Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis

Abstract Background To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. Methods FEP (N = 191) were recruited from in- and outpatient services 1997–2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15–65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. Results CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. Conclusion Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.
Physical fitness of children and adolescents with moderate to severe intellectual disabilities

Abstract Background: Low levels of physical fitness are associated with low physical and mental health. The aims of this study were to assess the health-related physical fitness of children with intellectual disability (ID), and study the association of physical activity and motor development with physical fitness. Methods: One hundred and twenty-eight children with moderate to severe ID (83 boys; age 2–18 years) visiting specialised day programme centres engaged in field-based physical fitness tests (body composition, muscular strength, muscular endurance, and cardiorespiratory fitness). Scores were compared to reference values, and with linear regression analysis the association between the fitness outcomes and physical activity and motor development was studied. Results: High rates of overweight (23–25%) and obesity (10–15%) were found. A majority of the participants (71–91%) scored below reference values for muscular strength, endurance, and cardiorespiratory fitness tests. Physical activity and motor development were positively associated with scores on several fitness test (β = 0.27–0.44; p < 0.05). Conclusions: Children with moderate to severe ID visiting specialised day programme centres have strikingly low physical fitness levels. Policies and interventions to increase the physical fitness for this specific group of children are urgently needed, in which increasing physical activity and motor skills are expected to be effective components. Implications for rehabilitation Strikingly low levels of physical fitness were seen in children and adolescents with moderate to severe intellectual disabilities. This vulnerable group is in need of appropriate interventions to increase their physical fitness levels. Increasing the physical activity is a potential component in these interventions. Improving motor development will most likely lead to improved physical fitness as well.
Choosing to Regulate Emotions: Pursuing Emotion Goals in Autonomy-Supportive and Controlling Contexts

We applied self-determination theory to emotion regulation and tested the potential effects of autonomy-supportive and controlling contexts on the pursuit of emotion goals. In four experimental studies (N = 242), participants viewed a fear-eliciting film clip or emotion-eliciting pictures and were prompted to pursue emotion goals with either autonomy-supportive or controlling instructions. Participants in both conditions were equally likely to engage in emotion regulation when directly instructed to do so. However, when they were allowed to spontaneously choose whether to regulate emotions or not, participants in the autonomy-supportive contexts were more likely than those in the controlling ones to independently pursue emotion goals. The latter also engaged in more defensive processing of emotion-eliciting stimuli than the former. These results indicate that people are more likely to pursue emotion goals of their own accord when the context in which they pursue them is autonomy supportive, rather than controlling.
Complete Genome Sequence of Iris Severe Mosaic Virus Isolated in Japan

The complete genome sequence of an iris severe mosaic virus isolate (ISMV) from Iris tectorum in Japan was determined for the first time. According to sequence identity analyses, our specimen is closely related to isolates reported from China. ABSTRACT The complete genome sequence of an iris severe mosaic virus isolate (ISMV) from Iris tectorum in Japan was determined for the first time. According to sequence identity analyses, our specimen is closely related to isolates reported from China.
Evolution of HIV-1 Drug Resistance after Virological Failure of First-line Antiretroviral Therapy in Lusaka, Zambia

Background HIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia. Methods We analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death. Results Of 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%. Conclusions We found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.
The Cavan-Monaghan First Episode Psychosis Study (CAMFEPS): arbitrary diagnostic boundaries across the gene–environment interface and within evolving models of care

As research into psychotic illness evolves along established lines, insights are emerging that deviate from those lines and challenge more fundamentally our understanding. On the background of a new generation of studies on first-episode psychosis, investigations across the gene–environment interface and the intersection with ‘normal’ human mentation heighten these concerns. Using findings from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) as an exemplar, we here review the complexity of these challenges from the perspective of this real-world setting. They range from trans-diagnostic epidemiology and clinical characterisation, through molecular genetics, social milieu, developmental pathobiology and functional outcome across arbitrary diagnostic boundaries, to the evidence base for early intervention and more radical conceptualisations and structures for provision of mental health care.
Identification of Oocyst-Driven Toxoplasma gondii Infections in Humans and Animals through Stage-Specific Serology—Current Status and Future Perspectives

The apicomplexan zoonotic parasite Toxoplasma gondii has three infective stages: sporozoites in sporulated oocysts, which are shed in unsporulated form into the environment by infected felids; tissue cysts containing bradyzoites, and fast replicating tachyzoites that are responsible for acute toxoplasmosis. The contribution of oocysts to infections in both humans and animals is understudied despite being highly relevant. Only a few diagnostic antigens have been described to be capable of discriminating which parasite stage has caused an infection. Here we provide an extensive overview of the antigens and serological assays used to detect oocyst-driven infections in humans and animals according to the literature. In addition, we critically discuss the possibility to exploit the increasing knowledge of the T. gondii genome and the various ‘omics datasets available, by applying predictive algorithms, for the identification of new oocyst-specific proteins for diagnostic purposes. Finally, we propose a workflow for how such antigens and assays based on them should be evaluated to ensure reproducible and robust results.
The LncRNA LINC00963 facilitates osteosarcoma proliferation and invasion by suppressing miR-204-3p/FN1 axis

ABSTRACT Purpose: It remains unclear that long noncoding RNAs’ role in cancer initiation and progression, including osteosarcoma. Long noncoding RNA LINC00963 was found to be participated in carcinogenesis and progression of osteosarcoma. However, the molecular mechanisms of LINC00963 engaged in osteosarcoma (OS) still needs to be explored. Methods: LINC00963 and miR-204-3p RNA expression levels were quantified by PCR in OS tissues and cells. CCK 8 assay, wound healing assay and transwell migration and invasion assay were chosen to assess cell growth, viability, migration, and invasion. Luciferase reporter assays were performed to verify direct interaction between LINC00963 and miR-204-3p and miR-204-3p and Fibronectin-1. Western blot was conducted to evaluate Fibronectin-1 expression in OS cells. Results: LINC00963 was verified to be highly expressed in OS samples and cells. Specifically, elevated expression of LINC00963 was correlated with poor prognosis in patients. Furthermore, LINC00963 overexpression was found to promote proliferation, migration, and invasion in vitro. The luciferase reporter assay showed that LINC00963 can suppress miR-204-3p by directly binding miR-204-3p. Rescue experiment results indicated that function of LINC00963 in osteosarcoma was miR-204-3p dependant. Besides, we initially explored Fibronectin-1 (FN1) as the target of LINC00963/miR-204-3p axis in osteosarcoma. Conclusions: Our findings implied that LINC00963/miR-204-3p/FN1 can play an important role in proliferation and progression in osteosarcoma. LINC00963 has the potential to be a therapeutic target for osteosarcoma treatment.
Environmental DNA for improved detection and environmental surveillance of schistosomiasis

Significance Accurate detection and delineation of schistosomiasis transmission sites will be vital in ongoing efforts to control and ultimately eliminate one of the most neglected tropical parasitic diseases affecting >250 million people worldwide. Conventional methods to detect parasites in the environment are cumbersome and have low sensitivity. We therefore developed an environmental DNA (eDNA)-based method for schistosome detection in aquatic environments. Aquatic eDNA showed higher sensitivity than conventional snail surveys. We conclude that eDNA is a promising noninvasive and sensitive tool for environmental surveillance of schistosomiasis transmission. As the efforts and aims to control the disease are transitioning toward complete transmission interruption, this could be the robust and cost-effective surveillance tool needed in the “endgame” of schistosomiasis. Schistosomiasis is a water-based, infectious disease with high morbidity and significant economic burdens affecting >250 million people globally. Disease control has, with notable success, for decades focused on drug treatment of infected human populations, but a recent paradigm shift now entails moving from control to elimination. To achieve this ambitious goal, more sensitive diagnostic tools are needed to monitor progress toward transmission interruption in the environment, especially in low-intensity infection areas. We report on the development of an environmental DNA (eDNA)-based tool to efficiently detect DNA traces of the parasite Schistosoma mansoni directly in the aquatic environment, where the nonhuman part of the parasite life cycle occurs. This is a report of the successful detection of S. mansoni in freshwater samples by using aquatic eDNA. True eDNA was detected in as few as 10 cercariae per liter of water in laboratory experiments. The field applicability of the method was tested at known transmission sites in Kenya, where comparison of schistosome detection by conventional snail surveys (snail collection and cercariae shedding) with eDNA (water samples) showed 71% agreement between the methods. The eDNA method furthermore detected schistosome presence at two additional sites where snail shedding failed, demonstrating a higher sensitivity of eDNA sampling. We conclude that eDNA provides a promising tool to substantially improve the environmental surveillance of S. mansoni. Given the proper method and guideline development, eDNA could become an essential future component of the schistosomiasis control tool box needed to achieve the goal of elimination.
Age-Related Changes in the Auditory Brainstem Response and Suprathreshold Processing of Temporal and Spectral Modulation

The purpose of this study was to determine whether cochlear synaptopathy can be shown to be a viable basis for age-related hearing difficulties in humans and whether it manifests as deficient suprathreshold processing of temporal and spectral modulation. Three experiments were undertaken evaluating the effects of age on (a) the auditory brainstem response as a function of level, (b) temporal modulation detection as a function of level and background noise, and (c) spectral modulation as a function of level. Across the three experiments, a total of 21 older listeners with near-normal audiograms and 29 young listeners with audiometrically normal hearing participated. The auditory brainstem response experiment demonstrated reduced Wave I amplitudes and concomitant reductions in the amplitude ratios of Wave I to Wave V in the older listener group. These findings were interpreted as consistent with an electrophysiological profile of cochlear synaptopathy. The temporal and spectral modulation detection experiments, however, provided no support for the hypothesis of compromised suprathreshold processing in these domains. This pattern of results suggests that even if cochlear synaptopathy can be shown to be a viable basis for age-related hearing difficulties, then temporal and spectral modulation detection paradigms are not sensitive to its presence.
Effect of Femoral Head Size, Subject Weight, and Activity Level on Acetabular Cement Mantle Stress Following Total Hip Arthroplasty

In cases where cemented components are used in total hip arthroplasty, damage, or disruption of the cement mantle can lead to aseptic loosening and joint failure. Currently, the relationship between subject activity level, obesity, and prosthetic femoral head size and the risk of aseptic loosening of the acetabular component in cemented total hip arthroplasty is not well understood. This study aims to provide an insight into this. Finite element models, validated with experimental data, were developed to investigate stresses in the acetabular cement mantle and pelvic bone resulting from the use of three prosthetic femoral head sizes, during a variety of daily activities and one high impact activity (stumbling) for a range of subject body weights. We found that stresses in the superior quadrants of the cortical bone‐cement interface increased with prosthetic head size, patient weight, and activity level. In stumbling, average von Mises stresses (22.4 MPa) exceeded the bone cement yield strength for an obese subject (143 kg) indicating that the cement mantle would fail. Our results support the view that obesity and activity level are potential risk factors for aseptic loosening of the acetabular component and provide insight into the increased risk of joint failure associated with larger prosthetic femoral heads. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1771–1783, 2019
Synthesis and Antitumor Evaluation in Vitro of NO‐Donating Ursolic Acid‐Benzylidene Derivatives

Antitumor activity of triterpenoid and its derivatives has attracted great attention recently. Our previous efforts led to the discovery of a series of NO‐donor betulin derivatives with potent antitumor activity. Herein, we prepared eight compounds derived from ursolic acid (UA). All the compounds were evaluated for their in vitro cytotoxicity against four human cancer cell lines (HepG‐2, MCF‐7, HT‐29 and A549). Among the compounds tested, compound 4a was found to be most active against HT‐29 (IC50=4.28 μm). Further biological assays demonstrated that compound 4a could induce cell cycle arrest at G1 phase and apoptosis in a dose‐dependent manner. In addition, compound 4a was found to upregulate pro‐apoptotic Bax, p53 and downregulate anti‐apoptotic Bcl‐2. All these results suggested that compound 4a is a potential candidate drug for the therapy of colon cancer.
The role of pain catastrophizing in cyberchondria among emerging adults

ABSTRACT Chronic pain is a prevalent and debilitating health problem that often persists in the absence of an identifiable biomedical cause. Uncertainty regarding the origins of a pain problem may lead to pain catastrophizing and unfruitful healthcare seeking behaviors. Individuals with chronic pain often turn to the internet to identify possible causes or sources of their pain symptoms, thus affirming their pain experience. Despite evidence that pain catastrophizing amplifies distress about pain complaints, no studies have investigated whether it is associated with escalations in health anxiety that result from searching for online health information (i.e., cyberchondria). The aim of the present study was to investigate whether pain catastrophizing predicted variance in cyberchondria above and beyond health anxiety. Undergraduate students (N = 221, 70.6% female) completed questionnaires assessing pain catastrophizing, health anxiety, and cyberchondria. Results from hierarchical regression models indicated that pain catastrophizing predicted unique variance in four dimensions of cyberchondria: compulsion, distress, excessiveness, and reassurance. Findings are consistent with research highlighting the consequences of pain catastrophizing on myriad psychological outcomes. Individuals who catastrophize about pain experiences may be vulnerable to developing severe health anxiety from searching the internet for health information. Implications for research among individuals with chronic pain are discussed.
Efficient Electrochemical Reduction of CO2 to HCOOH over Sub-2 nm SnO2 Quantum Wires with Exposed Grain Boundaries.

Electrochemical reduction of CO2 could mitigate environmental problems originating from CO2 emission. Although grain boundaries (GBs) have been tailored to tune binding energies of reaction intermediates and consequently accelerate the CO2 reduction reaction (CO2 RR), it is challenging to exclusively clarify the correlation between GBs and enhanced reactivity in nanostructured materials with small dimension (<10 nm). Now, sub-2 nm SnO2 quantum wires (QWs) composed of individual quantum dots (QDs) and numerous GBs on the surface were synthesized and examined for CO2 RR toward HCOOH formation. In contrast to SnO2 nanoparticles (NPs) with a larger electrochemically active surface area (ECSA), the ultrathin SnO2 QWs with exposed GBs show enhanced current density (j), an improved Faradaic efficiency (FE) of over 80 % for HCOOH and ca. 90 % for C1 products as well as energy efficiency (EE) of over 50 % in a wide potential window; maximum values of FE (87.3 %) and EE (52.7 %) are achieved.
Providing sex and relationships education for looked-after children: a qualitative exploration of how personal and institutional factors promote or limit the experience of role ambiguity, conflict and overload among caregivers

Objectives To explore how personal and institutional factors promote or limit caregivers promoting sexual health and relationships (SHR) among looked-after children (LAC). In so doing, develop existing research dominated by atheoretical accounts of the facilitators and barriers of SHR promotion in care settings. Design Qualitative semistructured interview study. Setting UK social services, residential children’s homes and foster care. Participants 22 caregivers of LAC, including 9 foster carers, 8 residential carers and 5 social workers; half of whom had received SHR training. Methods In-depth interviews explored barriers/facilitators to SHR discussions, and how these shaped caregivers’ experiences of discussing SHR with LAC. Data were systematically analysed using predetermined research questions and themes identified from reading transcripts. Role theory was used to explore caregivers’ understanding of their role. Results SHR policies clarified role expectations and increased acceptability of discussing SHR. Training increased knowledge and confidence, and supported caregivers to reflect on how personally held values impacted practice. Identified training gaps were how to: (1) Discuss SHR with LAC demonstrating problematic sexual behaviours. (2) Record the SHR discussions that had occurred in LAC’s health plans. Contrary to previous findings, caregivers regularly discussed SHR with LAC. Competing demands on time resulted in prioritisation of discussions for sexually active LAC and those ‘at risk’ of sexual exploitation/harm. Interagency working addressed gaps in SHR provision. SHR discussions placed emotional burdens on caregivers. Caregivers worried about allegations being made against them by LAC. Managerial/pastoral support and ‘safe care’ procedures minimised these harms. Conclusions While acknowledging the existing level of SHR promotion for LAC there is scope to more firmly embed this into the role of caregivers. Care needs to be taken to avoid role ambiguity and tension when doing so. Providing SHR policies and training, promoting interagency working and providing pastoral support are important steps towards achieving this.