Miracle-dz/UniFAR-FTUs huggingface dataset:
A longitudinal study of the impact of social network size and loneliness on cognitive performance in depressed older adults

Abstract Objectives: To examine the association of social network size and loneliness with cognitive performance and -decline in depressed older adults. Method: A sample of 378 older adults [70.7 (7.4) years] with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of current depressive disorder were recruited from primary care and specialized mental health care. Cognitive performance was assessed at baseline and 2 years follow-up with the Stroop colored-word test, a modified version of the Auditory Verbal Learning Task and the Digit Span subtest from the Wechsler Adult Intelligence Scale, encompassing four cognitive domains; processing speed, interference control, memory, and working memory. Social network size was assessed with the Close Person Inventory and loneliness with the de Jong Gierveld Loneliness Scale at baseline. Results: After adjusting for baseline working memory performance, loneliness was associated with impaired working memory after 2 years [B = −0.08 (−0.17 to 0.00)]. This association was no longer significant after adjusting for age, sex, education level, physical activity, alcohol use and depressive symptom severity [B = −0.07 (−0.16 to 0.03)]. A backward elimination procedure revealed education level to be the only covariable to explain this association. Loneliness was not associated with impairments or decline in other cognitive domains. Social network size was not associated with cognitive impairments or decline. Conclusion: Social network size and loneliness do not predict cognitive decline in depressed older adults.
Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials

Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. Methods: We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. Results: Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0–1: odds ratio, 1.77; 95% confidence interval, 0.89–3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0–1: odds ratio, 2.33; 95% confidence interval, 1.13–5.94; P=0.032) than those treated with alteplase. Conclusions: Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion–defined target mismatch. Clinical Trial Registration: URL: http://www.clinicaltrials. gov. Unique identifier: NCT01472926. URL: https://www.anzctr. org.au. Unique identifier: ACTRN12608000466347.
Origin and role of path integration in the cognitive representations of the hippocampus: computational insights into open questions

ABSTRACT Path integration is a straightforward concept with varied connotations that are important to different disciplines concerned with navigation, such as ethology, cognitive science, robotics and neuroscience. In studying the hippocampal formation, it is fruitful to think of path integration as a computation that transforms a sense of motion into a sense of location, continuously integrated with landmark perception. Here, we review experimental evidence that path integration is intimately involved in fundamental properties of place cells and other spatial cells that are thought to support a cognitive abstraction of space in this brain system. We discuss hypotheses about the anatomical and computational origin of path integration in the well-characterized circuits of the rodent limbic system. We highlight how computational frameworks for map-building in robotics and cognitive science alike suggest an essential role for path integration in the creation of a new map in unfamiliar territory, and how this very role can help us make sense of differences in neurophysiological data from novel versus familiar and small versus large environments. Similar computational principles could be at work when the hippocampus builds certain non-spatial representations, such as time intervals or trajectories defined in a sensory stimulus space. Summary: Path integration is one of the fundamental computations giving rise to the cognitive map and possibly other non-spatial representations in the hippocampal formation and its subcortical afferents.
Linking genetic, metabolic, and phenotypic diversity among Saccharomyces cerevisiae strains using multi-omics associations

Abstract Background The selection of bioengineering platform strains and engineering strategies to improve the stress resistance of Saccharomyces cerevisiae remains a pressing need in bio-based chemical production. Thus, a systematic effort to exploit genotypic and phenotypic diversity to boost yeast's industrial value is still urgently needed. Results We analyzed 5,400 growth curves obtained from 36 S. cerevisiae strains and comprehensively profiled their resistances against 13 industrially relevant stresses. We observed that bioethanol and brewing strains exhibit higher resistance against acidic conditions; however, plant isolates tend to have a wider range of resistance, which may be associated with their metabolome and fluxome signatures in the tricarboxylic acid cycle and fatty acid metabolism. By deep genomic sequencing, we found that industrial strains have more genomic duplications especially affecting transcription factors, showing that they result from disparate evolutionary paths in comparison with the environmental strains, which have more indels, gene deletions, and strain-specific genes. Genome-wide association studies coupled with protein-protein interaction networks uncovered novel genetic determinants of stress resistances. Conclusions These resistance-related engineering targets and strain rankings provide a valuable source for engineering significantly improved industrial platform strains.
Sox2 Expression Marks Castration‐Resistant Progenitor Cells in the Adult Murine Prostate

Identification of defined epithelial cell populations with progenitor properties is critical for understanding prostatic development and disease. Here, we demonstrate that Sox2 expression is enriched in the epithelial cells of the proximal prostate adjacent to the urethra. We use lineage tracing of Sox2‐positive cells during prostatic development, homeostasis, and regeneration to show that the Sox2 lineage is capable of self‐renewal and contributes to prostatic regeneration. Persisting luminal cells express Sox2 after castration, highlighting a potential role for Sox2 in cell survival and castration‐resistance. In addition to revealing a novel progenitor population in the prostate, these data implicate Sox2 as a regulatory factor of adult prostate epithelial stem cells. Stem Cells 2019;37:690–700
Heat Inactivation Renders Sputum Safe and Preserves Mycobacterium tuberculosis RNA for Downstream Molecular Tests

The World Health Organization End Tuberculosis (TB) strategy has called for the development of—and increased access to—effective tools for diagnosis and treatment of TB disease. Mycobacterium tuberculosis , the causative agent of TB, is categorized as a highly infectious agent. ABSTRACT The World Health Organization End Tuberculosis (TB) strategy has called for the development of—and increased access to—effective tools for diagnosis and treatment of TB disease. Mycobacterium tuberculosis , the causative agent of TB, is categorized as a highly infectious agent. Consequently, diagnostic tests that involve comprehensive manipulation of specimens from presumed tuberculosis cases must be performed in a category 3 laboratory. We have evaluated the use of heat inactivation to render TB samples safe to work with while preserving RNA for downstream molecular tests. Using Mycobacterium bovis bacillus Calmette-Guérin (BCG) cultures and TB-positive sputum samples, we show that boiling for 20 min at 80, 85, and 95°C inactivates all M. tuberculosis bacilli. The efficiency of inactivation was verified by culturing heat-treated and untreated (live) fractions of BCG and TB sputum samples for 42 days. No growth was observed in the cultures of heat-treated samples. In contrast, the optical density of untreated BCG in Middlebrook 7H9 broth rose from 0.04 to 0.85, and the untreated sputum samples flagged positive at 3 days of incubation in mycobacterial growth indicator tubes. Quantification of reference genes 16S rRNA, transfer-messenger RNA (tmRNA), pre-16S rRNA, and rpoB by reverse transcriptase quantitative PCR (RT-qPCR) showed minimal loss in estimated bacterial load. The loss was RNA species dependent, <1 log10, 1.1 log10, 1.3 log10, and 2.4 log10 estimated CFU/ml for 16S rRNA, tmRNA, pre-16S rRNA, and rpoB, respectively. The RNA loss was independent of inactivation temperature. These findings show that heat inactivation could obviate the need for category 3 laboratories to perform RNA-based testing of TB samples.
Bringing Prostate Cancer Germline Genetics into Clinical Practice.

PURPOSE Until recently the role of germline genetics in prostate cancer care was not well defined. While important questions remain, we reviewed the current understanding of germline genetic alterations related to prostate cancer. We discuss the clinical implications for genetic counseling, genetic testing, early detection and treatment in men with these mutations. MATERIALS AND METHODS We searched PubMed® for English language articles published since 2001 with the key words "germline mutations," "BRCA," "family history" or "prostate cancer genetics. " We also used relevant data from websites, including the CMS (Centers for Medicare and Medicaid Services), the NCCN (National Comprehensive Cancer Network®), the BLS (Bureau of Labor Statistics) and the NSGC (National Society of Genetic Counselors) websites. RESULTS A number of germline mutations in DNA damage repair genes ( BRCA1, BRCA2, CHEK2, ATM and PALB2) and in DNA mismatch repair genes ( MLH1, MSH2, MSH6 and PMS2) can drive the development of prostate cancer. Careful genetic counseling coupled with multipanel gene testing can help identify men with these mutations and provide enhanced understanding of the disease risk. Cascade testing of family members can then have an impact extending well beyond the index patient. In men with a pathogenic germline mutation the optimal early detection paradigm is not well defined. Data from the IMPACT study ( ClinicalTrials.gov NCT00261456) that the cancer detection rate is substantially elevated in BRCA1 and BRCA2 carriers at PSA greater than 3 ng/ml has helped establish the importance of close PSA screening in these men. Additionally, BRCA2 and likely other DNA damage repair mutations are associated with aggressive disease, although it is not yet clear how this impacts localized disease management. However, there is strong evidence that patients with metastatic, castration resistant prostate cancer who have DNA damage repair defects respond positively to targeting PARP enzymes. In many cancers there is also evidence that patients with an increased tumor mutational burden, such as in Lynch syndrome, are particularly sensitive to immune checkpoint inhibitors. CONCLUSIONS Emerging evidence supports the implementation of germline genetic counseling and testing as a key component of prostate cancer management. Further research is needed to elucidate the clinical significance of lesser known germline mutations and develop optimal screening, early detection and treatment paradigms in this patient population.
Early Interactive Acoustic Experience with Non-speech Generalizes to Speech and Confers a Syllabic Processing Advantage at 9 Months

Abstract During early development, the infant brain is highly plastic and sensory experiences modulate emerging cortical maps, enhancing processing efficiency as infants set up key linguistic precursors. Early interactive acoustic experience (IAE) with spectrotemporally-modulated non-speech has been shown to facilitate optimal acoustic processing and generalizes to novel non-speech sounds at 7-months-of-age. Here we demonstrate that effects of non-speech IAE endure well beyond the immediate training period and robustly generalize to speech processing. Infants who received non-speech IAE differed at 9-months-of-age from both naïve controls and those with only passive acoustic exposure, demonstrating broad modulation of oscillatory dynamics. For the standard syllable, increased high-gamma (>70 Hz) power within auditory cortices indicates that IAE fosters native speech processing, facilitating establishment of phonemic representations. The higher left beta power seen may reflect increased linking of sensory information and corresponding articulatory patterns, while bilateral decreases in theta power suggest more mature automatized speech processing, as less neuronal resources were allocated to process syllabic information. For the deviant syllable, left-lateralized gamma (<70 Hz) enhancement suggests IAE promotes phonemic-related discrimination abilities. Theta power increases in right auditory cortex, known for favoring slow-rate decoding, implies IAE facilitates the more demanding processing of the sporadic deviant syllable.
De-identified linkage of data across separate registers: a proposal for improved protection of personal information in registry-based clinical research

Abstract Over the last decades the advent of digital documentation has provided research communities with valuable resources of information for clinical research. To utilize the potential of information about patients, their health care, and its outcome that is already available in different registers, the possibility to cross-reference information from different registers is inevitably required. When performing linkage, we are currently forced to disclose information of participating subjects either to the administration of the other register(s) or to the researcher. Considering the increased concern of issues around personal integrity, this is a limitation that affects the ethical implications of proposed research and that might in the end affect the willingness of subjects to participate in registers. For this reason we propose a different methodology for performing cross-referencing, one that effectively prevents information leakage between the different organizations participating in linking the data. We believe that it is possible to use commonly adopted technologies within the area of data security and encryption to perform linkage without disclosing any sensitive information between different participants. In this paper we demonstrate how common techniques of encryption could be implemented to achieve that and furthermore significantly simplify discovery and feasibility surveying ahead of studies.
Treatment outcome in juvenile‐onset myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Approximately 10%–15% of MG patients have juvenile (<18 years of age) onset. We aimed to assess the clinical course, outcome, and subjectively perceived health status of a cohort of juvenile MG patients.
Semiempirical Quantum-Chemical Methods with Orthogonalization and Dispersion Corrections

We present two new semiempirical quantum-chemical methods with orthogonalization and dispersion corrections: ODM2 and ODM3 (ODMx). They employ the same electronic structure model as the OM2 and OM3 (OMx) methods, respectively. In addition, they include Grimme’s dispersion correction D3 with Becke–Johnson damping and three-body corrections EABC for Axilrod–Teller–Muto dispersion interactions as integral parts. Heats of formation are determined by adding explicitly computed zero-point vibrational energy and thermal corrections, in contrast to standard MNDO-type and OMx methods. We report ODMx parameters for hydrogen, carbon, nitrogen, oxygen, and fluorine that are optimized with regard to a wide range of carefully chosen state-of-the-art reference data. Extensive benchmarks show that the ODMx methods generally perform better than the available MNDO-type and OMx methods for ground-state and excited-state properties, while they describe noncovalent interactions with similar accuracy as OMx methods with a posteriori dispersion corrections.
A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I‐related chain A

The major histocompatibility complex (MHC) class I‐related chain A (MICA) is induced upon stress, and labels malfunctioning cells for their recognition by cytotoxic lymphocytes. Alterations in this recognition and also abnormal natural killer (NK) functions have been found in systemic lupus erythematosus (SLE). MICA can be shed from cells, subsequently acting as a soluble decoy receptor (sMICA). Our purpose was to study circulating sMICA levels in relationship with the activation of innate pathways in PBMC in a cohort of lupus patients. NK cells were characterized by flow cytometry. Gene expression of Toll‐like receptors (TLR), interferon (IFN)‐I sensitive genes and MICA were separately analyzed in monocytes, T cells and B cells. Serum sMICA was measured with enzyme‐linked immunosorbent assay (ELISA). In our cohort, NK cell counts dropped in relationship with disease activity. sMICA showed an inverse trend with NK cell counts, as well as a significant association with activity indices, but not with complement decrease. Levels of sMICA associated to proteinuria and active nephritis. A multivariate regression model revealed anti‐nuclear antibody (ANA) titres, the up‐regulation of TLR‐4 in T cells and lower vitamin D as predictors of sMICA enhancement. Interestingly, vitamin D showed an inverse association with proteinuria and a strong correlation with T cell MICA mRNA levels. According to our data, circulating sMICA identifies a subgroup of lupus patients with low vitamin D, innate activation of T cells and nephritis. We propose that lymphocyte shedding could account for the enhancement of sMICA and reflect an immune evasion mechanism driving disease activation in lupus.
Pumping human milk in the early postpartum period: its impact on long-term practices for feeding at the breast and exclusively feeding human milk in a longitudinal survey cohort.

BACKGROUND Most American mothers who feed human milk (HM) now use pumps to produce some of the HM they feed. Pumping is nationally recommended, but associations between pumping and HM-feeding durations are unknown. OBJECTIVES We examined whether and how the pumping frequency and types of reasons for pumping between 1.5 and 4.5 mo postpartum are associated with HM-feeding durations. We classified pumping reasons as nonelective [e.g., because of a difficulty feeding at the breast (FAB)] or elective (e.g., to produce HM to mix with solids). We hypothesized that women who pumped more frequently or nonelectively would have shorter HM-feeding durations. DESIGN We used data from 1116 mothers in a longitudinal cohort who fed and pumped HM 1.5-4.5 mo postpartum. We used χ(2) and Cox proportional hazards regression models to examine the survival of any HM feeding, exclusive HM feeding, and FAB. RESULTS Compared with mothers who pumped for elective reasons, mothers who reported one nonelective reason had greater hazards of stopping feeding any HM (HR: 1.12; 95% CI: 1.05, 1.21) or exclusive HM (HR: 1.14; 95% CI: 1.09, 1.20) and of stopping FAB (HR: 2.07; 95% CI: 1.77, 2.42). Mothers who pumped most frequently had the highest mean hazards of stopping feeding any HM (HR: 1.82; 95% CI: 1.68, 1.93) and feeding exclusive HM (HR: 1.21; 95% CI: 1.14, 1.26). Hazards of stopping FAB varied across the year. Compared with the least-frequent pumpers, the most-frequent pumpers had a 2.6-fold higher hazard of stopping FAB at 3 mo postpartum and a 1.7-fold higher hazard at 6 mo postpartum. CONCLUSIONS Nonelective pumping reasons and higher pumping frequency were associated with shorter HM-feeding durations. Mothers who report that they use a breast pump for reasons related to either employment or FAB difficulty and their infants may be more vulnerable to risks associated with a shorter HM-feeding duration.