Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of biopsychological trait markers in functional neurological disorders

Abstract Stress is a well-known risk factor to develop a functional neurological disorder, a frequent neuropsychiatric medical condition in which patients experience a variety of disabling neurological symptoms. Only little is known about biological stress regulation, and how it interacts with predisposing biological and psychosocial risk factors. Dysregulation of the hypothalamic–pituitary–adrenal axis in patients with functional neurological disorders has been postulated, but its relationship to preceding psychological trauma and brain anatomical changes remains to be elucidated. We set out to study the hypothalamic–pituitary–adrenal axis analysing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and the severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations in brain regions particularly sensitive to psychosocial stress, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure. Overall, patients had a significantly flatter cortisol awakening response (P < 0.001) and reported longer (P = 0.01) and more severe (P < 0.001) emotional neglect as compared to healthy controls. Moreover, volumes of the bilateral amygdala and hippocampus were found to be reduced in patients. Using a partial least squares correlation, we found that in patients, emotional neglect plays a role in the multivariate pattern between trauma history and hypothalamic–pituitary–adrenal axis dysfunction, while cortisol did not relate to reduced brain volumes. This suggests that psychological stress acts as a precipitating psychosocial risk factor, whereas a reduced brain volume rather represents a biological predisposing trait marker for the disorder. Contrarily, an inverse relationship between brain volume and cortisol was found in healthy controls, representing a potential neurotoxic effect of cortisol. These findings support the theory of reduced subcortical volumes representing a predisposing trait factor in functional neurological disorders, rather than a state effect of the illness. In summary, this study supports a stress–diathesis model for functional neurological disorders and showed an association between different attributes of trauma history and abnormalities in hypothalamus–pituitary–adrenal axis function. Moreover, we suggest that reduced hippocampal and amygdalar volumes represent a biological ‘trait marker’ for functional neurological disorder patients, which might contribute to a reduced resilience to stress.
A STUDY OF VARIATIONS OF THE GENERAL CIRCULATION

Abstract Changes of the general circulation, especially the strength of the upper westerlies, over 28 months are investigated quantitatively.The role of the high troposphere, represented by the 300-mb level, is stressed and it is sought to determine whether the tropics have any measurable influence on middle-latitude weather. Computations cover the latitude belt 10°N to 70°N, at least for part of the periods studied. To bring out the fluctuations clearly, they are expressed in terms of deviations from seasonal and mean latitudinal gradients. These deviations amount to over 20 per cent of the mean circulation, even in the belt of strongest westerlies. The concern is not with very small values whose accuracy would be questionable. When the latitudinal distribution of deviations, especially those of momentum of the westerlies, is plotted against time, definite long-term trends appear. Bands of high and low westerly momentum gradually traverse the latitude circles, sometimes from north to south, but usually f.
Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities

Background and Objectives Previous research has examined the association between cognition and flavonoids: bioactives found in foods, known to possess anti-inflammatory and antioxidant properties. We extend this research by investigating associations of dietary intakes of total flavonols and constituents (kaempferol, quercetin, myricetin, and isorhamnetin) on the change in cognitive performance in global cognition, episodic memory, semantic memory, visuospatial ability, perceptual speed, and working memory. Methods The study was conducted using 961 participants (aged 60–100 years) of the Rush Memory and Aging Project, a prospective cohort of community-dwelling Chicagoans who were followed for an average of 6.9 years. Diet was assessed using a validated semiquantitative food frequency questionnaire. Cognitive performance was assessed annually with a battery of 19 standardized tests. Flavonol intake was analyzed as a continuous variable using linear mixed-effects models. Cognitive domain scores were regressed on baseline calorie-adjusted flavonol variables. Results Higher dietary intakes of total flavonols and flavonol constituents were associated with a slower rate of decline in global cognition and multiple cognitive domains. In continuous models adjusted for age, sex, education, APOE ɛ4, late-life cognitive activity, physical activity, and smoking, total flavonol intake was associated with slower decline in global cognition β estimate = 0.004 (95% CI 0.001–0.006), episodic memory β = 0.004 (95% CI 0.002–0.006), semantic memory β = 0.003 (95% CI 0.001–0.007), perceptual speed β = 0.003 (95% CI 0.001–0.004), and working memory β = 0.003 (95% CI 0.001–0.005) and marginally associated with visuospatial ability β = 0.001 (95% CI −0.001 to 0.003). Analyses of individual flavonol constituents demonstrated that intakes of kaempferol and quercetin were associated with slower global cognitive decline (β = 0.01 [95% CI 0.006–0.02] and β = 0.004 [95% CI 0.0005–0.007]), respectively. Myricetin and isorhamnetin were not associated with global cognition. Discussion Results suggest that dietary intakes of total flavonols and several flavonol constituents may be associated with slower decline in global cognition and multiple cognitive abilities with older age.
A Measure of Association Based on Gini's Mean Difference

A measure of association between two random variables is proposed, which represents a compromise between the classical correlation coefficient and the rank correlation coefficient. The new measure is based on the covariance between two variables where one variable is taken in its variate values while the other is ranked. The large sample distribution of this measure is studied and some possible applications are mentioned.
Machine learning identifies a profile of inadequate responder to methotrexate in rheumatoid arthritis

Abstract Objectives Around 30% of patients with RA have an inadequate response to MTX. We aimed to use routine clinical and biological data to build machine learning models predicting EULAR inadequate response to MTX and to identify simple predictive biomarkers. Methods Models were trained on RA patients fulfilling the 2010 ACR/EULAR criteria from the ESPOIR and Leiden EAC cohorts to predict the EULAR response at 9 months (± 6 months). Several models were compared on the training set using the AUROC. The best model was evaluated on an external validation cohort (tREACH). The model's predictions were explained using Shapley values to extract a biomarker of inadequate response. Results We included 493 therapeutic sequences from ESPOIR, 239 from EAC and 138 from tREACH. The model selected DAS28, Lymphocytes, Creatininemia, Leucocytes, AST, ALT, swollen joint count and corticosteroid co-treatment as predictors. The model reached an AUROC of 0.72 [95% CI (0.63, 0.80)] on the external validation set, where 70% of patients were responders to MTX. Patients predicted as inadequate responders had only 38% [95% CI (20%, 58%)] chance to respond and using the algorithm to decide to initiate MTX would decrease inadequate-response rate from 30% to 23% [95% CI: (17%, 29%)]. A biomarker was identified in patients with moderate or high activity (DAS28 > 3.2): patients with a lymphocyte count superior to 2000 cells/mm3 are significantly less likely to respond. Conclusion Our study highlights the usefulness of machine learning in unveiling subgroups of inadequate responders to MTX to guide new therapeutic strategies. Further work is needed to validate this approach.
Pregnancy and sickle cell disease: an overview of complications and suggested perinatal care

ABSTRACT Introduction Pregnancy in women with sickle cell disease (SCD) has been identified as high risk owing to increased incidence of materno-fetal complications across various studies and reports. These complications include consequences related to the underlying hemoglobinopathy; chronic anemia/associated inflammation, and pregnancy related including the risk for thromboembolism, bleeding and maternal mortality. Outcomes of neonates born to women with SCD has been suboptimal over the years with recent improvement due to strict monitoring, preventive and therapeutic measures. Much is yet to be unraveled regarding the optimal management of women with SCD during pregnancy, identifying target hemoglobin, delivery mode or timing among others. Areas covered This review includes a summary of available data of the maternal and fetal outcomes; in addition to current recommendations for monitoring and management of women with SCD during pregnancy. Expert opinion To have a successful pregnancy, women should be closely monitored, and interventions provided as needed to guarantee adequate management of anemia, as well as prevention, diagnosis and management of disease. They should also be educated regarding their reproductive health, emphasizing that pregnancy is possible, and achieving optimal results depends on providing adequate care in a health care facility with expertise in high-risk pregnancies and SCD.
The changes of electroencephalography in mountaineers on Mount Jade, Taiwan: An observational study

Background The diagnosis of acute mountain sickness, which lacks a reliable and objective diagnostic tool, still depends on the clinical symptoms and signs and remains a major threat and unpredictable disease affecting millions of mountaineers. Objectives To record electroencephalography signals with small, convenient, wireless equipment and to test whether electroencephalography parameters, which are more sensitive and reliable markers, could predict the symptoms of acute mountain sickness. Methods Twenty-five participants were enrolled and separated into two groups to climb Mount Jade in Taiwan. We collected electrocardiography signals and arterial oxygen saturation data at ground, moderate (2,400 m), and high altitude (3,400 m). A spectral analysis of the electrocardiography was performed to assess the study subjects’ electroencephalography activity at different frequencies (α, β, θ, δ) and the mean power frequency of electrocardiography. The clinical symptoms and Lake Louise Acute Mountain Sickness scores of the subjects were recorded for comparison. Results A significant change in the δ power of electroencephalography was recorded in subjects ascending from the ground to a high altitude of 3,400 m in a 4-day itinerary. In addition, between the two groups of subjects with and without acute mountain sickness (Lake Louise Acute Mountain Sickness scores < 3 and ≥ 3), the δ power of electroencephalography at the fronto-parietal 1 and parietal 3 electrodes at moderate altitude as well as the changes of δ power and mean power frequency of electrocardiography over parietal 4 at high altitude showed a significant difference. At moderate altitude, the increasing δ power of electroencephalography at the parietal 4 electrode was related to the headache symptom of acute mountain sickness before ascending to high altitude. Conclusion At moderate altitude, the δ power increase of electroencephalography at the P4 electrode could be a predictor of acute mountain sickness symptoms before ascending to high altitude. Thus, electroencephalography had the potential to identify the risk of acute mountain sickness.
Characterization of FcγRIa (CD64) as a Ligand Molecule for Site-Specific IgG1 Capture: A Side-By-Side Comparison with Protein A

Fc γ receptors (FcγRs) are one of the structures that can initiate effector function for monoclonal antibodies. FcγRIa has the highest affinity toward IgG1-type monoclonal antibodies among all FcγRs. In this study, a comprehensive characterization was performed for FcγRIa as a potential affinity ligand for IgG1-type monoclonal antibody binding. The binding interactions were assessed with the SPR technique using different immobilization techniques such as EDC-NHS coupling, streptavidin–biotin interaction, and His-tagged FcγRIa capture. The His-tagged FcγRIa capture was the most convenient method based on assay repeatability. Next, a crude IgG1 sample and its fractions with different monomer contents obtained from protein A affinity chromatography were used to evaluate FcγRIa protein in terms of monoclonal antibody binding capacity. The samples were also compared with a protein A-immobilized chip (a frequently used affinity ligand) for IgG1 binding responses. The antibody binding capacity of the protein A-immobilized chip surface was significantly better than that of the FcγRIa-immobilized chip surface due to its 5 Ig binding domains. The antibody binding responses changed similarly with protein A depending on the monomer content of the sample. Finally, a different configuration was used to assess the binding affinity of free FcγRs (FcγRIa, FcγRIIa, and FcγRIIIa) to three different immobilized IgGs by immobilizing protein L to the chip surface. Unlike previous immobilization techniques tested where the FcγRIa was utilized as a ligand, nonimmobilized or free FcγRIa resulted in a significantly higher antibody binding response than free protein A. In this configuration, kinetics data of FcγRI revealed that the association rate (ka 50–80 × 105 M–1 s–1) increased in comparison to His capture method (1.9–2.4 × 105 M–1 s–1). In addition, the dissociation rate (kd 10–5 s–1) seemed slower over the His capture method (10–4 s–1) and provided stability on the chip surface during the dissociation phase. The KD values for FcγRIa were found in the picomolar range (2.1–10.33 pM from steady-state affinity analysis and 37.5–46.2 pM from kinetic analysis) for IgG1-type antibodies. FcγRIa possesses comparable ligand potential as well as protein A. Even though the protein A-immobilized surface bound more antibodies than the FcγRIa-captured surface, FcγRIa presented a significant antibody binding capacity in protein L configuration. The results suggest FcγRIa protein as a potential ligand for site-oriented immobilization of IgG1-type monoclonal antibodies, and it needs further performance investigation on different surfaces and interfaces for applications such as sensing and antibody purification.
The impact of context on pattern separation for objects among younger and older apolipoprotein ϵ4 carriers and noncarriers

Abstract Objective: On continuous recognition tasks, changing the context objects are embedded in impairs memory. Older adults are worse on pattern separation tasks requiring identification of similar objects compared to younger adults. However, how contexts impact pattern separation in aging is unclear. The apolipoprotein (APOE) ϵ4 allele may exacerbate possible age-related changes due to early, elevated neuropathology. The goal of this study is to determine how context and APOE status affect pattern separation among younger and older adults. Method: Older and younger ϵ4 carriers and noncarriers were given a continuous object recognition task. Participants indicated if objects on a Repeated White background, Repeated Scene, or a Novel Scene were old, similar, or new. The proportions of correct responses and the types of errors made were calculated. Results: Novel scenes lowered recognition scores compared to all other contexts for everyone. Younger adults outperformed older adults on identifying similar objects. Older adults misidentified similar objects as old more than new, and the repeated scene exacerbated this error. APOE status interacted with scene and age such that in repeated scenes, younger carriers produced less false alarms, and this trend switched for older adults where carriers made more false alarms. Conclusions: Context impacted recognition memory in the same way for both age groups. Older adults underutilized details and over relied on holistic information during pattern separation compared to younger adults. The triple interaction in false alarms may indicate an even greater reliance on holistic information among older adults with increased risk for Alzheimer’s disease.
Acute Effect of Resistance Training With Blood Flow Restriction on Perceptual Responses: A Systematic Review and Meta-Analysis

Context: Several studies have compared perceptual responses between resistance exercise with blood flow restriction and traditional resistance exercise (non-BFR). However, the results were contradictory. Objectives: To analyze the effect of RE+BFR versus non-BFR resistance exercise [low-load resistance exercise (LL-RE) or high-load resistance exercise (HL-RE)] on perceptual responses. Data Sources: CINAHL, Cochrane Library, PubMed®, Scopus, SPORTDiscus, and Web of Science were searched through August 28, 2021, and again on August 25, 2022. Study Selection: Studies comparing the effect of RE+BFR versus non-BFR resistance exercise on rate of perceived exertion (RPE) and muscle pain/discomfort were considered. Meta-analyses were conducted using the random effects model. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 2. Data Extraction: All data were reviewed and extracted independently by 2 reviewers. Disagreements were resolved by a third reviewer. Results: Thirty studies were included in this review. In a fixed repetition scheme, the RPE [standardized mean difference (SMD) = 1.04; P < 0.01] and discomfort (SMD = 1.10; P < 0.01) were higher in RE+BFR than in non-BFR LL-RE, but similar in sets to voluntary failure. There were no significant differences in RPE in the comparisons between RE+BFR and non-BFR HL-RE; after sensitivity analyses, it was found that the RPE was higher in non-BFR HL-RE in a fixed repetition scheme. In sets to voluntary failure, discomfort was higher in RE+BFR versus non-BFR HL-RE (SMD = 0.95; P < 0. 01); however, in a fixed scheme, the results were similar. Conclusion: In sets to voluntary failure, RPE is similar between RE+BFR and non-BFR exercise. In fixed repetition schemes, RE+BFR seems to promote higher RPE than non-BFR LL-RE and less than HL-RE. In sets to failure, discomfort appears to be similar between LL-RE with and without BFR; however, RE+BFR appears to promote greater discomfort than HL-RE. In fixed repetition schemes, the discomfort appears to be no different between RE+BFR and HL-RE, but is lower in non-BFR LL-RE.
Chronic obstructive pulmonary disease is associated with an increased risk of herpes zoster: A retrospective United States claims database analysis

Chronic obstructive pulmonary disease (COPD) has been reported as a potential risk factor for developing herpes zoster (HZ). We aimed at comparing incidence rates of HZ between people with versus without COPD in the US. This retrospective cohort study used data from Optum's de‐identified Clinformatics Data Mart database from 1/1/2013 through 12/31/2018. We identified two cohorts of people ≥40 years without prior HZ, HZ vaccination, postherpetic neuralgia (PHN) or HZ ophthalmicus: those with (COPD+) and those without (COPD−) a COPD diagnosis. Adjusted incidence rate ratios (aIRRs) of HZ and PHN were calculated using generalized linear models, controlling for the propensity score of being diagnosed with COPD and relevant demographic and clinical characteristics. People in the COPD+ cohort (n = 161 970) were considerably older, had more comorbidities and were more likely to use corticosteroids than those in the COPD− cohort (n = 9 643 522). The incidence rate of HZ was 5.7‐fold higher in the COPD+ versus COPD− cohorts (13.0 vs. 2.3 per 1000 person‐years [PY]; aIRR, 2.77; 95% confidence interval [CI], 2.69 to 2.85; P < 0.001). The unadjusted incidence rate of PHN was 1.7‐fold higher in the COPD+/HZ+ versus COPD−/HZ+ cohort (64.8 vs. 37.1 per 1000 PY), but not after adjustment (aIRR, 1.07; 95% CI, 0.79 to 1.45). HZ and PHN incidence rates increased with age. After adjustment, COPD+ adults had a 2.8‐fold increased risk of developing HZ. These results may help to increase awareness about potential risk factors for HZ and highlight the need for vaccination among those at increased risk.
The recognition problem for topological manifolds: a survey

This is a survey of recent work on the problem of recognizing topological manifolds among topological spaces, including the results of J.L. Bryant, S.C. Ferry, W. Mio and S. Weinberger in higher dimensions, and M.V. Brahm, R.J. Daverman and D. Repovs in dimen-
How providing public COVID-19 mitigation instructions in a foreign language can increase people’s sense of control

Processing information in a learned foreign language can alter one’s judgment or cognitive evaluation of stimuli. Documented consequences include a reduction in perceived negativity and perceived severity of crime or diseases. The global COVID-19 pandemic has offered a unique opportunity to investigate this phenomenon in a real-life public health communication context. The aim of this study is to investigate how foreign language processing influences people’s reaction towards freedom-restrictive messages. In our experimental study (N = 605), we presented participants with pandemic mitigation instructions in their native language versus a learned foreign language and assessed their perceived sense of control, cognitive evaluation of the instructions, and the intention to adhere to them. The results indicated that the use of a foreign language influenced people’s perceived sense of control in a way that might intuitively be surprising: foreign language enhanced sense of control. This positively influenced the cognitive evaluation of the instructions’ effectiveness and the intention to comply with them. The present research demonstrates that foreign language processing influences individuals’ responses to specific, real-life instructions. Our results provide important contributions to the literature on foreign language effects and public communication and enable practitioners to more accurately predict recipient responses to global crisis communications.
MPC2 variants disrupt mitochondrial pyruvate metabolism and cause an early-onset mitochondriopathy

Abstract Pyruvate is an essential metabolite produced by glycolysis in the cytosol and must be transported across the inner mitochondrial membrane into the mitochondrial matrix, where it is oxidized to fuel mitochondrial respiration. Pyruvate import is performed by the mitochondrial pyruvate carrier (MPC), a hetero-oligomeric complex composed by interdependent subunits MPC1 and MPC2. Pathogenic variants in the MPC1 gene disrupt mitochondrial pyruvate uptake and oxidation and cause autosomal-recessive early-onset neurological dysfunction in humans. The present work describes the first pathogenic variants in MPC2 associated with human disease in four patients from two unrelated families. In the first family, patients presented with antenatal developmental abnormalities and harboured a homozygous c.148T>C (p.Trp50Arg) variant. In the second family, patients that presented with infantile encephalopathy carried a missense c.2T>G (p.Met1? ) variant disrupting the initiation codon. Patient-derived skin fibroblasts exhibit decreased pyruvate-driven oxygen consumption rates with normal activities of the pyruvate dehydrogenase complex and mitochondrial respiratory chain and no defects in mitochondrial content or morphology. Re-expression of wild-type MPC2 restored pyruvate-dependent respiration rates in patient-derived fibroblasts. The discovery of pathogenic variants in MPC2 therefore broadens the clinical and genetic landscape associated with inborn errors in pyruvate metabolism.