Miracle-dz/UniFAR-FTUs huggingface dataset:
Ertugliflozin: a novel anti-diabetic drug

Diabetes Mellitus is a disorder of global proportion. Despite various treatment modalities presently being available, yet the desired glycaemic control and patient outcomes have not been achieved completely. Sodium glucose co-transporter type 2 inhibitors (SGLT2 inhibitors) are one such promising group of emerging drugs in diabetes treatment. Ertugliflozin prevents the reabsorption of glucose by inhibiting sodium-glucose cotransporter-2 (SGLT2) at proximal convoluted tubules. Ertugliflozin is available as 5mg and 15mg tablets. Ertugliflozin has been related to genital mycotic infections and urinary tract infections. Benefits of Ertugliflozin include better control on blood glucose, body weight and blood pressure.
The Role of Circulating Tumor Cells in the Metastatic Cascade: Biology, Technical Challenges, and Clinical Relevance

Metastases and cancer recurrence are the main causes of cancer death. Circulating Tumor Cells (CTCs) and disseminated tumor cells are the drivers of cancer cell dissemination. The assessment of CTCs’ clinical role in early metastasis prediction, diagnosis, and treatment requires more information about their biology, their roles in cancer dormancy, and immune evasion as well as in therapy resistance. Indeed, CTC functional and biochemical phenotypes have been only partially characterized using murine metastasis models and liquid biopsy in human patients. CTC detection, characterization, and enumeration represent a promising tool for tailoring the management of each patient with cancer. The comprehensive understanding of CTCs will provide more opportunities to determine their clinical utility. This review provides much-needed insights into this dynamic field of translational cancer research.
FASPR: an open-source tool for fast and accurate protein side-chain packing

MOTIVATION Protein structure and function are essentially determined by how the side-chain atoms interact with each other. Thus, accurate protein side-chain packing (PSCP) is a critical step towards protein structure prediction and protein design. Despite the importance of the problem, however, the accuracy and speed of current PSCP programs are still not satisfactory. RESULTS We present FASPR for fast and accurate PSCP by using an optimized scoring function in combination with a deterministic searching algorithm. The performance of FASPR was compared with four state-of-the-art PSCP methods (CISRR, RASP, SCATD and SCWRL4) on both native and non-native protein backbones. For the assessment on native backbones, FASPR achieved a good performance by correctly predicting 69.1% of all the side-chain dihedral angles using a stringent tolerance criterion of 20°, compared favorably with SCWRL4, CISRR, RASP and SCATD which successfully predicted 68.8%, 68.6%, 67.8% and 61.7%, respectively. Additionally, FASPR achieved the highest speed for packing the 379 test protein structures in only 34.3 seconds, which was significantly faster than the control methods. For the assessment on non-native backbones, FASPR showed an equivalent or better performance on I-TASSER predicted backbones and the backbones perturbed from experimental structures. Detailed analyses showed that the major advantage of FASPR lies in the optimal combination of the dead-end elimination and tree decomposition with a well optimized scoring function, which makes FASPR of practical use for both protein structure modeling and protein design studies. AVAILABILITY The web server, source code and datasets are freely available at https://zhanglab.ccmb. med.umich. edu/FASPR and https://github.com/tommyhuangthu/FASPR. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Repurposing the Antiamoebic Drug Diiodohydroxyquinoline for Treatment of Clostridioides difficile Infections

Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for the treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. ABSTRACT Clostridioides difficile, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for the treatment of Clostridioides difficile infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against C. difficile and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 C. difficile isolates, inhibiting growth of 50% and 90% of these isolates at concentrations of 0.5 μg/ml and 2 μg/ml, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3 log10 within 6 h. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against C. difficile in vitro. Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of C. difficile, toxin production and spore formation. Additionally, DIHQ did not inhibit the growth of key species that compose the host intestinal microbiota, such as Bacteroides, Bifidobacterium, and Lactobacillus spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.
Stability of Early Auditory Evoked Potential Components Over Extended Test-Retest Intervals in Young Adults.

OBJECTIVES Synaptic damage from noise exposures can occur even in the absence of changes in hearing sensitivity in animal models. There is an unmet clinical need for measurements sensitive to such damage to the human auditory system that can augment the pure-tone audiogram. Early components (i.e., <10 msec) of the auditory evoked potential (AEP) may be useful noninvasive indicators of synaptic integrity. Wave I is a measure of synchronous neural activity at the level of the synapse between cochlear inner hair cells and the auditory nerve and may be of particular clinical utility. This amplitude measure has historically been classified as too variable in humans to be used for clinical waveform interpretation, though several recent reliability studies have challenged this view. The focus of the present study is to examine across-session stability of early AEP amplitude measures. DESIGN In this study, amplitudes of early components (wave I, wave V, summating potential [SP]) of the AEP were measured in a cohort of 38 young adults aged 19 to 33 years (21 female). Stability of these amplitude measures was examined in a subset of 12 young adults (8 female), at time intervals ranging from 15 hr to 328 days between tests. Eligibility criteria included normal pure-tone hearing sensitivity, normal tympanometry, and intact acoustic reflexes. Participants were tested at up to four time points. Each evaluation included pure-tone thresholds, tympanometry, speech-in-noise testing, distortion-product otoacoustic emissions (DPOAE), and early AEPs. AEPs were collected in response to click and tone burst stimuli, with both ear canal and mastoid electrode montages. RESULTS No clinical changes in pure-tone hearing were found between baseline and follow-up visits. Intraclass correlation coefficients (ICCs) indicated good to excellent reliability for wave I and wave V peak-to-trough amplitudes within individuals across time, with greatest reliability (0.92, 95% confidence interval [0.81 to 0.96]) and largest amplitudes for wave I when measured from the ear canal in response to a click stimulus. Other measures such as amplitude ratios of waves V/I and the SP and action potential (AP) showed lower ICC values when measured from the ear canal, with SP/AP ratio demonstrating the lowest reliability. CONCLUSIONS The results of this study suggest that, when recorded under certain conditions, wave I amplitude can be a stable measure in humans. These findings are consistent with previous work and may inform the development of clinical protocols that utilize wave I amplitude to infer inner ear integrity.
Tunable Fano Resonance and Enhanced Sensing in a Simple Au/TiO2 Hybrid Metasurface

We investigate Fano resonances and sensing enhancements in a simple Au/TiO2 hybrid metasurface through the finite-different time-domain (FDTD) simulation and coupled mode theory (CMT) analysis. The results show that the Fano resonance in the proposed simple metasurface is caused by the destructive interaction between the surface plasmon polaritons (SPPs) and the local surface plasmon resonances (LSPRs), the quality factor and dephasing time for the Fano resonance can be effectively tuned by the thickness of Au and TiO2 structures, the length of each unit in x and y directions, as well as the structural defect. In particular, single Fano resonance splits into multiple Fano resonances caused by a stub-shaped defect, and multiple Fano resonances can be tuned by the size and position of the stub-shaped defect. Moreover, we also find that the sensitivity in the Au/TiO2 hybrid metasurface with the stub-shaped defect can reach up to 330 nm/RIU and 535 nm/RIU at the Fano resonance 1 and Fano resonance 2, which is more than three times as sensitive in the Au/TiO2 hybrid metasurface without the stub-shaped defect, and also higher than that in the TiO2 metasurface reported before. These results may provide further understanding of Fano resonances and guidance for designing ultra-high sensitive refractive index sensors.
Educação alimentar e nutricional para população idosa: uma revisão integrativa

Introduction: Research has shown the accelerated population growth of the elderly, and healthy eating is an important means of achieving active and healthy aging. Objective: To describe the scientific evidence published in the literature about publications in the food and nutritional education (FNE) area for the elderly population. Materials and Methods: An integrative review was performed in the electronic databases (SCIELO, MEDLINE and LILACS) using the terms “food and nutrition education”, “health education” and “seniors”. Articles published in the period 2006 to 2016 were included in the English, Spanish and Portuguese languages, which approached the theme. Results: In the final sample, 5 articles remained, 1 national and 4 international. It was verified that the analyzed articles used as an FNE practice culinary and recreational activities, 3 studies also carried out the evaluation of nutritional status as a form of evaluating the intervention, as well as questionnaires and field diary. Research has shown the benefits of FNE in the elderly population. Conclusion: FNE can contribute not only to healthy eating, but also to improving the mental health and socialization of the elderly, contributing to aging with autonomy and independence.
The Role of Bcl-xL Protein Research in Veterinary Oncology

Due to their significant impact on human and animal health, cancer diseases are an area of considerable concern for both human and veterinary medicine. Research on the cancer pathogenesis in companion animals, such as dogs, allows not only for improving canine cancer treatment, but also for translating the results into human oncology. Disruption of apoptosis in tumor-transformed cells is a well-known mechanism leading to the development of cancer. One of the main factors involved in this process are proteins belonging to the B-cell lymphoma 2 (Bcl-2) family, and the imbalance between pro-apoptotic and anti-apoptotic members of this family contributes to the development of cancer. Studies on the function of these proteins, including B-cell lymphoma-extra large (Bcl-xL), have also been intensively conducted in companion animals. The Bcl-xL gene was sequenced and found to share over 99% homology with the human protein. Research showed that the Bcl-2 family plays the same role in human and canine cells, and data from studies in dogs are fully translatable to other species, including humans. The role of this protein family in cancer development was also confirmed. The article presents the current state of knowledge on the importance of the Bcl-xL protein in veterinary oncology.
A serial diffusion kurtosis MRI study during acute, subacute and recovery periods after sport-related concussion.

Sport-related concussion (SRC) is common in contact sports, but there remains a lack of reliable, unbiased biomarkers of brain injury and recovery. Although the symptoms of SRC generally resolve over a period of days to weeks, the lack of a biomarker impairs detection and return-to-play decisions. To this date, the pathophysiological recovery profile and relationships between brain changes and symptoms remained unclear. In the current study, Diffusion Kurtosis Imaging (DKI) was used to monitor the effects of SRC on the brain and the trajectory of recovery in concussed American football players (n=96) at <48 hours, 8, 15 and 45-days post-injury and compared to a matched group of non-injured players (N=82). The concussed group reported significantly higher symptoms within 48 hours after injury compared to controls, which resolved by the 8-day follow-up. The concussed group also demonstrated poorer performance on balance testing at <48 hours and 8 days compared to controls. There were no significant differences between the groups in SAC, a cognitive screening measure. DKI data was acquired with 3mm isotropic resolution and analyzed using TBSS. Additionally, voxel and region of interest based analyses were also carried out. At <48 hours, the concussed group showed significantly higher axial kurtosis compared to the control group. These differences increased in extent and magnitude at 8 days, then receded at 15 days, and returned to the normal levels by 45 days. Kurtosis FA exhibited a delayed response, with a consistent increase by day 15 and 45. The results indicate that changes detected in the acute period appear to be prolonged compared to clinical recovery, but additional brain changes not observable acutely appear to progress. While further studies are needed to understand the pathological features of DKI changes after SRC, these findings highlight a potential disparity between clinical symptoms and pathophysiological recovery after SRC.
Cortical complexity and gyrification patterns in Parkinson’s disease

This study aimed to investigate the cortical complexity and gyrification patterns in Parkinson’s disease (PD) using local fractional dimension (LFD) and local gyrification index (LGI), respectively. In a cross-sectional study, LFD and LGI in 60 PD patients without dementia and 56 healthy controls (HC) were investigated using brain structural MRI data. LFD and LGI were estimated using the Computational Anatomy Toolbox (CAT12) and statistically analyzed between groups on a vertex level using statistical parametric mapping 12 (SPM12). Additionally, correlations between structural changes and clinical indices were further examined. PD patients showed widespread LFD reductions mainly in the left pre- and postcentral cortex, the left superior frontal cortex, the left caudal middle frontal cortex, the bilaterally superior parietal cortex and the right superior temporal cortex compared to HC. For LGI, there was no significant difference between PD and HC. In PD patients group, a significant negative correlation was found between LFD of the left postcentral cortex and duration of illness (DOI). Our results of widespread LFD reductions, but not LGI, indicate that LFD may provide a more sensitive diagnostic biomarker and encode specific information of PD. The significant negative correlation between LFD of the left postcentral cortex and DOI suggests that LFD may be a biomarker to monitor disease progression in PD.
High Transmission Potential of West Nile Virus Lineage 1 for Cx. pipiens s.l. of Iran

Vector competence is an important parameter in evaluating whether a species plays a role in transmission of an arbovirus. Although the protocols are similar, interpretation of results is unique given the specific interactions that exist between a mosquito population and a viral genotype. Here, we assessed the infection (IR), dissemination (DR), and transmission (TR) rates of Cx. pipiens s.l. , collected from Iran, for West Nile virus (WNV) lineage 1a. We showed that Cx. pipiens s.l. mosquitoes in Iran were susceptible to WNV with IR up to 89.7%, 93.6%, and 83.9% at 7, 14, and 21 days post-infection (dpi) respectively. In addition, DR and TR reached respectively 92.3% and 75.0% at 21 dpi, and the number of viral particles delivered with saliva reached up to 1.33 × 105 particles. Therefore, an unexpected high risk of WNV dissemination in the region where Cx. pipiens s.l. mosquitoes are well established should be considered carefully and surveillance measures implemented accordingly.
Help or hindrance: Exploring nurse practitioners' perceptions of transition to practice legislation

ABSTRACT Background: Fourteen states have adopted transition to practice (TP) legislation, which requires newly certified nurse practitioners (NPs) to practice under a senior clinician. States have adopted such legislation despite vast evidence indicating NPs provide safe care. Purpose: The purpose of this study is to explore NPs' perceptions of the effects of this legislation and to describe communication between NPs and senior clinicians working in TP states. Methods: Using a cross-sectional, descriptive design, we surveyed a convenience sample of NPs working in TP states. Descriptive statistical analysis and qualitative content analysis were conducted. Results: Most respondents believed TP legislation posed unnecessary regulatory barriers but also believed it promoted professional development. No statistically significant relationships between professional characteristics, regulatory variations, and these perceptions were identified. Implications for practice: Given the increasing number of states considering TP legislation, and the vast variability in TP models, additional research into the effects of this regulation is needed.
Unexpected Clues From Positron Emission Tomography in a Case of Fever of Unknown Origin.

A 17-year-old male adolescent, following a gym workout, presented with sore throat, fatigue, and fever at a pediatric hospital. A few days before, the patient had complained of diffuse myalgia and worsening pain in his shoulders and neck. Blood tests showed severe leukocytosis with polymorphonuclear cells greater than 80%. A complete workup for infectious diseases excluded viral or bacterial infections, whereas mild splenomegaly was detected by ultrasonography. Because of the persistence of high-grade fever (40°C) and elevated acute phase reactants, the patient underwent bone marrow aspiration to exclude hematological disorders and macrophage activation syndrome (MAS). Suspecting systemic juvenile idiopathic arthritis, a 3-day high-dose pulse therapy (6-mehtylprednisolone 3000mg total dose) was administered intravenously, followed by a rapid tapering scheme. However, 1 month after discharge, while taking 35 mg prednisone daily, the patient returned to the hospital with severe diffuse arthralgia. Procalcitonin, antinuclear autoantibodies, and antineutrophil cytoplasmic antibodies were negative. However, acute phase reactants resulted to be markedly elevated, together with hyperferritinemia and interleukin 18 (IL-18), measured while testing for autoinflammatory diseases. Furthermore, positron emission tomography (PET) showed an accumulation of F-FDG in the bone marrow and spleen, with a slightly enlarged liver (arrows; Fig. A and C). Complete genetic testing (Sanger sequencing) for familial Mediterranean fever, tumor necrosis factor receptor–associated periodic syndrome, hyper–immunoglobulin D syndrome, and NLRP3 deficiency were negative. No skin alterations or orogenital ulcerations were present, and there were no palpable superficial lymph nodes. Recurrence of an autoinflammatory disease was then suspected. Imaging studies performed at previous examinations were therefore reevaluated with nuclear medicine and immunology experts. F-fluorodeoxyglucose (FDG) PET showed a homogeneous, widespread, intense uptake in bone marrow of spine (arrowheads; Fig. A–C), pelvis (stars; Fig. A and E), ribs (circles; Fig. C), and sternum and shoulder girdle (arrows; Fig. D), with amaximum standardized uptake value of up to 3.6 ± 0.4, mimicking a lymphoma, with a normal morphological aspect at coregistered computed tomography.
Biological characterization of Euscelidius variegatus iflavirus 1

Virus-based biocontrol technologies represent sustainable alternatives to pesticides and insecticides. Phytoplasmas are prokaryotic plant pathogens causing severe losses to crops worldwide. Novel approaches are needed since insecticides against their insect vectors and rogueing of infected plants are the only available strategies to counteract phytoplasma diseases. A new iflavirus, named EVV-1, has been described in the leafhopper phytoplasma vector Euscelidius variegatus, raising the potential to use virus-based application strategies against phytoplasma disease. Here transmission routes of EVV-1 are characterized, and localization within the host reveals the mechanism of insect tolerance to virus infection. Both vertical and horizontal transmission of EVV-1 occur and vertical transmission was more efficient. The virus is systemic and occurs in all life-stages, with the highest loads measured in ovaries and first to third instar nymphs. The basic knowledge gained here on the biology of the virus is crucial for possible future application of iflaviruses as biocontrol agents.
Synthesis and Binding of Mannose-Specific Synthetic Carbohydrate Receptors.

Synthetic Carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C 2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and 5 biologically relevant C 1 -O-octyloxy glycans, α/β-glucoside ( α/β-Glc ), α/β-mannoside ( α/β-Man ), and β-galactoside ( β-Gal ), was studied by mass spectrometry, 1 H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to β-Glc . SCR019 (3-indole) binds only to β-Man. SCR020 (2-pyridine) binds β-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and β-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center perpendicular, and off-center. Many host•guest combinations formed higher stoichiometry complexes, 2:1 glycan•SCR or 1:2 glycan•SCR , where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts.