Miracle-dz/UniFAR-FTUs huggingface dataset:
Original Contribution Associations between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10 −6) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10 −7 , smallest P = 1.5 × 10 −9), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. Considerable differences exist among US racial/ethnic groups in the risk of lung cancer associated with cigarette smoking after accounting for self-reported dose and duration (1, 2). Differences in exposure and in response to tobacco smoke constituents, including nicotine and carcinogens, have been repeatedly cited as possible factors underlying the ethnic/ racial differences in lung cancer (3–6). For example, past studies have shown that nicotine uptake per cigarette was greater in African Americans (7, 8) when compared with whites; cigarettes per day-adjusted nicotine equivalents were lower in Asians compared with Native Hawaiians or whites (9); and slower clearance of serum cotinine and lower cotinine glucur-onidation were observed for African American than for white smokers (8, 10, 11). These differences suggest that genetic ancestry (resulting from ethnic-specific genetic polymor-phisms) and/or ethnic-specific " environmental " factors (such as dietary habits, lifestyle, medication history, etc.) may play a role in the metabolism of nicotine and tobacco smoke-derived carcinogens. Dissecting the contribution of genetic ancestral components from that of environmental factors may lead to discovery of genetic variants influencing the metabolism of tobacco smoke ingredients and, potentially, a better understanding of the disparity in lung cancer risk. In this study, we examined …
THERMAL STUDY OF VASOMOTOR LABILITY IN PREGNANCY: PRELIMINARY REPORT

That vascular tension is an important factor in the mechanism of the toxemias of pregnancy was postulated many years ago. Cohnheim, 1 in 1880, seems to have been the first to express the view that albuninuria and anuria in eclampsia might be due to a spasm of the renal vessels. In 1918, Volhard 2 advanced the hypothesis that a generalized arterial spasm accounted for the hypertension, convulsions and renal symptoms in eclampsia. Heynemann 3 also assumed that a general arterial spasm produced the symptoms. Various attempts to demonstrate vascular spasm have been more or less successful. Hinselmann 4 (1924) noted the capillary changes in the finger-nail beds. He assumed that the capillary stasis and the dilatation were secondary to an arteriolar spasm. Subsequent observations of the nicking of retinal arteries and veins and the beading and the contractions of these vessels have indicated that the vascular spasm is probably general.
A 3-Year Longitudinal Analysis of Changes in Body Mass Index

The aim of this study was to analyse whether Physical Activity Index (PAI), Physical Fitness, Screen Time (watching TV and computer use), Socio-economic Status and Commuting to School made a significant contribution to longitudinal changes in Body Mass Index (BMI) in youth. This longitudinal study was carried out over a period of 3 years with 345 students (147 boys) who were between 11 and 16 years old at the beginning of the study. Students were invited to perform tests from FITNESSGRAM Battery for Curl-Ups, Push-Ups, Back-Saver Sit and Reach, and 20 m Shuttle-Run (CRF). Fitness tests were categorized in "Healthy Zone" (HZ) and "Under Healthy Zone" (UHZ), PAI in "less active" and "active"; Socio-economic Status, in low, middle and high education level, and Commuting in active and passive. BMI was corrected for age and gender meaning that we subtracted the age-and-sex-specific cut points for overweight. Corrected body mass index was used as dependent variable in a Linear Mixed Model. The main result was the strong positive and independent association of individuals with CRF performances UHZ with corrected body mass index. In conclusion, the results of this longitudinal study showed markedly an important relationship of lower fitness levels with the risk of being overweight/obese, in particular CRF and abdominal strength.
A brief review of intradialytic hypotension with a focus on survival

Intradialytic hypotension (IDH), a common complication of ultrafiltration during hemodialysis therapy, is associated with high mortality and morbidity. IDH, defined as a nadir systolic blood pressure of less than 90 mm Hg on more than 30% of treatments, is a relevant definition and is correlated with mortality. Risk factors for IDH include patient demographics, anti‐hypertensive medication use, larger interdialytic weight gain, and dialysis prescription features as dialysate sodium, high ultrafiltration rate, and dialysate temperature. A high frequency of IDH events carries a substantial death risk. An ultrafiltration rate >10 mL/h/kg, and even more so >13 mL/h/kg, is highly predictive of cardiovascular and all‐cause mortality. Evidence suggests that IDH causes acute reversible segmental myocardial hypoperfusion and contractile dysfunction (myocardial stunning), which can result in long‐term loss of myocardial contractility, leading to premature death. IDH also has negative end‐organ effects on the brain and gut, contributing to mortality through stroke, and endotoxin translocation with associated inflammation and protein‐energy wasting. Given strong association of IDH and dialysis mortality, a paradigm shift to its approach is urgently needed. Randomized controlled trials are required to prospectively test drugs and monitoring devices which may reduce IDH.
Peritraumatic distress but not dissociation predicts posttraumatic stress disorder in the elderly

ABSTRACT Background: Post-traumatic stress disorder (PTSD) is a severe anxiety disorder whose symptoms include re-experiencing, avoidance, and hyperarousal after a particularly intense event. In view of the aging of the population, increased clinical knowledge is required for better understanding of PTSD in the elderly. Extending previous research in this field in adults and children, the aim of our study was to assess the utility of peri-traumatic dissociation and distress as a predictor of PTSD in the elderly. Methods: A prospective longitudinal study was conducted in a consecutive cohort of subjects aged 65 years and over admitted to emergency departments after a physical assault or a road traffic accident. Peri-traumatic responses of distress and of dissociation were measured. One, 6, and 12 months after trauma exposure, PTSD symptoms and diagnosis were assessed using both a dimensional and a semistructured interview. Results: Thirty-nine male and female participants with an average age of 72.4 years were recruited. Mixed model regression analyses did not detect a significant effect of age, sex, nor time. Significant associations were detected between peri-traumatic distress and the self-report PTSD Checklist (p = 0.008), as well as the Clinician-administered PTSD scale (p = 0.03). No association was detected between peri-traumatic dissociation and PTSD. Conclusions: Peri-traumatic distress predicts PTSD symptoms and diagnosis in the elderly, thereby suggesting its systematic evaluation at the emergency department would be a worthwhile thing to do.
Critical concepts in elder abuse research

ABSTRACT Background: This paper identifies core elements in principal definitions of elder abuse or mistreatment of older adults (EA/MOA) and discusses the relevance of four crucial concepts: age, vulnerability, trust, and power balance in relationships. Method: A critical analysis of selected literature in EA/MOA with a focus on works from the last 10 years. Results: Current definitions of EA/MOA share commonalities regarding an understanding of elder abuse as a status offence, the inclusion of both acts and omissions, and the consideration of multiple levels of behavior and its effects. Definitions differ with regard to aspects as crucial as the intentionality of an abusive action and its actual or potential harmful effects. EA/MOA can be considered as a complex subtype of victimization in later life limited to victim–perpetrator relationships, where the perpetrator has assumed responsibility for the victim, the victim puts trust in the offender, or the role assigned to the offending person creates the perception and expectation that the victim may trust the perpetrator. Vulnerability is identified as a key variable in EA/MOA theory and research. With regard to neglect, the mere possibility of being neglected presupposes a heightened level of vulnerability. Power imbalance often characterizes victim – perpetrator relationships but is not a necessary characteristic of abuse. Conclusion: Research on EA/MOA needs conceptual development. Confining phenomena of EA/MOA to specific relationships and tying them to notions of vulnerability has implications for research design and sampling and points to the limits of population-based victimization surveys.
Chinese Medical Psychiatry: A Textbook and Clinical Manual

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Fetuin-A and Risk of Diabetes Independent of Liver Fat Content: The Multi-Ethnic Study of Atherosclerosis

Fetuin-A is a hepatic secretory protein and a novel risk factor for diabetes. However, it remains unclear whether the association between high levels of fetuin-A and diabetes can be attributed to nonalcoholic fatty liver disease. We conducted a case-cohort study among 1,957 subcohort members and 455 incident diabetes cases in the Multi-Ethnic Study of Atherosclerosis, a multicenter US study of Caucasian, African-American, Hispanic, and Chinese-American adults aged 45–84 years. Serum fetuin-A and computed tomography-determined liver fat content were measured from samples collected at baseline (2000–2002). In multivariable Cox proportional hazards models with follow-up through 2012, a higher fetuin-A level was associated with a higher risk of diabetes, with a stronger association among women (for top quartile vs. bottom, hazard ratio (HR) = 3.36, 95% confidence interval (CI): 2.08, 5.44) than among men (HR = 1.47, 95% CI: 0.93, 2.35) (P-heterogeneity = 0.001). Adjustment for liver fat content attenuated these associations slightly (women: HR = 2.61, 95% CI: 1.59, 4.26; men: HR = 1.32, 95% CI: 0.84, 2.08). In this study, we observed a particularly strong association of fetuin-A with diabetes risk in women that could not be explained by liver fat.
Subjective depressive mood and regional cerebral blood flow in mild Alzheimer's disease

ABSTRACT Background: Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of subjective depressive symptoms in AD. Methods: Seventy-six consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. Subjective depressive symptoms were evaluated using the short version of the Geriatric Depression Scale (GDS). All patients underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by the Statistical Parametric Mapping 8 program. Results: No significant differences between groups with high and low GDS scores were found with respect to age, sex, years of education, and revised Addenbrooke's Cognitive Examination scores. Compared to patients with low scores on GDS, patients with high scores showed significant hypoperfusion in the left inferior frontal region. Conclusions: The left inferior frontal region may be significantly involved in the pathogenesis of subjective depressive symptoms in AD. Subjective and objective depressive symptoms may have somewhat different neural substrates in AD.
Tools for the Precision Medicine Era: How to Develop Highly Personalized Treatment Recommendations From Cohort and Registry Data Using Q-Learning

Q-learning is a method of reinforcement learning that employs backwards stagewise estimation to identify sequences of actions that maximize some long-term reward. The method can be applied to sequential multiple-assignment randomized trials to develop personalized adaptive treatment strategies (ATSs)-longitudinal practice guidelines highly tailored to time-varying attributes of individual patients. Sometimes, the basis for choosing which ATSs to include in a sequential multiple-assignment randomized trial (or randomized controlled trial) may be inadequate. Nonrandomized data sources may inform the initial design of ATSs, which could later be prospectively validated. In this paper, we illustrate challenges involved in using nonrandomized data for this purpose with a case study from the Center for International Blood and Marrow Transplant Research registry (1995-2007) aimed at 1) determining whether the sequence of therapeutic classes used in graft-versus-host disease prophylaxis and in refractory graft-versus-host disease is associated with improved survival and 2) identifying donor and patient factors with which to guide individualized immunosuppressant selections over time. We discuss how to communicate the potential benefit derived from following an ATS at the population and subgroup levels and how to evaluate its robustness to modeling assumptions. This worked example may serve as a model for developing ATSs from registries and cohorts in oncology and other fields requiring sequential treatment decisions.
The value of personalized psychosocial interventions to address behavioral and psychological symptoms in people with dementia living in care home settings: a systematic review

ABSTRACT Background: Several important systematic reviews and meta-analyses focusing on psychosocial interventions have been undertaken in the last decade. However, they have not focused specifically on the treatment of individual behavioral and psychological symptoms of dementia (BPSD) with personalized interventions. This updated systematic review will focus on studies reporting the effect of personalized psychosocial interventions on key BPSD in care homes. Methods: Systematic review of the evidence for psychosocial interventions for BPSD, focusing on papers published between 2000 and 2012. All care home and nursing home studies including individual and cluster randomized controlled trials (RCTs) and pre-/post-test studies with control conditions were included. Results: 641 studies were identified, of which 40 fulfilled inclusion and exclusion criteria. There was good evidence to support the value of personalized pleasant activities with and without social interaction for the treatment of agitation, and reminiscence therapy to improve mood. The evidence for other therapies was more limited. Conclusions: There is a growing body of evidence indicating specific effects of different personalized psychosocial interventions on individual BPSD and mood outcomes.
Geriatric Anxiety Scale: item response theory analysis, differential item functioning, and creation of a ten-item short form (GAS-10)

ABSTRACT Background: The Geriatric Anxiety Scale (GAS; Segal et al. (Segal, D. L., June, A., Payne, M., Coolidge, F. L. and Yochim, B. (2010). Journal of Anxiety Disorders, 24, 709–714. doi:10.1016/j.janxdis. 2010.05. 002) is a self-report measure of anxiety that was designed to address unique issues associated with anxiety assessment in older adults. This study is the first to use item response theory (IRT) to examine the psychometric properties of a measure of anxiety in older adults. Method: A large sample of older adults (n = 581; mean age = 72.32 years, SD = 7.64 years, range = 60 to 96 years; 64% women; 88% European American) completed the GAS. IRT properties were examined. The presence of differential item functioning (DIF) or measurement bias by age and sex was assessed, and a ten-item short form of the GAS (called the GAS-10) was created. Results: All GAS items had discrimination parameters of 1.07 or greater. Items from the somatic subscale tended to have lower discrimination parameters than items on the cognitive or affective subscales. Two items were flagged for DIF, but the impact of the DIF was negligible. Women scored significantly higher than men on the GAS and its subscales. Participants in the young-old group (60 to 79 years old) scored significantly higher on the cognitive subscale than participants in the old-old group (80 years old and older). Conclusions: Results from the IRT analyses indicated that the GAS and GAS-10 have strong psychometric properties among older adults. We conclude by discussing implications and future research directions.
Phenotypic Differences in Leucocyte Populations among Healthy Preterm and Full‐Term Newborns

The immune system of neonates has been considered functionally immature, and due to their high susceptibility to infections, the aim of this study was to analyse the phenotypic differences in leucocyte populations in healthy preterm and full‐term newborns. We evaluated the absolute numbers and frequencies of dendritic cells (DCs) and DC subsets, monocytes and T and B lymphocytes and subsets in the cord blood of healthy moderate and very preterm (Group 1), late preterm (Group 2) and full‐term (Group 3) newborns and in healthy adults, as controls, by flow cytometry. The analyses revealed statistically higher absolute cell numbers in neonates compared with adults due to the characteristic leucocytosis of neonates. We observed a lower frequency of CD80+ myeloid and plasmacytoid DCs in Group 1 and reduced expression of TLR‐4 on myeloid DCs in all neonates compared with adults. TLR‐2+ monocytes were reduced in Group 1 compared with Groups 2 and 3, and TLR‐4+ monocytes were reduced in Groups 1 and 2 compared with Group 3. The frequencies and numbers of naïve CD4+ T and CD19+ B cells were higher in the three groups of neonates compared with adults, while CD4+ effector and effector memory T cells and CD19+ memory B cells were elevated in adults compared with neonates, as expected. Our study provides reference values for leucocytes in cord blood from term and preterm newborns, which may facilitate the identification of immunological deficiencies in protection against extracellular pathogens.
Agreement Between 35 Published Frailty Scores in the General Population

Abstract In elderly populations, frailty is associated with higher mortality risk. Although many frailty scores (FS) have been proposed, no single score is considered the gold standard. We aimed to evaluate the agreement between a wide range of FS in the English Longitudinal Study of Ageing (ELSA). Through a literature search, we identified 35 FS that could be calculated in ELSA wave 2 (2004–2005). We examined agreement between each frailty score and the mean of 35 FS, using a modified Bland-Altman model and Cohen's kappa (κ). Missing data were imputed. Data from 5,377 participants (ages ≥60 years) were analyzed (44.7% men, 55.3% women). FS showed widely differing degrees of agreement with the mean of all scores and between each pair of scores. Frailty classification also showed a very wide range of agreement (Cohen's κ = 0.10–0.83). Agreement was highest among “accumulation of deficits”-type FS, while accuracy was highest for multidimensional FS. There is marked heterogeneity in the degree to which various FS estimate frailty and in the identification of particular individuals as frail. Different FS are based on different concepts of frailty, and most pairs cannot be assumed to be interchangeable. Research results based on different FS cannot be compared or pooled.