Miracle-dz/UniFAR-FTUs huggingface dataset:
HER2 status in recurrent/metastatic androgen receptor overexpressing salivary gland carcinoma patients

Background Overexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status. Methods Consecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS). Results Seventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance. Discussion In our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy.
Ten interleukins and risk of prostate cancer

Background Interleukins (ILs) have been reported to be related to prostate cancer. The aims of this study were to estimate the levels for several key interleukins in prostate cancer and the causal effects between them. Methods We conducted a bi-directional two-sample Mendelian randomization (MR) study to assess the causal associations between ILs and prostate cancer. Genetic instruments and summary-level data for 10 ILs were obtained from three genome-wide association meta-analyses. Prostate cancer related data were obtained from the PRACTICAL (79,148 cases and 61,106 controls), UK Biobank (7,691 cases and 169,762 controls) and FinnGen consortium (10,414 cases and 124,994 controls), respectively. Results The odds ratio of prostate cancer was 0.92 (95% confidence interval (CI), 0.89, 0.96; P=1.58×10-05) and 1.12 (95% CI, 1.07, 1.17; P=6.61×10-07) for one standard deviation increase in genetically predicted IL-1ra and IL-6 levels, respectively. Genetically predicted levels of IL-1ß, IL-2a, IL-6ra, IL-8, IL-16, IL-17, IL-18, and IL-27 were not associated with the risk of prostate cancer. Reverse MR analysis did not find the associations between genetic liability to prostate cancer and higher levels of IL-1ra (β, -0.005; 95% CI, -0.010, 0.001; P=0.111) and IL-6 (β, 0.002; 95% CI, -0.011, 0.014; P=0.755). Conclusion This MR study suggests that long-term IL-6 may increase the risk of prostate cancer and IL-1ra may reduce it.
The lung, the niche, and the microbe: Exploring the lung microbiome in cancer and immunity

The lung is a complex and unique organ system whose biology is strongly influenced by environmental exposure, oxygen abundance, connection to extrapulmonary systems via a dense capillary network, and an array of immune cells that reside in the tissue at steady state. The lung also harbors a low biomass community of commensal microorganisms that are dynamic during both health and disease with the capacity to modulate regulatory immune responses during diseases such as cancer. Lung cancer is the third most common cancer worldwide with the highest mortality rate amongst cancers due to the difficulty of an early diagnosis. This review discusses the current body of work addressing the interactions between the lung microbiota and the immune system, and how these two components of the pulmonary system are linked to lung cancer development and outcomes. Bringing in lessons from broader studies examining the effects of the gut microbiota on cancer outcomes, we highlight many challenges and gaps in this nascent field.
Spatial rehabilitation using virtual auditory space training paradigm in individuals with sensorineural hearing impairment

Purpose The present study aimed to quantify the effects of spatial training using virtual sources on a battery of spatial acuity measures in listeners with sensorineural hearing impairment (SNHI). Methods An intervention-based time-series comparison design involving 82 participants divided into three groups was adopted. Group I (n = 27, SNHI-spatially trained) and group II (n = 25, SNHI-untrained) consisted of SNHI listeners, while group III (n = 30) had listeners with normal hearing (NH). The study was conducted in three phases. In the pre-training phase, all the participants underwent a comprehensive assessment of their spatial processing abilities using a battery of tests including spatial acuity in free-field and closed-field scenarios, tests for binaural processing abilities (interaural time threshold [ITD] and level difference threshold [ILD]), and subjective ratings. While spatial acuity in the free field was assessed using a loudspeaker-based localization test, the closed-field source identification test was performed using virtual stimuli delivered through headphones. The ITD and ILD thresholds were obtained using a MATLAB psychoacoustic toolbox, while the participant ratings on the spatial subsection of speech, spatial, and qualities questionnaire in Kannada were used for the subjective ratings. Group I listeners underwent virtual auditory spatial training (VAST), following pre-evaluation assessments. All tests were re-administered on the group I listeners halfway through training (mid-training evaluation phase) and after training completion (post-training evaluation phase), whereas group II underwent these tests without any training at the same time intervals. Results and discussion Statistical analysis showed the main effect of groups in all tests at the pre-training evaluation phase, with post hoc comparisons that revealed group equivalency in spatial performance of both SNHI groups (groups I and II). The effect of VAST in group I was evident on all the tests, with the localization test showing the highest predictive power for capturing VAST-related changes on Fischer discriminant analysis (FDA). In contrast, group II demonstrated no changes in spatial acuity across timelines of measurements. FDA revealed increased errors in the categorization of NH as SNHI-trained at post-training evaluation compared to pre-training evaluation, as the spatial performance of the latter improved with VAST in the post-training phase. Conclusion The study demonstrated positive outcomes of spatial training using VAST in listeners with SNHI. The utility of this training program can be extended to other clinical population with spatial auditory processing deficits such as auditory neuropathy spectrum disorder, cochlear implants, central auditory processing disorders etc.
Pre-operative administration of butorphanol mitigates emergence agitation in patients undergoing functional endoscopic sinus surgery: A randomized controlled clinical trial

Background This study explored the effectiveness of pre-operative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS). Methods Patients (n = 708) were randomized into two groups. The butorphanol group (Group B, n = 358) received butorphanol infusion (20 ug/kg) before anesthesia induction, while the control group (Group C, n = 350) received an equal volume of normal saline infusion. General anesthesia was induced with sufentanil, propofol, and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the hemodynamic indices within 20% of the baseline. Results The incidence of EA was significantly lower in Group B than that in Group C (Group B vs. C: 24.3% vs. 31.4%, respectively; P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012), and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B. Conclusion Pre-operative intravenous injection of butorphanol decreased the incidence of EA after FESS and provided smooth and hemodynamically stable emergence without extending the stay in post-anesthesia care unit. Clinical trial registration https://www.clinicaltrials. gov/, identifier NCT03398759.
Optical manifestations of mass outflows from young stars - At atlas of CCD images of Herbig-Haro objects

An attempt is made to provide deep CCD images suitable for tracing the shock-excited and scattered-light components characterizing extended Herbig-Haro complexes. Tabular data include astrometric positions for all stars, shock-excited emission knots, prominent scattered-light patches, as well as an identification for all H-alpha emission objects within the CCD images. It is concluded that: (1) optical outflows are not always accompanied by molecular flows, (2) optical outflows show a higher degree of collimation than their molecular counterparts, and (3) the Herbig-Haro phenomenon is not restricted to low-mass young stellar objects.
Comparison of the risks of occupational diseases, avoidable hospitalization, and all-cause deaths between firefighters and non-firefighters: A cohort study using national health insurance claims data

Objectives National Health Insurance claims data were used to compare the incidence of occupational diseases, avoidable hospitalization, and all-cause death standardized incidence ratio and hazard ratio between firefighters and non-firefighters. Methods The observation period of the study was from 2006 to 2015 and a control group (general workers and national and regional government officers/public educational officers) and a firefighter group was established. The dependent variables were occupational diseases, avoidable hospitalization (AH), and all-cause death. The analysis was conducted in three stages. First, the standardized incidence ratios were calculated using the indirect standardization method to compare the prevalence of the disease between the groups (firefighter and non-firefighter groups). Second, propensity score matching was performed for each disease in the control group. Third, the Cox proportional hazards model was applied by matching the participants. Results The standardized incidence ratio and Cox regression analyses revealed higher rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, cancer, back pain, admission due to injury, mental illness, depression, and AH for firefighters than general workers. Similarly, the rates of noise-induced hearing loss, ischemic heart disease, asthma, chronic obstructive pulmonary disease, back pain, admission due to injury, mental illness, depression, and AH were higher in the firefighter group than in the national and regional government officer/public educational officer group. Conclusions The standardized incidence ratios and hazard ratios for most diseases were high for firefighters. Therefore, besides the prevention and management of diseases from a preventive medical perspective, management programs, including social support and social prescriptions in the health aspect, are needed.
Comparative Analysis of Volatiles of 15 Brands of Extra-Virgin Olive Oils Using Solid-Phase Micro-Extraction and Solvent-Assisted Flavor Evaporation

Aroma profiles, key aroma compound quantification, and cluster analysis of 15 brands of extra-virgin olive oils (EVOOs) from three countries (Spain, Italy, and Greece) were investigated in the current study. Aroma compounds were isolated from the oil by using solvent-assisted flavor evaporation (SAFE) and solid-phase micro-extraction (SPME) and analyzed by gas chromatography-olfactometry mass spectrometry (GC-MS/O). A total of 89 compounds were screened by SPME/SAFE-GC-MS/O with chromatographic columns in 15 brands of samples. Eighty and 54 compounds were respectively identified by SPME- and SAFE-GC-MS/O. Of those, 44 compounds were detected by both methods. Undecanol, (Z)-4-decenal, (E)-2-dodecenal, and 2-nonanone extracted by SAFE were not found in EVOOs before. Eight classes of aroma compounds were identified, including 17 alcohols, 22 aldehydes, 9 ketones, 4 acids, 14 esters, 5 aromatics, 12 alkene, and 6 others. Eleven compounds were identified as the key aroma compounds in alternative brands of EVOOs by SAFE-aroma extract dilution analysis (AEDA). Hexanal, (E)-2-hexenal, (E)-3-hexenol, acetic acid, and (E)-2-heptenal were the common key aroma compounds by AEDA and odor activity values (OAVs). From the cluster analysis of the heatmap, the aroma compounds of all the Spain EVOOs were similar, and there were some differences from the samples of Italy and Greece. It suggested that both the amount and concentration of aroma compounds determine the similarity of aroma in EVOOs.
Investigating bile acid-mediated cholestatic drug-induced liver injury using a mechanistic model of multidrug resistance protein 3 (MDR3) inhibition

Inhibition of the canalicular phospholipid floppase multidrug resistance protein 3 (MDR3) has been implicated in cholestatic drug-induced liver injury (DILI), which is clinically characterized by disrupted bile flow and damage to the biliary epithelium. Reduction in phospholipid excretion, as a consequence of MDR3 inhibition, decreases the formation of mixed micelles consisting of bile acids and phospholipids in the bile duct, resulting in a surplus of free bile acids that can damage the bile duct epithelial cells, i.e., cholangiocytes. Cholangiocytes may compensate for biliary increases in bile acid monomers via the cholehepatic shunt pathway or bicarbonate secretion, thereby influencing viability or progression to toxicity. To address the unmet need to predict drug-induced bile duct injury in humans, DILIsym, a quantitative systems toxicology model of DILI, was extended by representing key features of the bile duct, cholangiocyte functionality, bile acid and phospholipid disposition, and cholestatic hepatotoxicity. A virtual, healthy representative subject and population (n = 285) were calibrated and validated utilizing a variety of clinical data. Sensitivity analyses were performed for 1) the cholehepatic shunt pathway, 2) biliary bicarbonate concentrations and 3) modes of MDR3 inhibition. Simulations showed that an increase in shunting may decrease the biliary bile acid burden, but raise the hepatocellular concentrations of bile acids. Elevating the biliary concentration of bicarbonate may decrease bile acid shunting, but increase bile flow rate. In contrast to competitive inhibition, simulations demonstrated that non-competitive and mixed inhibition of MDR3 had a profound impact on phospholipid efflux, elevations in the biliary bile acid-to-phospholipid ratio, cholangiocyte toxicity, and adaptation pathways. The model with its extended bile acid homeostasis representation was furthermore able to predict DILI liability for compounds with previously studied interactions with bile acid transport. The cholestatic liver injury submodel in DILIsym accounts for several processes pertinent to bile duct viability and toxicity and hence, is useful for predictions of MDR3 inhibition-mediated cholestatic DILI in humans.
Preclinical species gene expression database: Development and meta-analysis

The evaluation of toxicity in preclinical species is important for identifying potential safety liabilities of experimental medicines. Toxicology studies provide translational insight into potential adverse clinical findings, but data interpretation may be limited due to our understanding of cross-species biological differences. With the recent technological advances in sequencing and analyzing omics data, gene expression data can be used to predict cross species biological differences and improve experimental design and toxicology data interpretation. However, interpreting the translational significance of toxicogenomics analyses can pose a challenge due to the lack of comprehensive preclinical gene expression datasets. In this work, we performed RNA-sequencing across four preclinical species/strains widely used for safety assessment (CD1 mouse, Sprague Dawley rat, Beagle dog, and Cynomolgus monkey) in ∼50 relevant tissues/organs to establish a comprehensive preclinical gene expression body atlas for both males and females. In addition, we performed a meta-analysis across the large dataset to highlight species and tissue differences that may be relevant for drug safety analyses. Further, we made these databases available to the scientific community. This multi-species, tissue-, and sex-specific transcriptomic database should serve as a valuable resource to enable informed safety decision-making not only during drug development, but also in a variety of disciplines that use these preclinical species.
Frequency and spectrum of M2 mutants and genetic variability in cyto-agronomic characteristics of fenugreek induced by caffeine and sodium azide

Trigonella foenum graecum L. (Fenugreek) is a valuable medicinal plant cultivated for decades for its therapeutic characteristics. Still no pronounced improvement concerning wild form was accomplished as it is a self-pollinating crop. Induced mutagenesis is encouraged as a remarkable tool on this plant to circumvent the genetic bottleneck of cultivated germplasms. As a result, novel allelomorphic combinations for short-term agronomic attributes were developed. Fenugreek cultivar Pusa Early Bunching, selected for the present experiment, was mutagenized with five doses (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) of caffeine and sodium azide (SA) to evaluate its impact on the qualitative and quantitative traits of M1 and M2 generation conducted in a Complete Randomized Block Design (CRBD), replicated five times during 2019–2020 and 2020–2021, respectively. The frequency of induced phenotypic variations was assessed in M2 progenies, resulting in the identification and isolation of a broad spectrum of mutants with altered phenotypes. Mutagenic effectiveness and efficiency were found to be maximum at lower concentrations of the mutagen treatments and highest in SA, followed by caffeine. Various morphological mutants with modified characters were observed at different concentrations in M2 generation. The spectrum of mutations was wider in SA than in caffeine, as caffeine produced 51 while SA produced 54 individual mutants under seven major categories. The maximum frequency of morphological mutants was associated with leaf, followed by plant size, plant growth habit, pod, seed size, seed shape, and seed color. Morphological and structural variations in the guard cells of stomata and seeds were observed through scanning electron microscopy. The variations created in the economically important traits may enrich the genetic diversity of this plant species. Moreover, these morphological mutants may serve as a source of elite genes in further breeding programs of fenugreek.
Algal oil alleviates antibiotic-induced intestinal inflammation by regulating gut microbiota and repairing intestinal barrier

Introduction Taking antibiotics would interfere with gut microbiota and increase the risk of opportunistic pathogen infection and inflammation. Methods In this study, 36 male C57BL/6 mice were divided into 4 groups (n = 9) to investigate whether two kinds of algal oil could alleviate the intestinal damage induced by CS (Ceftriaxone sodium). These algal oils were obtained from Schizochytrium sp. cultures using Yeast extract (YE) and Rapeseed meal (RSM) as substrate, respectively. All tested mice were administrated with CS for 8 days and then the colon pathological morphology, the expression levels of inflammatory factors and the gut microbial profile were analyzed in mice supplemented with or without algal oil. Results The results showed that both YE and RSM algal oils markedly reduced mucosal damage and intestinal inflammatory response in CS-treated mice by inhibiting the pro-inflammatory cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and myeloperoxidase (MPO) activity. In addition, fluorescence immunohistochemistry showed that the tight junction protein ZO-1 was increased in mice supplemented with YE and RSM algal oil. Furthermore, YE algal oil promoted the beneficial intestinal bacteria such as Lachnospiraceae and S24_7 compared with the CS group, while supplementation with RSM algal oil enriched the Robinsoniella. Spearman’s correlation analysis exhibited that Melissococcus and Parabacteroides were positively correlated with IL-6 but negatively correlated with IL-10. Discussion This study suggested that supplementation with algal oil could alleviate intestinal inflammation by regulating gut microbiota and had a protective effect on maintaining intestinal barrier against antibiotic-induced damage in mice.