Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinguishing mild cognitive impairment from healthy aging and Alzheimer’s Disease: The contribution of the INECO Frontal Screening (IFS)

Executive functions are affected differently in healthy aging, Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD), and evaluating them is important for differential diagnosis. The INECO Frontal Screening (IFS) is a brief neuropsychological screening tool, developed to assess executive dysfunction in neurodegenerative disorders. Goals: We aimed to examine whether and how MCI patients can be differentiated from cognitively healthy controls (HC) and mild to moderate AD patients based on IFS performance. We also explored how IFS scores are associated with age, years of education, and depressive/anxious symptoms (as assessed by the Hospital Anxiety and Depression Scale). Method: IFS total scores were compared between 26 HC, 32 MCI and 21 mild to moderate AD patients. The three groups were matched for age and education. The Area Under the Curve (AUC) was analyzed and optimal cut-offs were determined. Results: Healthy participants had higher IFS scores than both clinical groups, and MCI patients had higher scores than AD patients. IFS showed high diagnostic accuracy for the detection of MCI (AUC = .89, p < .001) and AD (AUC = .99, p < .001), and for the differentiation between the clinical groups (AUC = .76, p < .001). We provide optimal cut-offs for the identification of MCI and AD and for their differentiation. We also found that, in general, higher education predicted higher IFS scores (no associations with age and depressive/anxious symptoms were observed). Altogether, these findings indicate that evaluating executive functions with the IFS can be valuable for the identification of MCI, a high-risk group for dementia, and for differentiating this condition from healthy aging and AD.
Development of Daptomycin Susceptibility Breakpoints for Enterococcus faecium and Revision of the Breakpoints for other Enterococcal species by the Clinical and Laboratory Standards Institute.

Daptomycin is one of the few treatment options for infections caused by enterococci that are resistant to ampicillin and vancomycin, such as vancomycin-resistant Enterococcus faecium. The emergence and clinical significance of daptomycin-resistant enterococci and evolving microbiologic, pharmacokinetic-pharmacodynamic, and clinical data indicated that the pre-2019 Clinical and Laboratory Standards Institute (CLSI) susceptible-only breakpoint of ≤4 μg/mL for daptomycin and enterococci was no longer appropriate. After analyzing data that are outlined in this manuscript, the CLSI Subcommittee on Antimicrobial Susceptibility Testing established new breakpoints for daptomycin and enterococci. For E. faecium, a susceptible dose-dependent (SDD) breakpoint of ≤4 μg/mL was established based on an increased dosage of 8-12 mg/kg/day (≥8 μg/mL-resistant). CLSI suggests Infectious Diseases consultation to guide daptomycin use for the SDD category. For E. faecalis and other enterococcal species, revised breakpoints of ≤2 μg/mL-susceptible, 4 μg/mL-intermediate, and ≥8 μg/mL-resistant were established based upon a standard dosage of 6 mg/kg/day.
Identifying relations of medications with adverse drug events using recurrent convolutional neural networks and gradient boosting

OBJECTIVE To develop a natural language processing system that identifies relations of medications with adverse drug events from clinical narratives. This project is part of the 2018 n2c2 challenge. MATERIALS AND METHODS We developed a novel clinical named entity recognition method based on an recurrent convolutional neural network and compared it to a recurrent neural network implemented using the long-short term memory architecture, explored methods to integrate medical knowledge as embedding layers in neural networks, and investigated 3 machine learning models, including support vector machines, random forests and gradient boosting for relation classification. The performance of our system was evaluated using annotated data and scripts provided by the 2018 n2c2 organizers. RESULTS Our system was among the top ranked. Our best model submitted during this challenge (based on recurrent neural networks and support vector machines) achieved lenient F1 scores of 0.9287 for concept extraction (ranked third), 0.9459 for relation classification (ranked fourth), and 0.8778 for the end-to-end relation extraction (ranked second). We developed a novel named entity recognition model based on a recurrent convolutional neural network and further investigated gradient boosting for relation classification. The new methods improved the lenient F1 scores of the 3 subtasks to 0.9292, 0.9633, and 0.8880, respectively, which are comparable to the best performance reported in this challenge. CONCLUSION This study demonstrated the feasibility of using machine learning methods to extract the relations of medications with adverse drug events from clinical narratives.
L‐TRUST: Long‐term risk of cancer in patients under statins therapy. A systematic review and meta‐analysis

Statins are widely prescribed drugs with established efficacy in primary and secondary prevention of cardiovascular events. Although they are mostly well tolerated, several authors have been emphasizing that the statins' safety profile is not totally clarified especially when considering risk of cancer in patients with long‐term exposure to statins. This meta‐analysis was aimed at evaluating the risk of cancer in patients with prolonged exposure to statins.
Do habitual foot-strike patterns in running influence functional Achilles tendon properties during gait?

ABSTRACT The capacity of foot-strike running patterns to influence the functional properties of the Achilles tendon is controversial. This study used transmission-mode ultrasound to investigate the influence of habitual running foot-strike pattern on Achilles tendon properties during barefoot walking and running. Fifteen runners with rearfoot (RFS) and 10 with a forefoot (FFS) foot-strike running pattern had ultrasound transmission velocity measured in the right Achilles tendon during barefoot walking (≈1.1 ms−1) and running (≈2.0 ms−1). Temporospatial gait parameters, ankle kinematics and vertical ground reaction force were simultaneously recorded. Statistical comparisons between foot-strike patterns were made using repeated measure ANOVAs. FFS was characterised by a significantly shorter stance duration (−4%), greater ankle dorsiflexion (+2°), and higher peak vertical ground reaction force (+20% bodyweight) than RFS running (P < .05). Both groups adopted a RFS pattern during walking, with only the relative timing of peak dorsiflexion (3%), ground reaction force (1–2%) and peak vertical force loading rates (22–23%) differing between groups (P < .05). Peak ultrasound transmission velocity in the Achilles tendon was significantly higher in FFS during walking (≈100 ms−1) and running (≈130 ms−1) than RFS (P < .05). Functional Achilles tendon properties differ with habitual footfall patterns in recreational runners.
Poultry in the classroom: effectiveness of an online poultry-science-based education program for high school STEM instruction

Public knowledge of the poultry industry is limited, yet attitudes towards the industry shape consumer behavior and influence the attractiveness of poultry careers and future study. This study assessed an online learning program contextualizing STEM learning within poultry science which was designed to increase poultry knowledge and interest. High school student participants (n = 169) across 16 classes (n = 12 teachers) in Indiana completed seven 30-min online modules during the fall 2018 semester. This case study used a mixed-methods, sequential explanatory design. Student knowledge and interest in poultry and teacher perceptions of the program were examined using quantitative measures. The study's qualitative portion assessed perceptions of the learning experience and comprised open-ended student and teacher survey questions and a teacher focus group. Qualitative data suggested that students' poultry knowledge, including awareness of the industry and related careers, was improved following the modules. Paired t-tests showed moderate to large effect sizes regarding increases in content quiz scores following each module (P < 0.001, Cohen's d = 0.45 to 0.80). Students' mean interest in poultry was initially low and remained statistically similar upon completion of the program (M = 1.84, 1.87; p = 0.67). Student and teacher statements indicated that design features of the program enhanced interest for some students. Other students did not perceive the program and its poultry science topics to be interesting or relevant to their lives. Results from this study can be used to inform the creation of effective poultry learning resources to contribute to workforce development and enhance the industry's public image.
Maternal blood biomarkers and adverse pregnancy outcomes: a systematic review and meta-analysis

Abstract Background: Pregnancy is a vulnerable period for the mother and the infant and exposures to environmental chemicals in utero can influence neonatal morbidity and mortality. There is a momentum toward understanding and exploring the current maternal biological mechanisms specific to in utero effects, to improve birth outcomes. This study aims to examine the current understanding of the role of biomarkers that may be associated with term of pregnancy, infant birth weights and infant development in utero. Methods: Electronic searches were conducted in PubMed, Embase, OvidMD, and Scopus databases; and all relevant research articles in English were retrieved. Studies were selected if they evaluated maternal blood plasma/serum biomarkers proposed to influence adverse birth outcomes in the neonate. Data were extracted on characteristics, quality, and odds ratios from each study and meta-analysis was conducted. Results: A total of 54 studies (35 for meta-analysis), including 43,702 women, 50 plasma markers and six descriptors of birth outcomes were included in the present study. The random effect point estimates for risk of adverse birth outcomes were 1.61(95%CI: 1.39–1.85, p < 0.0001) for inflammation-related biomarkers and 1.65(95%CI: 1.22–2.25, p = 0.0013) for growth factor/hormone-related biomarkers. All subgroups of plasma markers showed significant associations with adverse birth outcomes with no apparent study bias. Conclusions: The two subsets of plasma markers identified in this study (inflammation-related and growth factor/hormone-related) may serve as potentially valuable tools in the investigation of maternal molecular mechanisms, especially select pathways underlying inflammatory and immunological mediation in terms of modulating adverse infant outcomes. Future large, prospective cohort studies are needed to validate the promising plasma biomarkers, and to examine other maternal biological matrices such as cervicovaginal fluid and urine.
Vector-Space Models of Semantic Representation From a Cognitive Perspective: A Discussion of Common Misconceptions

Models that represent meaning as high-dimensional numerical vectors—such as latent semantic analysis (LSA), hyperspace analogue to language (HAL), bound encoding of the aggregate language environment (BEAGLE), topic models, global vectors (GloVe), and word2vec—have been introduced as extremely powerful machine-learning proxies for human semantic representations and have seen an explosive rise in popularity over the past 2 decades. However, despite their considerable advancements and spread in the cognitive sciences, one can observe problems associated with the adequate presentation and understanding of some of their features. Indeed, when these models are examined from a cognitive perspective, a number of unfounded arguments tend to appear in the psychological literature. In this article, we review the most common of these arguments and discuss (a) what exactly these models represent at the implementational level and their plausibility as a cognitive theory, (b) how they deal with various aspects of meaning such as polysemy or compositionality, and (c) how they relate to the debate on embodied and grounded cognition. We identify common misconceptions that arise as a result of incomplete descriptions, outdated arguments, and unclear distinctions between theory and implementation of the models. We clarify and amend these points to provide a theoretical basis for future research and discussions on vector models of semantic representation.
Extracorporeal Shockwave Therapy Accelerates the Healing of a Meniscal Tear in the Avascular Region in a Rat Model

Background: The treatment of meniscal tears in the avascular region remains a clinical challenge. Extracorporeal shockwave therapy (ESWT) is a minimally invasive, safe, and effective therapy for various orthopaedic disorders. However, the therapeutic effect of ESWT on meniscal tears has not been reported. Purpose: To evaluate the therapeutic effect of ESWT in the treatment of meniscal tears. Study Design: Controlled laboratory study. Methods: Twelve-week-old male Wistar rats were divided into 3 groups (normal, ESWT–, and ESWT+). The authors made a full-thickness 2-mm longitudinal tear in the avascular region of the anterior horn in the latter 2 groups. At 1 week after surgery, the ESWT+ group received 800 impulses of shockwave at 0.22-mJ/mm2 energy flux density in a single session. The authors performed a histological examination to evaluate meniscal healing (n = 10 for each group) and immunohistochemistry to analyze the expression of bromodeoxyuridine (BrdU; n = 5 for each group) and CCN family member 2/connective tissue growth factor (CCN2/CTGF; n = 5 for each group) at 2, 4, and 8 weeks after ESWT. The mRNA levels of CCN2, SOX 9, VEGF-a, aggrecan, Col1a2, and Col2a1 at the site of the meniscal tear at 4 weeks after ESWT were quantitatively evaluated by a real-time polymerase chain reaction (n = 5 for each group). Results: The meniscus healing scores in the ESWT+ group were significantly higher than those in the ESWT– group at 4 weeks and 8 weeks. The ratio of BrdU-positive cells was the highest in the ESWT+ group at all observation periods. The ratio of CCN2-positive cells was highest in the ESWT+ group at 4 and 8 weeks. In the ESWT+ group, real-time polymerase chain reaction revealed that the levels of CCN2, SOX9, aggrecan, and Col2a1 were upregulated (All significant data were P < .05). Conclusion: ESWT promoted the healing of meniscal tears in the avascular area. ESWT stimulated proliferation of meniscal cells and the upregulation of cartilage-repairing factors such as CCN2, with the upregulation of cartilage-specific extracellular matrix expression. Clinical Relevance: ESWT may be an effective therapeutic option that promotes meniscal healing in the avascular region.
End-of-Life Dreams and Visions and Posttraumatic Growth: A Comparison Study.

Background: End-of-life dreams and visions (ELDVs) can provide both meaning and comfort to individuals nearing death. While research has examined the prevalence and content of ELDVs, little is known on how dreaming at end of life may affect psychological processes. Objective: This study aimed to explore differences in posttraumatic growth (PTG) between hospice patients who experience ELDVs and hospice patients who do not experience this phenomenon. Design: This is a multimethod cross-sectional comparison study. Settings/Subjects: 70 hospice patients (35 with ELDV experiences and 35 without ELDV experiences) were recruited after being admitted to a hospice inpatient unit. Measurements: PTG was assessed using a modified version of the Posttraumatic Growth Inventory (PTGI). Demographic information, ELDV occurrence, and a brief description of ELDVs were also collected. Results: Significant differences emerged between groups in terms of personal strength (p = 0.012), spiritual change (p = 0.002), and overall PTG (p = 0.019). Patients with ELDV experiences had higher scores on all subscales as well as overall PTG compared to nondreaming patients. Conclusions: Dreams and visions at the end of life affect PTG of dying individuals in hospice care. Further research should be conducted between groups to examine the effects ELDVs may have on other psychological processes.
Fixel-Based Analysis of Visual Pathway White Matter in Primary Open-Angle Glaucoma.

Purpose White matter (WM) degeneration of the visual pathways in primary open-angle glaucoma (POAG) is well documented, but its exact pathophysiology remains unclear. To date, glaucomatous WM degeneration has been exclusively studied using diffusion tensor imaging (DTI) only. However, DTI measures lack direct biological interpretation, and the approach itself suffers from multiple technical limitations. Fixel-based analysis (FBA) is a novel framework for studying WM degeneration, overcoming DTI's technical limitations and providing biologically meaningful metrics. FBA measures fiber density (FD), representing early microstructural changes, and fiber-bundle cross section (FC), representing late macrostructural changes. In this study, we use FBA to study glaucomatous degeneration of the pregeniculate optic tracts (OTs) and postgeniculate optic radiation (ORs) in POAG. Methods This was a cross-sectional case-control study with 12 POAG patients and 16 controls. Multi-shell diffusion-weighted images were acquired. FBA was used to produce a population template, and probabilistic tractography was used to track the OTs and ORs in template space. Finally, FD and FC of the tracts of interest were compared between the two groups. Results Compared with the controls, the OTs of the patients exhibited a significant (familywise error corrected P < 0.05) decrease in FD and FC, whereas their ORs exhibited a significant decrease in FD but not in FC. Conclusions FBA provides sensitive measures to assess WM changes in glaucoma. Our findings suggest that the OTs of glaucoma patients exhibit signs of more advanced WM degeneration compared with the ORs. This potentially implicates anterograde trans-synaptic propagation as the primary cause of glaucomatous spread along the visual pathways.
Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.

BACKGROUND Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. OBJECTIVES The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. METHODS Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. RESULTS MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. CONCLUSIONS Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.
Friend or foe—IDH1 mutations in glioma 10 years on

Abstract The identification of recurrent point mutations in the isocitrate dehydrogenase 1 (IDH1) gene, albeit in only a small percentage of glioblastomas a decade ago, has transformed our understanding of glioma biology, genomics and metabolism. More than 1000 scientific papers have been published since, propelling bench-to-bedside investigations that have led to drug development and clinical trials. The rapid biomedical advancement has been driven primarily by the realization of a neomorphic activity of IDH1 mutation that produces high levels of (d)-2-hydroxyglutarate, a metabolite believed to promote glioma initiation and progression through epigenetic and metabolic reprogramming. Thus, novel inhibitors of mutant IDH1 have been developed for therapeutic targeting. However, numerous clinical and experimental findings are at odds with this simple concept. By taking into consideration a large body of findings in the literature, this article analyzes how different approaches have led to opposing conclusions and proffers a counterintuitive hypothesis that IDH1 mutation is intrinsically tumor suppressive in glioma but functionally undermined by the glutamate-rich cerebral environment, inactivation of tumor-suppressor genes and IDH1 copy-number alterations. This theory also provides an explanation for some of the most perplexing observations, including the scarcity of proper model systems and the prevalence of IDH1 mutation in glioma.
Effects of dietary crude protein levels on ammonia emission, litter and manure composition, N losses, and water intake in broiler breeders

This study determined the effects of different dietary crude protein (CP) levels on ammonia emission (NH3), litter and manure composition, nitrogen (N) losses, and water intake in broiler breeders. A total of 480 females and 64 males (Ross 308) 20 wk of age were randomly allotted to 2 dietary treatments with 8 replicates of 30 females and 4 males per replicate. Birds were fed either high CP (CPh) or low CP diets (CPl) supplemented with free amino acids (AA). Both diets consisted of 3 sub-diets; 1 for each phase of the laying period. Diets were formulated to be iso-caloric and calculated CP content of the CPl diets was 15 g/kg lower than the CPh diets (Breeder 1 (23 to 34 wk): 135 vs. 150, Breeder 2 (35 to 46 wk): 125 vs. 140 and Breeder 3 (47 to 60 wk of age): 115 vs. 130 g/kg, respectively). Pens consisted of an elevated slatted floor (25% of the floor surface) and a litter floor. Water and feed intake were recorded daily. Litter (floor) and manure (below slatted floor) composition and ammonia concentration were measured at 34, 44, and 54 wk of age. Ammonia concentration was measured using a flux chamber on top of the litter or manure. Estimated N losses were calculated. Dietary protein level did not affect water intake and dry matter (DM) content of the litter or manure. Compared to birds fed the CPh diets, the litter and manure samples of broiler breeders fed the CPl had 8% lower total-N and 13% lower ammonia-N content resulting in a 9% lower ammonia concentration, 9% lower ammonia emission, and 11% lower total-N losses. In conclusion, this study shows that reducing CP level in the diet of broiler breeders reduces ammonia emission and total N-losses from litter and manure.