Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model

The protocol used to induce cell death for generating vaccines from whole tumor cells is a critical consideration that impacts vaccine efficacy. Here we compared how different protocols used to induce cell death impacted protection provided by a prophylactic whole tumor cell vaccine in a mouse melanoma model. We found that melanoma cells exposed to γ-irradiation or lysis combined with UV-irradiation (LyUV) provided better protection against tumor challenge than lysis only or cells exposed to UV-irradiation. Furthermore, we found that the immunoregulatory cytokine, IL-27 enhanced protection against tumor growth in a dose-dependent manner when combined with either LyUV or γ-irradiated whole tumor cell vaccine preparations. Taken together, this data supports the use of LyUV as a potential protocol for developing whole tumor cell prophylactic cancer vaccines. We also showed that IL-27 can be used at low doses as a potent adjuvant in combination with LyUV or γ-irradiation treated cancer cells to improve the protection provided by a prophylactic cancer vaccine in a mouse melanoma model.
Detecting COVID-19 Opacity in X-ray Images Using YOLO and RetinaNet Ensemble

Coronavirus disease(COVID-19) is caused by SARS-COV-2 virus and has been declared as a pandemic. After almost two years of this pandemic, over five million people have lost their lives worldwide due to complications like pneumonia and acute respiratory distress syndrome. Many countries have already witnessed the second wave of pandemic and a huge loss of lives. One way to curb the disease spread is by timely and accurate diagnosis. X-rays and CT-scans can help a radiologist to detect the disease, but detecting COVID-19 on chest radiographs can become challenging as it has similarities with other bacterial and viral pneumonias. Hence, there is a need to develop an algorithm for accurate and fast detection of COVID-19 in a patient. This work showcases the use of object detection deep learning models-You Only Look Once (YOLO) and RetinaNet for accurate localization of regions associated with COVID-19. Proposed method using ensemble of both the models achieves a mean average precision (mAP) score of 0.552, offering an improvement over their individual predictions.
Case Report: Successful Reperfusion of Pulmonary Thromboembolism Using tPA in a Cat

Pulmonary thromboembolism is a potentially life threatening condition that is uncommonly recognized in cats. Thrombolytic agents have been described as a treatment for this condition in human and canine patients, particularly in cases where hemodynamic instability is persistent despite supportive care. This report describes the clinical course, echocardiographic diagnosis, and successful thrombolysis of a cat with pulmonary thromboembolism. Despite confirmed reperfusion, the cat succumbed to thromboembolic disease highlighting the dearth of knowledge about optimal treatment of this disease process in small animals, particularly in cats.
Concurrent TMS-fMRI: Technical Challenges, Developments, and Overview of Previous Studies

Transcranial magnetic stimulation (TMS) is a promising treatment modality for psychiatric and neurological disorders. Repetitive TMS (rTMS) is widely used for the treatment of psychiatric and neurological diseases, such as depression, motor stroke, and neuropathic pain. However, the underlying mechanisms of rTMS-mediated neuronal modulation are not fully understood. In this respect, concurrent or simultaneous TMS-fMRI, in which TMS is applied during functional magnetic resonance imaging (fMRI), is a viable tool to gain insights, as it enables an investigation of the immediate effects of TMS. Concurrent application of TMS during neuroimaging usually causes severe artifacts due to magnetic field inhomogeneities induced by TMS. However, by carefully interleaving the TMS pulses with MR signal acquisition in the way that these are far enough apart, we can avoid any image distortions. While the very first feasibility studies date back to the 1990s, recent developments in coil hardware and acquisition techniques have boosted the number of TMS-fMRI applications. As such, a concurrent application requires expertise in both TMS and MRI mechanisms and sequencing, and the hurdle of initial technical set up and maintenance remains high. This review gives a comprehensive overview of concurrent TMS-fMRI techniques by collecting (1) basic information, (2) technical challenges and developments, (3) an overview of findings reported so far using concurrent TMS-fMRI, and (4) current limitations and our suggestions for improvement. By sharing this review, we hope to attract the interest of researchers from various backgrounds and create an educational knowledge base.
Psychosocial Safety Climate Moderates the Effect of Demands of Hospital Accreditation on Healthcare Professionals: A Longitudinal Study

Hospital accreditation has been studied comprehensively, yet few studies have observed its impacts on the burnout and work engagement levels of frontline healthcare professionals (HCPs). With a sample of 121 HCPs working in the United Arab Emirates' public hospitals, this study used a two-wave, cross-lagged panel design to examine the direct effects of job demands and job resources during hospital accreditations on burnout and work engagement and the moderating roles of psychosocial safety climate (PSC) on burnout and work engagement 3 months after accreditation. The data were analyzed using moderated structural equation modeling. As expected, we found that job demands (i.e., accreditation demands) had a direct effect on burnout, while job resources (i.e., social support) predicted work engagement. PSC moderated both relationships; however, it was not able to directly predict burnout or work engagement. Findings from this study show a positive relationship between accreditation demands and HCPs' health. Future research needs to examine the link between PSC and job demands-resources concepts before and after hospital accreditation more closely by using multiple time points to assess the causality relationships between predictor and outcome variables.
Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects

Objective: Omadacycline is a new type of aminomethylcycline antibiotic, having a broad antibacterial spectrum. But the pharmacokinetic characteristics and safety profile of the Chinese population remain unknown. It is also unclear whether the US-approved treatment regimen is applicable for the Chinese population. Methods: In a randomized, double-blinded, placebo-controlled dose-escalated trial, the pharmacokinetics of omadacycline was evaluated by a non-compartmental and compartmental model. Monte Carlo simulations were performed using the pharmacokinetic data from the Chinese population to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the US FDA-approved dose regimen. Results: The three-compartment model successfully described the rapid distribution and slow elimination of omadacycline after the intravenous infusion (i.v.). The double-peak concentration-time curve of the oral absorption (p.o.) was explained by the two-compartment model with two absorption compartments. The steady-state AUC of 100 mg omadacycline i.v. and 300 mg omadacycline p. o. were 12.1 and 19.4 mg h/L, respectively. Pharmacokinetics/pharmacodynamics (PK/PD) analysis showed that the omadacycline dosing regimen with a loading dose (200 mg i.v. q24 h, 100 mg i.v. q12 h, 450 mg p. o. q24 h × 2 days or 300 mg p. o. q12 h) and maintenance dose (100 mg i.v. q24 h or 300 mg p. o. q24 h) could cover the main pathogens of the indications acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP): Staphylococcus aureus and Streptococcus pneumoniae. Also, omadacycline had showed a good safety profile in the Chinese population. Conclusions: With the evidence provided, omadacycline could be a novel treatment option to Chinese patients with ABSSSI and CABP.
Identification of Pseudomonas aeruginosa From the Skin Ulcer Disease of Crocodile Lizards (Shinisaurus crocodilurus) and Probiotics as the Control Measure

The crocodile lizard (Shinisaurus crocodilurus) is an endangered ancient reptile species. Captive breeding is an important conservation measure for the potential restoration and recovery of their wild populations. However, a skin ulcer disease caused by an unknown pathogen has become a serious threat to captive breeding individuals. In the current study, based on microbial isolation, we identified Pseudomonas aeruginosa as the dominant pathogen in skin ulcer disease. Chinese skinks (Plestiodon chinensis) were used to verify the pathogenicity of P. aeruginosa in skin ulcer disease in vivo. As expected, subcutaneous inoculation of P. aeruginosa induced skin disease in healthy skinks and P. aeruginosa was re-isolated from the induced skin ulcers. Therefore, P. aeruginosa, an opportunistic and ubiquitous pathogen that causes a wide range of infections, appears to be the main pathogen of the skin disease affecting crocodile lizards. In the aquaculture industry, probiotics are widely used in the prevention and control of animal diseases caused by such pathogens. Here, we administered probiotics to the breeding crocodile lizards for 6 months. The three experiment groups treated with different kinds of probiotics showed significance at controlling case incidence. Three of the four groups treated with probiotics showed significant disease prevention (Effective Microorganisms mixed probiotics P = 0.0374; Double-dose Effective Microorganisms, P = 0.0299; Bacillus subtilis, P = 0.0140, T-test), and CFUs in the water of the breeding enclosures were also inhibited after probiotics usage (P < 0.001, T-test). Our study demonstrated the role of Pseudomonas aeruginosa in development of skin ulcer disease of crocodile lizards in a local zoo and offered the probiotic-based method for control measurements, which would be of benefit for the conservation of endangered reptiles.
Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience

Biological aging is the single most important risk factor for disease, disability, and ultimately death in geriatric dogs. The effects of aging in companion dogs also impose significant financial and psychological burdens on their human caregivers. The underlying physiologic processes of canine aging may be occult, or early signs of aging may be ignored because of the misconception that biological aging is natural and therefore inevitable. The ability to detect, quantify, and mitigate the deleterious processes of canine aging would greatly enhance veterinary preventative medicine and animal welfare. In this paper we propose a new conceptual framework for aging in dogs, the Canine Geriatric Syndrome (CGS). CGS consists of the multiple, interrelated physical, functional, behavioral, and metabolic changes that characterize canine aging as well as the resulting clinical manifestations, including frailty, diminished quality of life, and age-associated disease. We also identify potential key components of a CGS assessment tool, a clinical instrument that would enable veterinarians to diagnose CGS and would facilitate the development and testing of interventions to prolong healthspan and lifespan in dogs by directly targeting the biological mechanisms of aging. There are many gaps in our knowledge of the mechanisms and phenotype of aging in dogs that must be bridged before a CGS assessment tool can be deployed. The conceptual framework of CGS should facilitate identifying these gaps and should stimulate research to better characterize the processes and effects of aging in dogs and to identify the most promising preventative strategies to target these.
Trabecular Bone Score and Osteoprotegerin as Useful Tools in the Assessment of Bone Deterioration in Acromegaly

Purpose This study aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) in 61 patients from the acromegaly group (AG) with regard to the activity of the disease in comparison to 42 patients—control group (CG). We also analyzed selected bone markers and their association with BMD and TBS. Materials and Methods Lumbar spine and femoral neck BMD measurements were performed. TBS values were obtained. Serum concentrations of selected bone markers, including osteoprotegerin (OPG), were measured. Results We revealed a difference in TBS values between the AG and CG as well as between the TCA (treatment-controlled acromegaly) vs. CG and TCA+CA (cured acromegaly) vs. CG. We did not observe any statistically significant difference in BMD. OPG had a lower concentration in the CG compared to the AG. TBS correlated negatively with OPG in the AG (r = −0.31, p = 0.01) and in the TCA+ CA group (r = −0.3, p = 0.01). Conclusions The acromegalic patients have altered bone microstructure as indicated by the decreased TBS regardless of the activity of the disease and BMD. OPG could be a marker of the destruction of the bone microstructure, but further studies are needed.
Tip110/SART3-Mediated Regulation of NF-κB Activity by Targeting IκBα Stability Through USP15

To date, there are a small number of nuclear-restricted proteins that have been reported to play a role in NF-κB signaling. However, the exact molecular mechanisms are not fully understood. Tip110 is a nuclear protein that has been implicated in multiple biological processes. In a previous study, we have shown that Tip110 interacts with oncogenic ubiquitin specific peptidase 15 (USP15) and that ectopic expression of Tip110 leads to re-distribution of USP15 from the cytoplasm to the nucleus. USP15 is known to regulate NF-κB activity through several mechanisms including modulation of IκBα ubiquitination. These findings prompted us to investigate the role of Tip110 in the NF-κB signaling pathway. We showed that Tip110 regulates NF-κB activity. The expression of Tip110 potentiated TNF-α-induced NF-κB activity and deletion of the nuclear localization domain in Tip110 abrogated this potentiation activity. We then demonstrated that Tip110 altered IκBα phosphorylation and stability in the presence of TNF-α. Moreover, we found that Tip110 and USP15 opposingly regulated NF-κB activity by targeting IκBα protein stability. We further showed that Tip110 altered the expression of NF-κB-dependent proinflammatory cytokines. Lastly, by using whole-transcriptome analysis of Tip110 knockout mouse embryonic stem cells, we found several NF-κB and NF-κB-related pathways were dysregulated. Taken together, these findings add to the nuclear regulation of NF-κB activity by Tip110 through IκBα stabilization and provide new evidence to support the role of Tip110 in controlling cellular processes such as cancers that involve proinflammatory responses.
Molecular and Brain Volume Changes Following Aerobic Exercise, Cognitive and Combined Training in Physically Inactive Healthy Late-Middle-Aged Adults: The Projecte Moviment Randomized Controlled Trial

Behavioral interventions have shown promising neuroprotective effects, but the cascade of molecular, brain and behavioral changes involved in these benefits remains poorly understood. Projecte Moviment is a 12-week (5 days per week—45 min per day) multi-domain, single-blind, proof-of-concept randomized controlled trial examining the cognitive effect and underlying mechanisms of an aerobic exercise (AE), computerized cognitive training (CCT) and a combined (COMB) groups compared to a waitlist control group. Adherence was > 80% for 82/109 participants recruited (62% female; age = 58.38 ± 5.47). In this study we report intervention-related changes in plasma biomarkers (BDNF, TNF-α, HGF, ICAM-1, SDF1-α) and structural-MRI (brain volume) and how they related to changes in physical activity and individual variables (age and sex) and their potential role as mediators in the cognitive changes. Our results show that although there were no significant changes in molecular biomarker concentrations in any intervention group, changes in ICAM-1 and SDF1-α were negatively associated with changes in physical activity outcomes in AE and COMB groups. Brain volume changes were found in the CCT showing a significant increase in precuneus volume. Sex moderated the brain volume change in the AE and COMB groups, suggesting that men may benefit more than women. Changes in molecular biomarkers and brain volumes did not significantly mediate the cognitive-related benefits found previously for any group. This study shows crucial initial molecular and brain volume changes related to lifestyle interventions at early stages and highlights the value of examining activity parameters, individual difference characteristics and using a multi-level analysis approach to address these questions.
Content Analysis of Warning Signs Identified as Part of Crisis Response Planning in a Community Sample of Gun Owners and Non-owners

Background Assessing for and identifying those at imminent risk for suicide continues to present challenges, especially as many who die do not interact with specialty mental health treatment preceding suicide. Suicide-specific interventions in healthcare settings have been found to improve suicide-related outcomes, yet little is known about the confluence of behavioral, cognitive, emotional, and physiological indicators of emotional distress as they correspond to other key risk characteristics and high-risk groups like gun owners. Aim The purpose of this content analysis was to examine self-identified warning signs of distress between gun owners and non-owners through crisis response planning (CRP). Methods Participants completed a collaborative CRP. Warning signs were categorized as being either behavioral, cognitive, emotional, or physiological in nature. Bivariate logistic regression models were used to examine associations between firearm ownership and variables of interest. Participants were evenly split between men (n = 44) and women (n = 44) and were predominantly white (67.1%) with a mean age of 35.9 (SD = 13.6). Results Emotional warning signs of distress (68.2%) were reported slightly more often than behavioral (65.9%) followed by physiological (52.3%), and cognitive (46.6%). Firearm owners were significantly more likely to be male (OR = 2.5, 95%CI [1.07–6.0]). All participants were about a fourth as likely to report both a behavioral and physiological warning sign concurrently (OR = 0.26, 95% CI [0.09–0.67]). Conclusion Similarities and departures in warning signs of emotional distress may inform future research exploring both self-reported warning signs and related self-management strategies identified through suicide-specific interventions, particularly among high-risk groups such as gun owners.
Incorporating Blood Flow in Nerve Injury and Regeneration Assessment

Peripheral nerve injury is a significant public health challenge, with limited treatment options and potential lifelong impact on function. More than just an intrinsic part of nerve anatomy, the vascular network of nerves impact regeneration, including perfusion for metabolic demands, appropriate signaling and growth factors, and structural scaffolding for Schwann cell and axonal migration. However, the established nerve injury classification paradigm proposed by Sydney Sunderland in 1951 is based solely on hierarchical disruption to gross anatomical nerve structures and lacks further information regarding the state of cellular, metabolic, or inflammatory processes that are critical in determining regenerative outcomes. This review covers the anatomical structure of nerve-associated vasculature, and describes the biological processes that makes these vessels critical to successful end-organ reinnervation after severe nerve injuries. We then propose a theoretical framework that incorporates measurements of blood vessel perfusion and inflammation to unify perspectives on all mechanisms of nerve injury.
Ovarian Strumal Carcinoid: Case Report, Systematic Literature Review and Pooled Analysis

Background Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy. Methods We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: “strumal carcinoid of the ovary”, “strumal carcinoid case report”. A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included. Results Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained. Conclusion Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.