Miracle-dz/UniFAR-FTUs huggingface dataset:
Chapter 1 Issues in Diagnosis Conceptual Issues and Controversies

P diagnosis is fundamental to the understanding of mental illness. Without it, the study, assessment, and treatment of psychopathology would be in disarray. In this chapter, we examine (a) the raison d’être underlying psychiatric diagnosis, (b) widespread misconceptions regarding psychiatric diagnosis, (c) the present system of psychiatric diagnosis and its strengths and weaknesses, and (d) fruitful directions for improving this system. A myriad of forms of abnormality are housed under the exceedingly broad umbrella of mental disorders. Indeed, the current psychiatric classification system contains well over 300 diagnoses (American Psychiatric Association [APA], 2013). The enormous heterogeneity of psychopathology makes a formal system of organization imperative. Just as in the biological sciences, where Linnaeus’ hierarchical taxonomy categorizes fauna and flora, and in chemistry, where Mendeleev’s periodic table orders the elements, a psychiatric classification system helps to organize the bewildering subforms of abnormality. Such a system, if effective, permits us to parse the variegated universe of psychological disorders into more homogeneous, and ideally more clinically meaningful, categories. From the practitioner’s initial inchoate impression that a patient’s behavior is aberrant to later and better-elaborated case conceptualization, diagnosis plays an integral role in the clinical process. Indeed, the essential reason for initiating assessment and treatment is often the observer’s sense that “something is just not quite right” about the person. Meehl (1973) commented that the mental health professional’s core task is to answer the question: “What does this person have, or what befell him, that makes him different from those who have not developed clinical psychopathology? ” (p. 248). Therein lies the basis for psychiatric diagnosis.
Online Therapy for Depressive Symptoms: An Evaluation of Counselor-Led and Peer-Supported Life Review Therapy

Objectives Life review therapy is recognized as an evidence-based treatment for depression in later life. The current article evaluates an online life review therapy in middle-aged and older persons, comparing a counselor-led to a peer-supported mode of delivery. Methods A pilot randomized controlled trial (RCT) was carried out with 3 conditions and 4 measurement points: (a) online life review therapy with online counseling, (b) online life review therapy with online peer support, and (c) a waitlist control condition. A mixed methods study provided insight in the reach, adherence, effectiveness, user experiences, and acceptability. Results Fifty-eight people were included in the study. The intervention reached a vulnerable group of mainly middle-aged, college-educated women. The pilot RCT on effectiveness showed that participants in all conditions improved significantly in depressive symptoms, engaged living, mastery, and vitality, but not in ego integrity and despair, social support, loneliness, and well-being. The adherence, user experience, and acceptability were better in the counselor condition than in the peer condition. No differences were found between middle-aged and older adults. Conclusion Despite the nonsignificant effects, possibly due to the small sample size, online life review therapy might be a good method for alleviating depressive symptoms in people in their second half of life. Further research is needed, addressing how online life review is best offered.
Detectable Viral Load May Be Associated with Increased Pain Sensitivity in Persons Living with HIV: Preliminary Findings

Objective Animal models have previously shown that HIV is associated with hyperalgesia, or heightened sensitivity to painful stimuli. Efforts to determine whether this finding translates to humans are presently lacking. Among persons living with HIV (PLWH), those with detectable viral loads may be at greatest risk for heightened pain sensitivity. It was hypothesized that PLWH with detectable viral loads would be more sensitive to painful stimuli compared with PLWH without detectable viral loads and healthy controls without HIV. Design A total of 47 PLWH and 50 community-dwelling, healthy adults without HIV (controls) were recruited. Participants completed a quantitative sensory testing protocol to assess threshold, tolerance, and temporal summation in response to painful mechanical and heat stimuli. Most recent viral load was collected from medical records, and viral load was considered detectable if the count was greater than 50 copies/mL of blood. Of the 47 PLWH, 11 (23.4%) had detectable viral loads, the median viral load count was 10,200 copies/mL. Results PLWH with detectable viral loads demonstrated significantly lower pain thresholds for mechanical stimuli (F2,89 = 3.15, P = 0.049), significantly lower heat pain tolerances (F2,89 = 3.38, P = 0.039), and significantly greater temporal summation of heat pain at 48 °C (F2,89 = 10.66, P < 0.001) and 50 °C (F2,89 = 3.82, P = 0.026), compared with PLWH without detectable viral loads and healthy controls. Conclusions These preliminary results tentatively suggest that the detectable presence of the virus may sensitize PLWH to painful mechanical and heat stimuli.
Metabolic State Alters Economic Decision Making under Risk in Humans

Background Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity.
Can Conversational Agents Express Big Five Personality Traits through Language ? : Evaluating a Psychologically-Informed Language Generator

Conversation is an essential component of social behavior, one of the primary means by which humans express intentions, beliefs, emotions, attitudes and personality. Thus a key technical capability for dialogue-based conversational agents for interactive entertainment, therapeutic, or learning applications is the ability to support natural conversational interaction. To do so, natural language processing is often applied to allow users flexibility in what they say to the system, but the system’s output typically consists of highly handcrafted utterances, designed to portray a particular system personality or linguistic style. Although this approach produces high quality output, it leads to an authoring bottleneck, and makes it difficult to personalize or adapt the interaction. We propose a computational framework for system utterance generation that builds on the “Big Five” model of personality traits, and findings from psychology on the linguistic reflexes of personality. Our results show that our framework reliably generates utterances that humans perceive as manifesting each extreme of all Big Five traits, suggesting that the linguistic markers identified in previous work in naturally occurring language genres can be used to manifest personality in a controlled discourse situation of a conversational agent.
The Lumbar Lordosis in Males and Females, Revisited

Background Whether differences exist in male and female lumbar lordosis has been debated by researchers who are divided as to the nature of variations in the spinal curve, their origin, reasoning, and implications from a morphological, functional and evolutionary perspective. Evaluation of the spinal curvature is constructive in understanding the evolution of the spine, as well as its pathology, planning of surgical procedures, monitoring its progression and treatment of spinal deformities. The aim of the current study was to revisit the nature of lumbar curve in males and females. Methods Our new automated method uses CT imaging of the spine to measure lumbar curvature in males and females. The curves extracted from 158 individuals were based on the spinal canal, thus avoiding traditional pitfalls of using bone features for curve estimation. The model analysis was carried out on the entire curve, whereby both local and global descriptors were examined in a single framework. Six parameters were calculated: segment length, curve length, curvedness, lordosis peak location, lordosis cranial peak height, and lordosis caudal peak height. Principal Findings Compared to males, the female spine manifested a statistically significant greater curvature, a caudally located lordotic peak, and greater cranial peak height. As caudal peak height is similar for males and females, the illusion of deeper lordosis among females is due partially to the fact that the upper part of the female lumbar curve is positioned more dorsally (more backwardly inclined). Conclusions Males and females manifest different lumbar curve shape, yet similar amount of inward curving (lordosis). The morphological characteristics of the female spine were probably developed to reduce stress on the vertebral elements during pregnancy and nursing.
Biogenesis of Hydrogen Sulfide and Thioethers by Cystathionine Beta-Synthase.

AIMS The transsulfuration pathway enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase are thought to be the major source of hydrogen sulfide (H2S). In this study, we assessed the role of CBS in H2S biogenesis. RESULTS We show that despite discouraging enzyme kinetics of alternative H2S-producing reactions utilizing cysteine compared with the canonical condensation of serine and homocysteine, our simulations of substrate competitions at biologically relevant conditions suggest that cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of H2S. The leading H2S-producing reaction is condensation of cysteine with homocysteine, while cysteine desulfuration plays a dominant role when cysteine is more abundant than serine and homocysteine is limited. We found that the serine-to-cysteine ratio is the main determinant of CBS H2S productivity. Abundance of cysteine over serine, for example, in plasma, allowed for up to 43% of CBS activity being responsible for H2S production, while excess of serine typical for intracellular levels effectively limited such activity to less than 1.5%. CBS also produced lanthionine from serine and cysteine and a third of lanthionine coming from condensation of two cysteines contributed to the H2S pool. INNOVATION Our study characterizes the H2S-producing potential of CBS under biologically relevant conditions and highlights the serine-to-cysteine ratio as the main determinant of H2S production by CBS in vivo. CONCLUSION Our data clarify the function of CBS in H2S biogenesis and the role of thioethers as surrogate H2S markers. Antioxid. Redox Signal. 28, 311-323.
Hodgkin lymphoma: A review and update on recent progress

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed‐Sternberg cells in an inflammatory background. Patients are commonly diagnosed with HL in their 20s and 30s, and they present with supradiaphragmatic lymphadenopathy, often with systemic B symptoms. Even in advanced‐stage disease, HL is highly curable with combination chemotherapy, radiation, or combined‐modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk‐adapted approaches have helped de‐escalate therapy in low‐risk patients while intensifying treatment for higher risk patients. Even patients who are not cured with initial therapy can often be salvaged with alternate chemotherapy combinations, the novel antibody‐drug conjugate brentuximab, or high‐dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death‐1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL. Alternate donor sources and reduced‐intensity conditioning have made allogeneic hematopoietic stem cell transplantation a viable option for more patients. Future research will look to integrate novel strategies into earlier lines of therapy to improve the HL cure rate and minimize long‐term treatment toxicities. CA Cancer J Clin 2018;68:116‐132. © 2017 American Cancer Society.
Joint effect of physical activity and sedentary behaviour on cardiovascular risk factors in Chilean adults

Background To investigate the associations between combined categories of moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) with markers of adiposity and cardiovascular risk in adults. Methods Overall, 5040 participants (mean age 46.4 years and 59.3% women) from the cross-sectional Chilean National Health Survey 2009-2010 were included in this study. MVPA and SB were measured using the Global Physical Activity questionnaire. Four categories were computed using MVPA- and SB-specific cut-offs ('High-SB & Active', 'Low-SB & Active', 'High-SB & Inactive' and 'Low-SB & Inactive'). Results Compared to the reference group ('High-SB & Inactive'), those in 'High-SB & Active' and 'Low-SB & Active' were less likely to have an obese BMI (OR: 0.67 [0.54; 0.85], P = 0.0001 and 0.74 [0.59; 0.92] P = 0.0007, respectively) and less likely to have metabolic syndrome (OR: 0.63 [0.49; 0.82], P < 0.0001 and 0.72 [0.57; 0.91], P = 0.007), central obesity (OR: 0.79 [0.65; 0.96], P = 0.016 and 0.71 [0.59; 0.84], P < 0.0001), diabetes (OR: 0.45 [0.35; 0.59], P < 0.0001 and 0.44 [0.34; 0.56], P < 0.0001) and hypertension (OR: 0.52 [0.43; 0.63], P < 0.0001 and 0.60 [0.50; 0.72], P < 0.0001), respectively. Conclusions Being physically active and spending less time in SBs was associated with lower adiposity and improvements in cardiovascular risk factors.
A Decade of Streptococcus thermophilus Phage Evolution in an Irish Dairy Plant

ABSTRACT Phages of Streptococcus thermophilus present a major threat to the production of many fermented dairy products. To date, only a few studies have assessed the biodiversity of S. thermophilus phages in dairy fermentations. In order to develop strategies to limit phage predation in this important industrial environment, it is imperative that such studies are undertaken and that phage-host interactions of this species are better defined. The present study investigated the biodiversity and evolution of phages within an Irish dairy fermentation facility over an 11-year period. This resulted in the isolation of 17 genetically distinct phages, all of which belong to the so-called cos group. The evolution of phages within the factory appears to be influenced by phages from other dairy plants introduced into the factory for whey protein powder production. Modular exchange, primarily within the regions encoding lysogeny and replication functions, was the major observation among the phages isolated between 2006 and 2016. Furthermore, the genotype of the first isolate in 2006 was observed continuously across the following decade, highlighting the ability of these phages to prevail in the factory setting for extended periods of time. The proteins responsible for host recognition were analyzed, and carbohydrate-binding domains (CBDs) were identified in the distal tail (Dit), the baseplate proteins, and the Tail-associated lysin (Tal) variable regions (VR1 and VR2) of many isolates. This supports the notion that S. thermophilus phages recognize a carbohydrate receptor on the cell surface of their host. IMPORTANCE Dairy fermentations are consistently threatened by the presence of bacterial viruses (bacteriophages or phages), which may lead to a reduction in acidification rates or even complete loss of the fermentate. These phages may persist in factories for long periods of time. The objective of the current study was to monitor the progression of phages infecting the dairy bacterium Streptococcus thermophilus over a period of 11 years in an Irish dairy plant so as to understand how these phages evolve. A focused analysis of the genomic region that encodes host recognition functions highlighted that the associated proteins harbor a variety of carbohydrate-binding domains, which corroborates the notion that phages of S. thermophilus recognize carbohydrate receptors at the initial stages of the phage cycle.
Treating cancer with microRNA replacement therapy: A literature review

microRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression post‐transcriptionally by interfering with the translation of one or more target mRNAs. The unique miRNA sequences are involved in many physiological and pathological processes. Dysregulation of miRNAs contributes to the pathogenesis of all types of cancer. Notably, the diminished expression of tumor suppressor miRNAs, such as members of the Let‐7 and miR‐34 family, promotes tumor progression, invasion and metastasis. The past lustrum in particular, has witnessed substantial improvement of miRNA replacement therapy. This approach aims to restore tumor suppressor miRNA function in tumor cells using synthetic miRNA mimics or miRNA expression plasmids. Here, we provide a comprehensive review of recent advances in miRNA replacement therapy for treatment of cancer and its advantages over conventional gene therapy. We discuss a wide variety of delivery methods and vectors, as well as obstacles that remain to be overcome. Lastly, we review efforts to reverse epigenetic alterations, which affect miRNA expression in cancer cells, and the promising observation that restoring miRNA function re‐sensitizes resistant tumor cells to chemotherapeutic drugs. The fact that various miRNA replacement therapies are currently in clinical trial demonstrates the great potential of this approach to treat cancer.
The Role of Scavenger Receptor B1 in Infection with Mycobacterium tuberculosis in a Murine Model

Background The interaction between Mycobacterium tuberculosis (Mtb) and host cells is complex and far from being understood. The role of the different receptor(s) implicated in the recognition of Mtb in particular remains poorly defined, and those that have been found to have activity in vitro were subsequently shown to be redundant in vivo. Methods and Findings To identify novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA library and identified scavenger receptor B class 1 (SR-B1) as a receptor for mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol, and has also recently been implicated in the recognition of other pathogens. We show here that mycobacteria can bind directly to SR-B1 on transfected cells, and that this interaction could be inhibited in the presence of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage populations, including alveolar macrophages, that express this receptor, however, no differences in the recognition and response to mycobacteria were observed in macrophages isolated from SR-B1−/− or wild type mice in vitro. Moreover, when wild type and SR-B1−/− animals were infected with a low dose of Mtb (100 CFU/mouse) there were no alterations in survival, bacterial burdens, granuloma formation or cytokine production in the lung. However, significant reduction in the production of TNF, IFNγ, and IL10 were observed in SR-B1−/− mice following infection with a high dose of Mtb (1000 CFU/mouse), which marginally affected the size of inflammatory foci but did not influence bacterial burdens. Deficiency of SR-B1 also had no effect on resistance to disease under conditions of varying dietary cholesterol. We did observe, however, that the presence of high levels of cholesterol in the diet significantly enhanced the bacterial burdens in the lung, but this was independent of SR-B1. Conclusion SR-B1 is involved in mycobacterial recognition, but this receptor plays only a minor role in anti-mycobacterial immunity in vivo. Like many other receptors for these pathogens, the loss of SR-B1 can be functionally compensated for under normal conditions.
The invasive red alga Gracilaria vermiculophylla in the Baltic Sea: adaptation to brackish water may compensate for light limitation

The recent introduction of Gracilaria vermiculophylla (Rhodophyta) to the Kiel Fjord area was a reason for concern, since this red macroalga performs best under mesohaline conditions and thus appears well adapted to thrive and spread in the Baltic Sea environment, A systematic survey on a coastal range of 500 km in 2006 and 2007 indicated considerable Multiplication and spreading of G. vermiculophylla within Kiel Fjord, but provided little evidence of long-distance transport. Nonetheless, flow-through growth experiments conducted at a range of salinities under ambient light showed that G. vermiculophylla should be able to grow in most of the Baltic Sea. Growth declined only below a salinity of 5.5. High water temperatures in summer seem to reduce resistance against low salinity. Growth of G, vermiculophylla in the SW Baltic is limited by light and is only possible during summer and above a depth of 3 m. Drifting fragments are dispersed by currents. Either they sink to deeper waters, where they degrade, or they accumulate in shallow and sheltered waters, where they form perennial mats. These overgrow not only soft bottom sediments, but also stones, which are an important habitat to Fucus vesiculosus, the main native perennial alga in the Baltic Sea. As compared to F. vesiculosus, G. vermiculophylla seems to represent a preferred refuge for mesograzers and other invertebrates, particularly in winter. Nonetheless, feeding trials showed that potential grazers avoided G. vermiculophylla relative to F vesiculosus. Daily biomass uptake by grazers associated with G. vermiculophylla in nature did not exceed 2 g kg(-1) and is <11% of average daily net growth (18.5 g kg(-1)) in the first 2 m below sea level. Consequently, feeding may not be sufficient to control the spread of G. vermiculophylla in the SW Baltic. Our study suggests that absence of feeding enemies and adaptation to brackish water may allow G. vermiculophylla to invade most shallow coastal waters of the inner Baltic Sea despite light limitation.