Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive characterization of the bacterial community structure and metabolite composition of food waste fermentation products via microbiome and metabolome analyses

Few studies have characterized the microbial community and metabolite profile of solid food waste fermented products from centralized treatment facilities, which could potentially be processed into safe animal feeds. In this study, 16S rRNA gene sequencing and liquid/gas chromatography-mass spectrometry were conducted to investigate the bacterial community structure and metabolite profile of food waste samples inoculated with or without 0.18% of a commercial bacterial agent consisting of multiple unknown strains and 2% of a laboratory-made bacterial agent consisting of Enterococcus faecalis, Bacillus subtilis and Candida utilis. Our findings indicated that microbial inoculation increased the crude protein content of food waste while reducing the pH value, increasing lactic acid production, and enhancing aerobic stability. Microbial inoculation affected the community richness, community diversity, and the microbiota structure (the genera with abundances above 1.5% in the fermentation products included Lactobacillus (82.28%) and Leuconostoc (1.88%) in the uninoculated group, Lactobacillus (91.85%) and Acetobacter (2.01%) in the group inoculated with commercial bacterial agents, and Lactobacillus (37.11%) and Enterococcus (53.81%) in the group inoculated with homemade laboratory agents). Microbial inoculation reduced the abundance of potentially pathogenic bacteria. In the metabolome, a total of 929 substances were detected, 853 by LC-MS and 76 by GC-MS. Our results indicated that inoculation increased the abundance of many beneficial metabolites and aroma-conferring substances but also increased the abundance of undesirable odors and some harmful compounds such as phenol. Correlation analyses suggested that Leuconostoc, Lactococcus, and Weissella would be promising candidates to improve the quality of fermentation products. Taken together, these results indicated that inoculation could improve food waste quality to some extent; however, additional studies are required to optimize the selection of inoculation agents.
Rasa3 deficiency minimally affects thrombopoiesis but promotes severe thrombocytopenia due to integrin-dependent platelet clearance

Platelet homeostasis is dependent on a tight regulation of both platelet production and clearance. The small GTPase Rap1 mediates platelet adhesion and hemostatic plug formation. However, Rap1 signaling is also critical for platelet homeostasis as both Rap1 deficiency and uninhibited Rap1 signaling lead to marked thrombocytopenia in mice. Here, we investigated the mechanism by which deficiency in Rasa3, a critical negative regulator of Rap1, causes macrothrombocytopenia in mice. Despite marked morphological and ultrastructural abnormalities, megakaryocytes in hypomorphic Rasa3hlb/hlb (R3hlb/hlb) or Rasa3–/– mice demonstrated robust proplatelet formation in vivo, suggesting that defective thrombopoiesis is not the main cause of thrombocytopenia. Rather, we observed that R3hlb/hlb platelets became trapped in the spleen marginal zone/red pulp interface, with evidence of platelet phagocytosis by macrophages. Clearance of mutant platelets was also observed in the liver, especially in splenectomized mice. Platelet count and platelet life span in Rasa3-mutant mice were restored by genetic or pharmacological approaches to inhibit the Rap1/talin1/αIIbβ3 integrin axis. A similar pattern of splenic clearance was observed in mice injected with anti-αIIbβ3 but not anti–glycoprotein Ibα platelet-depleting antibodies. In summary, we describe a potentially novel, integrin-based mechanism of platelet clearance that could be critical for our understanding of select inherited and acquired thrombocytopenias.
Incidence of an Insulin-Requiring Hyperglycemic Syndrome in SARS-CoV-2–Infected Young Individuals: Is It Type 1 Diabetes?

Pancreatic ACE2 receptor expression, together with increased prevalence of insulin-requiring hyperglycemia in patients with coronavirus disease 2019 (COVID-19), suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pancreatic infection might trigger a β-cell–selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in patients with COVID-19 inside a large, global population using a “big data” approach. The incidence in 0–30-year-old patients with confirmed COVID-19 over an ∼15-month period from the beginning of the COVID-19 pandemic was compared with an age-matched population without COVID-19 inside the TriNetX COVID-19 Research Network (>80 million deidentified patient electronic medical records globally). The cohorts were used to generate outcomes of T1D postindex. In those up to 18 years of age, the incidence of insulin-requiring diabetes that could represent T1D in patients with already diagnosed, confirmed COVID-19 was statistically indistinguishable from the control population without COVID-19. In contrast, in those aged 19–30 years, the incidence was statistically greater. These data suggest that the incidence of T1D among patients with COVID-19 <30 years of age, at least up to this time since the beginning of the pandemic, is not greater when compared with an age-, sex-, and BMI-matched population without COVID-19. Nevertheless, we caution that patients with COVID-19 could be asymptomatic of a diabetic/prediabetic state and therefore would not be expected to come to medical attention, remaining undiagnosed. Hence, it is still possible that asymptomatic virus-infected individuals could acquire β-cell autoimmunity, eventually progressing to dysglycemia and clinical T1D at higher rates.
Sequential Phosphorylation of Hepatitis C Virus NS5A Protein Requires the ATP-Binding Domain of NS3 Helicase

For more than 20 years, NS3 was known to participate in NS5A sequential phosphorylation. In the present study, we show for the first time that the ATP-binding domain of NS3 is involved in NS5A phosphorylation. In vitro assays showed that casein kinase Iα is a very potent kinase responsible for NS5A phosphorylation at serines 225, 232, and 235. ABSTRACT The propagation of the hepatitis C virus (HCV) is regulated in part by the phosphorylation of its nonstructural protein NS5A that undergoes sequential phosphorylation on several highly conserved serine residues and switches from a hypo- to a hyperphosphorylated state. Previous studies have shown that NS5A sequential phosphorylation requires NS3 encoded on the same NS3-NS4A-NS4B-NS5A polyprotein. Subtle mutations in NS3 without affecting its protease activity could affect NS5A phosphorylation. Given the ATPase domain in the NS3 COOH terminus, we tested whether NS3 participates in NS5A phosphorylation similarly to the nucleoside diphosphate kinase-like activity of the rotavirus NSP2 nucleoside triphosphatase (NTPase). Mutations in the NS3 ATP-binding motifs blunted NS5A hyperphosphorylation and phosphorylation at serines 225, 232, and 235, whereas a mutation in the RNA-binding domain did not. The phosphorylation events were not rescued with wild-type NS3 provided in trans. When provided with an NS3 ATPase-compatible ATP analog, N6-benzyl-ATP-γ-S, thiophosphorylated NS5A was detected in the cells expressing the wild-type NS3-NS5B polyprotein. The thiophosphorylation level was lower in the cells expressing NS3-NS5B with a mutation in the NS3 ATP-binding domain. In vitro assays with a synthetic peptide and purified wild-type NS3 followed by dot blotting and mass spectrometry found weak NS5A phosphorylation at serines 222 and 225 that was sensitive to an inhibitor of casein kinase Iα but not helicase. When casein kinase Iα was included in the assay, much stronger phosphorylation was observed at serines 225, 232, and 235. We concluded that NS5A sequential phosphorylation requires the ATP-binding domain of the NS3 helicase and that casein kinase Iα is a potent NS5A kinase. IMPORTANCE For more than 20 years, NS3 was known to participate in NS5A sequential phosphorylation. In the present study, we show for the first time that the ATP-binding domain of NS3 is involved in NS5A phosphorylation. In vitro assays showed that casein kinase Iα is a very potent kinase responsible for NS5A phosphorylation at serines 225, 232, and 235. Our data suggest that ATP binding by NS3 probably results in conformational changes that recruit casein kinase Iα to phosphorylate NS5A, initially at S225 and subsequently at S232 and S235. Our discovery reveals intricate requirements of the structural integrity of NS3 for NS5A hyperphosphorylation and HCV replication.
The French MBAA2 sentence recognition in noise test for cochlear implant users

Abstract Objective The “Marginal benefit from acoustic amplification” version 2 (MBAA2) sentence test has been used in France in the routine evaluation of cochlear implant (CI) users for 20 years. Here we present four studies that characterise and validate the test, and compare it with the French matrix sentence test. Design and sample An analytic method was developed to obtain speech recognition threshold in noise (SNR50) from testing at a fixed signal to noise ratios (SNRs). Speech recognition was measured at several fixed SNRs in 18 normal-hearing listeners and 15 CI listeners. Then, the test–retest reliability of the MBAA2 was measured in an additional 15 CI listeners. Finally, list equivalence was evaluated in eight CI listeners. Results The MBAA2 test produced lower SNR50s and SNR50s were obtained in more CI listeners than with the French matrix test. For the MBAA2, the standard deviation of test–retest differences in CI listeners was around 1 dB SNR. Three lists had deviant difficulty and nine low item-to-total correlations. Conclusions We propose to reduce the number of MBAA2 test lists to reduce variability. The MBAA2 test has high test–retest reliability for percent correct and SNR50, and is suitable for the assessment of cochlear implant patients.
The impact of asynchronous online anatomy teaching and smaller learning groups in the anatomy laboratory on medical students’ performance during the Covid‐19 pandemic

Due to the Covid‐19 pandemic, National Taiwan University anatomy teachers adopted asynchronous online video teaching and reduced the size of anatomy laboratory groups in April 2020. The aim of this study was to investigate the impact of these changes on medical students’ learning. Before Covid‐19, the performance of the 2019–2020 cohort was significantly better than that of the 2018–2019 cohort. However, the implementation of modified teaching strategies significantly lowered the laboratory midterm score of the 2019–2020 cohort in the second semester. Conversely, the final laboratory examination score of the 2019–2020 cohort was significantly higher than that of the 2018–2019 cohort. Through correlation analysis, lecture and laboratory examination scores were highly correlated. Additionally, the difference in lecture and laboratory z‐scores between two cohorts, the Likert scale survey and free‐text feedback of the 2019–2020 cohort, were conducted to show the impact of modified teaching strategies. There were several important findings in this study. First, the change in teaching strategies may temporarily negatively influence medical students to learn anatomy. Besides, analyzing the performance of laboratory assessments could be a complementary strategy to evaluate online assessments. Applying lecture examination scores to predict laboratory performance was a feasible way to identify students who may have difficulty in learning practical dissection. Finally, reducing group size together with reduced peer discussion may have a negative effect on learning cadaver dissection for students with low academic performance. These findings should be taken into consideration when anatomy teachers apply new teaching strategies in anatomy courses.
Exploring Major Challenges and Benefits of M-learning Adoption

Recently, E-learning tools have proven to be potential platforms for management and progress in the education sector. The usage of mobile learning (M-learning) tools in the field of Learning Management Systems (LMS) is an interesting area of research that worth to be investigated. M-learning can offer higher learning and teaching autonomy for the education sectors and individual learners alike. M-learning can support ubiquitous learning hence portraying it as a potential candidate for future distance education. Various research works have been performed in M-learning related to its design needs and application development challenges. This paper highlights the trends of traditional learning systems and establishes a relation between modern mobile technologies and current learning paradigm. It discusses the major benefits that can reflect on the education sector, whereas the major challenges are also put into consideration while adopting M-learning services. The potential economic impact of M-learning adoption is also considered while taking into account the students, staffs and the concerned organizations. Three case studies were used to achieve and complement the research objectives in exploring major challenges
Are Current National Review Board Downstaging Protocols for Hepatocellular Carcinoma Too Restrictive?

BACKGROUND Liver transplantation (LT) is an effective strategy for patients with unresectable hepatocellular carcinoma (HCC). To qualify for standardized LT model for end-stage liver disease exception points, the United Network for Organ Sharing National Liver Review Board (NLRB) requires that the presenting and final HCC tumor burden be within the University of California San Francisco criteria, which were recently expanded (within expanded UCSF [W-eUCSF]). Current NLRB criteria may be too restrictive because it has been shown previously that the initial burden does not predict LT failure when tumors downstage to UCSF. This study aims to assess LT outcomes for HCC initially presenting beyond expanded UCSF (B-eUCSF) criteria in a large multicenter collaboration. STUDY DESIGN Comparisons of B-eUCSF and W-eUCSF candidates undergoing LT at seven academic institutions between 2001 and 2017 were made from a multi-institutional database. Survival outcomes were compared by Kaplan-Meier and Cox regression analyses. RESULTS Of 1,846 LT recipients with HCC, 86 (5%) met B-eUCSF criteria at initial presentation, with the remainder meeting W-eUCSF criteria. Despite differences in tumor burden, B-eUCSF candidates achieved comparable 1-, 5- and 10-year overall (89%, 70%, and 55% vs 91%, 74%, and 60%, respectively; p = 0.2) and disease-free (82%, 60%, and 53% vs 89%, 71%, and 59%, respectively; p = 0.07) survival to patients meeting W-eUCSF criteria after LT. Despite increased tumor recurrence in B-eUCSF vs W-eUCSF patients (24% vs 10%, p = 0.0002), post-recurrence survival was similar in both groups (p = 0.69). CONCLUSION Transplantation for patients initially presenting with HCC B-eUSCF criteria offers a survival advantage similar to those with tumors meeting W-eUCSF criteria at presentation. The current NLRB policy is too stringent, and considerations to expand criteria should be discussed.
SAR of Novel 3-Arylisoquinolinones: meta-Substitution on the Aryl Ring Dramatically Enhances Antiproliferative Activity through Binding to Microtubules

A set of meta-substituted 3-arylisoquinolinones have been identified that show substantial cytotoxicity in breast, liver, lung and colon cancer cell lines; these are up to 700-fold more active than the corresponding para analogues. These compounds were initially proposed as inhibitors of N-ribosyl dihydronicotinamide (NRH): quinone oxidoreductase 2 (NQO2) but were found to be inactive against the enzyme. Instead, COMPARE analysis suggested that 6-fluoro-3-(meta-fluorophenyl)isoquinolin-1(2H)-one (4) could mimic colchicine and interact with microtubules, a recognized target for cancer therapy. Subsequent docking, molecular dynamics simulations, and free energy analysis further suggested that compound 4 bound well into the colchicine-binding pocket of tubulin. Indeed, 4 suppressed tubulin polymerization, caused G2/M cell cycle arrest, and induced apoptosis. Also, 4 inhibited the formation of endothelial cell capillary-like tubes and further disrupted the structure of preestablished tubes; the effects were not observed with para analogue 5. In accordance with this, the computed free energy of binding of 5 to tubulin was lower in magnitude than that for 4 and appeared to arise in part from the inability of the para substituent to occupy a tubulin subpocket, which is possible in the meta orientation. In conclusion, the antiproliferative potential of the novel 3-arylisoquinolinones is markedly influenced by a subtle change in the structure (meta versus para). The meta-substituted isoquinolinone 4 is a microtubule-destabilizing agent with potential tumor-selectivity and antiangiogenic and vascular disrupting features.
Rare central nervous system lymphomas

Central nervous system (CNS) lymphomas are rare malignancies characterised by lymphoid infiltration into the brain, spinal cord, cranial nerves, meninges and/or eyes in the presence or absence of previous or concurrent systemic disease. Most CNS lymphomas are of the diffuse large B‐cell lymphoma (DLBCL) subtype for which treatment strategies, particularly the use of high‐dose methotrexate‐based protocols and consolidation with autologous stem cell transplantation, are well established. Other histopathological subtypes of CNS lymphoma are comparatively less common with published data on these rare lymphomas dominated by smaller case series and retrospective reports. Consequently, there exists little clinical consensus on the optimal methods to diagnose and manage these clinically and biologically heterogeneous CNS lymphomas. In this review article, we focus on rarer CNS lymphomas, summarising the available clinical data on incidence, context, diagnostic features, reported management strategies, and clinical outcomes.
Cognitive decline and brainstem hypometabolism in long COVID: A case series

To assess FDG cerebral PET in patients suffering from cognitive impairment linked to Long COVID. The COVID pandemic has affected dozens of millions of people around the world and has resulted in the deaths of more than 3 million people. Following the acute forms, it has been reported sometimes long forms of COVID, with involvements of several organs including the brain. Neurological complications can include cognitive disturbances (brain fog) that are very common and can seriously disturb the life of patients.
Characterizing physical trauma in children and youth with special health care needs

Using data from the 2018 National Trauma Databank, this study finds that Children and Youth with Special Health Care Needs (CYSHCN) have different patterns of physical trauma: a higher relative risk of private residence injury, assault, and self-injury than their non-SHCN peers. BACKGROUND Children and youth with special health care needs (CYSHCN) have or are at an increased risk for a chronic condition necessitating medical and related services beyond what children usually require. While evidence suggests that CYSHCN are at an increased risk of injury, little is known about this population within the trauma system. This study describes CYSHCN within the pediatric trauma system and examines patterns of injury risk (i.e., intent, place of injury, trauma type, and mechanism of injury) based on special health care need (SHCN) status. METHODS For this cross-sectional study, we used data from the 2018 National Trauma Data Bank to identify pediatric encounters (1–18 years, N = 115,578) and compare demographics (sex, race/ethnicity, insurance status, and age) by CYSHCN status using χ2 and t tests. Children and youth with special health care needs encounters were compared with non-SHCN encounters using multinomial logistic regression models, controlling for demographics. RESULTS Overall, 16.7% pediatric encounters reported an SHCN. Children and youth with special health care needs encounters are older, and a higher proportion is publicly insured than non-SHCN encounters (p < 0.001). Furthermore, CYSHCN encounters have a higher risk of assault (relative risk, 1.331) and self-inflicted (relative risk, 4.208) injuries relative to unintentional injury (p < 0.001), as well as a higher relative risk of traumatic injury occurring in a private residence (p < 0.01) than other locations such as school (relative risk, 0.894). Younger CYSHCN encounters have a higher risk of assault relative to unintentional injury when compared with non-SHCN encounters (p < 0.01). Pediatric trauma encounters reporting mental health and alcohol/substance use disorder SHCN have a higher probability of self-inflicted and assault injuries than non-SHCN encounters (p < 0.001). CONCLUSIONS These findings suggest that CYSHCN have different traumatic injury patterns than their non-SHCN peers, particularly in terms of intentional and private residence injury, and deserve a special focus for traumatic injury prevention. LEVEL OF EVIDENCE Prognostic/epidemiologic, level III.
Simulation Versus Written Fall Prevention Education in Older Hospitalized Adults: A Randomized Controlled Study

Using a randomized controlled, non-blinded, two-group design, differences in fall risk assessment, post-discharge sustainable fall risk changes, fall events and re-hospitalization were examined in 77 older adults who received a simulation (n = 36) or written (n = 41) education intervention. Between-group differences and changes in pre- versus post-fall risk assessment scores were examined using Pearson’s chi-square, Wilcoxon rank sum or Fisher’s exact tests (categorical variables) and two-sample t-tests (continuous variables). There were no statistically significant differences between groups in demographic characteristics. Patients who received simulation education had higher fall risk post-assessment scores than the written education group, p = . 022. Change in fall risk assessment scores (post-vs.-pre; 95% confidence intervals) were higher in the simulation group compared to the written education group, 1.43 (0.37, 2.50), p = . 009. At each post-discharge assessment, fall events were numerically fewer but not significantly different among simulation and education group participants. There were no statistically significant between-group differences in re-hospitalization.