Miracle-dz/UniFAR-FTUs huggingface dataset:
The diagnostic value of ADC histogram and direct ADC measurements for coexisting isocitrate dehydrogenase mutation and O6-methylguanine-DNA methyltransferase promoter methylation in glioma

Objectives To non-invasively predict the coexistence of isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in adult-type diffuse gliomas using apparent diffusion coefficient (ADC) histogram and direct ADC measurements and compare the diagnostic performances of the two methods. Materials and methods A total of 118 patients with adult-type diffuse glioma who underwent preoperative brain magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) were included in this retrospective study. The patient group included 40 patients with coexisting IDH mutation and MGMT promoter methylation (IDHmut/MGMTmet) and 78 patients with other molecular status, including 32 patients with IDH wildtype and MGMT promoter methylation (IDHwt/MGMTmet), one patient with IDH mutation and unmethylated MGMT promoter (IDHmut/MGMTunmet), and 45 patients with IDH wildtype and unmethylated MGMT promoter (IDHwt/MGMTunmet). ADC histogram parameters of gliomas were extracted by delineating the region of interest (ROI) in solid components of tumors. The minimum and mean ADC of direct ADC measurements were calculated by placing three rounded or elliptic ROIs in solid components of gliomas. Receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the diagnostic performances of the two methods. Results The 10th percentile, median, mean, root mean squared, 90th percentile, skewness, kurtosis, and minimum of ADC histogram analysis and minimum and mean ADC of direct measurements were significantly different between IDHmut/MGMTmet and the other glioma group (P < 0.001 to P = 0.003). In terms of single factors, 10th percentile of ADC histogram analysis had the best diagnostic efficiency (AUC = 0.860), followed by mean ADC obtained by direct measurements (AUC = 0.844). The logistic regression model combining ADC histogram parameters and direct measurements had the best diagnostic efficiency (AUC = 0.938), followed by the logistic regression model combining the ADC histogram parameters with statistically significant difference (AUC = 0.916) and the logistic regression model combining minimum ADC and mean ADC (AUC = 0.851). Conclusion Both ADC histogram analysis and direct measurements have potential value in predicting the coexistence of IDHmut and MGMTmet in adult-type diffuse glioma. The diagnostic performance of ADC histogram analysis was better than that of direct ADC measurements. The combination of the two methods showed the best diagnostic performance.
How physical activity and passion color the passage of time: A response with ultra-trail runners

The aim of this study was to replicate the results of a lengthening effect caused by physical activity already observed in duration length judgment, using the time passage judgment measure, while exploring the effects of passion types (obsessive vs. harmonious) on time perception. A total of 378 ultra-trail runners responded to an online questionnaire in which the type of passion and the passage of time (PoT) judgments associated with both an ultra-trail context and a non-trail daily context were collected. The results showed that participants systematically judged the time as being dilated in a situation of sports practice, thus extending the results obtained in interval duration judgment studies. This study also showed an influence of the type of passion: higher levels of harmonious passion were related to greater feelings of time dilation, while higher levels of obsessive passion were related to greater feelings of both time contraction and time dilation. Results are discussed in light of the two major factors that influence the PoT referenced in the literature, namely, attention and happiness level.
COVID-19 pandemic impairs medical care of vasculitis patients in Germany: Results of a national patient survey

Objective To analyze the impact of the COVID-19 pandemic on medical care and vaccination acceptance of vasculitis patients in Germany. Methods A web-based national survey was developed by rheumatology centers and vasculitis patient advocacy groups. The survey was distributed nationwide by mail and flyers and could be accessed via a QR-code or weblink from December 2021 to April 2022. Descriptive statistics [mean, median, standard derivation (SD), 25%, 75% quantile] were calculated. 95% confidence intervals were presented for responses that were directly related to the impact of COVID-19 on parameters associated with vasculitis patient care. Results The online survey was completed by 117 patients with small and large vessel vasculitis [granulomatosis with polyangiitis (n = 69), eosinophilic granulomatosis with polyangiitis (n = 16), microscopic polyangiitis (n = 12), giant cell arteritis (n = 17) and Takayasu's arteritis (n = 3)]. Prescheduled rheumatological appointments had been canceled due to the COVID-19 pandemic in 12.6% of the respondents [95% confidence interval (CI), 7.3–20.0%); in 9% (95% CI, 4.5–15.6%)] appointments had been replaced by digital services. Therapeutic regimens were changed (shifted, reduced, or discontinued) due to the pandemic in 15.5% (95% CI 9.5–22.2%). Vaccination coverages were generally high compared to patients with other rheumatic diseases and the general population. Highest vaccination coverage was observed against COVID-19 (98.1% 95% CI 93.9–99.6%). Conclusion Vasculitis patients experienced changes in medical care during COVID-19 pandemic such as cancelation of prescheduled rheumatology appointments and modifications in therapeutic regimens. The overall acceptance rate for vaccination was comparatively high, particularly for vaccination against COVID-19.
Rescue stenting after the failure of mechanical thrombectomy to treat acute intracranial atherosclerotic occlusion

Background Acute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion. Methods We retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated. Results Among the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0–2 (48.8 vs. 52.3%, p = 0.76). Conclusions Rescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.
3D-printed patient-specific instrumentation decreases the variability of patellar height in total knee arthroplasty

Objective Three-dimensionally (3D) printed patient-specific instrumentation (PSI) might help in this regard with individual design and more accurate osteotomy, but whether the utility of such instrumentations minimizes the variability of patellar height in total knee arthroplasty (TKA) and the reasons for this effect are unknown. Our aim is to compare and analyze the variability of patellar height with PSI and conventional instrumentation (CI) in TKA. Methods Between March 2018 and November 2021, 215 patients with severe knee osteoarthritis who were treated with primary unilateral TKA were identified for this observational study. The patients were divided into the CI-TKA group and PSI-TKA group according to the osteotomy tools used in TKA. Preoperative and postoperative radiographic parameters including hip–knee–ankle angle (HKA), posterior tibial slope (PTS), Insall–Salvati ratio, modified Caton–Deschamps (mCD) ratio, anterior condylar offset (ACO), and posterior condylar offset (PCO) were evaluated. Results The groups were similar in patients' demographic data, clinical scores, and radiographic parameters preoperatively. Overall, according to the results of the Insall–Salvati ratio, postoperative patellar height reduction was noted in 140 patients (65.1%). Interestingly, the variability of patellar height was smaller in the PSI-TKA group. Radiographic evaluation revealed that the Insall–Salvati ratio after TKA had a minor change in the PSI-TKA group (p = 0.005). Similarly, the mCD ratio after TKA also had a minor change in the PSI-TKA group (p < 0.001). Compared to those in the CI-TKA group, the ACO (p < 0.001) and PCO (p = 0.011) after TKA had a minor change in the PSI-TKA group, but no minor PTS change (p = 0.951) was achieved in the PSI-TKA group after TKA. However, even with 3D-printed patient-specific instrumentation, there were still significant reductions in patellar height, ACO, PCO, and PTS after TKA (p < 0.001). Conclusion The variability of patellar height was sufficiently minimized with more accurate anterior and posterior femoral condyle osteotomy when 3D printed PSI was used. Furthermore, there was a trend in over-resection of the femoral anterior and posterior condyle and a marked reduction in PTS during TKA, which could lead to a change in patellar height and might result in more patellofemoral complications following TKA. Level of evidence Level II.
Natural alleles of the clock gene timeless differentially affect life-history traits in Drosophila

Circadian clocks orchestrate a variety of physiological and behavioural functions within the 24-h day. These timekeeping systems have also been implicated in developmental and reproductive processes that span more (or less) than 24 h. Whether natural alleles of cardinal clock genes affect entire sets of life-history traits (i.e., reproductive arrest, developmental time, fecundity), thus providing a wider substrate for seasonal adaptation, remains unclear. Here we show that natural alleles of the timeless (tim) gene of Drosophila melanogaster, previously shown to modulate flies’ propensity to enter reproductive dormancy, differentially affect correlated traits such as early-life fecundity and developmental time. Homozygous flies expressing the shorter TIM isoform (encoded by the s-tim allele) not only show a lower dormancy incidence compared to those homozygous for ls-tim (which produce both the short and an N-terminal additional 23-residues longer TIM isoform), but also higher fecundity in the first 12 days of adult life. Moreover, s-tim homozygous flies develop faster than ls-tim homozygous flies at both warm (25°C) and cold (15°C) temperatures, with the gap being larger at 15°C. In summary, this phenotypic analysis shows that natural variants of tim affect a set of life-history traits associated with reproductive dormancy in Drosophila. We speculate that this provides further adaptive advantage in temperate regions (with seasonal changes) and propose that the underlying mechanisms might not be exclusively dependent on photoperiod, as previously suggested.
Leveraging genetic diversity in mice to inform individual differences in brain microstructure and memory

In human Alzheimer’s disease (AD) patients and AD mouse models, both differential pre-disease brain features and differential disease-associated memory decline are observed, suggesting that certain neurological features may protect against AD-related cognitive decline. The combination of these features is known as brain reserve, and understanding the genetic underpinnings of brain reserve may advance AD treatment in genetically diverse human populations. One potential source of brain reserve is brain microstructure, which is genetically influenced and can be measured with diffusion MRI (dMRI). To investigate variation of dMRI metrics in pre-disease-onset, genetically diverse AD mouse models, we utilized a population of genetically distinct AD mice produced by crossing the 5XFAD transgenic mouse model of AD to 3 inbred strains (C57BL/6J, DBA/2J, FVB/NJ) and two wild-derived strains (CAST/EiJ, WSB/EiJ). At 3 months of age, these mice underwent diffusion magnetic resonance imaging (dMRI) to probe neural microanatomy in 83 regions of interest (ROIs). At 5 months of age, these mice underwent contextual fear conditioning (CFC). Strain had a significant effect on dMRI measures in most ROIs tested, while far fewer effects of sex, sex*strain interactions, or strain*sex*5XFAD genotype interactions were observed. A main effect of 5XFAD genotype was observed in only 1 ROI, suggesting that the 5XFAD transgene does not strongly disrupt neural development or microstructure of mice in early adulthood. Strain also explained the most variance in mouse baseline motor activity and long-term fear memory. Additionally, significant effects of sex and strain*sex interaction were observed on baseline motor activity, and significant strain*sex and sex*5XFAD genotype interactions were observed on long-term memory. We are the first to study the genetic influences of brain microanatomy in genetically diverse AD mice. Thus, we demonstrated that strain is the primary factor influencing brain microstructure in young adult AD mice and that neural development and early adult microstructure are not strongly altered by the 5XFAD transgene. We also demonstrated that strain, sex, and 5XFAD genotype interact to influence memory in genetically diverse adult mice. Our results support the usefulness of the 5XFAD mouse model and convey strong relationships between natural genetic variation, brain microstructure, and memory.
scMODD: A model-driven algorithm for doublet identification in single-cell RNA-sequencing data

Single-cell RNA sequencing (scRNA-seq) data often contain doublets, where a doublet manifests as 1 cell barcode that corresponds to combined gene expression of two or more cells. Existence of doublets can lead to spurious biological interpretations. Here, we present single-cell MOdel-driven Doublet Detection (scMODD), a model-driven algorithm to detect doublets in scRNA-seq data. ScMODD achieved similar performance compared to existing doublet detection algorithms which are primarily data-driven, showing the promise of model-driven approach for doublet detection. When implementing scMODD in simulated and real scRNA-seq data, we tested both the negative binomial (NB) model and the zero-inflated negative binomial (ZINB) model to serve as the underlying statistical model for scRNA-seq count data, and observed that incorporating zero inflation did not improve detection performance, suggesting that consideration of zero inflation is not necessary in the context of doublet detection in scRNA-seq.
Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model

Introduction Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.
No difference in anti-spike antibody and surrogate viral neutralization following SARS-CoV-2 booster vaccination in persons with HIV compared to controls (CO-HIV Study)

Background Understanding the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination will enable accurate counseling and inform evolving vaccination strategies. Little is known about antibody response following booster vaccination in people living with HIV (PLWH). Methods We enrolled SARS-CoV-2 vaccinated PLWH and controls without HIV in similar proportions based on age and comorbidities. Participants completed surveys on prior SARS-CoV-2 infection, vaccination, and comorbidities, and provided self-collected dried blood spots (DBS). Quantitative anti-spike IgG and surrogate viral neutralization assays targeted wild-type (WT), Delta, and Omicron variants. We also measured quantitative anti-nucleocapsid IgG. The analysis population had received full SARS-CoV-2 vaccination plus one booster dose. Bivariate analyses for continuous outcomes utilized Wilcoxon tests and multivariate analysis used linear models. Results The analysis population comprised 140 PLWH and 75 controls with median age 58 and 55 years, males 95% and 43%, and DBS collection on 112 and 109 days after the last booster dose, respectively. Median CD4 count among PLWH was 760 cells/mm3 and 91% had an undetectable HIV-1 viral load. Considering WT, Delta, and Omicron variants, there was no significant difference in mean quantitative anti-spike IgG between PLWH (3.3, 2.9, 1.8) and controls (3.3, 2.9, 1.8), respectively (p-values=0. 771, 0.920, 0.708). Surrogate viral neutralization responses were similar in PLWH (1.0, 0.9, and 0.4) and controls (1.0, 0.9, 0.5), respectively (p-values=0.594, 0.436, 0.706). Conclusions PLWH whose CD4 counts are well preserved and persons without HIV have similar anti-spike IgG antibody levels and viral neutralization responses after a single SARS-CoV-2 booster vaccination.
Potential mechanisms involved in regulating muscle protein turnover after acute exercise: A brief review

It is well established that resistance training increases muscle mass. Indeed, there is evidence to suggest that a single session of resistance training is associated with an increase in muscle protein synthesis in young adults. However, the fundamental mechanisms that are involved in regulating muscle protein turnover rates after an acute bout of physical exercise are unclear. Therefore, this review will briefly focus on summarizing the potential mechanisms behind the growth of skeletal muscle after physical exercise. We also present mechanistic differences that may exist between young and older individuals during muscle protein synthesis and breakdown after physical exercise. Pathways leading to the activation of AKT/mTOR signals after resistance exercise and the activation of AMPK signaling pathway following a HIIT (High intensity interval training) are discussed.
Antiviral effects of Pediococcus acidilactici isolated from Tibetan mushroom and comparative genomic analysis

Rotavirus is one of the main pathogens that cause diarrhoea in young animals, and countless animals have died of rotavirus infection worldwide. Three strains of lactic acid bacteria isolated from Tibetan mushrooms were used to study the inhibition of rotavirus in vitro and in vivo. One part was to identify and study the biochemical and probiotic characteristics of three isolated lactic acid bacteria, and the other part was to evaluate the inhibitory effect on rotavirus via in vivo and in vitro experiments. The whole genome of the lactic acid bacteria with the best antiviral effect was sequenced, and the differences between them and the standard strains were analyzed by comparative genomic analysis, so as to provide a theoretical basis for exploring the antiviral effect of lactic acid bacteria.The three strains were identified as Pediococcus acidilactici, Lactobacillus casei and Lactobacillus paracasei. Pediococcus acidilactici showed good acid tolerance, bile salt tolerance, survival in artificial intestinal fluid, survival in gastric fluid and bacteriostasis. In in vitro experiments, pig intestinal epithelial cells cocultured with Pediococcus acidilactici exhibited reduced viral infection. In the in vivo experiment, the duodenum of mice fed Pediococcus acidilactici had extremely low numbers of virus particles. The total genome size was 2,026,809 bp, the total number of genes was 1988, and the total length of genes was 1,767,273 bp. The proportion of glycoside hydrolases and glycoside transferases in CAZy was 50.6 and 29.6%, respectively. The Metabolism function in KEEG had the highest number of Global and overview maps. Among the comparative genomes, Pediococcus acidilactici had the highest homology with GCF 000146325.1, and had a good collinearity with GCF 013127755.1, without numerous gene rearrangement events such as insertion, deletion, inversion and translocation. In conclusion, Pediococcus acidilactici was a good candidate strain for antiviral probiotics.
Risk factors and complications associated with intra-operative or post-operative identification of a PFO in cardiac surgery patients: A cohort study

Introduction It is unknown whether patent foramen ovale (PFO) reopening in the peri-operative setting of cardiac surgery affects the risk for stroke and post-operative outcomes. Methods We performed a single-center, retrospective study based on a prospectively collected database in a tertiary cardiac surgery center. Using logistic regression, we assessed risk factors of PFO finding around surgery and subsequent clinical complications. Results Between January 2007 and July 2019, 11034 patients who underwent cardiac surgery in our center were included. A total of 233 patients (2.1%) presented a finding of PFO including 138 per-operative disclosures and 95 post-operative finding for hypoxemia. In the whole cohort, the mean age was 68.4 ± 11.5 years including 73.9% of men. Post-operative PFO finding was associated with more ischemic strokes compared with per-operative finding and control group [7(7.4%) vs. 3(2.2%) vs. 236(2.2), respectively; p = 0.003]. Moreover, patients with post-operative PFO reopening experienced a higher rate of pneumonia, reintubation, and longer length of stay in the ICU. Post-operative reopening of PFO, but not per-operative finding, was independently associated with ischemic strokes {adjusted odds-ratio = 3.5, 95% confidence interval (CI) [1.6–7.8]; p = 0.002}. Other variables associated with stroke incidence included age, mitral valve surgery, and ascending aorta surgery. Per- or post-operative PFO closure was associated with reduced adverse respiratory outcomes and a trend of the lower cerebral ischemic event. Conclusion Patent foramen ovale finding incidence in peri-operative cardiac surgery care was rare (2%) but post-operative finding of PFO was associated with a increased risk of ischemic strokes, worsened respiratory outcomes, and prolonged hospitalization.