Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurobehavioural mechanisms of threat generalization moderate the link between childhood maltreatment and psychopathology in emerging adulthood

Background Childhood maltreatment is a transdiagnostic risk factor for later psychopathology and has been associated with altered brain circuitry involved in the processing of threat and safety. Examining threat generalization mechanisms in young adults with childhood maltreatment and psychiatric symptoms may elucidate a pathway linking early-life adversities to the presence of subclinical psychopathology. Methods We recruited youth aged 16–25 years with subclinical psychiatric symptomatology and healthy controls. They were dichotomized into 2 groups: 1 with a high level of childhood maltreatment (n = 58) and 1 with no or a low level of childhood maltreatment (n = 55). Participants underwent a functional MRI threat generalization paradigm, measuring self-reported fear, expectancy of an unconditioned stimulus (US) and neural responses. Results We observed interactions between childhood maltreatment and threat generalization indices on subclinical symptom load. In individuals reporting high levels of childhood maltreatment, enhanced generalization in self-reported fear and US expectancy was related to higher levels of psychopathology. Imaging results revealed that in the group with high levels of childhood maltreatment, lower activation in the left hippocampus during threat generalization was associated with a higher symptom load. Associations between threat generalization and psychopathology were nonsignificant overall in the group with no or low levels of childhood maltreatment. Limitations The data were acquired in a cross-sectional manner, precluding definitive insight into the causality of childhood maltreatment, threat generalization and psychopathology. Conclusion Our results suggest that threat generalization mechanisms may moderate the link between childhood maltreatment and subclinical psychopathology during emerging adulthood. Threat generalization could represent a vulnerability factor for developing later psychopathology in individuals being exposed to childhood maltreatment.
Characterization of the Apelin/Elabela Receptors (APLNR) in Chickens, Turtles, and Zebrafish: Identification of a Novel Apelin-Specific Receptor in Teleosts

Apelin receptor(s) (APLNR) are suggested to mediate the actions of apelin and Elabela (ELA) peptides in many physiological processes, including cardiovascular development and food intake in vertebrates. However, the functionality of APLNR has not been examined in most vertebrate groups. Here, we characterized two APLNRs APLNR1, APLNR2) in chickens and red-eared sliders, and three APLNRs in zebrafish (APLNR2a, APLNR2b, APLNR3a), which are homologous to human APLNR. Using luciferase-reporter assays or Western blot, we demonstrated that in chickens, APLNR1 (not APLNR2) expressed in HEK293 cells was potently activated by chicken apelin-36 and ELA-32 and coupled to Gi-cAMP and MAPK/ERK signaling pathways, indicating a crucial role of APLNR1 in mediating apelin/ELA actions; in red-eared sliders, APLNR2 (not APLNR1) was potently activated by apelin-36/ELA-32, suggesting that APLNR2 may mediate apelin/ELA actions; in zebrafish, both APLNR2a and APLNR2b were potently activated by apelin-36/ELA-32 and coupled to Gi-cAMP signaling pathway, as previously proposed, whereas the novel APLNR3a was specifically and potently activated by apelin. Similarly, an apelin-specific receptor (APLNR3b) sharing 57% sequence identity with zebrafish APLNR3a was identified in Nile tilapia. Collectively, our data facilitates the uncovering of the roles of APLNR signaling in different vertebrate groups and suggests a key functional switch between APLNR1 and APLNR2/3 in mediating the actions of ELA and apelin during vertebrate evolution.
Electrostatic effects, band distortions, and superconductivity in twisted graphene bilayers

Significance For small twist angles, bilayer graphene forms long-wavelength Moiré patterns. For specific, so-called magic, angles of the order of 1 degree, very narrow bands have been seen that lead to superconductivity. The underlying mechanisms have since been discussed in a variety of theoretical approaches. We show that the modulation of the charge density significantly modifies the electronic structure. These changes can make an important contribution to superconductivity through electron-assisted hopping. Bilayer graphene twisted by a small angle shows a significant charge modulation away from neutrality, as the charge in the narrow bands near the Dirac point is mostly localized in a fraction of the Moiré unit cell. The resulting electrostatic potential leads to a filling-dependent change in the low-energy bands, of a magnitude comparable to or larger than the bandwidth. These modifications can be expressed in terms of new electron–electron interactions, which, when expressed in a local basis, describe electron-assisted hopping terms. These interactions favor superconductivity at certain fillings.
A Web-Based Intervention for Relatives of People Experiencing Psychosis or Bipolar Disorder: Design Study Using a User-Centered Approach

Background Relatives of people experiencing bipolar mood episodes or psychosis face a multitude of challenges (eg, social isolation, limited coping strategies, and issues with maintaining relationships). Despite this, there is limited informational and emotional support for people who find themselves in supporting or caring roles. Digital technologies provide us with an opportunity to offer accessible tools, which can be used flexibly to provide evidence-based information and support, allowing relatives to build their understanding of mental health problems and learn from others who have similar experiences. However, to design tools that are useful to relatives, we first need to understand their needs. Objective The aim of this study was to use a user-centered design approach to develop an accessible Web-based intervention, based on the Relatives Education And Coping Toolkit (REACT) booklet, to support the informational and emotional needs of relatives of people experiencing psychosis or bipolar disorder. Methods We engaged relatives of people with experiences of bipolar disorder or psychosis in workshops to identify their needs and design requirements for developing a Web-based version of a paper-based toolkit. We used a 2-phase qualitative approach to explore relatives’ views on content, design, and functionalities, which are considered to be engaging and useful in a Web-based intervention. In phase 1, we consulted 24 relatives in 2 workshops to better understand their existing support infrastructure, their barriers for accessing support, unmet needs, and relatives’ views on online support. On the basis of the results of these workshops, we developed a set of design considerations to be explored in a smaller workshop. Workshop 3 then involved working with 2 digitally literate relatives to design a usable and acceptable interface for our Web-based toolkit. Finally, in phase 2, we conducted a heuristic evaluation to assess the usability of the toolkit. Results Our findings indicated that relatives require technologies that (1) they can place their trust in, particularly when discussing a highly sensitive topic, (2) enable learning from the lived experiences of others while retaining confidentiality, and (3) they can work through at their own pace in a personalized manner. Conclusions Our study highlights the need for providing a trustworthy, supportive tool where relatives can engage with people who have similar experiences to their own. Our heuristic evaluation showed promise in terms of perceived usability of the REACT Web-based intervention. Through this work, we emphasize the need to involve stakeholders with various characteristics, including users with limited computer literacy or experience in online support.
Clinical and radiographic comparison of single-sugar-tong splint to long-arm cast immobilization for pediatric forearm fractures.

The purpose of this study was to compare the efficacy of a single-sugar-tong splint (SSTS) to a long-arm cast (LAC) in maintaining reduction of pediatric forearm fractures, while avoiding secondary intervention. One hundred patients age 3-15 with a forearm fracture requiring a reduction and immobilization were evaluated (50 LAC and 50 SSTS). Medical records and radiographs were reviewed at injury, postreduction, and at 1, 2, and 4 weeks postinjury. Sagittal and coronal angular deformities were recorded. Any secondary intervention due to loss of reduction was documented. The groups were matched by age (P=0.19), sex (P=0.26), mechanism of injury (P=0.66), average injury sagittal deformity (LAC 27.4°, SSTS 25.4°; P=0.50), and average injury coronal deformity (LAC 15.5°, SSTS 16°; P=0.80) At 4 weeks postinjury follow-up, there were no statistically significant differences between use of an SSTS or LAC when comparing postimmobilization sagittal alignment (LAC 10.3±7.2, SSTS 8.4±5.1°; P=0.46), coronal alignment (LAC 6.9±4.6, SSTS 7.6±9.3°; P=0.46), or need for repeat manipulation or surgery (LAC 4/50, SSTS 3/50; P=0.70).
Anterior Guided Growth of the Distal Femur for Knee Flexion Contracture: Clinical, Radiographic, and Motion Analysis Results

Background: Fixed knee flexion deformity is common in children with neuromuscular disorders. Anterior guided growth (AGG) of the distal femur can achieve gradual correction in patients who are skeletally immature. Little outcome data are available on this procedure. Methods: This is a retrospective matched cohort study. Forty-two knees (26 patients) underwent AGG surgery at our institution between 2007 and 2017. All patients underwent instrumented 3-dimensional gait analysis (3DGA). A nonsurgical control group of 49 knees (43 patients) was selected that matched for age, severity of preoperative knee contracture, and 3DGA parameters. Clinical, radiographic, and 3DGA outcomes were assessed and compared. Results: Average preoperative knee flexion deformity in AGG group was 13±8 degrees. Following AGG, deformity improved by 8±7 degrees (P<0.001) as measured radiographically and by 7±7 degrees (P<0.001) as measured on physical examination. Average rate of correction was 0.7±0.6 degrees per month or 8±8 degrees per year. The 3DGA parameters such as minimum stance phase knee flexion and knee flexion at initial contact were also significantly improved following AGG. In contrast, flexion deformity as measured radiographically worsened by 3±3 degrees (P=0.002) in the control group. Twelve knees (29%) had failure of correction. Predictors of failure included older age, lower level of function, and greater severity of preoperative deformity. The age at time of surgery and the anteroposterior position of plate fixation relative to the distal femoral physis were associated with rate of correction. Conclusions: In children with neuromuscular disorders, AGG of the distal femur is effective in improving degree of fixed knee flexion deformity as well as objective gait parameters. A significant portion of knees experience inadequate correction. Addressing factors associated with correction failure (ie, age and plate placement) may improve the procedure’s success. Level of Evidence: Level III—case control study
Tau PET Imaging for Staging of Alzheimer's Disease in Down Syndrome

Alzheimer's disease (AD) pathology and early‐onset dementia develop almost universally in Down syndrome (DS). AD is defined neuropathologically by the presence of extracellular plaques of aggregated amyloid β protein and intracellular neurofibrillary tangles (NFTs) of aggregated hyperphosphorylated tau protein. The development of radiolabeled positron emission tomography (PET) ligands for amyloid plaques and tau tangles enables the longitudinal assessment of the spatial pattern of their accumulation in relation to symptomatology. Recent work indicates that amyloid pathology develops 15–20 years before neurodegeneration and symptom onset in the sporadic and autosomal dominant forms of AD, while tau pathology correlates more closely with symptomatic stages evidenced by cognitive decline and dementia. Recent work on AD biomarkers in DS illustrates similarities between DS and sporadic AD. It may soon be possible to apply recently developed staging classifications to DS to obtain a more nuanced understanding of the development AD in DS and to provide more accurate diagnosis and prognosis in the clinic.
The partitioning of gross primary production for young Eucalyptus tereticornis trees under experimental warming and altered water availability.

The allocation of carbon (C) is an important component of tree physiology that influences growth and ecosystem C storage. Allocation is challenging to measure, and its sensitivity to environmental changes such as warming and altered water availability is uncertain. We exposed young Eucalyptus tereticornis trees to +3°C warming and elimination of summer precipitation in the field using whole-tree chambers. We calculated C allocation terms using detailed measurements of growth and continuous whole-crown CO2 and water exchange measurements. Trees grew from small saplings to nearly 9 m height during this 15-month experiment. Warming accelerated growth and leaf area development, and it increased the partitioning of gross primary production (GPP) to aboveground respiration and growth while decreasing partitioning below ground. Eliminating summer precipitation reduced C gain and growth but did not impact GPP partitioning. Trees utilized deep soil water and avoided strongly negative water potentials. Warming increased growth respiration, but maintenance respiration acclimated homeostatically. The increasing growth in the warmed treatment resulted in higher rates of respiration, even with complete acclimation of maintenance respiration. Warming-induced stimulations of tree growth likely involve increased C allocation above ground, particularly to leaf area development, whereas reduced water availability may not stimulate allocation to roots.
Coenzyme Q10 protects against β‐cell toxicity induced by pravastatin treatment of hypercholesterolemia

New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin‐treated hypercholesterolemic LDL receptor knockout (LDLr−/−) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q 10 (CoQ 10), an intermediate generated in the cholesterol synthesis pathway. LDLr −/− mice were treated with pravastatin and/or CoQ 10 for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ 10 content. Dietary CoQ 10 supplementation of pravastatin‐treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2‐fold), and fully restored islet glucose‐stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild‐type mice. In vitro, insulin‐secreting INS1E cells cotreated with CoQ 10 were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose‐dependent INS1E cell death (10–15‐fold), which were also attenuated by CoQ 10 cotreatment. Together, these results demonstrate that statins impair β‐cell redox balance, function and viability. However, CoQ 10 supplementation can protect the statins detrimental effects on the endocrine pancreas.
Decreased mortality, laparotomy, and embolization rates for liver injuries during a 13-year period in a major Scandinavian trauma center

Background Although non-operative management (NOM) has become the treatment of choice in hemodynamically normal patients with liver injuries, the optimal management of Organ Injury Scale (OIS) grades 4 and 5 injuries is still controversial. Oslo University Hospital Ulleval (OUHU) has since 2008 performed angiography only with signs of bleeding. Simultaneously, damage control resuscitation was implemented. Would these changes result in a decreased laparotomy rate and need for angioembolization (AE), as well as decreased mortality? Methods We performed a retrospective study on all adult patients with liver injuries admitted at OUHU between 2002 and 2014. The total study population and patients with OIS grades 4 and 5 liver injuries underwent comparison between the periods before (P1) and after (P2) August 1, 2008. Results 583 patients were included (P1: 237, P2: 346), with a median Injury Severity Score (ISS) of 29. The total population and the subgroup of OIS 4 and 5 injuries were comparable in age, gender, mechanism of injury, injury severity and physiology. Overall laparotomy rates decreased from P1 to P2 (35%–24%; p<0.01), as did the AE rate (11%–5%; p<0.01). The 30-day crude mortality decreased from 14% to 7% (p<0.05). A logistic regression model predicted an OR of 0.45 (95% CI 0.21 to 0.98) for dying when admitted in P2. In OIS grades 4 and 5 injuries (n=149, median ISS 34), similar reduction in AE rate was seen (30%–12%; p<0.05). The NOM rate for OIS grades 4 and 5 injuries was 70%, with 98% success rate. For the 30% requiring surgery, the mortality remained high (P1 52%; P2 40%), despite more balanced transfusion strategy. Discussion Changes in resuscitation and treatment protocols were associated with decreased laparotomy, and AE rates as well as overall mortality. NOM is safe in 70% of patients with OIS grades 4 and 5 injuries, in contrast to the critically ill 30% requiring surgery who still have poor outcome. Level of evidence IV.
Heat acclimation does not affect maximal aerobic power in thermoneutral normoxic or hypoxic conditions

What is the central question of this study? Controlled‐hyperthermia heat‐acclimation protocols induce an array of thermoregulatory and cardiovascular adaptations that facilitate exercise in hot conditions. We investigated whether this ergogenic potential can be transferred to thermoneutral normoxic or hypoxic exercise conditions. What is the main finding and its importance? We showed that heat acclimation did not affect maximal cardiac output or maximal aerobic power in thermoneutral normoxic or hypoxic conditions. Heat acclimation augmented the sweating response in thermoneutral normoxic conditions. The cross‐adaptation theory, according to which heat acclimation could facilitate hypoxic exercise capacity, is not supported by our data.
Identification of barley powdery mildew resistances in gene bank accessions and the use of gene diversity for verifying seed purity and authenticity

Human activities including those in crop gene banks are subject to errors, especially during seed multiplication and maintenance of seed germination. Therefore, the most serious problem of gene banks is authenticity of the accessions and their genotypic purity. There are many methods for determining the identity of varieties, but comparisons between current data and past records are not easy since the latter are often missing. Breeding barley resistant to powdery mildew caused by Blumeria graminis f. sp. hordei (Bgh) was traditionally based on incorporating major genes into new varieties and the results have been published. Our goal was to identify resistance genes to powdery mildew in accessions of the Czech spring barley core collection and compare these data with earlier information to establish the authenticity of the accessions. Two hundred and twenty-three accessions of the collection including 665 single plant progenies were tested. Sixty-four selected reference isolates of Bgh representing the world diversity of the pathogen were used for resistance tests. Twenty-two known resistance genes were postulated either separately or in combinations. In the collection, 151 homogeneous accessions were found, but the resistances of nine of them were inconsistent with published data and in 12 accessions their authenticity is doubtful. The remaining 72 accessions were heterogeneous and comprised 176 resistance genotypes, 54 of which were probably mechanical admixtures of other varieties. There are several pathogens of cereals, e.g. rusts and mildews, against which many resistance genes in host crops have also been exploited. Knowledge of these resistances can assist in maintaining pure and genuine stocks in gene banks. Seed purity and the authenticity of accessions can subsequently be checked with more advanced methods.
Immediate remote ischemic postconditioning reduces cerebral damage in ischemic stroke mice by enhancing leptomeningeal collateral circulation

Remote ischemic postconditioning (RIPC) is a promising neuroprotective strategy for ischemic stroke. Here, we employed a focal ischemic stroke mouse model to test the hypothesis that poststroke collateral circulation as a potent mechanism of action underlying the therapeutic effects of immediate RIPC. During reperfusion of cerebral ischemia, the mice were randomly assigned to receive RIPC, granulocyte colony‐stimulating factor (G‐CSF) as a positive control, or no treatment. At 24 hr, we found RIPC and G‐CSF increased monocytes/macrophages in the dorsal brain surface and in the spleen, coupled with enhanced leptomeningeal collateral flow compared with nontreatment group. Blood monocytes depletion by 5‐fluorouracil (5‐FU) significantly limited the neuroprotection of RIPC or G‐CSF treatment. The protein expression of proangiogenic factors such as Ang‐2 was increased by ischemia, but treatment with either RIPC or G‐CSF showed no further upregulation. Thus, immediate RIPC confers neuroprotection, in part, by enhancing leptomeningeal collateral circulation in a mouse model of ischemic stroke.
Short-term effect of a chronic pain self-management intervention delivered by an easily accessible primary healthcare service: a randomised controlled trial

Objectives To investigate the effects on persons with chronic pain after 3 months of a group-based chronic pain self-management course compared with a drop-in, low-impact outdoor physical group activity on patient activation and a range of secondary outcomes. Design An open, pragmatic, parallel group randomised controlled trial. Analyses were performed using a two-level linear mixed model. Setting An easily accessible healthcare service provided by Norwegian public primary healthcare. Participants A total of 121 participants with self-reported chronic pain for 3 months or more were randomised with 60 participants placed in the intervention group and 61 placed in the control group (mean age 53 years, 88% women, 63% pain for 10 years or more). Interventions The intervention group was offered a group-based chronic pain self-management course with 2.5-hour weekly sessions for a period of 6 weeks. The sessions consisted of education, movement exercises and emphasised group discussions. The control group was offered a low-impact outdoor group physical activity in 1-hour weekly sessions that consisted of walking and simple strength exercises for a period of 6 weeks. Main outcomes The primary outcome was patient activation assessed using the Patient Activation Measure. Secondary outcomes measured included assessments of pain, anxiety and depression, pain self-efficacy, sense of coherence, health-related quality of life, well-being and the 30 s chair to stand test. Results There was no effect after 3 months of the group-based chronic pain self-management course compared with the control group for the primary outcome, patient activation (estimated mean difference: −0.5, 95% CI –4.8 to 3.7, p=0.802). Conclusions There was no support for the self-management course having a better effect after 3 months than a low-impact outdoor physical activity offered the control group. Trial registration number NCT02531282; Results.