Miracle-dz/UniFAR-FTUs huggingface dataset:
Latent Variable Approaches for Understanding Heterogeneity in Depression: A Dissertation

Background: Major depression is one of the most prevalent, disabling, and costly illnesses worldwide. Despite a 400% increase in antidepressant medication use since 1988, fewer than half of treated depression patients experience a clinically meaningful reduction in symptoms and uncertainty exists regarding how to successfully obtain symptom remission. Identifying homogenous subgroups based on clinically observable characteristics could improve the ability to efficiently predict who will benefit from which treatments. Methods: Latent class analysis and latent transition analysis (LTA) were applied to data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to explore how to efficiently identify subgroups comprised of the multiple dimensions of depression and examine changes in subgroup membership during treatment. The specific aims of this dissertation were to: 1) evaluate latent depression subgroups for men and women prior to antidepressant treatment; 2) examine transitions in these subgroups over 12 weeks of citalopram treatment; and 3) examine differences in functional impairment between women’s depression subgroups throughout treatment. Results: Four subgroups of depression were identified for men and women throughout this work. Men’s subgroups were distinguished by depression severity and psychomotor agitation and retardation. Severity, appetite changes, insomnia, and psychomotor disturbances characterized women’s subgroups. Psychiatric comorbidities, especially anxiety disorders, were related to increased odds of membership in baseline moderate and severe depression subgroups for men and women. After 12 weeks of citalopram
Trafficking mechanisms underlying neuronal voltage‐gated ion channel localization at the axon initial segment

Voltage‐gated ion channels are diverse and fundamental determinants of neuronal intrinsic excitability. Voltage‐gated K+ (Kv) and Na+ (Nav) channels play complex yet fundamentally important roles in determining intrinsic excitability. The Kv and Nav channels located at the axon initial segment (AIS) play a unique and especially important role in generating neuronal output in the form of anterograde axonal and backpropagating action potentials. Aberrant intrinsic excitability in individual neurons within networks contributes to synchronous neuronal activity leading to seizures. Mutations in ion channel genes give rise to a variety of seizure‐related “channelopathies,” and many of the ion channel subunits associated with epilepsy mutations are localized at the AIS, making this a hotspot for epileptogenesis. Here we review the cellular mechanisms that underlie the trafficking of Kv and Nav channels found at the AIS, and how Kv and Nav channel mutations associated with epilepsy can alter these processes.
Bateman Gradients in Field and Laboratory Studies: A Cautionary Tale1

Abstract Since tools of molecular genetics became readily available, our understanding of bird mating systems has undergone a revolution. The majority of passerine species investigated are socially monogamous, but have been shown to be genetically polygamous. Data sets from natural populations of juncos suggest that multiple mating by females results in a sexual selection gradient as steep for females as for males (a result that does not support Bateman's predictions). However, in males, fitness is enhanced directly through fertilization success with multiple matings; in females fitness benefits may be enhanced immediately through direct access to food, protection against predators, or other resources received from males, or they may be delayed through improvement in offspring quality (e.g., through good genes, or greater genetic compatibility between the female and the extra-pair male). But a steep sexual selection gradient for females can be difficult to interpret. If all females copulate with multiple partners that are equally likely to fertilize eggs, then females that produce larger clutch sizes, for any reason, will appear to have copulated with more males. That is, multiple sires have a higher probability of detection in larger clutches than in smaller ones, giving the impression that females that mate with multiple males increase their reproductive success. Yet, in most studies in which there is a correlation between number of offspring produced by females and number of extra-pair males, causation has not been clearly established and other factors may explain the results. Additional complications in understanding male and female reproductive strategies are: (1) Molecular studies cannot detect extra-pair copulations that did not result in fertilizations; yet if a female acquires food or other resources from extra-pair males, such extra-pair matings may have significant effects on female fitness. Thus, molecular studies provide only a conservative estimate of the number of extra-pair copulations or “mates” that a female has. (2) Clutch size affects the probability that any given male will be successful in fertilizing a female's eggs. Specifically, at any given point, a male's chances of fertilizing at least one egg in the female's clutch will be greater as clutch size increases. We predict that in avian species with small clutch sizes, males may be selected to be choosy and avoid extra-pair copulations, while females should be selected to be less discriminating. Moreover, if extra-pair males provide resources that increase female fitness, the females should seek extra-pair copulations, whether or not the males are likely to fertilize any of her eggs. Laboratory studies with insects have yielded clearer evidence of the causal relationship between multiple mating and increased female fitness. We review studies on a tenebrionid beetle in which female fecundity increases directly with number of mates. In these experiments, the nutritive value of the spermatophores does not fully explain the increase in female reproductive success.
Disability during the last two years of life.

IMPORTANCE Whereas many persons at advanced ages live independently and are free of disability, we know little about how likely older people are to be disabled in the basic activities of daily living that are necessary for independent living as they enter the last years of life. OBJECTIVE To determine national estimates of disability during the last 2 years of life. DESIGN Prospective cohort study. SETTING A nationally representative study of older adults in the United States. PARTICIPANTS Participants 50 years and older who died while enrolled in the Health and Retirement Study between 1995 and 2010. Each participant was interviewed once at a varying time point in the last 24 months of life. We used these interviews to calculate national estimates of the prevalence of disability across the 2 years prior to death. We modeled the prevalence of disability in the 2 years prior to death for groups defined by age at death and sex. MAIN OUTCOMES AND MEASURES Disability was defined as need for help with at least 1 of the following activities of daily living: dressing, bathing, eating, transferring, walking across the room, and using the toilet. RESULTS There were 8232 decedents (mean [SD] age at death, 79 [11] years; 52% women). The prevalence of disability increased from 28% (95% CI, 24%-31%) 2 years before death to 56% (95% CI, 52%-60%) in the last month of life. Those who died at the oldest ages were much more likely to have disability 2 years before death (ages 50-69 years, 14%; 70-79 years, 21%; 80-89 years, 32%; 90 years or more, 50%; P for trend, <.001). Disability was more common in women 2 years before death (32% [95% CI, 28%-36%]) than men (21% [95% CI, 18%-25%]; P < .001), even after adjustment for older age at death. CONCLUSIONS AND RELEVANCE Those who live to an older age are likely to be disabled, and thus in need of caregiving assistance, many months or years prior to death. Women have a substantially longer period of end-of-life disability than men.
Alport's syndrome, Goodpasture's syndrome, and type IV collagen.

Defects in type IV collagen, a collagenous protein involved in the formation of basement membranes, have been implicated in hereditary Alport's syndrome and acquired Goodpasture's syndrome. Mutations in genes corresponding to the building blocks of type IV collagen cause Alport's syndrome, whereas autoantibodies against structures that are usually hidden in the recesses of collagen IV cause Goodpasture's syndrome.
Viral hepatitis in HIV infection.

Liver disease due to chronic HBV or HCV infection is becoming a leading cause of death among persons with HIV infection. Both the risk of hepatocellular carcinoma and the risk of hepatotoxicity due to antiretroviral drugs increase in patients with coinfection. This review presents an approach to the use of newer treatments for both HCV and HBV infections in patients with HIV infection, and it provides an update on optimal management to prevent complications of advanced liver disease.
Management of psychogenic nonepileptic seizures

The International League Against Epilepsy (ILAE) Neuropsychobiology Commission gave the charge to provide practical guidance for health professionals for the pharmacologic and nonpharmacologic treatment of patients with psychogenic nonepileptic seizures (PNES). Using a consensus review of the literature, an international group of clinician‐researchers in epilepsy, neurology, neuropsychology, and neuropsychiatry evaluated key management approaches for PNES. These included the following: presentation of the diagnosis, early phase treatment, psychological and pharmacologic interventions, and maintenance management. The aim of this report is to provide greater clarity about the range and current evidence base for treatment for patients with PNES, with the intention of improving the care of patients with PNES and patients who develop PNES as a comorbidity of epilepsy.
Lack of dietary sources of iodine and the prevalence of iodine deficiency in rural women from Sidama zone, southern Ethiopia

Iodine deficiency has been reported to affect a large number of people in Ethiopia. Although significant progress against iodine deficiency disorders (IDD) has been reported worldwide, millions of people remain with insufficient iodine intake. Multiple factors may contribute to iodine deficiency. Hence, the objective of this study was to investigate iodine deficiency and dietary intake of iodine. A cross-sectional survey design was used to assess urinary iodine concentration (UIC), goiter and dietary intake of iodine in a sample of 202 non-pregnant women living in three rural communities of Sidama Zone, southern Ethiopia. Urinary iodine concentration was analyzed using the Sandell-Kolthoff reaction, goiter was assessed using palpation and dietary source of iodine was assessed using a food frequency questionnaire. Data were analyzed using selected descriptive and analytical statistical measures with SAS software. Mean (SD) age, mid upper arm circumference (MUAC) and body mass index [BMI -Wt(kg)/(Ht(m))2] were 30.8(7.9) y, 24.8(2.5) cm and 20 (2.2) respectively. Median UIC was 37.2 µg/L. Participants with UIC <20 µg/L, classified as severely iodine deficient were 22.8%; 46.5% had UIC between 20 to <50 µg/L, classified as moderately iodine deficient, and 27.2 % had UIC in the mild deficiency range of 50 to <100 µg/L. Only 3.5% of the women had UIC ≥ 100 μg/L. The total goiter rate was 15.9%, which was 1.5% visible and 14.4% palpable goiter. A majority of the participants consumed Enset (E. ventricosum), corn and kale frequently and meat was consumed rarely. None of the participants reported ever consuming iodized salt or ever having heard about use of iodized salt. Adjacent communities (Alamura, Tullo and Finchawa) showed significant differences in UIC, goiter rate and frequency of fish and dairy consumption. The findings of the present study revealed that iodine status of the population is a significant public health problem. Hence, there is a need to supply iodized salt in order to achieve the goal of elimination of iodine deficiency disorders in the community.
Effect of in Utero and Early-life Conditions on Adult Health and Disease Epidemiol Ogic a Nd Clinic a L Observations

A long latency period between an environmental trigger and the onset of subsequent disease is widely recognized in the etiology of certain cancers, yet this phenomenon is not generally considered in the etiology of other conditions such as cardiovascular disease, metabolic disease, or osteopo-rosis. However, many lines of evidence, including epidemiologic data and data from extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. An increased understanding of developmental plasticity (defined as the ability of an organism to develop in various ways, depending on the particular environment or setting) provides a conceptual basis for these observations. 1 Developmental plasticity requires stable modulation of gene expression, and this appears to be mediated, at least in part, by epigenetic processes such as DNA methylation and histone modification. Thus, both the genome and the epigenome interactively influence the mature phenotype and determine sensitivity to later environmental factors and the subsequent risk of disease. In this review, we synthesize evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation. The epidemiologic observations that smaller size or relative thinness at birth and during infancy is associated with increased rates of coronary heart disease, stroke, type 2 diabetes mellitus, adiposity, the metabolic syndrome, and osteoporosis in adult life 2-6 have been extensively replicated. Perinatal events appear to exert effects that are independent of environmental risk factors in adults 7,8 or may be amplified by other risk factors. 9 Slow growth in utero may be associated with increased allocation of nutrients to adipose tissue during development and may then result in accelerated weight gain during childhood, 10,11 which may contribute to a relatively greater risk of coronary heart disease, hypertension, and type 2 diabetes mellitus. There is a continuous relation between birth weight and future risk — not just for extreme weights but also for normal weights. 12 Prematurity itself, independent of size for gestational age, has been associated with insulin resistance and glucose intolerance in prepubertal children 13 that may track into young adulthood and may be accompanied by elevated blood pressure. 14 In mammalian development, the mother transduces environmental information such as nutritional status to her embryo or fetus through the placenta or to her The New England Journal of Medicine Downloaded from nejm.org at UC SHARED JOURNAL …
Abnormal white matter correlates with neuropsychological impairment in children with localization‐related epilepsy

The white matter (WM) is considered critical for linking cortical processing networks necessary for cognition. The aim of this study was to assess diffusion tensor imaging (DTI) measures of regional WM in children with nonlesional localization‐related epilepsy in comparison to controls, and to determine the relation between lobar WM and neuropsychological performance.
DNA damage, aging, and cancer.

NA damage has emerged as a major culprit in cancer and many diseases related to aging. The stability of the genome is supported by an intricate machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. In addition, DNA damage and other stresses can trigger a highly conserved, anticancer, antiaging survival response that suppresses metabolism and growth and boosts defenses that maintain the integrity of the cell. Induction of the survival response may allow interventions that improve health and extend the life span. Recently, the first candidate for such interventions, rapamycin (also known as sirolimus), has been identified. 1 Compromised repair systems in tumors also offer opportunities for intervention, making it possible to attack malignant cells in which maintenance of the genome has been weakened. Time-dependent accumulation of damage in cells and organs is associated with gradual functional decline and aging. 2 The molecular basis of this phenomenon is unclear, 3-5 whereas in cancer, DNA alterations are the major culprit. In this review, I present evidence that cancer and diseases of aging are two sides of the DNAdamage problem. An examination of the importance of DNA damage and the systems of genome maintenance in relation to aging is followed by an account of the derailment of genome guardian mechanisms in cancer and of how this cancerspecific phenomenon can be exploited for treatment.
Quantitative assessment of gait parameters in horses: Useful for aiding clinical decision making?

Summary Gait analysis in horses has moved from the laboratory into the outside world enabling researchers and clinicians to make use of quantitative measurements to provide evidence aiding clinical decision making. In this article we explain how the two major visual signs of lameness – head nod and hip hike –are linked to the mechanics of lameness. These parameters should be regarded as well suited for incorporation into clinical decision making being easily measurable e.g. with inertial sensors under nonlaboratory conditions and representative of the underlying mechanical changes. A brief overview of the results of validation studies of the use of inertial sensors for quantification of movement symmetry shows that accuracy, precision and repeatability with current sensor generations are in the order of 3–7 mm; this is below the reported detection threshold for movement symmetries ‘by eye’. Recent studies with inertial sensors have investigated conditions relevant to the clinical lameness examination: lungeing, flexion tests and diagnostic analgesia. Lungeing introduces kinematic adaptations rendering head and pelvic movement asymmetrical, even in sound horses. First guideline values are available for changes after flexion tests and diagnostic analgesia, and we understand which parameters show consistent changes. This is crucial for investigating the effects in horses with different orthopaedic deficits. In conclusion, the current inertial sensor systems, while not quantifying all the gait adaptations seen in lame horses, characterise the major mechanical changes affecting fore- and hindlimb lame horses. In order to avoid misinterpretation of the generated data, users should have a thorough understanding of the gait parameters and be aware of sensor limitations in terms of accuracy, precision and repeatability.
Atypical hemolytic-uremic syndrome

Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow. Atypical hemolytic-uremic syndrome is characterized by three major features related to abnormal clotting: hemolytic anemia, thrombocytopenia, and kidney failure.
SERUM LACTATE IS A USEFUL PREDICTOR OF DEATH IN SEVERE SEPSIS AND SEPTIC SHOCK

Article type Review article Article history The severe sepsis and septic shock are as common and lethal that emergency physicians routinely confront. Actually, more than two thirds of sepsis patients present initially to the ED. Only a few laboratory tests for markers of sepsis are currently available. The serum lactate level can help in determining prognosis and to risk-stratify patients with severe sepsis. This independent review of the literature includes 83 studies published in all electronic-based database such as Elsevier, PubMed, and SID during the last 18 years (40-320 patients in each). Data gathered from English language articles and books published between 1995 and 2013. The serum lactate concentrations measured in almost all patients with severe sepsis raised at admission and were higher in patients who had the worst outcomes such as higher Apache-II and SOFA score. Serum lactate was associated with mortality independent of clinically apparent organ dysfunction and shock in patients with severe sepsis admitted to the emergency department and intensive care unit. This review focuses on the association between initial and serial serum lactate level and mortality in patients presenting to the emergency department with severe sepsis.
Computer-aided detection in mammography: downstream effect on diagnostic testing, ductal carcinoma in situ treatment, and costs.

Since 2001, Medicare has reimbursed computer-aided detection (CAD) during screening mammography. The CAD software tool is used by radiologists to identify lesions suggestive of malignant disease. Research suggests that CAD use increases the rate of false-positive findings of screening mammography and the detection of ductal carcinoma in situ (DCIS). 1 Increased DCIS detection could lead to overdiagnosis of breast cancer, particularly among older women at risk for competing causes of death. We estimated the fraction of diagnostic tests, DCIS treatments, and costs attributable to CAD dissemination within the Medicare population, among whom the risk for overdiagnosis may be elevated.
People with epilepsy who use multiple hospitals; prevalence and associated factors assessed via a health information exchange

Hospital crossover occurs when people seek care at multiple hospitals, creating information gaps for physicians at the time of care. Health information exchange (HIE) is technology that fills these gaps, by allowing otherwise unaffiliated physicians to share electronic medical information. However, the potential value of HIE is understudied, particularly for chronic neurologic conditions like epilepsy. We describe the prevalence and associated factors of hospital crossover among people with epilepsy, in order to understand the epidemiology of who may benefit from HIE.
In response: Effects of epilepsy treatments on sleep architecture and daytime sleepiness: An evidence‐based review of objective sleep metrics

submission deadline: April 30, 2014. Registration deadline: May 31, 2014. Congress website: www.epilepsykorea. org. For information, email ls@ls-comm.co.kr. Canadian League Against Epilepsy (CLAE) Biennial Meeting 17–19 October, 2014. London, Ontario, Canada. More information available soon.
Limitaciones de los indicadores bibliométricos en la evaluación de la actividad científica biomédica

SUMMARY The use of bibliometrics indicators to study research activity is based on which the scientific publications are essential product of this activity, and provide information about the research process, its volume, evolution, visibility and structure. So, they allow to value the scientific activity, and influences (or impact) of the work and the sources. The bibliometrics studies, altogether with other indicators, allows an objective quantification of the knowledge, and are harnessed by the present explosion of the knowledge and its compilation in bibliographical data bases.
Antiepileptic activity of preferential inhibitors of persistent sodium current

Evidence from basic neurophysiology and molecular genetics has implicated persistent sodium current conducted by voltage‐gated sodium (NaV) channels as a contributor to the pathogenesis of epilepsy. Many antiepileptic drugs target NaV channels and modulate neuronal excitability, mainly by a use‐dependent block of transient sodium current, although suppression of persistent current may also contribute to the efficacy of these drugs. We hypothesized that a drug or compound capable of preferential inhibition of persistent sodium current would have antiepileptic activity.