) and gastrin markers were evaluated, and clinicopathologic and follow-up data were obtained for all cases. The average age at diagnosis was 8.9 y, and breeds included 6 Boston Terriers, 2 Bichon Frise, 1 Poodle, 1 English Bulldog, 1 French Bulldog, and 2 mixed-breed dogs. Boston Terriers were overrepresented in this cohort, and therefore a breed predilection is possible. Most dogs were presented with emesis and elevated liver enzyme activities: 13 of 13 had elevated alanine aminotransferase and alkaline phosphatase activities; 8 of 13 had elevated aspartate aminotransferase activity; 7 of 13 had elevated gamma-glutamyl transferase activity. Abdominal ultrasound and/or exploratory surgery revealed a gallbladder mass. All neoplasms had similar histologic features and positive immunoreactivity for NSE, chromogranin A, synaptophysin, and gastrin. Vascular invasion was noted in 8 of 13 neoplasms, and metastasis was present in 6 of 13 cases (4 hepatic and 2 pulmonary metastases). The median survival time was 3.7 y in patients who died; 5 of 8 deaths were directly attributed to the GB-NEC, 3 of which had metastatic spread. GB-NECs have the potential to metastasize; however, surgical excision may be curative in a subset of dogs.
Dimensions of Misinformation About the HPV Vaccine on Instagram: Content and Network Analysis of Social Media Characteristics

Background The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram. Objective The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine network. Methods From April 2018 to December 2018, we collected publicly available English-language Instagram posts containing hashtags #HPV, #HPVVaccine, or #Gardasil using Netlytic software (n=16,607). We randomly selected 10% of the sample and content analyzed relevant posts (n=580) for text, image, and social media features as well as holistic attributes (eg, sentiments, personal stories). Among antivaccine posts, we organized elements of misinformation within four broad dimensions: 1) misinformation theoretical domains, 2) vaccine debate topics, 3) evidence base, and 4) health beliefs. We conducted univariate, bivariate, and network analyses on the subsample of posts to quantify the role and position of individual posts in the network. Results Compared to provaccine posts (324/580, 55.9%), antivaccine posts (256/580, 44.1%) were more likely to originate from individuals (64.1% antivaccine vs 25.0% provaccine; P<.001) and include personal narratives (37.1% vs 25.6%; P=.003). In the antivaccine network, core misinformation characteristics included mentioning #Gardasil, purporting to reveal a lie (ie, concealment), conspiracy theories, unsubstantiated claims, and risk of vaccine injury. Information/resource posts clustered around misinformation domains including falsification, nanopublications, and vaccine-preventable disease, whereas personal narrative posts clustered around different domains of misinformation, including concealment, injury, and conspiracy theories. The most liked post (6634 likes) in our full subsample was a positive personal narrative post, created by a non-health individual; the most liked post (5604 likes) in our antivaccine subsample was an informational post created by a health individual. Conclusions Identifying characteristics of misinformation related to HPV vaccine on social media will inform targeted interventions (eg, network opinion leaders) and help sow corrective information and stories tailored to different falsehoods.
Nonlinear Optical Response of Reflective MXene Molybdenum Carbide Films as Saturable Absorbers

Molybdenum carbide (Mo2C) is a two-dimensional (2D) MXene material which makes it a promising photoelectric material. In this study, reflective type MXene Mo2C thin films were coated on a silver mirror by a magnetron sputtering method and were subsequently used in a passively Q-switched solid-state pulsed laser generator at the central wavelengths of 1.06 and 1.34 μm, respectively. The fabricated thin films of reflective type MXene Mo2C exhibited large modulation depth of 6.86% and 5.38% at the central wavelengths of 1064 and 1342 nm, respectively. By inserting the Mo2C saturable absorbers (SAs) into V-shaped Nd:YAG laser, short pulses were generated having a pulse duration, pulse energy, and average output power of 254 ns, 2.96 μJ, and 275 mW, respectively, at a wavelength of 1.06 μm. Similarly, shorter laser pulses were obtained in Nd:YVO4 laser at 1.34 μm. Our results illustrated potential of the 2D MXene Mo2C films for laser applications.
Nitrate respiration and diel migration patterns of diatoms are linked in sediments underneath a microbial mat.

Diatoms are among the few eukaryotes known to store nitrate (NO3 - ) and to use it as an electron acceptor for respiration in the absence of light and O2 . Using microscopy and 15 N stable isotope incubations, we studied the relationship between dissimilatory nitrate/nitrite reduction to ammonium (DNRA) and diel vertical migration of diatoms in phototrophic microbial mats and the underlying sediment of a sinkhole in Lake Huron (USA). We found that the diatoms rapidly accumulated NO3 - at the mat-water interface in the afternoon and 40% of the population migrated deep into the sediment, where they were exposed to dark and anoxic conditions for ~75 % of the day. The vertical distribution of DNRA rates and diatom abundance maxima coincided, suggesting that DNRA was the main energy generating metabolism of the diatom population. We conclude that the illuminated redox-dynamic ecosystem selects for migratory diatoms that can store nitrate for respiration in the absence of light. A major implication of this study is that the dominance of DNRA over denitrification is not explained by kinetics or thermodynamics. Rather, the dynamic conditions select for migratory diatoms that perform DNRA and can outcompete sessile denitrifiers. This article is protected by copyright. All rights reserved.
Poor Appetite and Eating Difficulties Can Predict the Long-Term Risk of Falling: A Longitudinal Study in Middle-Aged and Older Adults

Objectives: This study investigates whether self-reported nutritional status affects falling among middle-aged and older adults. Method: We used 8-year follow-up data from the Taiwan Longitudinal Study on Aging. At baseline, respondents’ appetite, changes in amount of food intake, and eating difficulties were assessed in a questionnaire-based survey in addition to anthropometric measurements (body mass index, mid-arm circumferences, and involuntary body weight loss). Their associations with falls in the follow-up were examined using multivariable log-binomial regression. Results: The study included 2,519 respondents aged 50 years and older. Poor appetite (prevalence ratio [PR] = 1.25, 95% confidence interval [CI] = [1.07, 1.46]) and eating difficulties (PR = 1.16, 95% CI = [1.02, 1.32]) significantly predicted falling 8 years later with adjustments for sociodemographics, health behaviors, comorbidities, and anthropometric measures by taking into account probabilities of follow-up. Conclusion: Poor appetite and eating difficulties can predict falling in the long-term independent of anthropometric measurements among middle-aged and older adults.
Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment‐related mortality

Hypomethylating agents (HMA) with venetoclax is a new standard for older/unfit patients with acute myeloid leukemia (AML). However, it is unknown how HMA with venetoclax compare to intensive chemotherapy (IC) in patients who are “fit” or “unfit” for IC. We compared outcomes of older patients with newly diagnosed AML receiving 10‐day decitabine with venetoclax (DEC10‐VEN) vs IC. DEC10‐VEN consisted of daily venetoclax with decitabine 20 mg/m2 for 10 days for induction and decitabine for 5 days as consolidation. The IC cohort received regimens containing cytarabine ≥1 g/m2/d. A validated treatment‐related mortality score (TRMS) was used to classify patients at high‐risk or low‐risk for TRM with IC. Propensity scores were used to match patients to minimize bias. Median age of the DEC10‐VEN cohort (n = 85) was 72 years (range 63‐89) and 28% patients were at high‐risk of TRM with IC. The comparator IC group (n = 85) matched closely in terms of baseline characteristics. DEC10‐VEN was associated with significantly higher CR/CRi compared to IC (81% vs 52%, P < .001), and lower rate of relapse (34% vs 56%, P = .01), 30‐day mortality (1% vs 24%, P < .01), and longer overall survival (OS; 12.4 vs 4.5 months, HR = 0.48, 95%CI 0.29‐0.79, P < .01). In patients at both at high‐risk and low‐risk of TRM, DEC10‐VEN showed significantly higher CR/CRi, lower 30‐day mortality, and longer OS compared to IC. Patients at both high‐risk and low‐risk of TRM had comparable outcomes with DEC10‐VEN. In conclusion, DEC10‐VEN offers better outcomes compared to intensive chemotherapy in older patients with newly diagnosed AML, particularly in those at high‐risk of TRM.
Manganese Porphyrin and Radiotherapy Improves Local Tumor Response and Overall Survival in Orthotopic Murine Mammary Carcinoma Models

Novel synthetic compounds, known as manganese porphyrins (MnPs), have been designed to shift the redox status of both normal cells and cancer cells. When MnPs are coupled with cancer therapies, such as radiation, they have been shown to sensitize tumor cells to treatment and protect normal tissues from damage through the modulation of the redox status of various tissue types. Until now, our preclinical studies have focused on local effects of MnPs and radiation; however, we recognize that successful outcomes for cancer patients involve control of tumor cells throughout the body. In this study, using murine orthotopic mammary tumor models, we investigated how MnPs and radiation influence the development of distant metastasis. We hypothesized that the combination of MnP (MnP/RT), such as MnTnBuOE-2-PyP5+ and radiation treatment (RT) would increase local tumor control via a shift in the intratumoral redox environment, leading to subsequent downregulation of HIF-1 in the primary tumor. Secondarily, we hypothesized that these primary tumor treatment effects would result in a reduction in pulmonary metastatic burden. Balb/c mice with orthotopic 4T1 mammary carcinomas were treated with saline, MnP, RT or MnP/RT. We found MnP/RT did extend local tumor growth delay and overall survival compared to controls and was associated with increased intratumoral oxidative stress. However, the primary tumor growth delay observed with MnP/RT was not associated with a reduced pulmonary metastatic burden. Future directions to investigate the effects of MnP/RT on the development of distant metastasis may include modifications to the radiation dose, the experimental timeline or using a murine mammary carcinoma cell line with a less aggressive metastatic behavior. Clinical trials are underway to investigate the clinical utility of MnTnBuOE-2-PyP5+ for patients undergoing radiotherapy for various tumor types. The promising preclinical data from this study, as well as others, provides support that MnP/RT has the potential to improve local tumor control for these patients.
Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss

The pathophysiology underlying spiral ganglion cell defect–induced deafness remains elusive. Using the whole exome sequencing approach, in combination with functional assays and a mouse disease model, we identified the potentially novel deafness-causative MAP1B gene encoding a highly conserved microtubule-associated protein. Three novel heterozygous MAP1B mutations (c.4198A>G, p.1400S>G; c.2768T>C, p.923I>T; c.5512T>C, p.1838F>L) were cosegregated with autosomal dominant inheritance of nonsyndromic sensorineural hearing loss in 3 unrelated Chinese families. Here, we show that MAP1B is highly expressed in the spiral ganglion neurons in the mouse cochlea. Using otic sensory neuron–like cells, generated by pluripotent stem cells from patients carrying the MAP1B mutation and control subject, we demonstrated that the p.1400S>G mutation caused the reduced levels and deficient phosphorylation of MAP1B, which are involved in the microtubule stability and dynamics. Strikingly, otic sensory neuron–like cells exhibited disturbed dynamics of microtubules, axonal elongation, and defects in electrophysiological properties. Dysfunctions of these derived otic sensory neuron–like cells were rescued by genetically correcting MAP1B mutation using CRISPR/Cas9 technology. Involvement of MAP1B in hearing was confirmed by audiometric evaluation of Map1b heterozygous KO mice. These mutant mice displayed late-onset progressive sensorineural hearing loss that was more pronounced in the high frequencies. The spiral ganglion neurons isolated from Map1b mutant mice exhibited the deficient phosphorylation and disturbed dynamics of microtubules. Map1b deficiency yielded defects in the morphology and electrophysiology of spiral ganglion neurons, but it did not affect the morphologies of cochlea in mice. Therefore, our data demonstrate that dysfunctions of spiral ganglion neurons induced by MAP1B deficiency caused hearing loss.
GENCODE 2021

Abstract The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes. org.
Bacterial Immunogenicity Prediction by Machine Learning Methods

The identification of protective immunogens is the most important and vigorous initial step in the long-lasting and expensive process of vaccine design and development. Machine learning (ML) methods are very effective in data mining and in the analysis of big data such as microbial proteomes. They are able to significantly reduce the experimental work for discovering novel vaccine candidates. Here, we applied six supervised ML methods (partial least squares-based discriminant analysis, k nearest neighbor (kNN), random forest (RF), support vector machine (SVM), random subspace method (RSM), and extreme gradient boosting) on a set of 317 known bacterial immunogens and 317 bacterial non-immunogens and derived models for immunogenicity prediction. The models were validated by internal cross-validation in 10 groups from the training set and by the external test set. All of them showed good predictive ability, but the xgboost model displays the most prominent ability to identify immunogens by recognizing 84% of the known immunogens in the test set. The combined RSM-kNN model was the best in the recognition of non-immunogens, identifying 92% of them in the test set. The three best performing ML models (xgboost, RSM-kNN, and RF) were implemented in the new version of the server VaxiJen, and the prediction of bacterial immunogens is now based on majority voting.
How Posting Online Reviews Can Influence the Poster’s Evaluations

The current research demonstrates that posting online reviews can influence the evaluations of the individual posting the review. Across four studies, we examine the impact of individuals’ naive theories about the meaning of their own posting on subsequent attitudes. In these experiments, individuals were assigned to write either positive or negative reviews about various products and services and then post them. The meaning associated with posting a review was varied to indicate either high validity (e.g., saving, extending, sharing) or low validity (e.g., deleting, hiding, archiving) with respect to their previously written reviews. When posting was associated with a high validity meaning, it increased reliance on those thoughts polarizing attitudes and behavioral intentions compared with when the posting was associated with a low validity meaning. These findings were mediated by the impact of meaning on thought confidence.
Determinação de cumarina em extrato fluido e tintura de guaco por espectrofotometria derivada de primeira ordem

The objective of this work was to develop a method for coumarin(1,2-benzopyran) dosage in fluid extract and tinture of "guaco" (Mikania glomerata Sprengel). First derivative spectrophotometry was developed and proved to be accurate, exact, reprodutive and of easy execution.
Carbenoxolone and 18β‐glycyrrhetinic acid inhibit inositol 1,4,5‐trisphosphate‐mediated endothelial cell calcium signalling and depolarise mitochondria

Coordinated endothelial control of cardiovascular function is proposed to occur by endothelial cell communication via gap junctions and connexins. To study intercellular communication, the pharmacological agents carbenoxolone (CBX) and 18β‐glycyrrhetinic acid (18βGA) are used widely as connexin inhibitors and gap junction blockers.
The NPR1-WRKY46-WRKY6 signaling cascade mediates probenazole/salicylic acid-elicited leaf senescence in Arabidopsis thaliana.

Endogenous salicylic acid (SA) regulates leaf senescence, but the underlying mechanism remains largely unexplored. The exogenous application of SA to living plants is not efficient for inducing leaf senescence. By taking advantage of probenazole (PBZ)-induced biosynthesis of endogenous SA, we previously established a chemical inducible leaf senescence system that depends on SA biosynthesis and its core signaling receptor NPR1 in Arabidopsis thaliana. Here, using this system, we identified WRKY46 and WRKY6 as key components of the transcriptional machinery downstream of NPR1 signaling. Upon PBZ treatment, the wrky46 mutant exhibited significantly delayed leaf senescence. We demonstrate that NPR1 is essential for PBZ/SA-induced WRKY46 activation, whereas WRKY46 in turn enhances NPR1 expression. WRKY46 interacts with NPR1 in the nucleus, binding to the W-box of the WRKY6 promoter to induce its expression in response to SA signaling. Dysfunction of WRKY6 abolished PBZ-induced leaf senescence, while overexpression of WRKY6 was sufficient to accelerate leaf senescence even under normal growth conditions, suggesting that WRKY6 may serve as an integration node of multiple leaf senescence signaling pathways. Taken together, these findings reveal that the NPR1-WRKY46-WRKY6 signaling cascade plays a critical role in PBZ/SA-mediated leaf senescence in Arabidopsis. This article is protected by copyright. All rights reserved.
Synergistic Effect of Propidium Iodide and Small Molecule Antibiotics with the Antimicrobial Peptide Dendrimer G3KL against Gram-Negative Bacteria

There is an urgent need to develop new antibiotics against multidrug-resistant bacteria. Many antimicrobial peptides (AMPs) are active against such bacteria and often act by destabilizing membranes, a mechanism that can also be used to permeabilize bacteria to other antibiotics, resulting in synergistic effects. We recently showed that G3KL, an AMP with a multibranched dendritic topology of the peptide chain, permeabilizes the inner and outer membranes of Gram-negative bacteria including multidrug-resistant strains, leading to efficient bacterial killing. Here, we show that permeabilization of the outer and inner membranes of Pseudomonas aeruginosa by G3KL, initially detected using the DNA-binding fluorogenic dye propidium iodide (PI), also leads to a synergistic effect between G3KL and PI in this bacterium. We also identify a synergistic effect between G3KL and six different antibiotics against the Gram-negative Klebsiella pneumoniae, against which G3KL is inactive.
Handgrip strength as a complementary test for mobility limitations assessment in acutely hospitalized oldest old.

INTRODUCTION Clinically viable screening tools for detecting individuals at heightened risk for mobility limitations is warranted. However, it remains unclear in acutely hospitalized patients (> 75 years) whether handgrip strength might be a good predictor for "proxy" muscle strength. OBJECTIVE To examine the reliability and validity of handgrip strength test in acute hospitalized older adults in comparison with other standardized muscular strength tests, and (ii) to examine its ability to discriminate between presence and absence of mobility limitations. DESIGN Cross-sectional study. SETTINGS AND PARTICIPANTS A total of 223 patients (mean 86.5 years old, 46% women) admitted to a tertiary public hospital between 2016 and 2017 were recruited. METHODS Maximal (1RM) and power muscle output of the upper and lower extremity along with functional capacity (as assessed with Barthel index and the Short Physical Performance Battery [SPPB]), and cognitive function was measured at admission. Functional impairment (mobility limitations) was defined at SPPB≤7 points. Pearson's correlation and multivariable linear regression were evaluated between handgrip test and maximal and muscle power output as the reference method to assess concurrent validity. Receiver operating characteristic analysis was used to estimate handgrip strength cutoff point for likelihood of mobility limitations to assess predictive validity. RESULTS Findings show moderate-to-strong correlations between standardized muscular strength (reference methods) and handgrip strength test (r= 0.501 to 0.779). All muscular strength tests show moderate accuracy (area under curve >0.7). Handgrip strength shows the higher positive predictive value (87%), and therefore a lower number of false positives. The overall handgrip strength cutoff point for likelihood of mobility limitations was 18.4 kg for men and women. CONCLUSIONS AND IMPLICATIONS Handgrip strength may be a useful tool for detecting acutely hospitalized older who are at risk of mobility limitations and could aid in focusing interventions on those with higher risk.