Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Supplemented or Human Material to Simulate PD Behavior of Antibiotics at the Target Site In Vitro

In antimicrobial drug development, in vitro antibiotic susceptibility testing is conducted in standard growth media, such as Mueller–Hinton broth (MHB). These growth media provide optimal bacterial growth, but do not consider certain host factors that would be necessary to mimic the in vivo bacterial environment in the human body. The present review aimed to include relevant data published between 1986 and 2019. A database search (PubMed) was done with text keywords, such as “MIC” (minimal inhibitory concentration), “TKC” (time kill curve), “blood”, “body fluid”, “PD” (pharmacodynamic), and “in vitro”, and 53 papers were ultimately selected. Additionally, a literature search for physiologic characteristics of body fluids was conducted. This review gives an excerpt of the complexity of human compartments with their physiologic composition. Furthermore, we present an update of currently available in vitro models operated either with adapted growth media or body fluids themselves. Moreover, the feasibility of testing the activity of antimicrobials in such settings is discussed, and pro and cons for standard practice methods are given. The impact on bacterial killing varies between individual adapted microbiological media, as well as direct pharmacodynamic simulations in body fluids, between bacterial strains, antimicrobial agents, and the compositions of the adjuvants or the biological fluid itself.
Design of Readout Circuit with Quadrature Error and Auxiliary PLL for MEMS Vibratory Gyroscope

Traditional MEMS gyroscope readout eliminates quadrature error and relies on the phase relationship between the drive displacement and the Coriolis position to accomplish a coherent demodulation. This scheme shows some risk, especially for a mode-matching gyro. If only a slight resonant frequency deviation between the drive and sense mode occurs, a dramatic change in the phase relationship follows, which leads to a wrong demodulation. To solve this, this paper proposes a new readout based on the quadrature error and an auxiliary phase-locked loop (PLL). By tuning the phase shifter in the sense-mode circuit, letting the quadrature error and the carrier of the mixer be in 90° phase alignment, the Coriolis was simultaneously in phase with the carrier. Hence, the demodulation was accomplished. The carrier comes from the PLL output of the drive-mode circuit due to its low jitter and independence of the work mode of the gyro. Moreover, an auxiliary PLL is used to filter the quadrature error to enhance the phase alignment accuracy. Through an elaborate design, a printed circuit board was used to verify the proposed idea. The experimental results show the readout circuit functioned well. The scale factor of the gyro was 6.8 mV/°/s, and the bias instability was 204°/h.
A Preliminary Study on the Characteristics of microRNAs in Ovarian Stroma and Follicles of Chuanzhong Black Goat during Estrus

microRNAs (miRNAs) play a significant role in ovarian follicular maturity, but miRNA expression patterns in ovarian stroma (OS), large follicles (LF), and small follicles (SF) have been rarely explored. We herein aimed to identify miRNAs, their target genes and signaling pathways, as well as their interaction networks in OS, LF, and SF of Chuanzhong black goats at the estrus phase using small RNA-sequencing. We found that the miRNA expression profiles of LF and SF were more similar than those of OS—32, 16, and 29 differentially expressed miRNAs were identified in OS vs. LF, OS vs. SF, and LF vs. SF, respectively. Analyses of functional enrichment and the miRNA-targeted gene interaction network suggested that miR-182 (SMC3), miR-122 (SGO1), and miR-206 (AURKA) were involved in ovarian organogenesis and hormone secretion by oocyte meiosis. Furthermore, miR-202-5p (EREG) and miR-485-3p (FLT3) were involved in follicular maturation through the MAPK signaling pathway, and miR-2404 (BMP7 and CDKN1C) played a key role in follicular development through the TGF-β signaling pathway and cell cycle; nevertheless, further research is warranted. To our knowledge, this is the first study to investigate miRNA expression patterns in OS, LF, and SF of Chuanzhong black goats during estrus. Our findings provide a theoretical basis to elucidate the role of miRNAs in follicular maturation. These key miRNAs might provide candidate biomarkers for the diagnosis of follicular maturation and will assist in developing new therapeutic targets for female goat infertility.
Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients.

OBJECTIVE To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer. METHODS 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS). RESULTS Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/β ratio 10 Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7% vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively (p = 0.05). There was no severe toxicity. CONCLUSION SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 >72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies. ADVANCES IN KNOWLEDGE SBRT with a BED10 >72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.
Hydrolyzed Yeast Supplementation in Calf Starter Promotes Innate Immune Responses in Holstein Calves under Weaning Stress Condition

Simple Summary New-born Holstein calves are vulnerable to infectious diseases owing to incomplete immune system development. This study aimed to evaluate the effects of six weeks of hydrolyzed yeast supplementation in Holstein calf starter on stress and immune responses after weaning. Hydrolyzed yeast supplementation facilitated the innate immune response after weaning, with a limited stress response. Therefore, the supplementation of hydrolyzed yeast in calf starters may help weaned calves adapt to diet-induced stresses. These results suggest that hydrolyzed yeast may be an effective feed additive for modulating stress-related immune responses. Abstract Weaned calves are susceptible to infectious diseases because of the stress and malnutrition that occurs during weaning. Therefore, the dairy industry requires effective feed additives to ameliorate stress responses and promote immunity. This study aimed to investigate the effects of hydrolyzed yeast (HY) supplementation on the growth performance, immune and stress parameters, and health status of calves after weaning. Eighteen Holstein calves were randomly assigned to two groups, either receiving a control calf starter or 0.2% HY calf starter from one week of age. All calves were weaned at six weeks of age as a stress challenge. The HY-fed calves had a significantly-higher body weight gain during the post-weaning period (kg/week) compared to the control. Cortisol levels at three days post-weaning (DPW) were significantly lower in the HY group than the control group. Calves fed HY had significantly-higher serum levels of tumor necrosis factor-α and interleukin-1β at one DPW. The HY-fed calves also had higher concentrations of the acute-phase proteins, haptoglobin, serum amyloid A, and transferrin at one DPW. In addition, the diarrhea severity in HY-fed calves was milder after weaning compared to the control group. Our results indicate that HY supplementation reduces stress responses and may promote innate immunity in newly-weaned calves.
Preparation and Characterization of TPP-Chitosan Crosslinked Scaffolds for Tissue Engineering

Scaffolds are three-dimensional porous structures that must have specific requirements to be applied in tissue engineering. Therefore, the study of factors affecting scaffold performance is of great importance. In this work, the optimal conditions for cross-linking preformed chitosan (CS) scaffolds by the tripolyphosphate polyanion (TPP) were investigated. The effect on scaffold physico-chemical properties of different concentrations of chitosan (1 and 2% w/v) and tripolyphosphate (1 and 2% w/v) as well as of cross-linking reaction times (2, 4, or 8 h) were studied. It was evidenced that a low CS concentration favored the formation of three-dimensional porous structures with a good pore interconnection while the use of more severe conditions in the cross-linking reaction (high TPP concentration and crosslinking reaction time) led to scaffolds with a suitable pore homogeneity, thermal stability, swelling behavior, and mechanical properties, but having a low pore interconnectivity. Preliminary biocompatibility tests showed a good osteoblasts’ viability when cultured on the scaffold obtained by CS 1%, TPP 1%, and an 8-h crosslinking time. These findings suggest how modulation of scaffold cross-linking conditions may permit to obtain chitosan scaffold with properly tuned morphological, mechanical and biological properties for application in the tissue regeneration field.
An update on autoimmune retinopathy

Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.
Salmonella Hessarek Gastroenteritis with Bacteremia: A Case Report and Literature Review

Salmonella enterica subspecies enterica serotype Hessarek (Salmonella Hessarek) is considered a serovar with high host specificity and is an uncommon cause of disease in humans; no cases of S. Hessarek bacteremia have been reported in humans to date. On 16 July 2019, a young male presented abdominal pain, vomit, diarrhea, and fever up to 41 °C, a few hours after a kebab meal containing goat meat; he went to the Emergency Room, where a Film Array® GI Panel (BioFire, Biomerieux Company, Marcy-L´Étoile, France) was performed on his feces and results were positive for Salmonella. The culture of the feces was negative, but the blood culture was positive for Salmonella spp. , which was identified as Salmonella Hessarek by seroagglutination assays. The patient was treated with ceftriaxone 2 g intravenously qd for 8 days; he was discharged in good general conditions, and ciprofloxacin 500 mg per os bid for 7 more days was prescribed, after exclusion of endocarditis and of clinical signs of complicated bacteremia. This case of Salmonella Hessarek gastroenteritis with bacteremia is probably the first case of bloodstream human infection due to this agent ever described. Further studies are needed to ascertain the global burden of S. Hessarek disease in humans.
Regulation of Microbial Activity Rates by Organic Matter in the Ross Sea during the Austral Summer 2017

The active prokaryotic communities proliferate in the ecosystems of the Antarctic Ocean, participating in biogeochemical cycles and supporting higher trophic levels. They are regulated by several environmental and ecological forcing, such as the characteristics of the water masses subjected to global warming and particulate organic matter (POM). During summer 2017, two polynyas in the Ross Sea were studied to evaluate key-microbiological parameters (the proteasic, glucosidasic, and phosphatasic activities, the microbial respiratory rates, the prokaryotic abundance and biomass) in relation to quantitative and qualitative characteristics of POM. Results showed significant differences in the epipelagic layer between two macro-areas (Terra Nova Bay and Ross Sea offshore area). Proteins and carbohydrates were metabolized rapidly in the offshore area (as shown by turnover times), due to high enzymatic activities in this zone, indicating fresh and labile organic compounds. The lower quality of POM in Terra Nova Bay, as shown by the higher refractory fraction, led to an increase in the turnover times of proteins and carbohydrates. Salinity was the physical constraint that played a major role in the distribution of POM and microbial activities in both areas.
Using the Redundant Convolutional Encoder–Decoder to Denoise QRS Complexes in ECG Signals Recorded with an Armband Wearable Device

Long-term electrocardiogram (ECG) recordings while performing normal daily routines are often corrupted with motion artifacts, which in turn, can result in the incorrect calculation of heart rates. Heart rates are important clinical information, as they can be used for analysis of heart-rate variability and detection of cardiac arrhythmias. In this study, we present an algorithm for denoising ECG signals acquired with a wearable armband device. The armband was worn on the upper left arm by one male participant, and we simultaneously recorded three ECG channels for 24 h. We extracted 10-s sequences from armband recordings corrupted with added noise and motion artifacts. Denoising was performed using the redundant convolutional encoder–decoder (R-CED), a fully convolutional network. We measured the performance by detecting R-peaks in clean, noisy, and denoised sequences and by calculating signal quality indices: signal-to-noise ratio (SNR), ratio of power, and cross-correlation with respect to the clean sequences. The percent of correctly detected R-peaks in denoised sequences was higher than in sequences corrupted with either added noise (70–100% vs. 34–97%) or motion artifacts (91.86% vs. 61.16%). There was notable improvement in SNR values after denoising for signals with noise added (7–19 dB), and when sequences were corrupted with motion artifacts (0.39 dB). The ratio of power for noisy sequences was significantly lower when compared to both clean and denoised sequences. Similarly, cross-correlation between noisy and clean sequences was significantly lower than between denoised and clean sequences. Moreover, we tested our denoising algorithm on 60-s sequences extracted from recordings from the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database and obtained improvement in SNR values of 7.08 ± 0.25 dB (mean ± standard deviation (sd)). These results from a diverse set of data suggest that the proposed denoising algorithm improves the quality of the signal and can potentially be applied to most ECG measurement devices.
Chapter 22: Preparation and Characterization of 6-Azidoh-exyl 2, 3, 4, 6-tetra- O-acetyl-β-d-glucopyranoside, By Divya Kushwaha, Pavol Kováč, and Marek Baráth

Azidoalkyl glycosides are popular intermediates in the syntheses of their amino counterparts, and also in preparation of glycoconjugates through click chemistry.1,2 Several preparations of the per-O-acetate of the simplest compound in this series, 6-azidohexyl 2, 3, 4, 6-tetra-O-acetyl-β-d-glucopyranoside (3), were previously described, but despite the obvious interest in glycoside 3, the compound has not been fully characterized. Here, we describe preparation of the title glucopyranoside 3, obtained in crystalline form for the rst time, from the hitherto unknown 6chlorohexyl 1842,3,4,6-tetra-O-acetyl-β-d-glucopyranoside (2). The latter was prepared by BF3·Et2O-catalyzed reaction of 6-chlorohexanol with 1 in a yield comparable to that of its bromo analog. However, similar to 6bromohexanol, 6-chlorohexanol is also commercially available but it is a several times less-expensive reagent. Our product 2 crystallized readily from the crude reaction mixture, and it was fully characterized. Its structure follows from the mode of synthesis, and was confirmed by the spectral data (NMR and MS).
Health Benefits of Plant-Derived Sulfur Compounds, Glucosinolates, and Organosulfur Compounds

The broad spectrum of the mechanism of action of immune-boosting natural compounds as well as the complex nature of the food matrices make researching the health benefits of various food products a complicated task. Moreover, many routes are involved in the action of most natural compounds that lead to the inhibition of chronic inflammation, which results in a decrease in the ability to remove a pathogen asymptomatically and is connected to various pathological events, such as cancer. A number of cancers have been associated with inflammatory processes. The current review strives to answer the question of whether plant-derived sulfur compounds could be beneficial in cancer prevention and therapy. This review focuses on the two main sources of natural sulfur compounds: alliaceous and cruciferous vegetables. Through the presentation of scientific data which deal with the study of the chosen compounds in cancer (cell lines, animal models, and human studies), the discussion of food processing’s influence on immune-boosting food content is presented. Additionally, it is demonstrated that there is still a need to precisely demonstrate the bioavailability of sulfur-containing compounds from various types of functional food, since the inappropriate preparation of vegetables can significantly reduce the content of beneficial sulfur compounds. Additionally, there is an urgent need to carry out more epidemiological studies to reveal the benefits of several natural compounds in cancer prevention and therapy.
A Randomized, Placebo-Controlled Clinical Trial of Famciclovir in Shelter Cats with Naturally Occurring Upper Respiratory Tract Disease

Simple Summary Upper respiratory tract disease (URTD) impacts the health and welfare of shelter cats. Mitigation strategies include stress reduction and population-level approaches; effective treatment plans focus on reducing the clinical signs in cats affected by URTD. This study evaluated the use of famciclovir, an antiviral therapy, in reducing clinical signs in shelter cats with URTD when administered at a target dose range of 40–90 mg/kg twice daily for up to 21 days. Cats were randomized into either a famciclovir treatment group (n = 11) or placebo group (n = 11). Testing for viral pathogen identification was performed at enrollment in the study, and clinical scoring was completed daily to evaluate the severity of signs. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, cats in the famciclovir treatment group had a significantly lower risk of worsening clinical signs with each day compared to the placebo group. Feline herpesvirus, a common pathogen causing URTD, was identified in 11/21 cats. The results of this small study justify the need for further research to determine the utility of famciclovir as part of treatment protocols for improving clinical signs and overall impacts of URTD in shelter cats. Abstract Upper respiratory tract disease (URTD) is a clinically relevant infectious disease in shelter cats, with individual and population-level welfare implications. The purpose of this study was to evaluate the effectiveness of famciclovir in reducing clinical signs of URTD in shelter cats during a therapeutic period of up to 21 days. Cats at two Northeastern United States animal shelters with URTD clinical signs were enrolled in a pragmatic, prospective, randomized, placebo-controlled clinical trial. Cats received either famciclovir (n = 11, target dose range 40–90 mg/kg) or placebo (n = 11), administered orally twice daily for up to 21 days with once-daily clinical scoring. At enrollment, conjunctival and oropharyngeal samples were collected for respiratory pathogen identification by RT-PCR. Zero-inflated Poisson regression was used to evaluate the treatment group effects and changes in clinical scoring over time. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, the risk of worsening scores with each day of treatment was significantly less in the famciclovir group compared to placebo (p = 0.006). Feline herpesvirus (FHV-1) DNA was detected in 11/21 cats. The findings justify further pragmatic studies to determine whether famciclovir treatment can contribute to a clinically relevant reduction in URTD morbidity in shelter cats.
Systemic immunosuppressive therapies for uveitis in developing countries

There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides.