Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytokinesis-block micronucleus assay performed in 0 and 2 Gy irradiated whole blood and isolated PBMCs in a six-well transwell co-culture system

Abstract Purpose Cytokinesis-block micronucleus (CBMN) assay in cytogenetic biodosimetry uses micronucleus (MN) frequency scored in binucleated cells (BNC) for dose estimation. Cell-cycle progression parameters of nuclear division index (NDI) and percentage of BNC (% BNC) are also evaluated. Whole blood (WB) or peripheral mononuclear cells (PBMCs) isolated from WB can be used for lymphocyte culture. Previously, 2 Gy PBMCs showed higher NDI and lower MN frequency than WB in 15 ml polypropylene tube single cultures. In this follow-up study, we wanted to assess if soluble factors present in WB but absent in PBMCs could increase MN frequency or decrease NDI in PBMCs co-cultured with WB. Materials and methods Peripheral blood from four healthy donors (two males: 25, 51; two females: 23, 26 years old) was irradiated with X-ray at 1 Gy/min. CBMN assay was performed with different combinations of 0 and 2 Gy WB and PBMC (WB, WB-IR, PBMC, PBMC-IR) mono- and co-cultures in a polystyrene six-well plate. Co-cultures were separated by 0.4 µm transwell inserts. Log2 fold changes and values of NDI, % BNC and MN frequency analyzed by three scorers were obtained. Results As upper and lower wells of the same culture condition showed some significant differences, wells of the same level were compared. NDI of PBMCs increased when PBMC or PBMC-IR was co-cultured with WB or WB-IR, respectively, as compared to mono-cultures. There was no increase in PBMC-IR’s MN frequency when co-cultured with WB or WB-IR. MN frequency was consistently higher in WB-IR than PBMC-IR in both mono- and co-cultures. NDI, % BNC and MN frequency were similar when WB or PBMC were co-cultured with PBMC-IR or WB-IR, respectively. Significantly lower NDI and % BNC, and higher MN frequency were also seen in some conditions of 15 ml cultures than six-well mono-cultures. Conclusions Instead of the hypothesized decrease in NDI and increase in MN frequency, our co-culture set-up showed that in the absence of direct cell–cell interaction, soluble factors in WB increased NDI but not MN frequency in PBMCs. Moreover, radiation-induced bystander effects could not be observed. As the type of cell culture (WB, PBMC) and culture vessels could influence NDI and MN frequency, CBMN culture protocols should be kept consistent for dose–response calibration curve construction and dose estimation.
The NLRP3 inflammasome mediates liver failure by activating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling

Objectives In this prospective case–control study, we explored the regulatory roles of the NLRP3 inflammasome in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods Thirty patients with HBV-ACLF, 30 patients with chronic hepatitis B, and 30 healthy individuals were enrolled. Real-time reverse transcription polymerase chain reaction was used to assess mRNA levels in peripheral blood mononuclear cells and serum protein levels were assessed by enzyme-linked immunosorbent assay. Results Serum levels of alanine aminotransferase, asparagine aminotransferase, total bilirubin, and direct bilirubin in patients with HBV-ACLF were increased. Transcript levels of NLRP3 and ASC and protein levels of interleukin (IL)-1β, IL-18, and sCD40L were elevated in patients with HBV-ACLF. Expression of the NLRP3 inflammasome signaling pathway components procaspase-1 and pro-IL-1β was elevated in patients with HBV-ACLF. Conclusions This prospective case-control study demonstrated that significant activation of the NLRP3 inflammasome occurs in patients with HBV-ACLF. The activated NLRP3 inflammasome mediated liver failure by stimulating procaspase-1 and pro-IL-1 β and regulating downstream CD40-CD40L signaling.
Prior infection and age impacts antibody persistence after SARS-CoV-2 mRNA vaccine

Abstract Determining the duration of immunity to SARS-CoV-2 vaccines is critical for informing the timing of booster immunization. Many host factors could influence both the magnitude and persistence of the antibody response. Here, we showed that SARS-CoV-2 infection before vaccination and age affected the decay of antibody responses to the SARS-CoV-2 mRNA vaccine.
Effects of a Health Promotion Intervention on Physical Activity in African American Men Living with HIV: Randomized Controlled Trial

HIV and its treatment with antiretroviral therapy increase the risk of noncommunicable diseases (NCDs) tied to physical inactivity. Older African American men are also at high risk for NCDs. We tested the efficacy of a theory-based intervention to increase adherence to federal aerobic and muscle-strengthening physical activity (PA) guidelines among African American men aged 40 years and older living with HIV. We randomized African American men aged 40 years and older living with HIV to a three-session social cognitive theory-informed health promotion intervention targeting PA or a one-session health awareness control condition. The primary outcome was PA guideline adherence assessed (self-reported) preintervention, immediate postintervention, and 3, 6, and 12 months postintervention. Secondary outcomes were the number of days on which participants reported moderate-intensity aerobic PA, vigorous-intensity aerobic PA, and muscle-strengthening PA in the past 7 days. Of 302 participants, 255 completed the 12-month postintervention measures. Generalized estimated equation logistic regression indicated that the health promotion intervention participants had higher odds of meeting PA guidelines than health awareness control participants, adjusting for baseline adherence (p = 0.011). Health promotion intervention participants also reported more muscle-strengthening PA (p = 0.001), vigorous-intensity aerobic PA (p = 0.049), and moderate-intensity aerobic PA (p = 0.010) than control participants. The rise in self-reported adherence to PA guidelines and improvements in muscle-strengthening and aerobic PA considered separately suggest that a relatively brief behavioral intervention can increase PA among African American men aged 40 years and older living with HIV and potentially curb their risk of NCDs that PA can prevent.
Microencapsulated Wharton Jelly-derived adult mesenchymal stem cells as a potential new therapeutic tool for patients with COVID-19 disease: an in vitro study.

BACKGROUND The recent newly appeared Coronavirus disease (COVID-19), caused by an enveloped RNA virus named "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)", is associated with severe respiratory morbidity and mortality. Recent studies have shown that lymphopenia and a cytokine mass release represent important pathogenic features, with clinical evidence of dyspnea and hypoxemia, often leading to acute respiratory distress syndrome (ARDS), in severely ill patients, with a high death toll. Currently, stem cells are actively being investigated for their potential use in many "untreatable" diseases. In this regard and in particular, Mesenchymal Stem Cells (MSC), due to their intrinsic features, including either ability to impact on regulation of the immune system, or association with both anti-viral and anti-inflammatory properties, or potential for differentiation into several cell lineages, have become a promising tool for cell and molecular-based therapies. On this background, we wished to explore whether human umbilical cord-derived mesenchymal stem cells (hUCMS) would represent a potential viable therapeutic approach for the management of critically ill COVID19 patients. METHODS We tested the hUCMS effects on peripheral blood mononuclear cell (PBMCs) retrieved from patients with COVID19 (Ethical Committee CEAS Umbria, Italy CER N°3658/20 7, May, 2020), both as free cell monolayers and after envelopment in sodium alginate microcapsules. Both cell systems, after priming with IFN-γ, proved able to produce several immunomodulatory molecules such as IDO1 and HLAG5, although only the microencapsulated hUCMS were associated with massive and dose-dependent production of these factors. RESULTS The microencapsulated hUCMS improved allo-suppression in mixed lymphocytes reactions (MLRs), while also blunting T helper 1 and T helper 17 responses, that are involved with the cytokine storm and greatly contribute to the patient death. Moreover, we observed that both free and microencapsulated hUCMS permitted 5 days survival of in vitro culture maintained PBMCs extracted from very ill patients. CONCLUSION We have provided evidence that microencapsulated hUCMS in vitro, seem to represent a powerful tool to impact on several immune pathways, clearly deranged in COVID19 patients. Further study is necessary to begin in vivo assessment of this experimental system, upon determining both, the most appropriate time of the disease onset for intervention, and cell dosage/patient of our experimental product.
Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24‐year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long‐term outcomes of liver transplant. Sixty‐nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42–59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty‐nine patients (56.5%) were red blood celltransfusion‐dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post‐transplant (p = .001) and excellent post‐transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child–Turcotte–Pugh score, transfusion dependence had an odds ratio (OR) for 90‐day mortality of 9.14 (95% CI, 2.46–34.00) and reduced pre‐transfusion hematocrit had an OR of 4.73 (95% CI, 1.42–15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90‐day mortality. Model for end‐stage liver disease (MELD)‐Na and Child–Turcotte–Pugh scores consistently significantly underestimated 90‐day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD‐Na 20–29, SMR 2.42 (1.18–4.44); Child—Turcotte–Pugh class B, SMR 4.46 (1.64–9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD‐Na or Child–Turcotte–Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90‐day mortality.
Multiple Sclerosis: Microglia, Monocytes, and Macrophage-Mediated Demyelination

Abstract This study examined the roles of microglia and monocytes in myelin destruction in patients with early multiple sclerosis (MS). Twenty-two cases were studied; the clinical duration was <9 weeks in 10 cases. Twenty myeloid cell subtypes or categories were identified including 2 cell types not known previously to occur in demyelinating diseases. Commencing myelin breakdown in plaques and in perivascular and subpial tissues occurred in the immediate presence of infiltrating monocytes and was effected by a homogeneous population of IgG-positive Fc receptor-bearing early phagocytes interacting with abnormal myelin. Oligodendrocyte apoptosis was observed in intact myelinated tissue bordering areas of active demyelination. Capillaries in the cerebral cortex plugged by large numbers of monocytes were common in acute cases of MS and in a patient with a neuromyelitis optica variant and extreme systemic recruitment of monocytes. In an MS patient with progressive disease, microglial nodules centered on MHC-II-positive capillaries plugged by monocytes were present in the cerebral cortex. This constitutes a new gray matter lesion in MS.
Renoprotection by long‐term low‐dose tolvaptan in patients with heart failure and hyponatremia

In previous randomized controlled trials, the use of tolvaptan (TLV) at a fixed dose of 30 mg/day for 1 year did not provide renal benefits in patients with heart failure (HF). This retrospective, cohort study examined the renoprotective effects of long‐term, flexible‐dose, and lower‐dose TLV use.
A review of diabetic wound models—Novel insights into diabetic foot ulcer

Diabetic foot ulcer (DFU) is a major debilitating complication of diabetes. Many research investigations have been conducted with the aims to uncover the diabetic wound healing mechanisms, develop novel therapeutics, and screen bioactive wound dressings in order to improve the current management of DFU. These would have not been possible without the utilization of an appropriate wound model, especially in a diabetic wound context. This review focuses on the different in vitro research models used in DFU investigations such as the 2D scratch wound assay, 3D skin model, and 3D angiogenesis model as well as their limitations. The current efforts and challenges to apply the 2D and 3D in vitro models in a hyperglycemic context to provide insights into DFU modeling will be reviewed. Perspectives of utilizing 3D bioprinting and skin‐on‐the‐chip model as a diabetic wound model in the future will also be highlighted. By leveraging knowledge from past experiences and current research, an improved experimental model for DFU is anticipated to be established in near future.
Comparison of clinical and radiological outcomes of full-endoscopic versus microscopic lumbar decompression laminectomy for the treatment of lumbar spinal stenosis: a systematic review and meta-analysis.

BACKGROUND To determine the clinical and radiological outcomes of full-endoscopic (FE) versus microscopic (MI) lumbar decompression laminectomy in the treatment of lumbar spinal stenosis (LSS), we performed a meta-analysis to explore the best choice for patients with LSS requiring surgical relief. METHODS Literature searches of the PubMed, the Cochrane Library, Embase, Medline, Embase, and Web of Science databases were performed. The searches covered all indexed studies published between 2008 and 2020, using keywords identifying the patient group (lumbar spine stenosis) and the interventions (fullendoscopic lumbar decompression laminectomy and microscopic lumbar decompression laminectomy). A total of 1,727 patients were included in 10 studies. The primary outcomes of the analysis were visual analogue scale (VAS) scores for leg and back pain, and Oswestry Disability Index (ODI) score. RESULTS The meta-analysis of the VAS score for low back pain showed that in the first 24 hours postoperatively, participants who underwent FE had better pain control than those who underwent MI [FE: mean difference (MD) =-0.78, 95% confidence interval (CI): -1.11, -0.45; MI: MD =-1.53, 95% CI: -1.94, -1.12]. In all subgroup analyses, the VAS score for back pain was lower in the FE group than in the MI group (MD =-0.71, 95% CI: -0.96, -0.47). Regarding the VAS score for leg pain, the FE group had a significantly lower score than the MI group in the first 24 hours (Total: MD =-1.02, 95% CI: -1.31, -0.73). The metaanalysis demonstrated that the FE group had a significantly lower ODI score than the MI group (MD =-1.03, 9% CI: -1.54, -0.51). At 6 months, the MI group had a significantly lower score than the FE group (MD =1.09, 95% CI: 0.53, 1.64), but at 12 months, the FE group had a significantly lower score than the MI group (MD =-2.40, 95% CI: -3.12, -1.67). CONCLUSIONS Compared to MI decompression, the FE decompression method resulted in better pain control in the early postoperative period, both in the lower back and legs, as well as shorter operative and shorter hospitalization times.
Impact of era of diagnosis on cause‐specific late mortality among 77 423 five‐year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium

Late mortality of European 5‐year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause‐specific mortality among older European survivors. PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five‐year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million person‐years to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow‐up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69‐10.09), AER 6.47 per 1000 person‐years, (95% CI 6.32‐6.62). At 60 to 68 years of attained age all‐cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90‐3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5‐20.4) to 7.3% (95% CI 6.7‐8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). PanCareSurFup is the largest study with the longest follow‐up of late mortality among European childhood and adolescent cancer 5‐year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long‐term care needs.
Southwestern Assessment of Processing Speed (SWAPS): A new brief test with demographically-corrected norms in an ethnically and educationally diverse population

Abstract Objective. Neuropsychological measures of processing speed have long been used as sensitive indices of cognitive functioning. Most of these commonly used tests are proprietary, and there is a need for brief, freely available tools that can be used in diverse clinical and research settings. The Southwestern Assessment of Processing Speed (SWAPS) is a 60-second digit-symbol transcription task developed as a brief alternative to commercially available coding tests. Demographically-corrected normative data are presented along with reliability and sensitivity/specificity values in older adults with and without cognitive impairment. Method. SWAPS data from 915 healthy aging individuals (NC) and 858 subjects with clinical diagnoses of mild cognitive impairment (MCI; n = 430) and Alzheimer’s disease clinical syndrome (ADCS; n = 428) were obtained from the Texas Alzheimer’s Research and Care Consortium (TARCC). TARCC participants represent ethnically and educationally diverse community-dwelling individuals age 50+. Results. SWAPS scores showed the expected associations with age, sex, and education, and the interaction between age and education were significant predictors of SWAPS scores. Test-retest reliability in NC was good, and the SWAPS distinguished impaired and non-impaired groups with adequate to excellent sensitivity and specificity for the primary analyses, with optimal cut-off points provided. Raw score- to uncorrected normalized T-scores and demographically-corrected SWAPS T-scores using regression-based norms are presented along with scoring programs for the calculation of each. Conclusions. The SWAPS is a brief, free, easily administered test with demographically-corrected regression-based norms and promising utility for detection of cognitive impairment and efficient assessment of processing speed.
An explanation of the very low fluorescence and phosphorescence in pyridine: a CASSCF/CASMP2 study

ABSTRACT In this work, we applied the multiconfigurational complete active space self-consistent field method and the multiconfigurational second-order perturbation theory CASMP2 to study the fundamental excited states of pyridine and its possible photophysical and photochemical transformations. Our calculations, which are in agreement with the experimental results corresponding to excitations around the 0–0 transition, showed that the very low experimentally observed fluorescence of pyridine is due to the presence of two almost isoenergetic crossings, one of triple character, S1/T1/S0 and the other of S1/S0 character. Both crossings are below the minimum of S1(nπ*) and have a common transition state (S1(TS)) with a very low energy barrier (1.85 kcal/mol or 0.08 eV at the CASMP2 level of theory) separating them. A third triple crossing of the type S1/T1/S0 lying lower with respect to the other two elucidates the observed T1→S0 radiationless transition. This explains not only pyridine's very low fluorescence and phosphorescence but also its almost negligible photochemistry, showing that photophysics is the prevalent process in this molecule.
Ghostwriter: A Cache Coherence Protocol for Error-Tolerant Applications

Coherence induced cache misses are an important aspect limiting the scalability of shared memory parallel programs. Many coherence misses are avoidable, namely misses due to false sharing – when different threads write to different memory addresses that are contained within the same cache block causing unnecessary invalidations. Past work has proposed numerous ways to mitigate false sharing from coherence protocols optimized for certain sharing patterns, to software tools for false-sharing detection and repair. Our work leverages approximate computing and store value similarity in error-tolerant multi-threaded applications. We introduce a novel cache coherence protocol which implements an approximate store instruction and coherence states to allow some limited incoherence within approximatable shared data to mitigate both coherence misses and coherence traffic for various sharing patterns. For applications from the Phoenix and AxBench suites, we see dynamic energy improvements within the NoC and memory hierarchy of up to 50.1% and speedup of up to 37.3% with low output error for approximate applications that exhibit false sharing.