Miracle-dz/UniFAR-FTUs huggingface dataset:
Marine CO2 Patterns in the Northern Salish Sea

Marine carbon dioxide (CO2) system data has been collected from December 2014 to June 2018 in the northern Salish Sea (NSS; British Columbia, Canada) and consisted of continuous measurements at two sites as well as spatially- and seasonally-distributed discrete seawater samples. The array of CO2 observing activities included high-resolution CO2 partial pressure (pCO2) and pHT (total scale) measurements made at the Hakai Institute’s Quadra Island Field Station (QIFS) and from an Environment Canada weather buoy, respectively, as well as discrete seawater measurements of pCO2 and total dissolved inorganic carbon (TCO2) obtained during a number of field campaigns. A relationship between NSS alkalinity and salinity was developed with the discrete datasets and used with the continuous measurements to highly resolve the marine CO2 system. Collectively, these datasets provided insights into the seasonality in this historically under-sampled region and detail the area’s tendency for aragonite saturation state () to be at non-corrosive levels (i.e. > 1) only in the upper water column during spring and summer months. This depth zone and time period of reprieve can be periodically interrupted by strong northwesterly winds that drive short-lived (~1 week) episodes of high-pCO2, low-pH, and low- conditions throughout the region. Interannual variability in summertime conditions was evident and linked to reduced northwesterly winds and increased stratification. Anthropogenic CO2 in NSS surface water was estimated using data from 2017 combined with the global atmospheric CO2 forcing for the period 1765 to 2100, and projected a mean value of 49 ± 5 µmol kg-1 for 2018. The estimated trend in anthropogenic CO2 was further used to assess the evolution of and pHT levels in NSS surface water, and revealed that wintertime corrosive conditions were likely absent pre-1900. The percent of the year spent above = 1 has dropped from ~98% in 1900 to ~60% by 2018. Over the coming decades, winter pHT and spring and summer are projected to decline to conditions below identified biological thresholds for select vulnerable species.
A Perspective of Coagulation Dysfunction in Multiple Sclerosis and in Experimental Allergic Encephalomyelitis

A key role of both coagulation and vascular thrombosis has been reported since the first descriptions of multiple sclerosis (MS). Subsequently, the observation of a close concordance between perivascular fibrin(ogen) deposition and the occurrence of clinical signs in experimental allergic encephalomyelitis (EAE), an animal model of MS, led to numerous investigations focused on the role of thrombin and fibrin(ogen). Indeed, the activation of microglia, resident innate immune cells, occurs early after fibrinogen leakage in the pre-demyelinating lesion stage of EAE and MS. Thrombin has both neuroprotective and pro-apoptotic effects according to its concentration. After exposure to high concentrations of thrombin, astrocytes become reactive and lose their neuroprotective and supportive functions, microglia proliferate, and produce reactive oxygen species, IL-1β, and TNFα. Heparin inhibits the thrombin generation and suppresses EAE. Platelets play an important role too. Indeed, in the acute phase of the disease, they begin the inflammatory response in the central nervous system by producing of IL-1alpha and triggering and amplifying the immune response. Their depletion, on the contrary, ameliorates the course of EAE. Finally, it has been proven that the use of several anticoagulant agents can successfully improve EAE. Altogether, these studies highlight the role of the coagulation pathway in the pathophysiology of MS and suggest possible therapeutic targets that may complement existing treatments.
EEG-Based Neurocognitive Metrics May Predict Simulated and On-Road Driving Performance in Older Drivers

The number of older drivers is steadily increasing, and advancing age is associated with a high rate of automobile crashes and fatalities. This can be attributed to a combination of factors including decline in sensory, motor, and cognitive functions due to natural aging or neurodegenerative diseases such as HIV-Associated Neurocognitive Disorder (HAND). Current clinical assessment methods only modestly predict impaired driving. Thus, there is a need for inexpensive and scalable tools to predict on-road driving performance. In this study EEG was acquired from 39 HIV+ patients and 63 healthy participants (HP) during: 3-Choice-Vigilance Task (3CVT), a 30-min driving simulator session, and a 12-mile on-road driving evaluation. Based on driving performance, a designation of Good/Poor (simulator) and Safe/Unsafe (on-road drive) was assigned to each participant. Event-related potentials (ERPs) obtained during 3CVT showed increased amplitude of the P200 component was associated with bad driving performance both during the on-road and simulated drive. This P200 effect was consistent across the HP and HIV+ groups, particularly over the left frontal-central region. Decreased amplitude of the late positive potential (LPP) during 3CVT, particularly over the left frontal regions, was associated with bad driving performance in the simulator. These EEG ERP metrics were shown to be associated with driving performance across participants independent of HIV status. During the on-road evaluation, Unsafe drivers exhibited higher EEG alpha power compared to Safe drivers. The results of this study are 2-fold. First, they demonstrate that high-quality EEG can be inexpensively and easily acquired during simulated and on-road driving assessments. Secondly, EEG metrics acquired during a sustained attention task (3CVT) are associated with driving performance, and these metrics could potentially be used to assess whether an individual has the cognitive skills necessary for safe driving.
Insights From Analysis of Human Antigen-Specific Memory B Cell Repertoires

Memory B cells that are generated during an infection or following vaccination act as sentinels to guard against future infections. Upon repeat antigen exposure memory B cells differentiate into new antibody-secreting plasma cells to provide rapid and sustained protection. Some pathogens evade or suppress the humoral immune system, or induce memory B cells with a diminished ability to differentiate into new plasma cells. This leaves the host vulnerable to chronic or recurrent infections. Single cell approaches coupled with next generation antibody gene sequencing facilitate a detailed analysis of the pathogen-specific memory B cell repertoire. Monoclonal antibodies that are generated from antibody gene sequences allow a functional analysis of the repertoire. This review discusses what has been learned thus far from analysis of diverse pathogen-specific memory B cell compartments and describes major differences in their repertoires. Such information may illuminate ways to advance the goal of improving vaccine and therapeutic antibody design.
Role of Vonoprazan in Helicobacter pylori Eradication Therapy in Japan

Complete eradication of Helicobacter pylori is important for preventing the development of gastric cancer. The outcome of H. pylori eradication therapy is mainly dependent on bacterial susceptibility to antimicrobial agents and potent neutralization of intragastric pH across 24 h, especially when using acid-sensitive antimicrobial agents such as clarithromycin (CLR), amoxicillin and sitafloxacin. However, conventional regimens comprising twice-daily doses (bid) of proton pump inhibitors (PPIs) are generally insufficient for maintaining the required gastric acid secretion for 24 h for successful eradication in all H. pylori-positive patients. Further, the increasing prevalence of CLR-resistant strains with each year has led to a decrease in eradication rates of first-line PPI- and CLR-containing therapies in developed countries, including Japan. In 2015, the potassium-competitive acid blocker vonoprazan (VPZ) became clinically available in Japan. VPZ competitively inhibits H+/K+-ATPase activity more potently than PPIs (e.g., omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole). Therefore, a VPZ-containing H. pylori eradication regimen is expected to increase the eradication rate compared with conventional regimens containing a standard dose of PPI. In fact, a recent meta-analysis that investigated the efficacy of first-line eradication therapy showed that a VPZ-containing regimen achieved a higher eradication rate than a PPI-containing regimen. While the Maastricht V/Florence Consensus Report recommends selecting a bismuth or non-bismuth quadruple therapy and concomitant therapy for patients living in areas with high prevalence of CLR resistance, a VPZ-containing regimen demonstrates effectiveness for patients infected with CLR-resistant strains and patients living in areas where the prevalence of CLR-resistant strains is >15%. As a next step, studies are needed to determine the factors affecting the clinical outcome of VPZ-containing therapy and optimal VPZ-containing alternative regimens for tailored treatments. In this review, we summarize the advantages and disadvantages of VPZ in H. pylori eradication therapy.
In Pursuit of the Epithelial Mechanosensitivity Mechanisms

Mechanosensation is critical for normal gastrointestinal (GI) function. Disruption in GI mechanosensation leads to human diseases. Mechanical forces in the GI tract are sensed by specialized mechanosensory cells, as well as non-specialized mechanosensors, like smooth muscle cells. Together, these cellular mechanosensors orchestrate physiologic responses. GI epithelium is at the interface of the body and the environment. It encounters a variety of mechanical forces that range from shear stress due to flow of luminal contents to extrinsic compression due to smooth muscle contraction. Mechanical forces applied to the GI mucosa lead to a large outflow of serotonin, and since serotonin is concentrated in a single type of an epithelial cell, called enterochromaffin cell (ECC), it was assumed that ECC is mechanosensitive. Recent studies show that a subset of ECCs is indeed mechanosensitive and that Piezo2 mechanosensitive ion channels are necessary for coupling force to serotonin release. This review aims to place this mechanism into the larger context of ECC mechanotransduction.
The Academic Anxiety Inventory: Evidence for Dissociable Patterns of Anxiety Related to Math and Other Sources of Academic Stress

Anxiety about mathematics can have detrimental effects on performance and understanding, yet little research has investigated how math anxiety is related to other types of anxiety. Here we develop the Academic Anxiety Inventory (AAI), an efficient and valid self-report measure designed to test math anxiety, as well as differentiate anxiety associated with mathematics from other contributions of anxiety across various academic domains. In Study 1, we isolated items that independently measure each domain of anxiety, reducing the overlapping variance between math anxiety and other constructs, and determining which components can or cannot be differentiated. Studies 2 and 3 demonstrate that the AAI is consistent and reliable for undergraduate and adolescent populations. In Study 3, anxiety-related performance deficits in a high school math class were associated with scores the AAI-Math subscale. In Study 4, the AAI-Math subscale was associated with perceptions of increased mathematical complexity, decreased estimations of accuracy, and increased negative emotion when participants viewed mathematical expressions. Across four studies, we demonstrate the AAI is a reliable and valid measure of math anxiety and other domains of academic anxiety, providing an efficient questionnaire to determine areas in which students may require extra support in order to reach their full potential.
Linking Parenting and Social Competence in School-Aged Boys and Girls: Differential Socialization, Diathesis-Stress, or Differential Susceptibility?

Girls generally demonstrate superior skill levels in social competence compared to boys. The exact relations of parenting with these gender differences are currently unclear. Gender differences may occur due to exposure to different parenting strategies (differential socialization model) or due to a different impact of similar parenting strategies for boys and girls (differential susceptibility and diathesis-stress model). Objective: In this study we assessed both hypotheses using a multi-method multi-informant approach. We investigated (1) to what extent different parenting strategies mediate the relation between gender and social competence and (2) whether gender and age moderate the relation between parenting strategies and social competence. Design: Parenting strategies were observed during home visits and social competence was assessed using parent and teacher questionnaires and performance-based neurocognitive tasks (N = 98, aged 4 to 8). Results: (1) Parenting strategies did not mediate the relation between gender and social competence. (2) Gender moderated the association between parental questioning style and children’s level of social competence: parents asking fewer questions was associated with poorer social cognitive skills in boys only. Parental supportive presence and intrusiveness were related to aspects of social competence irrespective of gender. Age moderated the relation between parenting and aspects of social competence, though in various (unexpected) directions. Conclusion: Our findings do not support the differential socialization hypothesis and provide partial evidence for a diathesis-stress model as an explanation for parental influence on gender differences in social competence.
Cerebellum, Predictions and Errors

Making predictions and validating the predictions against actual sensory information is thought to be one of the most fundamental functions of the nervous system. A growing body of evidence shows that the neural mechanisms controlling behavior, both in motor and non-motor domains, rely on prediction errors, the discrepancy between predicted and actual information. The cerebellum has been viewed as a key component of the motor system providing predictions about upcoming movements and receiving feedback about motor errors. Consequentially, studies of cerebellar function have focused on the motor domain with less consideration for the wider context in which movements are generated. However, motor learning experiments show that cognition makes important contributions to motor adaptation that involves the cerebellum. One of the more successful theoretical frameworks for understanding motor control and cerebellar function is the forward internal model which states that the cerebellum predicts the sensory consequences of the motor commands and is involved in computing sensory prediction errors by comparing the predictions to the sensory feedback. The forward internal model was applied and tested mainly for effector movements, raising the question whether cerebellar encoding of behavior reflects task performance measures associated with cognitive involvement. Electrophysiological studies based on pseudo-random tracking in monkeys show that the discharge of Purkinje cell, the sole output neurons of the cerebellar cortex, encodes predictive and feedback signals not only of the effector kinematics but also of task performance. The implications are that the cerebellum implements both effector and task performance forward models and the latter are consistent with the cognitive contributions observed during motor learning. The implications of these findings include insights into recent psychophysical observations on moving with reduced feedback and motor learning. The findings also support the cerebellum’s place in hierarchical generative models that work in concert to refine predictions about behavior and the world. Therefore, cerebellar representations bridge motor and non-motor domains and provide a better understanding of cerebellar function within the functional architecture of the brain.
Comparison of Different Lymph Node Staging Systems in Patients With Resectable Colorectal Cancer

Background and Objectives: Currently, the United States Joint Commission on Cancer (AJCC) N staging, lymph node positive rate (LNR), and log odds of positive lymph nodes (LODDS) are the main lymph node (LN) staging systems. However, the type of LN staging system that is more accurate in terms of prognostic performance remains controversial. We compared the prognostic accuracy of the three staging systems in patients with CRC and determine the best choice for clinical applications. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, 56,747 patients were identified who were diagnosed with CRC between 2004 and 2013. Akaike's Information Criterion (AIC) and Harrell's Consistency Index (c-index) were used to assess the relative discriminative abilities of different LN staging systems. Results: In 56,747 patients, when using classification cut-off values for evaluation, the LNR of Rosenberg et al. showed significantly better predictive power, especially when the number of dissected lymph nodes (NDLN) were insufficient. When analyzed as a continuous variable, the LODDS staging system performed the best and was not affected by the NDLN. Conclusions: We suggest that the LNR of Rosenberg et al. should be introduced into the AJCC system as a supplement when the NDLN is insufficient until the optimal LODDS cut-off values are calculated.
Effect of Estrogen on Musculoskeletal Performance and Injury Risk

Estrogen has a dramatic effect on musculoskeletal function. Beyond the known relationship between estrogen and bone, it directly affects the structure and function of other musculoskeletal tissues such as muscle, tendon, and ligament. In these other musculoskeletal tissues, estrogen improves muscle mass and strength, and increases the collagen content of connective tissues. However, unlike bone and muscle where estrogen improves function, in tendons and ligaments estrogen decreases stiffness, and this directly affects performance and injury rates. High estrogen levels can decrease power and performance and make women more prone for catastrophic ligament injury. The goal of the current work is to review the research that forms the basis of our understanding how estrogen affects muscle, tendon, and ligament and how hormonal manipulation can be used to optimize performance and promote female participation in an active lifestyle at any age.
Comprehensive Genetic Results for Primary Immunodeficiency Disorders in a Highly Consanguineous Population

Objective: To present the genetic causes of patients with primary immune deficiencies (PIDs) in Kuwait between 2004 and 2017. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders Registry. Genomic DNA from patients with clinical and immunological features of PID was sequenced using Sanger sequencing (SS), next generation sequencing (NGS) of targeted genes, whole exome sequencing (WES), and/or whole genome sequencing (WGS). Functional assays were utilized to assess the biologic effect of identified variants. Fluorescence in situ hybridization (FISH) for 22q11.2 deletion and genomic hybridizations arrays were performed when thymic defects were suspected. Results: A total of 264 patients were registered during the study period with predominance of patients with immunodeficiencies affecting cellular and humoral immunity (35.2%), followed by combined immunodeficiencies with associated syndromic features (24%). Parental consanguinity and family history suggestive of PID were reported in 213 (81%) and 145 patients (55%), respectively. Genetic testing of 206 patients resulted in a diagnostic yield of 70%. Mutations were identified in 46 different genes and more than 90% of the reported genetic defects were transmitted by in an autosomal recessive pattern. The majority of the mutations were missense mutations (57%) followed by deletions and frame shift mutations. Five novel disease-causing genes were discovered. Conclusions: Genetic testing should be an integral part in the management of primary immunodeficiency patients. This will help the delivery of precision medicine and facilitate proper genetic counseling. Studying inbred populations using sophisticated diagnostic methods can allow better understanding of the genetics of primary immunodeficiency disorders.
Putative Role of Respiratory Muscle Training to Improve Endurance Performance in Hypoxia: A Review

Respiratory/inspiratory muscle training (RMT/IMT) has been proposed to improve the endurance performance of athletes in normoxia. In recent years, due to the increased use of hypoxic training method among athletes, the RMT applicability has also been tested as a method to minimize adverse effects since hyperventilation may cause respiratory muscle fatigue during prolonged exercise in hypoxia. We performed a review in order to determine factors potentially affecting the change in endurance performance in hypoxia after RMT in healthy subjects. A comprehensive search was done in the electronic databases MEDLINE and Google Scholar including keywords: “RMT/IMT,” and/or “endurance performance,” and/or “altitude” and/or “hypoxia. ” Seven appropriate studies were found until April 2018. Analysis of the studies showed that two RMT methods were used in the protocols: respiratory muscle endurance (RME) (isocapnic hyperpnea: commonly 10–30′, 3–5 d/week) in three of the seven studies, and respiratory muscle strength (RMS) (Powerbreathe device: commonly 2 × 30 reps at 50% MIP (maximal inspiratory pressure), 5–7 d/week) in the remaining four studies. The duration of the protocols ranged from 4 to 8 weeks, and it was found in synthesis that during exercise in hypoxia, RMT promoted (1) reduced respiratory muscle fatigue, (2) delayed respiratory muscle metaboreflex activation, (3) better maintenance of SaO2 and blood flow to locomotor muscles. In general, no increases of maximal oxygen uptake (VO2max) were described. Ventilatory function improvements (maximal inspiratory pressure) achieved by using RMT fostered the capacity to adapt to hypoxia and minimized the impact of respiratory stress during the acclimatization stage in comparison with placebo/sham. In conclusion, RMT was found to elicit general positive effects mainly on respiratory efficiency and breathing patterns, lower dyspneic perceptions and improved physical performance in conditions of hypoxia. Thus, this method is recommended to be used as a pre-exposure tool for strengthening respiratory muscles and minimizing the adverse effects caused by hypoxia related hyperventilation. Future studies will assess these effects in elite athletes.