Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue Distribution of Several Series of Cationic Surfactants in Rainbow Trout (Oncorhynchus mykiss) Following Exposure via Water

Bioaccumulation assessment is important for cationic surfactants in light of their use in a wide variety of consumer products and industrial processes. Because they sorb strongly to natural surfaces and to cell membranes, their bioaccumulation behavior is expected to differ from other classes of chemicals. Divided over two mixtures, we exposed rainbow trout to water containing 10 alkyl amines and 2 quaternary alkylammonium surfactants for 7 days, analyzed different fish tissues for surfactant residues, and calculated the tissues’ contribution to fish body burden. Mucus, skin, gills, liver, and muscle each contributed at least 10% of body burden for the majority of the test chemicals. This indicates that both sorption to external surfaces and systemic uptake contribute to bioaccumulation. In contrast to the analogue alkylamine bases, the permanently charged quaternary ammonium compounds accumulated mostly in the gills and were nearly absent in internal tissues, indicating that systemic uptake of the charged form of cationic surfactants is very slow. Muscle–blood distribution coefficients were close to 1 for all alkyl amines, whereas liver–blood distribution coefficients ranged from 13 to 90, suggesting that the dominant considerations for sorption in liver are different from those in blood and muscle. The significant fraction of body burden on external surfaces can have consequences for bioaccumulation assessment.
Downregulation of a Mitochondrial NAD+ Transporter (NDT2) Alters Seed Production and Germination in Arabidopsis

Abstract Despite the fundamental importance of nicotinamide adenine dinucleotide (NAD+) for metabolism, the physiological roles of NAD+ carriers in plants remain unclear. We previously characterized the Arabidopsis thaliana gene (At1g25380), named AtNDT2, encoding a protein located in the mitochondrial inner membrane, which imports NAD+ from the cytosol using ADP and AMP as counter-exchange substrates for NAD+. Here, we further investigated the physiological roles of NDT2, by isolating a T-DNA insertion line, generating an antisense line and characterizing these genotypes in detail. Reduced NDT2 expression affected reproductive phase by reducing total seed yield. In addition, reduced seed germination and retardation in seedling establishment were observed in the mutant lines. Moreover, remarkable changes in primary metabolism were observed in dry and germinated seeds and an increase in fatty acid levels was verified during seedling establishment. Furthermore, flowers and seedlings of NDT2 mutants displayed upregulation of de novo and salvage pathway genes encoding NAD+ biosynthesis enzymes, demonstrating the transcriptional control mediated by NDT2 activity over these genes. Taken together, our results suggest that NDT2 expression is fundamental for maintaining NAD+ balance amongst organelles that modulate metabolism, physiology and developmental processes of heterotrophic tissues.
Plasma and intracellular pharmacokinetics of tenofovir disoproxil fumarate and emtricitabine in transgender women receiving feminizing hormone therapy.

BACKGROUND Transwomen have an increased risk of HIV acquisition compared with other adults. Drug-drug interactions between pre-exposure prophylaxis (PrEP) and gender-affirming therapy are cited as a reason for poor PrEP uptake among transwomen. We evaluated plasma tenofovir and emtricitabine pharmacokinetics and their active intracellular anabolites, tenofovir-diphosphate and emtricitabine-triphosphate, in transwomen receiving feminizing hormones. METHODS We enrolled HIV-negative transwomen (≥19 years) not receiving PrEP. Participants took oral tenofovir disoproxil fumarate/emtricitabine 300/200 mg daily for 14 days. Plasma was collected at 0 h (pre-dose), 0.5, 1, 2, 3, 4, 6, 8 and 12 h on day 14 post-tenofovir disoproxil fumarate/emtricitabine dose. The plasma AUC0-24 was calculated using the trapezoidal rule and compared with historical HIV-negative cisgender adults as geometric mean ratios (GMRs, 90% CI). Secondarily, tenofovir-diphosphate and emtricitabine-triphosphate from PBMCs collected at 0 h and 12 h were reported descriptively as geometric means (90% CI). Clinical trials registration: NCT03270969. RESULTS Among 15 transwomen (mean age 32 years), geometric mean tenofovir and emtricitabine plasma AUC0-24 were lower compared with controls: tenofovir, 2.10 versus 2.76 mg·h/L, GMR 0.76 (0.65-0.90), P = 0.01; emtricitabine, 9.15 versus 10.64 mg·h/L, GMR 0.86 (0.75-0.98), P = 0.07. Tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in the literature: 167.1 (146.6-190.5) fmol/106 cells and 15.4 (13.8-17.3) pmol/106 cells, respectively. CONCLUSIONS We observed lower plasma tenofovir and emtricitabine concentrations in transwomen compared with historical cisgender adults, yet intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations were higher than previously reported in PBMCs. Understanding the differences of PrEP pharmacokinetics in plasma and tissue compartments and the resultant impact on efficacy remains important for transwomen.
Interfaith dialogue in medicine

Abstract A moral crisis has swept through the United States dividing social, political, and religious organizations with corrupt and ineffectual leadership. However, the present moral crisis has its roots in the technological and cultural shifts of the last half century. The goal of interfaith dialogue is not merely to exchange pleasantries, but to build a mutual collaboration addressing the moral and ethical issues with a unified voice. Interfaith dialogue has the potential to pull us out of our individualism and, in focusing on our relationships, create a new sensibility about being human. And were that new sensibility understood to reflect some of the fundamentals of science, it would strengthen the ability of religions to pursue a more healing inclusivity and reveal a rich unity among religious faiths, stretching down from our personal relationships with each other to the divine and the very fabric of reality.
ZIC2 is downregulated and represses tumor growth via the regulation of STAT3 in breast cancer

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP‐seq and RNA‐seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.
Associations of caregiver-oncologist discordance in prognostic understanding with caregiver-reported therapeutic alliance and anxiety.

CONTEXT Discordance in prognostic understanding between caregivers of adults with advanced cancer and the oncologist may shape caregivers' views of the oncologist and bereavement outcomes. OBJECTIVES We examined prospective associations of caregiver-oncologist discordance with caregiver-oncologist therapeutic alliance and caregiver anxiety following patient death. METHODS We conducted a secondary analysis of data collected in a cluster randomized controlled trial from August 2012 to June 2014 in Western New York and California. At enrollment, caregivers and oncologists used a 7-point scale to rate their beliefs about the patient's curability and living ≥2 years: 100%, about 90%, about 75%, about 50/50, about 25%, about 10%, and 0%. Discordance was defined as a difference of ≥2 points. Outcomes at 7 months after patient death included caregiver-oncologist therapeutic alliance [modified 5-item Human Connection (THC) scale] and caregiver anxiety (Generalized Anxiety Disorder-7). We conducted multivariable linear regression models to assess the independent associations of discordance with alliance and anxiety. RESULTS We included 97 caregivers (mean age=63) and 38 oncologists; 41% of caregiver-oncologist dyads had discordant beliefs about the patient's curability and 63% of caregiver-oncologist dyads had discordant beliefs about living ≥2 years. On multivariate analysis, discordance in beliefs about curability was associated with lower anxiety (β=-2.20, SE=0.77, p=0.005). Discordance in beliefs about length of life was associated with a weaker alliance (β=-5.87, SE=2.56, p=0.02). CONCLUSION A better understanding of how caregivers understand and come to terms with poor prognoses will guide interventions to improve cancer care delivery and outcomes of cancer treatment.
Natural language processing of clinical mental health notes may add predictive value to existing suicide risk models

Abstract Background This study evaluated whether natural language processing (NLP) of psychotherapy note text provides additional accuracy over and above currently used suicide prediction models. Methods We used a cohort of Veterans Health Administration (VHA) users diagnosed with post-traumatic stress disorder (PTSD) between 2004–2013. Using a case-control design, cases (those that died by suicide during the year following diagnosis) were matched to controls (those that remained alive). After selecting conditional matches based on having shared mental health providers, we chose controls using a 5:1 nearest-neighbor propensity match based on the VHA's structured Electronic Medical Records (EMR)-based suicide prediction model. For cases, psychotherapist notes were collected from diagnosis until death. For controls, psychotherapist notes were collected from diagnosis until matched case's date of death. After ensuring similar numbers of notes, the final sample included 246 cases and 986 controls. Notes were analyzed using Sentiment Analysis and Cognition Engine, a Python-based NLP package. The output was evaluated using machine-learning algorithms. The area under the curve (AUC) was calculated to determine models' predictive accuracy. Results NLP derived variables offered small but significant predictive improvement (AUC = 0.58) for patients that had longer treatment duration. A small sample size limited predictive accuracy. Conclusions Study identifies a novel method for measuring suicide risk over time and potentially categorizing patient subgroups with distinct risk sensitivities. Findings suggest leveraging NLP derived variables from psychotherapy notes offers an additional predictive value over and above the VHA's state-of-the-art structured EMR-based suicide prediction model. Replication with a larger non-PTSD specific sample is required.
A systematic review of the views of health care professionals on the provision of long acting reversible contraception.

RESEARCH QUESTION What are the views of health care professionals outside of the general practice setting on long-acting reversible contraception? BACKGROUND Despite global sexual health organisations advocating for widespread prescription of long-acting reversible contraception, uptake in developed countries remains relatively low. The role of health care professionals outside of the general practice setting in long-acting reversible contraception provision requires further attention. DESIGN Systematic review. METHODS Five electronic databases were searched for existing qualitative findings using terms related to long-acting reversible contraception and health care professional views for the period 2013-2018. A rigorous protocol was applied following the Preferred Reporting Items for Systematic Meta-Analyses checklist and flow diagram. The Critical Appraisal Skills Program tool was used to assess the quality of studies. A total of six studies were included for thematic analysis. RESULTS Three key themes emerged through analysis that had significant impact on health care professional views of long-acting reversible contraception: (1) Contraceptive counselling practices and constraints; (2) Knowledge and training about long-acting reversible contraception; (3) Concerns and personal beliefs about long-acting reversible contraception. CONCLUSIONS Health care professional views on long-acting reversible contraception are shaped by practical time constraints, levels of knowledge and training, and personal beliefs and concerns. Further research is required to address these issues in order to improve clinical training and guidelines for all settings, not just general practice. RELEVANCE TO CLINICAL PRACTICE Settings outside of general practice need to be included within the scope of initiatives that aim to improve clinical practice around access to new and emerging contraceptive methods. Further research could inform models of clinical practice that enable health care professionals to take enough time to talk through all contraceptive options with patients in a way that both focusses on their individual needs and is fully informed by up-to-date evidence and training.
Liver Imaging Reporting and Data System (LI-RADS) v2018: Review of the CT/MRI Diagnostic Categories

Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system that provides standardization in the interpretation and reporting of observations in patients at risk of developing hepatocellular carcinoma (HCC). Computed tomography/magnetic resonance imaging (CT/MRI) LI-RADS v2018 includes 8 diagnostic categories, which reflect the probability of benignity, malignancy in general, or HCC specifically. This article reviews the diagnostic categories of CT/MRI LI-RADS v2018, highlighting the key imaging features, diagnostic criteria, and management implications.
Accurate Neural Network Representation of the ab initio Determined Spin-Orbit Interaction in the Diabatic Representation including the Effects of Conical Intersections.

A method for fitting ab initio determined spin-orbit coupling interactions, in the Breit-Pauli approximation, based on quasi diabatic representations using neural network fits is reported. The algorithm generalizes our recently reported neural network approach for representing the dipole interaction. The S0, S1 and T1 states of formaldehyde are used as an example. First, the two singlet states S0 and S1 are diabatized with a modified Boys Localization diabatization method. Second, the spin-orbit coupling between singlet and triplet states is transformed to the diabatic representation. This removes the discontinuities in the adiabatic representation. The diabatized spin-orbit couplings are then fit with smooth neural network functions. The analytic representation of spin-orbit coupling interactions in a diabatic basis by neural networks will make accurate full-dimensional quantum dynamical treatment of both internal conversion and intersystem crossing possible, which will help us to gain better understanding of both processes.
Prolactin attenuates global cerebral ischemic injury in rat model by conferring neuroprotection

ABSTRACT Primary Objective: Limited available therapeutics for ischemic stroke necessitate dire need of designing novel strategies for combating ischemic pathophysiological cascade among which neuroprotective strategies emerge as positive approaches. The neuropeptide prolactin is a pleiotropic hormone that affects various physiological conditions and reportedly combats neurotoxicity, neuronal stress and provides neuroprotection to hippocampal neurons in vitro. Research Design: The study explores the ability of prolactin in conferring neuroprotection in global cerebral ischemia in vivo and attempts to optimize the dose of prolactin which will be effective for the same. Methods and Procedure: Global cerebral ischemia was induced in male rats by bilateral common carotid occlusion (BCCAO) and different physiological and biochemical parameters were evaluated. Also, cerebral infarction and percentage of brain edema were measured. Results: The results revealed that prolactin significantly reduces cerebral infarct, brain water content and restores the physiological conditions like blood pressure, heart rate and cerebral blood flow. Also, prolactin markedly reduces the increased levels of the neurotransmitters (ɣ-aminobutyric acid and glutamate), cerebral calcium and nitrate in different brain compartments of ischemic rats. Conclusion: Prolactin is able to ameliorate ischemia-reperfusion injury in rat brain and might be a potent candidate for further neuro-therapeutics development.
Focused attention meditation training modifies neural activity and attention: longitudinal EEG data in non-meditators

Abstract Focused attention meditation (FAM) is a basic meditation practice that cultivates attentional control and monitoring skills. Cross-sectional studies have highlighted high cognitive performance and discriminative neural activity in experienced meditators. However, a direct relationship between neural activity changes and improvement of attention caused by meditation training remains to be elucidated. To investigate this, we conducted a longitudinal study, which evaluated the results of electroencephalography (EEG) during three-stimulus oddball task, resting state and FAM before and after 8 weeks of FAM training in non-meditators. The FAM training group (n = 17) showed significantly higher P3 amplitude during the oddball task and shorter reaction time (RT) for target stimuli compared to that of the control group (n = 20). Furthermore, a significant negative correlation between F4-Oz theta band phase synchrony index (PSI) during FAM and P3 amplitude during the oddball task and a significant positive correlation between F4-Pz theta band PSI during FAM and P3 amplitude during the oddball task were observed. In contrast, these correlations were not observed in the control group. These findings provide direct evidence of the effectiveness of FAM training and contribute to our understanding of the mechanisms underpinning the effects of meditation on brain activity and cognitive performance.
Using multidimensional scaling in model choice for congenital oesophageal atresia: similarity analysis of human autopsy organ weights with those from a comparative assessment of Aachen Minipig and Pietrain piglets

Swine models had been popular in paediatric oesophageal surgery in the past. Although being largely replaced by rodent models, swine experienced a revival with the establishment of minipig models. However, none of them has ever been investigated for similarity to humans. We conducted a pilot study to determine whether three-week old Pietrain piglets and three-month old Aachen Minipigs are suitable for experimental paediatric oesophageal atresia surgery. We tested the operation's feasibility, performed a necropsy, weighed organs, measured organ length and calculated relative weights and lengths, and measured laboratory parameters. We used multidimensional scaling to assess the similarity of the swine breeds with previously published human data. Pietrain piglets had a higher a priori bodyweight than Aachen Minipigs (Δ = 1.31 kg, 95% confidence interval (CI): 0.37–2.23, p = 0.015), while snout-to-tail length was similar. Pietrain piglets had higher absolute and relative oesophageal lengths (Δ = 5.43 cm, 95% CI: 2.2–8.6; p = 0.0062, q 1 * = 0.0083 and Δ = 11.4%, 95% CI: 5.1–17.6; p = 0.0025, q 3 * = 0.0053). Likewise, absolute and relative small intestinal lengths were higher in Pietrains, but all other parameters did not differ, with the exception of minor differences in laboratory parameters. Multidimensional scaling revealed three-week old Pietrain piglets to be similar to two-month old humans based on their thoracoabdominal organ weights. This result indicates three-week old Pietrain piglets are a suitable model of paediatric oesophageal atresia surgery, because clinically many procedures are performed at around eight weeks age. Three-month old Aachen Minipigs were more dissimilar to eight-week old humans than three-week old Pietrain piglets.
Sex differences in symptom presentation and functional outcomes: a pilot study in a matched sample of veterans with mild TBI

ABSTRACT Primary Objective: Research focused on mild traumatic brain injury in active military and veteran populations details the psychological, neurological and functional outcomes of mTBI, in a primarily male (~95%) cohort. This may misrepresent female symptoms and outcomes. Here we assess for genuine sex differences in symptom presentation and functional outcomes. Research Design: We used matched pairs to preclude potential sex bias in outcome data. Methods and Procedures: We matched 49 female/male pairs on; 1) mechanism of injury, 2) time from injury to assessment and 3) age at assessment. Statistics were t-tests, chi-square, correlations and post hoc linear regression. Main outcomes and results: Outcome assessment revealed four significant (p < .05) sex differences; Living situation, Marital status, Vocation and Branch of service. Only the Neurobehavioral Symptom Inventory (NSI) composite cognitive domain factor was significantly different between females (mean: 10.26) and males (mean: 7.58). Linear regression confirmed a significant effect of sex for the cognitive composite (p = .002). Conclusion: We conclude that sex has a moderate effect on mTBI post-concussive symptom presentation. The significant sex difference in the NSI cognitive domain characterizes sex-related symptomology profiles providers can focus on for better rehabilitation management. Replication in the larger cohort would improve generalizability. Abbreviation: TBI: Traumatic Brain Injuries; mTBI: mild Traumatic Brain Injuries; OIF: Operation Iraqi Freedom; OEF: Operation Enduring Freedom; VA: Veterans Affairs Health Care System; PSC: Polytrauma System of Care; PRC: Polytrauma Rehabilitation Center; PTRP: Polytrauma Transitional Rehabilitation Program; PNS: Polytrauma Network Site; PTSD: Post Traumatic Stress Disorder; DoD: Department of Defense; NSI: Neurobehavioral Symptom Inventory; LOC: loss of consciousness; AOC: alteration of consciousness; PTA: posttraumatic amnesia; CPRS: computerized patient record system; CTBIE: Comprehensive TBI Evaluation; OCD: obsessive compulsive disorder; ETOH: alcohol abuse