Miracle-dz/UniFAR-FTUs huggingface dataset:
Mobile Health Technologies for Continuous Monitoring of Cancer Patients in Palliative Care Aiming to Predict Health Status Deterioration: A Feasibility Study.

Background: Unplanned readmissions or emergency visits (EVs) after discharge from hospital are frequent in patients in palliative care. Strategies to anticipate and prevent rapid deterioration of health are needed. Objective: Assessing feasibility and predictive ability of remote monitoring using wearables. Design: Prospective observational feasibility study in a single center. Setting/Subjects: Thirty cancer patients with an estimated life expectancy of >8 weeks to <12 months, aged >18 years and being discharged from inpatient to outpatient care were included. Measurements: Patients were provided with a smartphone, including the preinstalled "Activity Monitoring" application and a sensor-equipped bracelet. Follow-up was 12 weeks. Both devices recorded several features (e.g., vital signs). Visual analog scale (VAS) for pain and distress was reported once daily and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) once weekly. Statistical methods were applied to explore relationship between sensor data, self-reports, and EVs or readmissions or death. Results: Between February 2017 and May 2018, 30 patients were included. Twenty-five of 30 participants (83%) completed 12 weeks of follow-up. On average, bracelet was worn on 53% and smartphone on 85% of study days. Completion rate of daily digital questionnaires for subjective ratings was 73%. Eight unplanned hospital readmissions occurred. Ratings of pain, distress, and QLQ-C30 scores were not associated with readmission, whereas resting heart rate, resting heart rate variability, as well as speed of steps differed significantly in patients with and without readmission. Conclusions: Monitoring of palliative cancer patients using wearables is feasible. First results indicate that mobile health features might be promising biomarkers to predict unplanned readmissions.
Effectiveness of the Goldmann Applanation Tonometer, the Dynamic Contour Tonometer, the Ocular Response Analyzer and the Corvis ST in Measuring Intraocular Pressure following FS-LASIK

ABSTRACT Purpose: To test the performance of the four tonometers in providing IOP measurements that were free of the effects of corneal biomechanics changes caused by refractive surgery. Methods: Four tonometers were employed to provide IOP measurements for 65 participants who accepted Femtosecond laser-assisted LASIK (FS-LASIK). The measurements included GAT-IOP by the Goldmann Applanation Tonometer, DCT-IOP by the Dynamic Contour Tonometer, Goldmann-correlated IOP (ORA-IOPg) and corneal-compensated IOP (ORA-IOPcc) by the Ocular Response Analyzer, and uncorrected IOP (CVS-IOP) and biomechanically corrected IOP (CVS-bIOP) by the Corvis ST. Statistical analyses were performed to assess the association of the differences in IOP caused by FS-LASIK with central corneal thickness (CCT), mean corneal curvature (Km), age, refractive error correction (REC), optical zone diameter (OZD), ablation zone diameter (AZD), residual stromal bed thickness (RSB) and RSB ratio (RSB/CCT). Multiple linear regression models were constructed to explore factors influencing IOP changes. Results: All four tonometers exhibited significant differences between IOP measurements taken pre and post-surgery except for CVS-bIOP in the low to moderate myopia group (t = 1.602, p = .12). CVS-bIOP, followed by DCT-IOP, provided the best agreement between pre and post-FS-LASIK measurements with the lowest differences in IOP and the narrowest limits of agreement. The pre-post IOP differences were also significantly associated with the reduction in CCT in only GAT-IOP, ORA-IOPg, and CVS-IOP. CVS-bIOP and ORA-IOPcc were the only measurements that were not correlated with CCT, Km or age both before and after FS-LASIK. Conclusions: The biomechanically corrected bIOP from the Corvis ST provided post-FS-LASIK measurements that were in closest agreement with those obtained before surgery. In comparison, GAT-IOP, ORA-IOPg, ORA-IOPcc, and CVS-IOP appeared to be more influenced by the changes in corneal biomechanics caused by FS-LASIK.
Cyclophosphamide-Induced Cystitis Results in NLRP3-Mediated Inflammation in the Hippocampus and Symptoms of Depression in Rats.

Recent breakthroughs demonstrate that peripheral diseases can trigger inflammation in the brain, causing psychosocial maladies, including depression. While few direct studies have been made, anecdotal reports associate urological disorders with mental dysfunction. Thus, we investigated if insults targeted at the bladder might elicit behavioral alterations. Moreover, the mechanism of neuroinflammation elicited by other peripheral diseases involves the NLRP3 inflammasome, which is present in microglia in the brain and cleaves and activates proinflammatory cytokines such as IL-1β. Thus, we further explored the importance of NLRP3 in behavioral and neuroinflammatory changes. Here we have employed the well-studied cyclophosphamide (CP)-treated rat model. Importantly, CP and its metabolites do not cross the blood brain barrier or trigger inflammation in the gut, so that any neuroinflammation is likely secondary to bladder injury. We found that CP triggered an increase in inflammasome activity (caspase-1 activity) in the hippocampus, but not in the pons. Evans blue extravasation demonstrated breakdown of the blood brain barrier in the hippocampal region and activated microglia were present in the fascia dentata. Both changes were dependent on NLRP3 activation and prevented with 2-mercaptoethane sulfonate sodium (Mesna) which masks the effects of the CP metabolite acrolein in the urine. Finally, CP-treated rats displayed depressive symptoms that were prevented by NLRP3 inhibition or treatment with Mesna or an antidepressant. Thus, we conclude that, CP-induced cystitis causes NLRP3-dependent hippocampal inflammation leading to depression symptoms in rats. This study proposes the first-ever causative explanation of the previously anecdotal link between benign bladder disorders and mood disorders.
Antibodies to the RNA binding protein heterogeneous nuclear ribonucleoprotein A1 contribute to neuronal cell loss in an animal model of multiple sclerosis

Neurodegeneration, including loss of neurons and axons, is a feature of progressive forms of multiple sclerosis (MS). The mechanisms underlying neurodegeneration are mostly unknown. Research implicates autoimmunity to nonmyelin self‐antigens as important contributors to disease pathogenesis. Data from our lab implicate autoimmunity to the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a possible mechanism of neurodegeneration in MS. MS patients make antibodies to hnRNP A1, which have been shown to lead to neuronal dysfunction in vitro. Using an animal model of MS, experimental autoimmune encephalomyelitis (EAE), we show here that injection of anti‐hnRNP A1 antibodies, in contrast to control antibodies, resulted in worsened disease and increased neurodegeneration. We found a reduction of NeuN+ neuronal cell bodies in areas of the ventral gray matter of the spinal cord where anti‐hnRNP A1 antibodies localized. Neurons displayed increased levels of hnRNP A1 nucleocytoplasmic mislocalization and stress granule formation, both markers of neuronal injury. Anti‐hnRNP A1 antibodies were found to surround neuronal cell bodies and interact with CD68+ immune cells via Fc receptors. Additionally, anti‐hnRNP A1 antibodies were found within neuronal cell bodies including those of the ventral spinocerebellar tract (VSCT), a tract previously shown to undergo neurodegeneration in anti‐hnRNP A1 antibody injected EAE mice. Finally, both immune cells and neurons showed increased levels of inducible nitric oxide synthase, another indicator of cell damage. These findings suggest that autoimmunity to RBPs, such as hnRNP A1, play a role in neurodegeneration in EAE with important implications for the pathogenesis of MS.
Reducing overtreatment associated with overdiagnosis in cervical cancer screening—A model‐based benefit–harm analysis for Austria

A general concern exists that cervical cancer screening using human papillomavirus (HPV) testing may lead to considerable overtreatment. We evaluated the trade‐off between benefits and overtreatment among different screening strategies differing by primary tests (cytology, p16/Ki‐67, HPV alone or in combinations), interval, age and diagnostic follow‐up algorithms. A Markov state‐transition model calibrated to the Austrian epidemiological context was used to predict cervical cancer cases, deaths, overtreatments and incremental harm–benefit ratios (IHBR) for each strategy. When considering the same screening interval, HPV‐based screening strategies were more effective compared to cytology or p16/Ki‐67 testing (e.g., relative reduction in cervical cancer with biennial screening: 67.7% for HPV + Pap cotesting, 57.3% for cytology and 65.5% for p16/Ki‐67), but were associated with increased overtreatment (e.g., 19.8% more conizations with biennial HPV + Papcotesting vs. biennial cytology). The IHBRs measured in unnecessary conizations per additional prevented cancer‐related death were 31 (quinquennial Pap + p16/Ki‐67‐triage), 49 (triennial Pap + p16/Ki‐67‐triage), 58 (triennial HPV + Pap cotesting), 66 (biennial HPV + Pap cotesting), 189 (annual Pap + p16/Ki‐67‐triage) and 401 (annual p16/Ki‐67 testing alone). The IHBRs increased significantly with increasing screening adherence rates and slightly with lower age at screening initiation, with a reduction in HPV incidence or with lower Pap‐test sensitivity. Depending on the accepted IHBR threshold, biennial or triennial HPV‐based screening in women as of age 30 and biennial cytology in younger women may be considered in opportunistic screening settings with low or moderate adherence such as in Austria. In organized settings with high screening adherence and in postvaccination settings with lower HPV prevalence, the interval may be prolonged.
Diffusion basis spectrum imaging provides insights into MS pathology

Objective To use diffusion basis spectrum imaging (DBSI) to assess how damage to normal-appearing white matter (NAWM) in the corpus callosum (CC) influences neurologic impairment in people with MS (pwMS). Methods Using standard MRI, the primary pathologies in MS of axonal injury/loss, demyelination, and inflammation are not differentiated well. DBSI has been shown in animal models, phantoms, and in biopsied and autopsied human CNS tissues to distinguish these pathologies. Fifty-five pwMS (22 relapsing-remitting, 17 primary progressive, and 16 secondary progressive) and 13 healthy subjects underwent DBSI analyses of NAWM of the CC, the main WM tract connecting the cerebral hemispheres. Tract-based spatial statistics were used to minimize misalignment. Results were correlated with scores from a battery of clinical tests focused on deficits typical of MS. Results Normal-appearing CC in pwMS showed reduced fiber fraction and increased nonrestricted isotropic fraction, with the most extensive abnormalities in secondary progressive MS (SPMS). Reduced DBSI-derived fiber fraction and increased DBSI-derived nonrestricted isotropic fraction of the CC correlated with worse cognitive scores in pwMS. Increased nonrestricted isotropic fraction in the body of the CC correlated with impaired hand function in the SPMS cohort. Conclusions DBSI fiber fraction and nonrestricted isotropic fraction were the most useful markers of injury in the NAWM CC. These 2 DBSI measures reflect axon loss in animal models. Because of its ability to reveal axonal loss, as well as demyelination, DBSI may be a useful outcome measure for trials of CNS reparative treatments.
Genotypic divergence in mouse oocyte transcriptomes:possible pathways tohybrid vigor impacting fertility and embryogenesis.

What causes hybrid vigor phenotypes in mammalian oocytes and preimplantation embryos? Answering this question should provide new insight into determinants of oocyte and embryo quality and infertility. Hybrid vigor could arise through a variety of mechanisms, many of which must operate through post-transcriptional mechanisms affecting oocyte mRNA accumulation, stability, translation and degradation. The differential regulation of such mRNAs may impact essential pathways and functions within the oocyte. We conducted in-depth transcriptome comparisons of immature and mature oocytes of C57BL/6J and DBA/2J inbred strains and C57BL/6J x DBA/2J F1 (BDF1) hybrid oocytes using RNA sequencing, combined with novel computational methods of analysis. We observed extensive differences in mRNA expression and regulation between parental inbred strains and between inbred and hybrid genotypes, including mRNAs encoding proposed markers of oocyte quality. Unique BDF1 oocyte characteristics arise through a combination of additive dominance and incomplete dominance features in the transcriptome, with a lesser degree of transgressive mRNA expression. Special features of the BDF1 transcriptome most prominently relate to histone expression, mitochondrial function, and oxidative phosphorylation. The study reveals the major underlying mechanisms that contribute to superior properties of hybrid oocytes in a mouse model.
Association between blood pressure and intracranial artery stenosis in a Chinese population

The association between blood pressure and intracranial artery stenosis (ICAS) in different age groups has not been elucidated. Using data from the “China Hypertension Survey,” we conducted a cross‐sectional analysis of the association between blood pressure parameters and ICAS. In this study, participants older than 35 years were selected by stratified, multistage random sampling. Blood pressure was measured repeatedly at rest, and ICAS was assessed by transcranial doppler ultrasound. Binary logistic regression analysis was used to demonstrate the association between different blood pressure indicators and ICAS. Of the 3640 participants included (mean age 63 ± 13 years old, 57.8% female), systolic blood pressure (SBP) and pulse pressure (PP) were associated with ICAS in the general population; the multivariable adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) of ICAS and multivessel stenosis were 1.32 (1.21, 1.45) and 1.29 (1.14, 1.46) per standard deviation (SD) increase in SBP and 1.44 (1.30, 1.59) and 1.52 (1.33, 1.74) for PP, respectively. Further analysis of this association in different age groups revealed inconsistent results between SBP and ICAS. Prehypertension (120 ≤ SBP < 140) could predict ICAS in the older group but not in the younger group, and the positive association between SBP and multivessel stenosis disappeared in the younger age group (P > .05 in all SBP subgroups). In conclusion, SBP and PP could not only identify ICAS in the middle‐aged and elderly population but could also provide some information about ICAS burden; however, these associations need to be interpreted differentially based on age subgroup.
Gene transfer across species boundaries in bryophytes: evidence from major life cycle stages in Homalothecium lutescens and H. sericeum.

BACKGROUND AND AIMS The mosses Homalothecium lutescens and H. sericeum are genetically, morphologically and ecologically differentiated, mixed populations sometimes occur. In sympatric populations, intermediate character states among gametophytes and sporophytes have been observed, suggesting hybridization and introgression in such populations. METHODS We determined genotypes using bi-allelic co-dominant single nucleotide polymorphism (SNP) markers, specific to either H. lutescens or H. sericeum, to estimate the degree of genetic mixing in 449 moss samples collected from seven sympatric and five allopatric populations on the island of Öland, south Sweden. The samples represented three generations: haploid maternal gametophytes, diploid sporophytes, and haploid sporelings. KEY RESULTS Admixture analyses of SNP genotypes identified a majority as pure H. lutescens or H. sericeum, but 76 samples were identified as mildly admixed (17%) and 17 samples (3.8%) as strongly admixed. Admixed samples were represented in all three generations in several populations. Hybridization and introgression was bidirectional. CONCLUSIONS Our results demonstrate that admixed genomes are transferred between the generations, so that the populations behave as true hybrid zones. Earlier studies of sympatric bryophyte populations with admixed individuals have not been able to show that admixed alleles are transferred beyond the first generation. The presence of true hybrid zones has strong evolutionary implications because genetic material transferred across species boundaries can be directly exposed to selection in the long-lived haploid generation of the bryophyte life cycle, and contribute to local adaptation, long-time survival and speciation.
Distinct effects of reward and navigation history on hippocampal forward and reverse replays

Significance Sequential firing patterns of hippocampal place cells during spatial navigation are replayed in both forward and reverse directions during offline idling states, but functional roles of these replays are not clearly understood. To clarify this matter, we examined hippocampal replays in a spatial sequence memory task. We found that reward increases the fidelity of forward replays, while increasing the rate of reverse replays for all possible trajectories heading toward a rewarding location. We also found more faithful reactivation of place-cell sequences for upcoming rewarding trajectories than for already rewarded trajectories in forward replays. Our results suggest that hippocampal forward and reverse replays contribute to constructing a map of potential navigation trajectories with associated values (“value map”) via distinct mechanisms. To better understand the functional roles of hippocampal forward and reverse replays, we trained rats in a spatial sequence memory task and examined how these replays are modulated by reward and navigation history. We found that reward enhances both forward and reverse replays during the awake state, but in different ways. Reward enhances the rate of reverse replays, but it increases the fidelity of forward replays for recently traveled as well as other alternative trajectories heading toward a rewarding location. This suggests roles for forward and reverse replays in reinforcing representations for all potential rewarding trajectories. We also found more faithful reactivation of upcoming than already rewarded trajectories in forward replays. This suggests a role for forward replays in preferentially reinforcing representations for high-value trajectories. We propose that hippocampal forward and reverse replays might contribute to constructing a map of potential navigation trajectories and their associated values (a “value map”) via distinct mechanisms.
Menstrual blood losses and body mass index are associated with serum ferritin concentrations among female varsity athletes.

Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes as it may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentrations in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intakes, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n=6/30; inflammation-adjusted ferritin <15 µg/L). Multiple linear regression was used to assess associations of a number of independent explanatory variables with log-transformed serum ferritin (µg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9-37%) higher mean ferritin concentrations and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1, 2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Key bullet points: Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, non-invasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.
Protocol for Rapid, Accurate, Electrophysiologic, Auditory Assessment of Infants and Toddlers

Abstract Background Audiologists often lack confidence in results produced by current protocols for diagnostic electrophysiologic testing of infants. This leads to repeat testing appointments and slow protocols which extend the time needed to complete the testing and consequently delay fitting of amplification. A recent publication (Sininger et al50) has shown how new technologies can be applied to electrophysiologic testing systems to improve confidence in results and allow faster test protocols. Average test times for complete audiogram predictions when using new technologies and protocols were found to be just over 32 minutes using auditory brainstem response (ABR) and just under 20 minutes using auditory steady-state response (ASSR) technology. Purpose The purpose of this manuscript is to provide details of expedited test protocols for infant and toddler diagnostic electrophysiologic testing. Summary Several new technologies and their role in test speed and confidence are described including CE-Chirp stimuli, automated detection of ABRs using a technique called F MP, Bayesian weighting which is an alternative to standard artifact rejection and Next-Generation ASSR with improved response detection and chirp stimuli. The test protocol has the following features: (1) preliminary testing includes impedance measures and otoacoustic emissions, (2) starting test levels are based on Broad-Band CE-Chirp thresholds in each ear, (3) ABRs or ASSRs are considered present based on automated detection rather than on replication of responses, (4) number of test levels is minimized, (5) ASSR generally evaluates four frequencies in each ear simultaneously with flexibility to change all test levels independently. Conclusions Combining new technologies with common-sense strategies has been shown to substantially reduce test times for predicting audiometric thresholds in infants and toddlers (Sininger et al50). Details and rationales for changing test strategies and protocols are given and case examples are used to illustrate.