Miracle-dz/UniFAR-FTUs huggingface dataset:
The Association of Antibiotic Stewardship With Fluoroquinolone Prescribing in Michigan Hospitals: A Multi-hospital Cohort Study

Abstract Background Fluoroquinolones increase the risk of Clostridioides difficile infection and antibiotic resistance. Hospitals often use pre-prescription approval or prospective audit and feedback to target fluoroquinolone prescribing. Whether these strategies impact aggregate fluoroquinolone use is unknown. Methods This study is a 48-hospital, retrospective cohort of general-care, medical patients hospitalized with pneumonia or positive urine culture between December 2015–September 2017. Hospitals were surveyed on their use of pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing during hospitalization (fluoroquinolone stewardship). After controlling for hospital clustering and patient factors, aggregate (inpatient and post-discharge) fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) exposure was compared between hospitals with and without fluoroquinolone stewardship. Results There were 11 748 patients (6820 pneumonia; 4928 positive urine culture) included at 48 hospitals. All hospitals responded to the survey: 29.2% (14/48) reported using pre-prescription approval and/or prospective audit and feedback to target fluoroquinolone prescribing. After adjustment, fluoroquinolone stewardship was associated with fewer patients receiving a fluoroquinolone (37.1% vs 48.2%; P = .01) and fewer fluoroquinolone treatment days per 1000 patients (2282 vs 3096 days/1000 patients; P = .01), driven by lower inpatient prescribing. However, most (66.6%) fluoroquinolone treatment days occurred after discharge, and hospitals with fluoroquinolone stewardship had twice as many new fluoroquinolone starts after discharge as hospitals without (15.6% vs 8.4%; P = .003). Conclusions Hospital-based stewardship interventions targeting fluoroquinolone prescribing were associated with less fluoroquinolone prescribing during hospitalization, but not at discharge. To limit aggregate fluoroquinolone exposure, stewardship programs should target both inpatient and discharge prescribing.
Dynamic cognitive remediation for a Traumatic Brain Injury (TBI) significantly improves attention, working memory, processing speed, and reading fluency

Background: In the U.S. 3.8 million people have a Traumatic Brain Injury (TBI) each year. Rapid brain training exercises to improve cognitive function after a mild TBI are needed. Objective: This study determines whether cognitive remediation by discriminating the direction a test pattern moves relative to a stationary background (movement figure-ground discrimination) improves the vision and cognitive deficits that result from a TBI, providing a paradigm shift in treatment methods. Methods: Movement-discrimination neurotraining was used to remediate low-level visual timing deficits in the dorsal stream to determine whether it improved high-level cognitive functions, such as processing speed, reading fluency, and the executive control functions of attention and working memory in four men with a TBI between the ages of 15–68. Standardized tests, as well as Magnetoencephalography (MEG) brain imaging, were administered at the beginning and end of 8–16 weeks of intervention training to evaluate improvements in cognitive skills. Results: Movement-discrimination cognitive neurotraining remediated both low-level visual timing deficits and high-level cognitive functioning, including selective and sustained attention, reading fluency, processing speed, and working memory for all TBI patients we studied. MEG brain imaging, using the Fast-VESTAL procedure, showed that this movement-discrimination training improved time-locked activity in the dorsal stream, attention, and executive control networks. Conclusions: Remediating visual timing deficits in the dorsal stream revealed the causal role of visual movement discrimination training in improving high-level cognitive functions such as focusing and switching attention, working memory, processing speed, and reading. This study found that movement-discrimination training was very rapid and effective in remediating cognitive deficits, providing a new approach that is very beneficial for treating a mild TBI.
Prediction of reader estimates of mammographic density using convolutional neural networks

Abstract. Mammographic density is an important risk factor for breast cancer. In recent research, percentage density assessed visually using visual analogue scales (VAS) showed stronger risk prediction than existing automated density measures, suggesting readers may recognize relevant image features not yet captured by hand-crafted algorithms. With deep learning, it may be possible to encapsulate this knowledge in an automatic method. We have built convolutional neural networks (CNN) to predict density VAS scores from full-field digital mammograms. The CNNs are trained using whole-image mammograms, each labeled with the average VAS score of two independent readers. Each CNN learns a mapping between mammographic appearance and VAS score so that at test time, they can predict VAS score for an unseen image. Networks were trained using 67,520 mammographic images from 16,968 women and for model selection we used a dataset of 73,128 images. Two case-control sets of contralateral mammograms of screen detected cancers and prior images of women with cancers detected subsequently, matched to controls on age, menopausal status, parity, HRT and BMI, were used for evaluating performance on breast cancer prediction. In the case-control sets, odd ratios of cancer in the highest versus lowest quintile of percentage density were 2.49 (95% CI: 1.59 to 3.96) for screen-detected cancers and 4.16 (2.53 to 6.82) for priors, with matched concordance indices of 0.587 (0.542 to 0.627) and 0.616 (0.578 to 0.655), respectively. There was no significant difference between reader VAS and predicted VAS for the prior test set (likelihood ratio chi square, p = 0.134). Our fully automated method shows promising results for cancer risk prediction and is comparable with human performance.
The hypothalamic-spinal dopaminergic system: a target for pain modulation

Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise, among others, noradrenergic, serotonergic, γ-aminobutyric acid (GABA)ergic, and dopaminergic fibers. The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood. The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.
De-escalation versus standard dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis

Abstract Switching from a potent P2Y12 blocker to clopidogrel is not uncommon for antiplatelet therapy in patients undergoing percutaneous coronary intervention. This meta-analysis aimed to investigate the efficacy and safety of this de-escalation strategy. Medical literature databases were searched for analysis comparing continued potent antiplatelet therapy and switching to clopidogrel with no language restrictions from inception to 07/May/2018. The primary endpoints of major adverse cardiovascular events (MACE) and major bleeding together with additional efficacy outcomes were assessed by random-effects and fixed-effects meta-analysis. A total of 17 896 patients in 13 studies were eligible for analysis, while 17 579 (98.2%) patients presented as acute coronary syndrome and 4105 (23%) patients received the de-escalation therapy. Incidence of MACE was virtually identical in both de-escalation and standard potent antiplatelet therapy groups (odds ratio 0.91, 95% CI 0.73–1.14; P = 0.43). Insignificant difference was also observed in major bleeding (0.99, 0.62–1.60; P = 0.97), all-cause death (0.95, 0.61–1.46; P = 0.81), cardiovascular death (0.66, 0.31–1.42; P = 0.29), myocardial infarction (1.12, 0.80–1.58; P = 0.51), stent thrombosis (1.09, 0.50–2.36; P = 0.83), unplanned revascularization (1.09, 0.83–1.41; P = 0.54), and stroke (1.16, 0.62–2.19; P = 0.64). In conclusion, de-escalation of antiplatelet therapy is associated with nonsignificant differences in both ischemic events and major bleeding compared with standard potent antiplatelet therapy in patients undergoing percutaneous coronary intervention. The feasibility and even superiority of this strategy need to be elucidated by further randomized trials.
The clinical impact of the left atrial posterior wall lesion formation by the cryoballoon application for persistent atrial fibrillation: Feasibility and clinical implications

The left atrial (LA) posterior wall (LAPW) has been targeted to improve the clinical outcomes in patients with persistent atrial fibrillation (PersAF). This study aimed to investigate the feasibility, safety, and clinical implications of cryoballoon (CB) applications on the LAPW to accomplish electrical isolation (EI) of the LAPW with CB.
Long‐Term Follow‐up of Patients with Tourette's Syndrome

Tourette's Syndrome (TS) is a childhood‐onset movement disorder marked by the chronic presence of motor and vocal tics. Research shows that tics associated with TS tend to fade in severity for some (but not all) affected youth, though psychiatric comorbidities that commonly accompany TS may be more persistent. The long‐term outcomes of individuals with TS have not been well characterized.
A Retrospective Review of High-level Performance After the Return to Run Clinical Pathway in Patients Using the Intrepid Dynamic Exoskeletal Orthosis.

BACKGROUND Severe ankle and foot injuries in the U.S. military can result in high-level functional limitation, lost duty days and medical discharge. OBJECTIVE To assess the effectiveness of the Return to Run Clinical Pathway (RTR) in returning patients with lower extremity fractures who utilize the Intrepid Dynamic Exoskeletal Orthosis (IDEO) to high-level mobility. METHODS Thirty service members with lower extremity fractures who utilized the IDEO unilaterally and completed the RTR at Naval Medical Center San Diego were included. The Comprehensive High-Level Activity Mobility Predictor (CHAMP) and all sub-tests were completed prior to and after completion of RTR as part of routine clinical care. An ANCOVA was utilized to compare CHAMP scores before and after RTR. RESULTS Significant improvements [mean change (95% Confidence Interval)] were found in the T-Test [-5.3 seconds (3.6 - 7.1), p=. 03] and total CHAMP score [4.2 (3.0 - 5.3), p<. 05]. No significant changes were noted in single legged stance subtest, the Edgren Side Step Test, or the Illinois Agility Test. CONCLUSIONS The RTR led to improvements in high-level, multi-directional mobility in IDEO users with history of fractures. Applicability of the intervention used in this study requires further validation before widespread use. LEVEL OF EVIDENCE Level 4. J Orthop Sports Phys Ther, Epub 13 Feb 2019. doi:10.2519/jospt.2019. 8763.
Ribosomal DNA harbors an evolutionarily conserved clock of biological aging

The ribosomal DNA (rDNA) is the most evolutionarily conserved segment of the genome and gives origin to the nucleolus, an energy intensive nuclear organelle and major hub influencing myriad molecular processes from cellular metabolism to epigenetic states of the genome. The rDNA/nucleolus has been directly and mechanistically implicated in aging and longevity in organisms as diverse as yeasts, Drosophila, and humans. The rDNA is also a significant target of DNA methylation that silences supernumerary rDNA units and regulates nucleolar activity. Here, we introduce an age clock built exclusively with CpG methylation within the rDNA. The ribosomal clock is sufficient to accurately estimate individual age within species, is responsive to genetic and environmental interventions that modulate life-span, and operates across species as distant as humans, mice, and dogs. Further analyses revealed a significant excess of age-associated hypermethylation in the rDNA relative to other segments of the genome, and which forms the basis of the rDNA clock. Our observations identified an evolutionarily conserved marker of aging that is easily ascertained, grounded on nucleolar biology, and could serve as a universal marker to gauge individual age and response to interventions in humans as well as laboratory and wild organisms across a wide diversity of species.
Conservation of physiological dysregulation signatures of aging across primates

Two major goals in the current biology of aging are to identify general mechanisms underlying the aging process and to explain species differences in aging. Recent research in humans suggests that one important driver of aging is dysregulation, the progressive loss of homeostasis in complex biological networks. Yet, there is a lack of comparative data for this hypothesis, and we do not know whether dysregulation is widely associated with aging or how well signals of homeostasis are conserved. To address this knowledge gap, we use unusually detailed longitudinal biomarker data from 10 species of nonhuman primates housed in research centers and data from two human populations to test the hypotheses that (a) greater dysregulation is associated with aging across primates and (b) physiological states characterizing homeostasis are conserved across primates to degrees associated with phylogenetic proximity. To evaluate dysregulation, we employed a multivariate distance measure, calculated from sets of biomarkers, that is associated with aging and mortality in human populations. Dysregulation scores positively correlated with age and risk of mortality in most nonhuman primates studied, and signals of homeostatic state were significantly conserved across species, declining with phylogenetic distance. Our study provides the first broad demonstration of physiological dysregulation associated with aging and mortality risk in multiple nonhuman primates. Our results also imply that emergent signals of homeostasis are evolutionarily conserved, although with notable variation among species, and suggest promising directions for future comparative studies on dysregulation and the aging process.
Effect of Previous-Season Influenza Vaccination on Serologic Response in Children During 3 Seasons, 2013–2014 Through 2015–2016

Abstract Background The effects of repeated influenza vaccination in children are not well understood. In this study, we evaluated previous vaccination effects on antibody response after vaccination with trivalent inactivated influenza vaccine (IIV) or quadrivalent live-attenuated influenza vaccine (LAIV) among school-aged children (5–17 years) across 3 seasons. Methods Children were enrolled in the fall of 2013, 2014, and 2015. The participants received IIV or LAIV according to parent preference (2013–2014) or our randomization scheme (2014–2015). All study children received IIV in 2015–2016. Hemagglutination-inhibition assays measured antibody response to egg-grown vaccine strains from prevaccination and postvaccination serum samples. Geometric mean titers (GMTs) and increases in GMTs from before to after vaccination (geometric mean fold rise [GMFR]) were estimated from repeated-measures linear mixed models. Results We enrolled 161 children in 2013–2014, 128 in 2014–2015, and 126 in 2015–2016. Among the IIV recipients, responses to the influenza A(H1N1)pdm09 and B vaccine strains were lowest among children who had received a previous-season IIV. The GMFRs for strains A(H1N1)pdm09 and B were 1.5 to 2.3 for previous-season IIV and 4.3 to 12.9 for previous-season LAIV or no previous vaccine. GMFRs were lower for strain A(H3N2), and differences according to previous-season vaccination history were smaller and not significant in most seasons. Most children had a post-IIV vaccination titer of ≥40 for vaccine strains in all seasons, regardless of previous-season vaccination history. Little to no increase in antibody levels was observed after vaccination with LAIV. Conclusions Serologic response to vaccination was greatest for IIV, but previous-season vaccination modified IIV response to A(H1N1)pdm09 and B. Influenza A(H3N2) responses were low in all groups, and LAIV generated minimal serologic response against all strains.
Hippocampal atrophy and intrinsic brain network dysfunction relate to alterations in mind wandering in neurodegeneration

Significance Humans spend much of their waking life engaged in mind wandering. Underlying brain systems supporting this complex ability have been established in healthy individuals, yet it remains unclear how mind wandering is altered in neuropsychiatric populations. We reveal changes in the thought profiles elicited during periods of low cognitive demand in dementia, resulting in reduced mind wandering and an increased propensity toward stimulus-bound thought. These altered thought profiles were associated with structural and functional brain changes in the hippocampus, default, and frontoparietal networks, key regions implicated in internal mentation in healthy individuals. Our findings provide a unique clinical validation of current theoretical models of mind wandering and reveal a dimension of cognitive dysfunction that has received scant attention in dementia. Mind wandering represents the human capacity for internally focused thought and relies upon the brain’s default network and its interactions with attentional networks. Studies have characterized mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This paper used a validated thought-sampling task to probe mind wandering capacity in two neurodegenerative disorders: behavioral variant frontotemporal dementia [(bvFTD); n = 35] and Alzheimer’s disease [(AD); n = 24], compared with older controls (n = 37). These patient groups were selected due to canonical structural and functional changes across sites of the default and frontoparietal networks and well-defined impairments in cognitive processes that support mind wandering. Relative to the controls, bvFTD patients displayed significantly reduced mind wandering capacity, offset by a significant increase in stimulus-bound thought. In contrast, AD patients demonstrated comparable levels of mind wandering to controls, in the context of a relatively subtle shift toward stimulus-/task-related forms of thought. In the patient groups, mind wandering was associated with gray matter integrity in the hippocampus/parahippocampus, striatum, insula, and orbitofrontal cortex. Resting-state functional connectivity revealed associations between mind wandering capacity and connectivity within and between regions of the frontoparietal and default networks with distinct patterns evident in patients vs. controls. These findings support a relationship between altered mind wandering capacity in neurodegenerative disorders and structural and functional integrity of the default and frontoparietal networks. This paper highlights a dimension of cognitive dysfunction not well documented in neurodegenerative disorders and validates current models of mind wandering in a clinical population.
Evolution of cranial epilepsy surgery complication rates: a 32-year systematic review and meta-analysis.

OBJECT Surgical interventions for medically refractory epilepsy are effective in selected patients, but they are underutilized. There remains a lack of pooled data on complication rates and their changes over a period of multiple decades. The authors performed a systematic review and meta-analysis of reported complications from intracranial epilepsy surgery from 1980 to 2012. METHODS A literature search was performed to find articles published between 1980 and 2012 that contained at least 2 patients. Patients were divided into 3 groups depending on the procedure they underwent: A) temporal lobectomy with or without amygdalohippocampectomy, B) extratemporal lobar or multilobar resections, or C) invasive electrode placement. Articles were divided into 2 time periods, 1980-1995 and 1996-2012. RESULTS Sixty-one articles with a total of 5623 patients met the study's eligibility criteria. Based on the 2 time periods, neurological deficits decreased dramatically from 41.8% to 5.2% in Group A and from 30.2% to 19.5% in Group B. Persistent neurological deficits in these 2 groups decreased from 9.7% to 0.8% and from 9.0% to 3.2%, respectively. Wound infections/meningitis decreased from 2.5% to 1.1% in Group A and from 5.3% to 1.9% in Group B. Persistent neurological deficits were uncommon in Group C, although wound infections/meningitis and hemorrhage/hematoma increased over time from 2.3% to 4.3% and from 1.9% to 4.2%, respectively. These complication rates are additive in patients undergoing implantation followed by resection. CONCLUSIONS Complication rates have decreased dramatically over the last 30 years, particularly for temporal lobectomy, but they remain an unavoidable consequence of epilepsy surgery. Permanent neurological deficits are rare following epilepsy surgery compared with the long-term risks of intractable epilepsy.
Development of vestibular ocular reflex and gross motor function in infants with common cavity deformity as a type of inner ear malformation

Abstract Background： The function of common cavity deformity demonstrated by temporal bone CT and MRI has been unknown. Aim/Objective: To investigate the developmental changes of vestibular ocular reflex and acquisition of postural control in infants with common cavity deformity. Material and methods: Eight infants who were congenitally deaf complicated by common cavity deformity were studied. The damped rotational chair test was carried out to evaluate vestibular ocular reflex. Acquisition of head control and independent walking in these infants was compared with that in normal infant’s milestones of gross motor development. Results: All of the eight infants with common cavity deformity did not show per-rotatory nystagmus in the damped rotational chair test around the first year of life. However, a normal number of beats and a longer duration of per-rotatory nystagmus for their age were recorded at around three or four years of age. Conclusions and significance: In the eight infants with common cavity deformity, vestibular ocular reflex was not present around the first year of life, but appeared after three or four years probably because of some vestibular sensory cells. Head control and independent walking were delayed but eventually acquired by the central vestibular compensation.