Miracle-dz/UniFAR-FTUs huggingface dataset:
Objective and biological markers in bipolar spectrum presentations

ABSTRACT Introduction: Subthreshold presentations of bipolarity (BSPs) pose a diagnostic conundrum, in terms of whether they should be conceptualized and treated similarly as traditionally defined bipolar disorders (BD). While it has been argued that BSPs are on a pathophysiologic continuum with traditionally defined BDs, there has been limited examination of biological and objective markers in these presentations to validate this assertion. Areas covered: The authors review studies examining genetic, neurobiological, cognitive and peripheral markers in BSPs, encompassing clinical and non-clinical populations with subthreshold hypo/manic symptoms. Results are placed in the context of previously identified markers in traditionally defined BDs. Expert commentary: There have been few studies of objective and biological markers in subthreshold presentations of BD, and results are mixed. While abnormalities in brain structure/functioning, peripheral inflammatory, and cognitive markers have been reported, it is unclear whether these findings are specific to BD or indicative of broad affective pathology. However, some studies suggest that increased sensitivity to reward and positive stimuli are shared between subthreshold and traditionally defined BDs, and may represent a point of departure from unipolar major depression. Further examination of such markers may improve understanding of subthreshold bipolar presentations, and provide guidance in terms of therapeutic strategies.
Numerical Study of Enhancement of Positive Dielectrophoresis Particle Trapping in Electrode-Multilayered Microfluidic Device

Enhancement of positive dielectrophoresis (pDEP) particle trapping by a co-occurring fluid flow under an ac electric field in an electrode-multilayered microfluidic device is investigated by three-dimensional particle-fluid flow simulations. The particle motion near one cross section of the microfluidic device is simulated under a zero flow condition by the Eulerian-Lagrangian method incorporating the ac electrothermal effect, thermal buoyancy, and dielectrophoresis. The mean trapping rate under the steady state <italic>R<sub>m</sub></italic> is evaluated from the simulated number of trapped particles <italic>N</italic><sub>trap</sub> for 54 cases with four parameters: electrode excitation pattern, medium conductivity <italic>σ</italic>, applied voltage <italic>φ</italic><sub>e</sub>, and the real part of the Clausius–Mossotti factor Re[<italic>K</italic>(<italic>ω</italic>)]. The simulated pDEP velocity in the upper part of the flow channel is validated by an experiment using cell suspension and is fitted so that the non-dimensional velocity error is within 15% of a typical velocity of pDEP. The mean trapping rate <italic>R<sub>m</sub></italic> is greatly increased by the fluid flow only in the high conductivity and high voltage cases. Regardless of the electrode excitation pattern, <italic>R<sub>m</sub></italic> increased almost proportionally to the inflow rate into the capture region, where the pDEP force is effective. From a fitted equation of the results, the increase of <italic>R<sub>m</sub></italic> when Re[<italic>K</italic>(<italic>ω</italic>)] = 0.1 to 0.5 is found to be about 20% to 30% of the number of particles transported into the capture regions. The results quantify the enhancement of pDEP trapping by the fluid flow occurring under practical conditions in the device.
The clinical presentation of cobalamin‐related disorders: From acquired deficiencies to inborn errors of absorption and intracellular pathways

This review gives an overview of clinical characteristics, treatment and outcome of nutritional and acquired cobalamin (Cbl; synonym: vitamin B12) deficiencies, inborn errors of Cbl absorption and intracellular trafficking, as well as methylenetetrahydrofolate dehydrogenase (MTHFD1) and methylene tetrahydrofolate reductase (MTHFR) deficiencies, which impair Cbl‐dependent remethylation. Acquired and inborn Cbl‐related disorders and MTHFR deficiency cause multisystem, often severe disease. Failure to thrive, neurocognitive or psychiatric symptoms, eye disease, bone marrow alterations, microangiopathy and thromboembolic events are characteristic. The recently identified MTHFD1 defect additionally presents with severe immune deficiency. Deficient Cbl‐dependent enzymes cause reduced methylation capacity and metabolite toxicity. Further net‐effects of perturbed Cbl function or reduced Cbl supply causing oxidative stress, altered cytokine regulation or immune functions are discussed.
In Search of Desire: The Role of Intimacy, Celebrated Otherness, and Object-of-Desire Affirmation in Sexual Desire in Women

Abstract While the interactive nature of sexual desire in women is increasingly recognized, dyadic factors affecting it, including partner interactions, have as yet received little research attention. In this cross-sectional study, we examined the associations among intimacy, celebrated otherness, and object-of-desire affirmation and explored how they complement each other in the prediction of sexual desire in women. Based on the reports of 662 participants, positive correlations were found among all factors. However, in a multiple regression analysis, object-of-desire affirmation emerged as the only positive predictor of sexual desire.
ICU Survivors Have a Substantial Higher Risk of Developing New Chronic Conditions Compared to a Population-Based Control Group

Objectives: To describe the types and prevalence of chronic conditions in an ICU population and a population-based control group during the year before ICU admission and to quantify the risk of developing new chronic conditions in ICU patients compared with the control group. Design: We conducted a retrospective cohort study, combining a national health insurance claims database and a national quality registry for ICUs. Claims data in the timeframe 2012–2014 were combined with clinical data of patients who had been admitted to an ICU during 2013. To assess the differences in risk of developing new chronic conditions, ICU patients were compared with a population-based control group using logistic regression modeling. Setting: Eighty-one Dutch ICUs. Patients: All patients admitted to an ICU during 2013. A population-based control group was created, and weighted on the age, gender, and socio-economic status of the ICU population. Interventions: None. Measurements and Main Results: ICU patients (n = 56,760) have more chronic conditions compared with the control group (n = 75,232) during the year before ICU admission (p < 0.0001). After case-mix adjustment ICU patients had a higher risk of developing chronic conditions, with odds ratios ranging from 1.67 (CI, 1.29–2.17) for asthma to 24.35 (CI, 14.00–42.34) for epilepsy, compared with the control group. Conclusions: Due to the high prevalence of chronic conditions and the increased risk of developing new chronic conditions, ICU follow-up care is advised and may focus on the identification and treatment of the new developed chronic conditions.
Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of chemotherapeutic agents in human glioma cells.

OBJECT The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. A considerable number of glioblastoma cases are refractory to TMZ, however, and the development of novel chemotherapeutic regimens is needed. The authors of previous studies have revealed that hsp90 is expressed at higher levels in human neoplastic tissues, including gliomas, than in normal tissues. Heat shock protein 90 is involved in a cytoprotective mechanism against cellular stressors such as DNA damage, and the authors hypothesized that hsp90 inhibitors might act as antitumor agents against gliomas and potentiate the cytotoxicity of DNA-damaging agents. METHODS The authors examined the cytotoxicity of an hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), both alone and in combination with 1 of 3 DNA-damaging agents (cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, and TMZ) in human glioma cell lines. The cytotoxicity of these agents to glioma cells was measured using a colony formation assay. The cell cycle phase distribution, protein expression, and number of apoptotic cells were measured using a fluorescence-activated cell sorting assay, immunoblot assays, and double staining with annexin V and propidium iodide. In an in vivo experiment, 17-AAG, cisplatin, or 17-AAG and cisplatin were administered intraperitoneally to mice with xenografted U87MG cells, and the resulting tumor volumes were measured. RESULTS The authors found that 17-AAG reduced the clonogenicity of U87MG cells, and at a low concentration (< 100 nM) potentiated the cytotoxicity of the DNA-crosslinking agents cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea, but not that of the DNA-methylating agent TMZ. This 17-AAG-induced potentiation of DNA crosslinking agent-induced cytotoxicity was a consequence of prolonged G(2)-M arrest accompanied by the suppression of cdc2 and cdc25C and of increased apoptotic cell death accompanied by the degradation of the antiapoptosis proteins Akt and survivin. Similar effects were observed when cells were treated with radicicol, another hsp90 inhibitor. The 17-AAG-induced enhancement of DNA crosslinking agent-induced cytotoxicity was also observed in other cell lines. In addition, 17-AAG sensitized xenografted U87MG cells to cisplatin in nude mice. CONCLUSIONS Heat shock protein 90-targeted therapy may be an effective strategy for potentiating chemotherapy using DNA-crosslinking agents for TMZ-refractory gliomas.
Metabolic responses to potassium availability and waterlogging reshape respiration and carbon use efficiency in oil palm.

Oil palm is by far the major oil-producing crop on the global scale, with c. 62 Mt oil produced each year. This species is a strong potassium (K)-demanding species cultivated in regions where soil K availability is generally low and waterlogging due to tropical heavy rains can limit further nutrient absorption. However, the metabolic effects of K and waterlogging have never been assessed precisely. Here, we examined the metabolic response of oil palm saplings in the glasshouse under controlled conditions (nutrient composition with low or high K availability, with or without waterlogging), using gas exchange, metabolomics and proteomics analyses. Our results showed that both low K and waterlogging have a detrimental effect on photosynthesis but stimulate leaf respiration, with differential accumulation of typical metabolic intermediates and enzymes of Krebs cycle and alternative catabolic pathways. In addition, we found a strong relationship between metabolic composition, the rate of leaf dark respiration, and cumulated respiratory loss. Advert environmental conditions (here, low K and waterlogging) therefore have an enormous effect on respiration in oil palm. Leaf metabolome and proteome appear to be good predictors of carbon balance, and open avenues for cultivation biomonitoring using functional genomics technologies.
SDF1α-induced chemotaxis of JAK2-V617F-positive cells is dependent on Bruton tyrosine kinase and its downstream targets PI3K/AKT, PLCγ1 and RhoA

JAK2-V617F is present in nearly 95% of patients with polycythemia vera and 50-60% of those with essential thrombocythemia or primary myelofibrosis. In addition to erythrocytosis, thrombocytosis and bone marrow fibrosis (as in polycythemia vera, essential thrombocythemia, and primary myelofibrosis, respectively), the clinical course of patients with myeloproliferative neoplasia (MPN) is characterized by increased risks of thrombosis, splenomegaly and an inflammatory response syndrome. Clinical studies of JAK kinase inhibitors have shown that these agents can produce considerable improvements of splenomegaly, constitutive symptoms, and overall survival in MPN patients. However, the therapeutic response is often limited and short-lived. In addition, transformation to acute leukemia remains a major problem. It is, therefore, essential to identify novel nodes of constitutive JAK2-V617F signaling and to develop better approaches to the therapy of these neoplasias. Downstream of JAK2-V617F, NFκB signaling (p65) is constitutively active and regulates expression of CXCL10 in MPN. In bortezomib-resistant multiple myeloma cells and in acute myeloid leukemia cells with MLL-AF9 rearrangements, constitutively active NFκB drives the expression of Bruton tyrosine kinase (BTK). Of note, it was found that BTK interacted with erythropoietin receptor-JAK2 and was tyrosine phosphorylated in response to treatment with erythropoietin. These observations led us to investigate whether JAK2-V617F kinase also induces BTK expression (via p65) and activation and to characterize its physiological relevance in JAK2V617F-positive cells. To investigate whether BTK is activated by JAK2V617F, we used 32D myeloid progenitor cells ectopically expressing human erythropoietin receptor and JAK2wildtype (32D JAK2-WT) or JAK2-V617F (32D JAK2V617F). Tyrosine phosphorylation of BTK was indeed elevated in whole cell lysates of 32D JAK2-V617F cells compared to the level in 32D JAK2-WT cells (Figure 1A). Consistent with this finding, erythropoietin additionally induced BTK phosphorylation in 32D JAK2-WT cells (Online Supplementary Figure S1A). Of note, BTK was overexpressed in 32D JAK2-V617F cells. In line with our
The complete mitochondrial genome of Eleotris oxycephala (Perciformes: Eleotridae)

Abstract In the present study, we obtained the complete mitochondrial genome sequence of Eleotris oxycephala, which was 16 527 bp in length. This genome consisted of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and a putative control region. Of the 37 genes, 28 were encoded by heavy strand, while nine were encoded by light strand. The overall base composition of this mitogenome was 28.21% for A, 16.81% for G, 24.75% for T, 30.23% for C, respectively, with a slight higher A + T content (52.96%). The phylogenetic analysis based on 13 concatenated protein-coding genes suggested that E. oxycephala as a sister species to Eleotris acanthopoma was clustered in family Eleotridae. This complete mitochondrial genome sequence of E. oxycephala should be helpful for the studies on population genetic structure, molecular evolution and phylogeny of E. oxycephala and related species.
Investigation of the Metabolic Profile and Toxigenic Variability of Fungal Species Occurring in Fermented Foods and Beverage from Nigeria and South Africa Using UPLC-MS/MS

Fungal species recovered from fermented foods and beverage from Nigeria and South Africa were studied to establish their toxigenic potential in producing an array of secondary metabolites including mycotoxins (n = 49) that could compromise human and animal safety. In total, 385 fungal isolates were grown on solidified yeast extract sucrose agar. Their metabolites were extracted and analyzed via ultra-performance liquid chromatography tandem mass spectrometry. To examine the grouping of isolates and co-occurrence of metabolites, hierarchal clustering and pairwise association analysis was performed. Of the 385 fungal strains tested, over 41% were toxigenic producing different mycotoxins. A. flavus and A. parasiticus strains were the principal producers of aflatoxin B1 (27–7406 µg/kg). Aflatoxin B1 and cyclopiazonic acid had a positive association. Ochratoxin A was produced by 67% of the A. niger strains in the range of 28–1302 µg/kg. The sterigmatocystin producers found were A. versicolor (n = 12), A. amstelodami (n = 4), and A. sydowii (n = 6). Apart from P. chrysogenum, none of the Penicillium spp. produced roquefortine C. Amongst the Fusarium strains tested, F. verticillioides produced fumonisin B1 (range: 77–218 µg/kg) meanwhile low levels of deoxynivalenol were observed. The production of multiple metabolites by single fungal species was also evident.
Single‐breath washout and association with structural lung disease in children with cystic fibrosis

In children with cystic fibrosis (CF) lung clearance index (LCI) from multiple‐breath washout (MBW) correlates with structural lung disease. As a shorter test, single‐breath washout (SBW) represents an attractive alternative to assess the ventilation distribution, however, data for the correlation with lung imaging are lacking.
Precision Versus Traditional Medicine-Clinical Questions Trigger Progress in Basic Science.

Genetics is a fast-growing tree bearing many different fruits. One of the most attractive is precision medicine. We all fell in love with it and still are. But, as grandmothers used to say, “even when in love, keep your eyes open if you don’t want to be fooled. ” The issue of precision medicine is especially relevant in arrhythmogenic disorders of genetic origin because channelopathies and cardiomyopathies carry a significant risk for sudden cardiac death. It follows that the affected patients could benefit from insights on prognosis, management strategies, and therapies based on geneand mutation-specific data.
IFN‐γ‐dependent nitric oxide suppresses Brucella‐induced arthritis by inhibition of inflammasome activation

Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a globally important zoonotic disease for which arthritis is the most common focal complication in humans. Wild‐type mice infected systemically with Brucella typically do not exhibit arthritis, but mice lacking IFN‐γ develop arthritis regardless of the route of Brucella infection. Here, we investigated mechanisms by which IFN‐γ suppresses Brucella‐induced arthritis. Several cell types, including innate lymphoid cells, contributed to IFN‐γ production and suppression of joint swelling. IFN‐γ deficiency resulted in elevated joint IL‐1β levels, and severe joint inflammation that was entirely inflammasome dependent, and in particular, reliant on the NLRP3 inflammasome. IFN‐γ was vital for induction of the nitric oxide producing enzyme, iNOS, in infected joints, and nitric oxide directly inhibited IL‐1β production and inflammasome activation in Brucella‐infected macrophages in vitro. During in vivo infection, iNOS deficiency resulted in an increase in IL‐1β and inflammation in Brucella‐infected joints. Collectively, this data indicate that IFN‐γ prevents arthritis both by limiting Brucella infection, and by inhibiting excessive inflammasome activation through the induction of nitric oxide.
What Can Dietary Patterns Tell Us about the Nutrition Transition and Environmental Sustainability of Diets in Uganda?

Uganda is undergoing dietary transition, with possible environmental sustainability and health implications, particularly for women. To explore evidence for dietary transitions and identify how environmentally sustainable women’s dietary patterns are, principal component analysis was performed on dietary data collected using a 24 h recall during the Uganda Food Consumption Survey (n = 957). Four dietary patterns explained 23.6% of the variance. The “traditional, high-fat, medium environmental impact” pattern was characterized by high intakes of nuts/seeds, fats, oils and spreads, fish and boiled vegetables. High intakes of bread and buns, rice and pasta, tea and sugar characterized the “transitioning, processed, low environmental impact’ pattern. The ‘plant-based, low environmental impact” pattern was associated with high intakes of legumes, boiled roots/tubers, boiled traditional vegetables, fresh fruit and fried traditional cereals. High intakes of red/organ meats, chicken, and soups characterized the “animal-based high environmental impact” pattern. Urban residence was positively associated with “transitioning, processed, low environmental impact” (β = 1.19; 1.06, 1.32) and “animal-based high environmental impact” (β = 0.45; 0.28, 0.61) patterns; but negatively associated with the “plant-based low environmental impact” pattern (β= −0.49; −0.62, −0.37). A traditional, high-fat dietary pattern with medium environmental impact persists in both contexts. These findings provide some evidence that urban women’s diets are transitioning.
Risk factors for peptic ulcer disease in patients with end-stage renal disease receiving dialysis

Background Compared to the general population, patients with end-stage renal disease have more gastrointestinal symptoms and a higher prevalence of peptic ulcer. Risk factors for peptic ulcer disease in patients with end-stage renal disease, however, remain poorly defined. This study aims to better identify those risk factors. Methods We analyzed 577 patients with end-stage renal disease from 2004 to 2016. We excluded patients with life-threatening conditions. All patients underwent upper endoscopy. We analyzed patient medical records, medication history, and endoscopic findings. Independent sample t test, chi-square test, Fisher’s exact test, and multiple logistic regression analysis were used in statistical analyses. Results Of the 577 patients with end-stage renal disease, 174 had peptic ulcer disease (gastric or duodenal ulcer). Patients on hemodialysis had a higher prevalence of peptic ulcer disease than those on peritoneal dialysis. Patients with peptic ulcer disease had lower serum albumin level and higher blood urea nitrogen level than those without peptic ulcer disease. Positive scores on two or more nutritional indices (albumin, serum cholesterol, uric acid, and creatinine levels) were associated with peptic ulcer disease in end-stage renal disease. Conclusion Hemodialysis, hypoalbuminemia, and multiple malnutrition indices were associated with the prevalence of peptic ulcer disease in patients with end-stage renal disease receiving dialysis.
An iterative penalized least squares approach to sparse canonical correlation analysis

It is increasingly interesting to model the relationship between two sets of high‐dimensional measurements with potentially high correlations. Canonical correlation analysis (CCA) is a classical tool that explores the dependency of two multivariate random variables and extracts canonical pairs of highly correlated linear combinations. Driven by applications in genomics, text mining, and imaging research, among others, many recent studies generalize CCA to high‐dimensional settings. However, most of them either rely on strong assumptions on covariance matrices, or do not produce nested solutions. We propose a new sparse CCA (SCCA) method that recasts high‐dimensional CCA as an iterative penalized least squares problem. Thanks to the new iterative penalized least squares formulation, our method directly estimates the sparse CCA directions with efficient algorithms. Therefore, in contrast to some existing methods, the new SCCA does not impose any sparsity assumptions on the covariance matrices. The proposed SCCA is also very flexible in the sense that it can be easily combined with properly chosen penalty functions to perform structured variable selection and incorporate prior information. Moreover, our proposal of SCCA produces nested solutions and thus provides great convenient in practice. Theoretical results show that SCCA can consistently estimate the true canonical pairs with an overwhelming probability in ultra‐high dimensions. Numerical results also demonstrate the competitive performance of SCCA.