Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations

Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA‐4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune checkpoint blockade (ICB). Although a variety of isolated immunostimulatory effects have been reported for several classes of chemotherapeutics, it is unclear which chemotherapeutics provide the most benefit when combined with ICB. We investigated 10 chemotherapies from the main canonical classes dosed at the clinically relevant maximum tolerated dose in combination with anti‐CTLA-4/anti-PD-L1 ICB. We screened these chemo-immunotherapy combinations in two murine mesothelioma models from two different genetic backgrounds, and identified chemotherapies that produced additive, neutral or antagonistic effects when combined with ICB. Using flow cytometry and bulk RNAseq, we characterized the tumor immune milieu in additive chemo-immunotherapy combinations. 5-fluorouracil (5-FU) or cisplatin were additive when combined with ICB while vinorelbine and etoposide provided no additional benefit when combined with ICB. The combination of 5-FU with ICB augmented an inflammatory tumor microenvironment with markedly increased CD8+ T cell activation and upregulation of IFNγ, TNFα and IL-1β signaling. The effective anti‐tumor immune response of 5-FU chemo-immunotherapy was dependent on CD8+ T cells but was unaffected when TNFα or IL-1β cytokine signaling pathways were blocked. Our study identified additive and non-additive chemotherapy/ICB combinations and suggests a possible role for increased inflammation in the tumor microenvironment as a basis for effective combination therapy.
Influence of Hearing Rehabilitation With Active Middle Ear and Bone Conduction Implants on Postural Control

Background As audition also seems to contribute to balance control, additionally to visual, proprioceptive, and vestibular information, we hypothesize that hearing rehabilitation with active middle ear and bone conduction implants can influence postural control. Methods In a prospective explorative study, the impact of hearing rehabilitation with active middle ear [Vibrant Soundbrige (VSB), MED-EL, Innsbruck, Austria] and bone conduction implants [Bonebridge (BB), MED-EL, Innsbruck, Austria] on postural control in adults was examined in three experiments. Vestibulospinal control was measured by cranio-corpography (CCG), trunk sway velocity (°/s) by the Standard Balance Deficit Test (SBDT), and postural stability with a force plate system, each time in best aided (BA) and unaided (UA) condition with frontal-noise presentation (Fastl noise, 65 dB SPL), followed by subjective evaluation, respectively. Results In 26 subjects [age 55.0 ± 12.8 years; unilateral VSB/BB: n = 15; bilateral VSB/BB: n = 3, bimodal (VSB/BB + hearing aid): n = 8], CCG-analysis showed no difference between BA and UA conditions for the means of distance, angle of displacement, and angle of rotation, respectively. Trunk sway measurements revealed a relevant increase of sway in standing on foam (p = 0.01, r = 0.51) and a relevant sway reduction in walking (p = 0.026, r = 0.44, roll plane) in BA condition. Selective postural subsystem analysis revealed a relevant increase of the vestibular component in BA condition (p = 0.017, r = 0.47). As measured with the Interactive Balance System (IBS), 42% of the subjects improved stability (ST) in BA condition, 31% showed no difference, and 27% deteriorated, while no difference was seen in comparison of means. Subjectively, 4–7% of participants felt that noise improved their balance, 73–85% felt no difference, and 7–23% reported deterioration by noise. Furthermore, 46–50% reported a better task performance in BA condition; 35–46% felt no difference and 4–15% found the UA situation more helpful. Conclusions Subjectively, approximately half of the participants reported a benefit in task performance in BA condition. Objectively, this could only be shown in one mobile SBDT-task. Subsystem analysis of trunk sway provided insights in multisensory reweighting mechanisms.
A Cross-National Comparison on Life Expectancy of Non-Hispanic White Americans

Objectives: Taking the life expectancy (LE) of Non-Hispanic White (NHW) Americans as an example to provide potential references for improving LE globally. Methods: We collected complete data from the United States (US) CDC, Office for National Statistics in the United Kingdom (UK), and the OECD publications, and described LE changes of NHW Americans by cross-national comparison and Arriaga’s method. Results: LE of NHW Americans was not as optimistic as European countries from 2006 to 2018. The LE annual average growth rate was 0.04% for NHW Americans, 0.19% for the UK population, and the median of 25 countries was 0.24%. Compared with the other age groups, the age group 30–34 revealed an inferior impact on the LE of NHW people, of which accidents and intentional self-harm were likely to be the top two direct causes. Conclusion: Finding out the direct causes that affect the LE growth in different age groups is conducive to making a targeted intervention or solving the LE growth bottleneck.
Mental Workload in Neuropsychology: An Example With the NASA-TLX in Adults With HIV

A preliminary set of analyses are presented, where workload was examined in 32 adults infected with the human immunodeficiency virus (HIV). Like the current COVID-19 pandemic (caused by the SARS-CoV-2 virus), HIV can produce a wide variety of symptoms, including various levels of cognitive dysfunction. In fact, a recent meta-analysis estimates that of the 39 million adults infected globally with HIV, 42.6% exhibit some form of HIV-associated neurocognitive disorder. A common cognitive symptom in HIV is decline in attention and executive functioning. Though typically examined by clinicians with less precise traditional paper-and-pencil neuropsychological tests, we examined this aspect of cognitive functioning using a more psychometrically sophisticated task as we had HIV-positive adults perform a computerized tracking task in single, dual, and tri-task conditions via the Multi-Attribute Task (MAT) Battery. Also assessed was mental workload, with the NASA-Task Load Index (NASA-TLX), rarely used in neuropsychology but a standard tool in human factors and neuroergonomics research. As expected, tracking performance declined with task condition difficulty (p < 0.001). Although no direct statistical comparisons were made, MAT performance here appeared worse than the MAT performance of various other groups reported in the research literature and in our laboratory. Ratings of workload also tended to increase as a function of task condition difficulty (p < 0.001). Plotting MAT tracking performance against the Mental Demand subscale scores, large individual differences in this aspect of workload were evident in both optimal and sub-optimal tracking performance. To examine likely variables with a potential impact on Mental Demand, a variety of variables (nadir CD4 count, viral load, depression symptoms, diagnosis of AIDS, presence of opportunistic infection, general cognitive status, etc.) were examined in relation to the Mental Demand scale, with age showing a significant association (r = 0.41, p = 0.022) and a diagnosis of AIDS showing trend associations (ps ≥ 0.066). Findings suggesting a deficit in metacognition or insight are also discussed. It is argued that assessment of workload (and its various aspects or components) can provide valuable additional information in neuropsychology.
Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems

Stress can increase ethanol drinking, and evidence confirms an association between post-traumatic stress disorder (PTSD) and the development of alcohol use disorder (AUD). Exposure to predator odor is considered a traumatic stressor, and predator stress (PS) has been used extensively as an animal model of PTSD. Our prior work determined that repeated exposure to intermittent PS significantly increased anxiety-related behavior, corticosterone levels, and neuronal activation in the hippocampus and prefrontal cortex in naïve male and female C57BL/6J mice. Intermittent PS exposure also increased subsequent ethanol drinking in a subgroup of animals, with heterogeneity of responses as seen with comorbid PTSD and AUD. The present studies built upon this prior work and began to characterize “sensitivity” and “resilience” to PS-enhanced drinking. Ethanol drinking was measured during baseline, intermittent PS exposure, and post-stress; mice were euthanized after 24-h abstinence. Calculation of median and interquartile ranges identified “sensitive” (>20% increase in drinking over baseline) and “resilient” (no change or decrease in drinking from baseline) subgroups. Intermittent PS significantly increased subsequent ethanol intake in 24% of male (↑60%) and in 20% of female (↑71%) C57BL/6J mice in the “sensitive” subgroup. Plasma corticosterone levels were increased significantly after PS in both sexes, but levels were lower in the “sensitive” vs. “resilient” subgroups. In representative mice from “sensitive” and “resilient” subgroups, prefrontal cortex and hippocampus were analyzed by Western Blotting for levels of corticotropin releasing factor (CRF) receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor, vs. separate naïve age-matched mice. In prefrontal cortex, CRF receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor levels were significantly higher in “sensitive” vs. naïve and “resilient” mice only in females. In hippocampus, CRF receptor 1, CRF receptor 2 and glucocorticoid receptor levels were significantly lower in “resilient” vs. naïve and “sensitive” mice across both sexes. These results indicate that sex strongly influences the effects of ethanol drinking and stress on proteins regulating stress and anxiety responses. They further suggest that targeting the CRF system and glucocorticoid receptors in AUD needs to consider the comorbidity of PTSD with AUD and sex of treated individuals.
B81 Bone Vibrator-Induced Vestibular-Evoked Myogenic Potentials: Normal Values and the Effect of Age

Objective To define the normal values and examine the influence of aging on B81 bone vibrator-induced cervical vestibular-evoked myogenic potentials (B81-cVEMPs) and ocular vestibular-evoked myogenic potentials (B81-oVEMPs). Methods Seventy healthy subjects, divided into seven groups according to their ages, were enrolled in this study. The 4–9-, 10–19-, 20–29-, 30–39-, 40–49-, 50–59-, and 60–70-year-old participants were divided into groups I–VII, respectively. B81-cVEMP and B81-oVEMP were recorded in each group. Results The B81-cVEMP response rates for groups I–VII were 100, 100, 100, 100, 95, 95, and 75%, respectively, with significant differences only between groups I–VI and group VII (p = 0.047, p < 0.05). The B81-oVEMP response rates for groups I–VII were 100, 100, 100, 100, 70, 65, and 40%, respectively, with significant differences only between groups I–IV and groups V–VII (p = 0.020, p = 0.008, p = 0.000; p < 0.05). The threshold, P13, and N23 latencies of B81-cVEMP positively correlated with age (r = 0.756, p = 0.000; r = 0.357, p = 0.003; r = 0.316, p = 0.009; p < 0.05). The raw amplitudes and corrected amplitudes negatively correlated with age (r = −0.641, p = 0.000; r = −0.609, p = 0.000, p < 0.05). For B81-oVEMP, the corrected amplitudes negatively correlated with age (r = −0.638, p = 0.000, p<0.05), but the threshold and N10 latency positively correlated with age (r = 0.768, p = 0.000; r = 0.334, p = 0.009, p < 0.05). Moreover, the interaural asymmetry ratio did not significantly correlate with age for B81-cVEMP and B81-oVEMP. Conclusion As age increased, the B81-cVEMP response rate decreased, the thresholds increased, P13 and N23 latencies were prolonged, and the raw amplitude and corrected amplitude decreased. The B81-oVEMP response rate and corrected amplitude decreased, the thresholds increased, and N10 latency was prolonged with age. These changes are probably due to the occurrence of morphological and functional changes in the vestibular system with aging. Therefore, we suggest establishing different reference values according to different age groups when evaluating the VEMP results in patients with vestibular diseases.
The Gut Microbiota of Healthy and Flavobacterium psychrophilum-Infected Rainbow Trout Fry Is Shaped by Antibiotics and Phage Therapies

In the aquaculture sector, there is an increased interest in developing environmentally friendly alternatives to antibiotics in the treatment and prevention of bacterial infections. This requires an understanding of the effects of different treatments on the fish microbiota as a measure for improving the fish health status. In this study, we focused on the freshwater pathogen Flavobacterium psychrophilum and investigated the effects of antibiotics (florfenicol) and phage therapies on the gut microbiota of healthy and infected rainbow trout fry (1–2 g). Florfenicol-coated feed was administered for 10 days, starting two days after the infection procedure. A two-component mix of phage targeting F. psychrophilum (FpV4 and FPSV-D22) was continuously delivered by feed with a prophylactic period of 12 days. Samples of the distal intestine were collected over time (day -1 and 1, 8, and 33 days post-infection) and analyzed by community analysis targeting the 16S rRNA gene (V3–V4 region). Results showed the dysbiosis effect caused both by the infection and by florfenicol administration. Shifts in the overall composition were detected by β-diversity analysis, and changes in specific populations were observed during taxonomic mapping. Measures of α-diversity were only affected in infected fish (large variation observed 1 and 8 dpi). These community alterations disappeared again when fish recovered from the infection and the antibiotic treatment was terminated (33 dpi). Interestingly, phage addition altered the microbiota of the fish independently of the presence of their target bacterium. The overall gut bacterial community in fish fed phage-treated feed was different from the controls at each time point as revealed by β-diversity analysis. However, it was not possible to identify specific bacterial populations responsible for these changes except for an increase of lactic acid bacteria 33 dpi. Overall, the results indicate that the administered phages might affect the complex network of phage-bacteria interactions in the fish gut. Nevertheless, we did not observe negative effects on fish health or growth, and further studies should be directed in understanding if these changes are beneficial or not for the fish health with an additional focus on the host immune response.
Burnout and Its Antecedents: Considering Both Work and Household Time Claims, and Flexibility in Relation to Burnout

This study contributes to the previous literature by examining how flexible work arrangements interact with work and family time claims to affect burnout. It does so by providing a theoretical framework and empirical test of the interaction of flexibility with the effect of work and family time claims on burnout. Hypotheses and predictions based on previous literature are tested by Ordinary Least Squared regression models using data from the Time Competition Survey, constituting a sample of 1,058 employees of 89 function groups within 30 organizations. We found no main effects of work and family time claims or flexible work arrangements on burnout. However, the results do show an interaction of flexible working hours with the effect of work and family time claims on burnout. Specifically, the higher an individual's work and family time claims, the more this person benefits from having flexible working hours. In general, the results support the proposition that the relationship between work and family time claims and burnout differs for individuals with different levels of flexible work arrangements.
Chronic Ethanol Causes Persistent Increases in Alzheimer’s Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment

Epidemiological studies have found that heavy alcohol use is associated with increased risk for Alzheimer’s disease (AD), with frequent drinking earlier in adulthood increasing risk. The increases in neuroinflammation featured in both heavy alcohol use and AD may be partially responsible for this link. However, it is unknown if abstinence mitigates this risk. We hypothesized that binge ethanol during mid adult life would persistently increase AD pathology even after prolonged abstinence. Male and female 3xTg-AD mice (APPSwe, tauP301, Psen1tm1Mpm) which feature progressive amyloid (Aβ) and tau pathology, received chronic binge ethanol (5g/kg/day, 5-days-on/2-days-off, i.g.) or water during adulthood (from 5.5 to 9 months of age), followed by abstinence and assessment at 14 months of age. The effects of ethanol on protective AD genes (e.g., APOE and TREM2) as well as proinflammatory genes were measured by PCR. Levels of pathologic tau and Aβ were measured by immunohistochemistry and western blot. Ethanol caused persistent reductions in protective AD genes: APOE (25% reduction, *p < 0.05), TREM2 (28%, *p < 0.05), LPL (40%, **p < 0.01), and CTSD (24%, *p < 0.05) and promoted a proinflammatory gene signature in female, but not male cortex. Concurrently, ethanol increased total and hyperphosphorylated tau (AT8) in piriform cortex and hippocampus of females, but not males. Levels of AT8 were negatively correlated with APOE (R = –0.67, *p < 0.05) and TREM2 (R = –0.78, **p < 0.005) suggesting protective roles in pathogenesis. No differences were found in levels of main regulators of tau phosphorylation state (GSK3β, PKA, PP2A), suggesting ethanol disrupted clearance of tau. Therefore, we measured the effect of ethanol on lysosomes, which degrade tau, and lysosomal localization of tau using co-immunofluorescence. In females, ethanol caused a persistent reduction in mature LAMP1 lysosomes in CA1 of hippocampus (35%, *p < 0.05), along with a 60% increase in total tau (*p < 0.05). Thus, chronic binge ethanol during mid adult life causes a persistent enhancement of tau pathology in cortical and hippocampal brain regions of females. Persistent AD pathology was associated with an increased proinflammatory signature and a reduction of mature lysosomes. This implicates binge ethanol exposure with increased risk of AD pathologic progression in females.
Factors That Influence Susceptibility Vessel Sign in Patients With Acute Stroke Referred for Mechanical Thrombectomy

Background and Purpose The presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time. Methods We retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis. Results Of the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS– and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS– was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS– was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]). Conclusion In the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset–imaging time for patients with a known symptom onset time.
A Generic User-Defined Modeling Method in PSS/E and Its Application in an MMC-HVDC System

This paper studies the user-defined modeling (UDM) method in PSS/E and applies it to a modular multilevel converter high-voltage direct current (MMC-HVDC) system. First, the mechanism of PSS/E UDM is discussed, including the requirements of the model call, storage space allocation, and flows of dynamic simulation. Then, a generic UDM method applicable to various objects is proposed in PSS/E, considering both the internal structures of models and their interfaces with the PSS/E main program. Next, the design of multiple time scales of UDM is presented for hybrid step size simulation. Accordingly, a user-defined MMC-HVDC system model is built in PSS/E considering the converter, DC-line, control system, and system interface. Finally, the model is compared with a PSCAD electromagnetic transient MMC-HVDC model in a modified two-area-four-generator system. The simulation results demonstrate the proposed UDM method.
Evaluation of the Effects on Uninfected Pregnant Women and Their Pregnancy Outcomes During the COVID-19 Pandemic in Beijing, China

Background People's lifestyles may have changed during the COVID-19 pandemic, which may have a profound impact on pregnant women and newborns. This study aims to assess the effects of the COVID-19 pandemic on uninfected pregnant women and their newborns, including potential environmental factors. Methods We retrospectively analyzed the pregnancy complications of 802 cases in the pandemic group and 802 controls in the pre-pandemic group in a matched nested case-control study, and evaluated the association with sociodemographic features, lifestyles, and other factors in 311 pregnant women with adverse pregnancy outcomes. Results Compared to the pre-pandemic group, the rates of anemia, vaginitis, shoulder dystocia, and adverse pregnancy outcomes such as preterm birth were increased in the pandemic group. After controlling for the covariates, we observed a higher risk of adverse pregnancy outcomes in the pandemic group. Pregnant women with adverse pregnancy outcomes had an increased rate of anemia and vaginal candidiasis. Conclusion COVID-19 pandemic has profound effects on adverse pregnancy outcomes, suggesting the importance of ensuring regular prenatal checkups and keeping a healthy lifestyle.