Miracle-dz/UniFAR-FTUs huggingface dataset:
Temporal Irreversibility of Large-Scale Brain Dynamics in Alzheimer’s Disease

Healthy brain dynamics can be understood as the emergence of a complex system far from thermodynamic equilibrium. Brain dynamics are temporally irreversible and thus establish a preferred direction in time (i.e., arrow of time). However, little is known about how the time-reversal symmetry of spontaneous brain activity is affected by Alzheimer's disease (AD). We hypothesized that the level of irreversibility would be compromised in AD, signaling a fundamental shift in the collective properties of brain activity toward equilibrium dynamics. We investigated the irreversibility from resting-state fMRI and EEG data in male and female human patients with AD and elderly healthy control subjects (HCs). We quantified the level of irreversibility and, thus, proximity to nonequilibrium dynamics by comparing forward and backward time series through time-shifted correlations. AD was associated with a breakdown of temporal irreversibility at the global, local, and network levels, and at multiple oscillatory frequency bands. At the local level, temporoparietal and frontal regions were affected by AD. The limbic, frontoparietal, default mode, and salience networks were the most compromised at the network level. The temporal reversibility was associated with cognitive decline in AD and gray matter volume in HCs. The irreversibility of brain dynamics provided higher accuracy and more distinctive information than classical neurocognitive measures when differentiating AD from control subjects. Findings were validated using an out-of-sample cohort. Present results offer new evidence regarding pathophysiological links between the entropy generation rate of brain dynamics and the clinical presentation of AD, opening new avenues for dementia characterization at different levels. SIGNIFICANCE STATEMENT By assessing the irreversibility of large-scale dynamics across multiple brain signals, we provide a precise signature capable of distinguishing Alzheimer’s disease (AD) at the global, local, and network levels and different oscillatory regimes. Irreversibility of limbic, frontoparietal, default-mode, and salience networks was the most compromised by AD compared with more sensory–motor networks. Moreover, the time-irreversibility properties associated with cognitive decline and atrophy outperformed and complemented classical neurocognitive markers of AD in predictive classification performance. Findings were generalized and replicated with an out-of-sample validation procedure. We provide novel multilevel evidence of reduced irreversibility in AD brain dynamics that has the potential to open new avenues for understating neurodegeneration in terms of the temporal asymmetry of brain dynamics.
Effect of Ice Slurry Beverages on Voluntary Fluid Intake and Exercise Performance

Abstract Ng, J and Wingo, JE. Effect of ice slurry beverages on voluntary fluid intake and exercise performance. J Strength Cond Res 37(6): e376–e383, 2023—Voluntary intake of cold fluid is greater than warm fluid as a result of more favorable palatability, resulting in better maintenance of hydration status and improved exercise performance. It remains unclear whether voluntary ingestion of ice slurry beverages compared with cold fluid during exercise yields superior results. Eight recreationally active subjects (mean ± SD; age = 24 ± 4 years, height = 175.2 ± 7.8 cm, mass = 79.6 ± 11.2 kg, body fat = 13.0 ± 5.2%) completed a pretest in 22° C to determine maximal workload (Wmax). Then, in 2, separate, counterbalanced trials, they cycled for 60 minutes at 50%Wmax in 35° C and 40% relative humidity with either ad libitum ice slurry (−1.3 ± 0.3° C) or cold fluid (11.1 ± 2.4° C) ingestion. This was immediately followed by a 15-minute cycling time trial. Subjects avoided 2% body mass loss in both conditions but ingested twice as much cold fluid as ice slurry (fluid: 1,074.7 ± 442.1 g, ice slurry: 526.9 ± 214.1 g; p = 0.001). Nonetheless, neither 15-minute performances (cold fluid: 119.5 ± 34.8 kJ, ice slurry: 114.6 ± 20.9 kJ; p = 0.59) nor whole-body sweat rates (fluid: 1,370 ± 311 ml·h−1, ice slurry: 1,242 ± 191 ml·h−1; p = 0.20) were different between the conditions. Despite ingesting half as much ice slurry as cold fluid, subjects experienced similar physiological responses and thus had similar performances under heat stress while avoiding excessive hypohydration. Under the conditions of this study, ice slurry ingestion was an effective alternative form of exercise hydration.
Association between impaired glucose metabolism and long-term prognosis at the time of diagnosis of depression: Impaired glucose metabolism as a promising biomarker proposed through a machine-learning approach

Abstract Background Predicting the course of depression is necessary for personalized treatment. Impaired glucose metabolism (IGM) was introduced as a promising depression biomarker, but no consensus was made. This study aimed to predict IGM at the time of depression diagnosis and examine the relationship between long-term prognosis and predicted results. Methods Clinical data were extracted from four electronic health records in South Korea. The study population included patients with depression, and the outcome was IGM within 1 year. One database was used to develop the model using three algorithms. External validation was performed using the best algorithm across the three databases. The area under the curve (AUC) was calculated to determine the model’s performance. Kaplan–Meier and Cox survival analyses of the risk of hospitalization for depression as the long-term outcome were performed. A meta-analysis of the long-term outcome was performed across the four databases. Results A prediction model was developed using the data of 3,668 people, with an AUC of 0.781 with least absolute shrinkage and selection operator (LASSO) logistic regression. In the external validation, the AUCs were 0.643, 0.610, and 0.515. Through the predicted results, survival analysis and meta-analysis were performed; the hazard ratios of risk of hospitalization for depression in patients predicted to have IGM was 1.20 (95% confidence interval [CI] 1.02–1.41, p = 0.027) at a 3-year follow-up. Conclusions We developed prediction models for IGM occurrence within a year. The predicted results were related to the long-term prognosis of depression, presenting as a promising IGM biomarker related to the prognosis of depression.
The relationship between emotional labor level and moral distress

Background The coronavirus disease (COVID-19) pandemic has implications for health professionals. Aim The aim of this study was to explain the relationship between emotional labor levels and moral distress in health professionals during the COVID-19 pandemic using the Structural Equation Modeling (SEM) technique. Research design A descriptive and cross-sectional study was adopted. Participants and research context Data were collected between 7 February and 7 March 2021. 302 health professionals who were not on leave (annual leave, sick leave, prenatal and postnatal leave, etc.) at the time of the research and who volunteered to participate in the research were included. Research data were collected using a “Personal Information Form,” the “Emotional Labor Scale” and the “Moral Distress Thermometer. ” Ethical considerations The Ethics Committee approved the study (dated 07.01.2021 and numbered 2021/1-3). The participants were informed of the study aim and written consent was obtained before completing the survey. Findings In the present study, the mediator role of emotional labor in the effect of providing service to a patient with COVID-19 and having had COVID-19 on moral distress was examined in health professionals and it was found that there was a correlation between providing service to a patient with COVID-19 and moral distress regardless of whether or not emotional labor had a role in this relationship. Conclusion In this study, the relationship between the level of emotional labor and moral distress in health professionals during the COVID-19 pandemic was evaluated with a structural equation model.
Myofibrillar Protein Synthesis and Acute Intracellular Signaling with Elastic Band Resistance Exercise in Young and Older Men

ABSTRACT Purpose Resistance exercise training (RET) attenuates age-related muscle and strength loss (“sarcopenia”). However, compared with machine-based RET, the efficacy of cost-effective, accessible elastic band RET (EB-RET) for muscle adaptive remodeling lacks supporting mechanistic evidence. Methods Eight young (YM; 24 ± 4 yr) and eight older (OM; 68 ± 6 yr) untrained males consumed an oral stable isotope tracer (D2O) combined with serial vastus lateralis muscle biopsies to measure integrated myofibrillar protein synthesis (iMyoPS) and regulatory signaling over ~48 h before (habitual) and after an acute bout of EB-RET (6 × 12 repetitions at ~70% of one-repetition maximum). iMyoPS was determined via gas chromatography–pyrolysis–isotope ratio mass spectroscopy and regulatory signaling expression by immunoblot. Results Habitual iMyoPS did not differ between YM and OM (1.62% ± 0.21% vs 1.43% ± 0.47%·d−1, respectively, P = 0.128). There was a significant increase in iMyoPS after EB-RET in YM (2.23% ± 0.69%·d−1, P = 0.02), but not OM (1.75% ± 0.54%·d−1, P = 0.30). EB-RET increased the phosphorylation of key anabolic signaling proteins similarly in YM and OM at 1 h postexercise, including p-IRS-1Ser636/639, p-AktSer473, p-4EBP-1Thr37/46, p-P70S6KThr389, and p-RPS6Ser240/244, whereas p-TSC2Thr1462 and p-mTORSer2448 increased only in YM (all P < 0.05). There were no differences in the expression of amino acid transporters/sensors or proteolytic markers after EB-RET. Conclusions iMyoPS was elevated after EB-RET in YM but not OM. However, the increase in acute anabolic signaling with EB-RET was largely similar between groups. In conclusion, the capacity for EB-RET to stimulate iMyoPS may be impaired in older age. Further work may be necessary to optimize prescriptive programming in YM and OM.
Changes in food and nutrient intakes in Korean adults before and during the COVID-19 pandemic: data from the 2011-2020 Korea National Health and Nutrition Examination Survey

OBJECTIVES This study was to examine the changes in dietary habits and food and nutrient intakes between before (2019) and during (2020) the coronavirus disease 2019 (COVID-19) pandemic from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS A total of 54,995 participants aged ≥19 years who participated in the 2011-2020 KNHANES were included. The 10-year trend (2011-2020) and differences between 2019 and 2020 for dietary habits and food and nutrient intakes were estimated using SAS. RESULTS In the past 10 years (2011-2020), the dietary habits (increase in skipping meals and eating out), food intake (increase in meats and decrease in fruits and vegetables), and nutrient intake (increase in fat and decrease in sodium) in adults have changed. When comparing between 2019 and 2020, there were 4.6%p decrease in the eating out more than once a day. On the other hand, there were no significant differences in the intakes of food, energy and most of nutrients between 2019 and 2020, except for the proportion of energy intake from fat (1.0%p increase) and carbohydrate (1.0%p decrease). CONCLUSIONS Although a change in dietary habits from before to during the COVID-19 pandemic was observed, food and nutrient intakes have not deteriorated markedly and appear similar to the trends in the past 10 years. Throughout the COVID-19 pandemic, it is necessary to monitor the effects of changes in dietary habits on health as well as food and nutrient intakes.
The Relationship Between Partial and Full Range of Motion Deadlift 1-Repetition Maximum: A Technical Note

Abstract Gillingham, B, Bishop, A, Higa, GK, Adams, KJ, and DeBeliso, M. The relationship between partial and full range of motion deadlift 1-repetition maximum: a technical note. J Strength Cond Res 37(4): 909–914, 2023—The full range of motion (FROM) or partial range of motion (PROM) deadlift (DL) are often included in resistance training (RT) programs and are performed by strength athletes in competition. This study examined the relationship between the FROM and PROM 1-repetition maximum (1RM) DL and if the PROM 1RM DL can be estimated by the FROM 1RM DL. Eighteen National Collegiate Athletic Association wrestlers (20.8 ± 1.2 years, 176.0 ± 5.2 cm, 78.9 ± 10.6 kg) performed a warm-up followed by the assessment of the FROM and PROM 1RM DLs. The FROM DLs were executed with a starting position of the bar resting on the lifting platform. Partial range of motion DLs were executed in a power rack with the bar starting position at ≈2.54 cm above the patella. Regression analysis was employed to estimate PROM 1RM DL based on FROM 1RM DL, body height, and mass. A Pearson’s correlation coefficient (r) was used to compare the PROM 1RM DL with FROM 1RM DL. A dependent t test was used to compare the PROM 1RM DL and FROM 1RM DL scores (α < 0.05). The PROM 1RM DL scores (226.0 ± 40.6 kg) were significantly greater than the FROM 1RM DL scores (191.7 ± 37.2 kg) (p < 0.05: effect size = 0.92). The PCC between the PROM and FROM 1RM DL was r = 0.85 (p < 0.05). The regression coefficient for the FROM 1RM DL was significant (p < 0.05; R = 0.85, R2 = 0.73). The regression coefficients for body mass and height were not significant (p > 0.05). The PROM and FROM DL may be interchangeable modalities within an RT program, and the PROM 1RM DL can be accurately predicted by the FROM 1RM DL.
[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant.

PURPOSE Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant. PATIENTS AND METHODS In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS). RESULTS The HS and PFS in the entire group did not correlate (n=16, Spearman's rho, P=0.06), but patients with a low HS (<25.0%, n=4) had a PFS of >5 months whereas patients with no [18F]FES uptake (HS 100.0%, n =3) had a PFS of <2 months. [18F]FES uptake was not affected by ESR1 mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤1-2 half-lives of rintodestrant whereas it restored in patients scanned ≥5 days after end of treatment. CONCLUSION Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.
Testosterone and Cortisol Salivary Samples Are Stable Across Multiple Freeze-Thaw Cycles

Abstract Sontag, SA, Cabarkapa, D, and Fry, AC. Testosterone and cortisol salivary samples are stable across multiple freeze-thaw cycles. J Strength Cond Res 37(4): 915–918, 2023—When processing salivary samples for biomarker analysis, avoiding multiple freeze-thaw cycles is generally recommended. However, confusing tissue handling instructions or challenges with collections in the field sometimes makes this problematic. Thus, the purpose of this study was to examine if the stability of salivary testosterone (T) and cortisol (C) hormones remains unchanged when exposed to multiple freeze-thaw cycles. Seven healthy recreationally active adults provided salivary samples at rest (i.e., 1600 hours) for analysis of T and C. Samples were separated into 4 aliquots for each hormone and underwent 4 freeze-thaw cycles (T1–T4 and C1–C4) before being analyzed by enzyme-linked immunosorbent assay. The overall analysis of variance model was significant for T (p = 0.008) and nonsignificant for C (p = 0.820). A follow-up post hoc comparison indicated significant differences in salivary hormonal concentrations between T1 and T4 (p = 0.029), T2 and T4 (p = 0.007), and T3 and T4 (p = 0.032). The findings of this study indicate that salivary steroid hormones seem to be relatively stable following multiple freeze-thaw cycles. However, C seems to be more stable when exposed to multiple freeze-thaw cycles, as T concentrations did reveal a significant decrease by the fourth thaw cycle.
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens

Mosquito saliva is a mix of numerous proteins that are injected into the skin while the mosquito searches for a blood meal. While mosquito saliva is known to be immunogenic, the salivary components driving these immune responses, as well as the types of immune responses that occur, are not well characterized. We investigated the effects of one potential immunomodulatory mosquito saliva protein, sialokinin, on the human immune response. We used flow cytometry to compare human immune cell populations between humanized mice bitten by sialokinin knockout mosquitoes or injected with sialokinin, and compared them to those bitten by wild-type mosquitoes, unbitten, or saline-injected control mice. Humanized mice received 4 mosquito bites or a single injection, were euthanized after 7 days, and skin, spleen, bone marrow, and blood were harvested for immune cell profiling. Our results show that bites from sialokinin knockout mosquitoes induced monocyte and macrophage populations in the skin, blood, bone marrow, and spleens, and primarily affected CD11c- cell populations. Other increased immune cells included plasmacytoid dendritic cells in the blood, natural killer cells in the skin and blood, and CD4+ T cells in all samples analyzed. Conversely, we observed that mice bitten with sialokinin knockout mosquitoes had decreased NKT cell populations in the skin, and fewer B cells in the blood, spleen, and bone marrow. Taken together, we demonstrated that sialokinin knockout saliva induces elements of a TH1 cellular immune response, suggesting that the sialokinin peptide is inducing a TH2 cellular immune response during wild-type mosquito biting. These findings are an important step towards understanding how mosquito saliva modulates the human immune system and which components of saliva may be critical for arboviral infection. By identifying immunomodulatory salivary proteins, such as sialokinin, we can develop vaccines against mosquito saliva components and direct efforts towards blocking arboviral infections.
Pressure drop due to the motion of neutrally buoyant particles in duct flows

The additional pressure drop arising from the presence of a neutrally-buoyant, eccentrically positioned, spherical particle in a Poiseuille flow is calculated to O(a/Ro)5 (a = sphere radius; Ro = tube radius). Similar calculations (of a lesser order of accuracy) are given for non-circular conduits and for ellipsoidal particles. Due to changes in particle orientation resulting from rotation, the instantaneous pressure drop for an ellipsoid of revolution varies periodically with time. This pressure diminution is averaged over one period to obtain the time-average pressure drop.
Trends in the incidence of hospital-treated suicide attempts during the COVID-19 pandemic in Oviedo, Spain

Abstract Background The potential impact of the COVID-19 pandemic on suicidal behavior has generated predictions anticipating an increase in suicidal tendencies. The aim of this research is to study its influence on the incidence of hospital-treated suicide attempts throughout the year 2020 in Oviedo, Spain. Methods Data were collected on all patients admitted to the emergency department of Central University Hospital of Asturias in Oviedo for attempted suicide during 2020. Incidence rates were calculated for three lockdown periods. Suicide attempt trends in 2020 were compared with a non-COVID-19 year (2009) to avoid seasonal variations bias. Chi-square and Fisher’s exact tests were performed. The influence of COVID-19 incidence in Oviedo was analyzed using Spearman’s correlation coefficient. Results The cumulative incidence rate of attempted suicide per 100,000 person-years was 136.33 (pre-lockdown), 115.15 (lockdown), and 90.25 (post-lockdown) in adults (over 19 years old), and 43.63 (pre-lockdown), 32.72 (lockdown), and 72.72 (post-lockdown) in adolescents (10–19 years old). No association was found with COVID-19 incidence rates (Spearman’s rho −0.222; p = 0.113). Comparing the years 2020 and 2009, statistically significant differences were observed in adolescents (Fisher’s exact test; p = 0.024), but no differences were observed in adults (chi-square test = 3.0401; p = 0.218). Conclusions Hospital-treated suicide rates attempted during the COVID-19 outbreak in Oviedo, Spain showed a similar trend compared with a non-COVID-19 year. In contrast, the number of adolescents hospital-treated for attempted suicide increased during lockdown, suggesting more vulnerability to COVID-19 restrictions after the initial lockdown period in this age group.
Inhibiting the Deubiquitinase UCHL1 Reduces SARS-CoV-2 Viral Uptake by ACE2

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a significant public health burden with limited treatment options. Many β-coronaviruses, including SARS-CoV-2, gain entry to host cells through the interaction of SARS-CoV-2 spike protein with membrane-bound ACE2 (angiotensin-converting enzyme 2). Given its necessity for SARS-CoV-2 infection, ACE2 represents a potential therapeutic target in COVID-19. However, early attempts focusing on ACE2 in COVID-19 have not validated it as a druggable target nor identified other ACE2-related novel proteins for therapeutic intervention. Here, we identify a mechanism for ACE2 protein modulation by the deubiquitinase (DUB) enzyme UCHL1 (ubiquitin carboxyl-terminal hydrolase isozyme L1). ACE2 is constitutively ubiquitinated and degraded by the proteasome in lung epithelia. SARS-CoV-2 spike protein cellular internalization increased ACE2 protein abundance by decreasing its degradation. Using an siRNA library targeting 96 human DUBs, we identified UCHL1 as a putative regulator of ACE2 function as a viral receptor. Overexpressed UCHL1 preserved ACE2 protein abundance, whereas silencing of the DUB in cells destabilized ACE2 through increased polyubiquitination. A commercially available small molecule inhibitor of UCHL1 DUB activity decreased ACE2 protein concentrations coupled with inhibition of SARS-CoV-2 infection in epithelial cells. These findings describe a unique pathway of ACE2 regulation uncovering UCHL1 as a potential therapeutic target to modulate COVID-19 viral entry as a platform for future small molecule design and testing.