Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidental Findings Suggestive of COVID-19 in Asymptomatic Patients Undergoing Nuclear Medicine Procedures in a High-Prevalence Region

Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may remain asymptomatic, leading to under-recognition of the related disease, coronavirus disease, 2019 (COVID-19), and to incidental findings in nuclear imaging procedures performed for standard clinical indications. Here, we report about our local experience in a region with high COVID-19 prevalence and dynamically increasing infection rates. Methods: Within the 8-d period of March 16–24, 2020, hybrid imaging studies of asymptomatic patients who underwent 18F-FDG PET/CT or 131I SPECT/CT for standard oncologic indications at our institution in Brescia, Italy, were analyzed for findings suggestive of COVID-19. The presence, radiologic features, and metabolic activity of interstitial pneumonia were identified, correlated with the subsequent short-term clinical course, and described in a case series. Results: Six of 65 patients (9%) who underwent PET/CT for various malignancies showed unexpected signs of interstitial pneumonia on CT and elevated regional 18F-FDG avidity. Additionally, 1 of 12 patients who received radioiodine for differentiated thyroid carcinoma also showed interstitial pneumonia on SPECT/CT. Five of 7 patients had subsequent proof of COVID-19 by reverse-transcriptase polymerase chain reaction. The remaining 2 patients were not tested immediately but underwent quarantine and careful monitoring. Conclusion: Incidental findings suggestive of COVID-19 may not be infrequent in hybrid imaging of asymptomatic patients in regions with an expansive spread of SARS-CoV-2. Nuclear medicine services should prepare accordingly.
A Retrospective Observational Study

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods:Medical records were collected of 85 fatal cases of COVID19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratorydistress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-a2b, respectively. Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptomforCOVID-19exacerbations. Eosinophilopenia may indicateapoorprognosis.Acombinationofantimicrobialdrugsdid not offer considerable benefit to the outcome of this group of patients.
Improvement of Cecal Commensal Microbiome Following the Insect Additive into Chicken Diet

Simple Summary Throughout their lifecycle, insects can be a rich source of many valuable nutrients and biologically active components. It was demonstrated that the additive of Tenebrio molitor (TM) and Zophobas morio (ZM) into broiler chicken diet can have a positive effect on their growth parameters as well as some microbial composition in the gastrointestinal tract (GIT). Therefore, the present study evaluated the effect of diet with the addition of Tenebrio molitor and Zophobas morio (0.2 and 0.3%) on the cecal microbiome in broilers. The addition of 0.2% ZM compared to the negative control (NC) group resulted in an increase in relative abundance of the Actinobacteria, including the family Bifidobacteriaceae, with the highest relative abundance of genus Bifidobacterium pseudolongum. The addition of 0.2% ZM resulted in an increase in the number of Lactobacillus agilis. The highest relative abundance of the family Ruminococcaceae was observed in the 0.2 TM group together with Lactobacillus reuteri but with no significant differences. Furthermore, a significant level of Clostridia was observed in the 0.2 TM group. A relatively small addition of Tenebrio molitor and Zophobas morio to broiler diet can modulate commensal and probiotic microbiome composition in the cecum and increase the relative abundance of positive bacteria to have a positive impact on gut health of broilers. Abstract Gastrointestinal microbiota play an important role in regulating the metabolic processes of animals and humans. A properly balanced cecal microbiota modulates growth parameters and the risk of infections. The study examined the effect of the addition of 0.2% and 0.3% of Tenebrio molitor and Zophobas morio on cecal microbiome of broilers. The material was the cecum digesta. The obtained DNA was analyzed using 16S rRNA next generation sequencing. The results of the study show that the addition of a relatively small amount of Z. morio and T. molitor modulates the broiler cecum microbiome composition. The most positive effect on cecal microbiota was recorded in the 0.2% Z. morio diet. A significant increase in the relative amount of genus Lactobacillus, represented by the species Lactobacillus agilis and the amount of bacteria in the Clostridia class, was observed. Moreover, the addition of 0.2% ZM resulted in a significant increase of relative abundance of the family Bifidobacteriaceae with the highest relative abundance of genus Bifidobacterium pseudolongum. The obtained results indicate that the addition of a relatively small amount of insect meal in broiler diet stimulates colonization by probiotic and commensal bacteria, which may act as barriers against infection by pathogenic bacteria.
A New Family of Iron(II)-Cyclopentadienyl Compounds Shows Strong Activity against Colorectal and Triple Negative Breast Cancer Cells

A family of compounds with the general formula [Fe(η5-C5H5)(CO)(PPh3)(NCR)]+ has been synthesized (NCR = benzonitrile (1); 4-hydroxybenzonitrile (2); 4-hydroxymethylbenzonitrile (3); 4-aminobenzonitrile (4); 4-bromobenzonitrile (5); and, 4-chlorocinnamonitrile (6)). All of the compounds were obtained in good yields and were completely characterized by standard spectroscopic and analytical techniques. Compounds 1, 4, and 5 crystallize in the monoclinc P21/c space group and packing is determined by short contacts between the phosphane phenyl rings and cyclopentadienyl (compounds 1 and 4) or π-π lateral interactions between the benzonitrile molecules (complex 5). DFT and TD-DFT calculations were performed to help in the interpretation of the experimental UV-Vis. data and assign the electronic transitions. Cytotoxicity studies in MDA-MB-231 breast and SW480 colorectal cancer-derived cell lines showed IC50 values at a low micromolar range for all of the compounds in both cell lines. The determination of the selectivity index for colorectal cells (SW480 vs. NCM460, a normal colon-derived cell line) indicates that the compounds have some inherent selectivity. Further studies on the SW480 cell line demonstrated that the compounds induce cell death by apoptosis, inhibit proliferation by inhibiting the formation of colonies, and affect the actin-cytoskeleton of the cells. These results are not observed for the hydroxylated compounds 2 and 3, where an alternative mode of action might be present. Overall, the results indicate that the substituent at the nitrile-based ligand is associated to the biological activity of the compounds.
Determining the Influencing Factors of Biogas Technology Adoption Intention in Pakistan: The Moderating Role of Social Media

Environmental degradation and rapid climate change have forced researchers and practitioners to find sustainable practices to save the world. Increasing energy demand is not only consuming scarce natural resources, but also damaging the climate and overall ecosystem. In this regard, biogas technology is beneficial in two ways—by meeting the energy demand and saving natural resources. Pakistan is an agricultural country and has a high potential for producing energy through biogas technology. Therefore, this study aims to find farmers’ intentions of adopting biogas technology in Pakistan by employing the extended norm activation model. Furthermore, the moderating role of social media was explored. Purposive sampling was used to collect data from farmers and results were extracted by using Partial least square structural equation modelling software. The results suggest that awareness of consequences, ascription of responsibility, environmental concern and perceived consumer effectiveness positively and significantly influence personal norms of the farmers. Consequently, personal norms affect farmers’ intentions of adopting biogas technology in Pakistan. The moderating role of social media was also confirmed by the results. This study considers the notable insights of biogas technology adoption in Pakistan. Finally, the limitations of the study and suggestions for future research are discussed.
Translating the promise of 5HT4 receptor agonists for the treatment of depression

Abstract Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.
Predictive Validity of a New Instrumental Activities of Daily Living Scale for Detecting the Incidence of Functional Disability among Community-Dwelling Older Japanese Adults: A Prospective Cohort Study

We examined the predictive validity of a newly developed scale—the National Center for Geriatrics and Gerontology Activities of Daily Living (NCGG-ADL)—to measure instrumental activities of daily living (IADL) ability. We tested the scale for detecting new incidences of functional disability among community-dwelling older Japanese adults. Participants were 2708 older adults (mean age = 79.0 years, 51.6% women) living in the community who had no functional decline at baseline. We assessed IADL ability using the NCGG-ADL scale, comprising 13 self-report questions. Next, we assessed their functional disability monthly for 24 months, based on the national long-term care insurance (LTCI) system. Among all participants, 430 (15.9%) had an IADL limitation at baseline, and 289 (10.7%) were newly certified as functionally disabled. Participants scoring ≤ 12 of 13 points in the NCGG-ADL showed a significantly higher risk of functional disability than did those scoring 13 points, even after adjusting for covariates (hazard ratio [95% confidence interval] = 1.58 [1.19–2.09]). We thus validated the NCGG-ADL as a screening tool for assessing the risk of functional disability among community-dwelling older Japanese adults. We conclude that IADL limitations, as measured by the NCGG-ADL, could be useful predictors of functional disability.
Progress and Prospects on Vaccine Development against SARS-CoV-2

In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.
Staging and Personalized Intervention for Infection and Sepsis.

Background: Sepsis is defined as a dysregulated host response to infection, resulting in life-threatening organ dysfunction. It is now understood that this dysregulation not only constitutes excessive inflammation, but also sustained immune suppression. Immune-modulatory therapies thus have great potential for novel sepsis therapies. Here, we provide a review of biomarkers and functional assays designed to immunologically stage patients with sepsis as well as therapies designed to alter the innate and adaptive immune systems of patients with sepsis beneficially. Methods: A search of PubMed/MEDLINE and clinicaltrials.gov was performed between October 1, 2019 and December 22, 2019 using search terms such as "sepsis immunotherapy," "sepsis biomarkers," "sepsis clinical trials," and variations thereof. Results: Despite more than 30 years of research, there is still no Food and Drug Administration (FDA)-cleared biomarker that has proven to be effective in either identifying patients with sepsis who are at an increased risk of adverse outcomes or responsive to specific interventions. Similarly, past clinical trials investigating new treatment strategies have rarely stratified patients with sepsis. Overall, the results of these trials have been disappointing. Novel efforts to properly gauge an individual patient's immune response and choose an appropriate immunomodulatory agent based on the results are underway. Conclusion: Our evolving understanding of the different mechanisms perturbing immune homeostasis during sepsis strongly suggests that future successes will depend on finding the right therapy for the right patient and administering it at the right time. For such a personalized medicine approach, novel biomarkers and functional assays to properly stage the patient with sepsis will be crucial. The growing repertoire of immunomodulatory agents at our disposal, as well as re-appraisal of agents that have already been tested in unstratified cohorts of patients with sepsis, may finally translate into successful treatment strategies for sepsis.
Secretome-Mediated Interactions with Intestinal Epithelial Cells: A Role for Secretome Components from Lactobacillus rhamnosus R0011 in the Attenuation of Salmonella enterica Serovar Typhimurium Secretome and TNF-α–Induced Proinflammatory Responses

Key Points Lactobacillus and Salmonella secretomes differentially impact IEC immune activity. LrS induces DUSP1, ATF3, and TRIB3 expression in STS- and TNF-α–challenged IEC. LrS induces MIF and attenuates proinflammatory mediator induction by STS or TNF-α. Recent evidence suggests that lactic acid bacteria communicate with host cells via secretome components to influence immune responses but less is known about gut-pathogen secretomes, impact of lactic acid bacteria secretomes on host–pathogen interactions, and the mechanisms underlying these interactions. Genome-wide microarrays and cytokine profiling were used to interrogate the impact of the Lactobacillus rhamnosus R0011 secretome (LrS) on TNF-α and Salmonella enterica subsp. enterica serovar Typhimurium secretome (STS)–induced outcomes in human intestinal epithelial cells. The LrS attenuated both TNF-α– and STS-induced gene expression involved in NF-κB and MAPK activation, as well as expression of genes involved in other immune-related signaling pathways. Specifically, the LrS induced the expression of dual specificity phosphatase 1 (DUSP1), activating transcription factor 3 (ATF3), and tribbles pseudokinase 3 (TRIB3), negative regulators of innate immune signaling, in HT-29 intestinal epithelial cells challenged with TNF-α or STS. TNF-α– and STS-induced acetylation of H3 and H4 histones was attenuated by the LrS, as was the production of TNF-α– and STS-induced proinflammatory cytokines and chemokines. Interestingly, the LrS induced production of macrophage migration inhibitory factor (MIF), a cytokine involved in host–microbe interactions at the gut interface. We propose that the LrS attenuates proinflammatory mediator expression through increased transcription of negative regulators of innate immune activity and changes in global H3 and H4 histone acetylation. To our knowledge, these findings provide novel insights into the complex multifaceted mechanisms of action behind secretome-mediated interdomain communication at the gut-mucosal interface.
Changes in Disease Activity and Damage Over Time in Patients With Morphea.

Importance Prospective studies of the disease course in patients with morphea are lacking, particularly those comparing adults and children. Objective To investigate the disease course in patients with morphea treated with standard-of-care therapy using validated clinical outcome measures. Design, Setting, and Participants Prospective cohort study of 130 adults and children from the Morphea in Adults and Children cohort with at least 2 years of clinical follow-up and Localized Scleroderma Cutaneous Assessment Tool scores recorded at each study visit. Study patients were seen at a tertiary referral center (UT Southwestern Medical Center, Dallas, Texas) from November 1, 2008, through April 1, 2016. The dates of analysis were May 2016 through July 2019. Exposures All patients received standard-of-care therapy. Main Outcomes and Measures Patterns in disease activity and recurrence were examined. The time to recurrence of morphea disease activity from the first visit with inactive disease was assessed using survival analysis with the log-rank test to compare differences between morphea subtypes. Results In total, 130 adults and children (663 study visits) were included in this study. The mean (SD) age of patients was 34.4 (23.8) years, and 101 of 130 (78%) were female. The mean (SD) follow-up was 4.3 (1.7) years. Fifty patients had at least 5 years of follow-up. Most patients were white individuals (96 of 130 [74%]) and had linear subtype (72 of 130 [55%]) or generalized subtype (40 of 130 [31%]). Overall, 13 of 30 (43%) with generalized subtype had recurrence of disease activity compared with 14 of 66 (21%) with linear subtype (hazard ratio, 3.28; 95% CI, 1.38-7.79). The median (interquartile range) time to first recurrence of disease activity after initial resolution of disease activity was 1.1 (0.8-1.9) years for generalized subtype and 2.3 (1.0-3.3) years for linear subtype. Of the 50 patients followed up for at least 5 years, 18 (36%) had recurrence of disease activity. Conclusions and Relevance Disease activity appeared to improve in most patients with morphea over 6 to 12 months using previously published treatment plans, underscoring their effectiveness. Sclerosis improved more slowly (over 2-5 years), often after discontinuation of treatment, but atrophy increased slightly as sclerosis subsided. Standard-of-care therapy appears to improve disease activity, which allows sclerosis to improve, and provides relative stability of other features of disease damage. A substantial number of patients, particularly those with generalized subtype, have a relapsing-remitting course over many years. Patients with morphea should be monitored for recurrent disease activity over extended periods.
How Psychosocial Factors Contribute to Japanese Older Adults’ Initiation of Advance Care Planning Discussions: A Qualitative Study

Objectives: This study aimed to reveal the features of older adults’ advance care planning (ACP) discussions by identifying psychosocial factors related to their discussions in Japan, where people value family-centered decision making. Methods: A qualitative study using in-depth interviews was conducted with 39 participants (aged ≥65 years) recruited from the outpatient department of a community hospital in Fukushima, Japan. Data were analyzed using the grounded theory approach. Results: Through experiences of family caregiving, participants became aware of their own feelings about the end of life. Equal relationship with family members was important for lowering the threshold for having discussions. Some participants and their families in the same generation reached agreements on ACP; however, they were willing to yield to children’s decision making despite these discussions. Discussions: These findings provide insights into the psychosocial factors in relation to ACP discussions and support for the role of ACP discussions in the family-centered decision-making culture.
Evaluation of partial oral antibiotic treatment for persons who inject drugs and are hospitalized with invasive infections.

BACKGROUND Persons who inject drugs (PWID) are at risk for invasive infections; however, hospitalizations to treat these infections are frequently complicated by against medical advice (AMA) discharges. This study compared outcomes among 1) PWID who completed a full course of inpatient intravenous (IV) antibiotics, 2) PWID who received a partial course of IV antibiotics but were not prescribed any antibiotics on AMA discharge, and 3) PWID who received a partial course of IV antibiotics and were prescribed oral antibiotics on AMA discharge. METHODS Retrospective, cohort study of PWID aged 18 years or older admitted to a tertiary referral center between 01/2016 and 07/2019, who received an Infectious Diseases consultation for an invasive bacterial or fungal infection. RESULTS 293 PWID were included in the study. 90-day all cause readmission rates were highest among PWID who did not receive oral antibiotic therapy on AMA discharge (n=46, 68.7%), compared with inpatient IV (n=43, 31.5%) and partial oral antibiotics (n=27, 32.5%). In a multivariate analysis, 90-day readmission risk was higher among PWID who did not receive oral antibiotic therapy on AMA discharge [adjusted hazard ratio (aHR)=2.32; 95% confidence interval (CI) 1.41 - 3.82] and not different among PWID prescribed oral antibiotic therapy on AMA discharge (aHR=0.99; 95% CI 0.62-1.62). Surgical source control (aHR=0.57; 95% CI 0.37 - 0.87) and addiction medicine consultation (aHR=0.57; 95% CI 0.38 - 0.86) were both associated with reduced readmissions. CONCLUSIONS Our single center study suggests access to oral antibiotic therapy for PWID who cannot complete prolonged inpatient IV antibiotic courses is beneficial.
A novel heterozygous HTRA1 mutation is associated with autosomal dominant hereditary cerebral small vessel disease

We investigated whether a heterozygous mutation that we newly identified in HTRA1 (high‐temperature requirement serine protease A1 gene) in a pedigree with autosomal dominant hereditary cerebral small vessel disease (SVD) reduces the function of HTRA1 and affects the transforming growth factor‐β1 (TGF‐β1)/Smad signaling.