Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of Liver Steatosis With a Novel Ultrasound-Based Technique: A Pilot Study Using MRI-Derived Proton Density Fat Fraction as the Gold Standard

OBJECTIVES: The primary aim of this study was to investigate the value of attenuation imaging (ATI), a novel ultrasound technique for detection of steatosis, by comparing the results to that obtained with controlled attenuation parameter (CAP) and by using MRI-derived proton density fat fraction (PDFF) as reference standard. METHODS: From March to November 2018, 114 consecutive adult subjects potentially at risk of steatosis and 15 healthy controls were enrolled. Each subject underwent ATI and CAP assessment on the same day. MRI-PDFF was performed within a week. RESULTS: The prevalence of steatosis, as defined by MRI-PDFF ≥ 5%, was 70.7%. There was a high correlation of ATI with MRI-PDFF (r = 0.81, P < 0.0001). The correlation of CAP with MRI-PDFF and with ATI, respectively, was moderate (r = 0.65, P < 0.0001 and r = 0.61, P < 0.0001). The correlation of ATI or CAP with PDFF was not affected by age, gender, or body mass index. Area under the receiver operating characteristics of ATI and CAP, respectively, were 0.91 (0.84–0.95; P < 0.0001) and 0.85 (0.77–0.91; P < 0.0001) for detecting S > 0 steatosis (MRI-PDFF ≥ 5%); 0.95 (0.89–0.98; P < 0.0001) and 0.88 (0.81–0.93; P < 0.0001) for detecting S > 1 steatosis (MRI-PDFF ≥ 16.3%). The cutoffs of ATI and CAP, respectively, were 0.63 dB/cm/MHz and 258 dB/m for detecting S > 0 liver steatosis; 0.72 dB/cm/MHz and 304 dB/m for detecting S > 1 steatosis. ATI performed better than CAP, and this improvement was statistically significant for S > 1 (P = 0.04). DISCUSSION: This study shows that, in patients with no fibrosis/mild fibrosis, ATI is a very promising tool for the noninvasive assessment of steatosis.
4D electron microscopy of T cell activation

Significance Photon-induced near-field electron microscopy (PINEM) enables the visualization of nanoscale structures and interfaces with enhanced contrast due to the energy gain of electrons from light-excited evanescent electromagnetic fields. Here we optimized a PINEM approach to directly image and quantify these fields at the surface of T cells as a function of various stimulation conditions. We found that while PINEM is sensitive to multiple biophysical changes associated with T cell activation, it strongly correlates with binding of specific antigen major histocompatibility complex, even without accompanying functional T cell activation. Our results suggest that PINEM can find use as a cellular imaging tool, with exquisite surface selectivity and high sensitivity to structural changes on the length scale of cell surface protein aggregates. T cells can be controllably stimulated through antigen-specific or nonspecific protocols. Accompanying functional hallmarks of T cell activation can include cytoskeletal reorganization, cell size increase, and cytokine secretion. Photon-induced near-field electron microscopy (PINEM) is used to image and quantify evanescent electric fields at the surface of T cells as a function of various stimulation conditions. While PINEM signal strength scales with multiple of the biophysical changes associated with T cell functional activation, it mostly strongly correlates with antigen-engagement of the T cell receptors, even under conditions that do not lead to functional T cell activation. PINEM image analysis suggests that a stimulation-induced reorganization of T cell surface structure, especially over length scales of a few hundred nanometers, is the dominant contributor to these PINEM signal changes. These experiments reveal that PINEM can provide a sensitive label-free probe of nanoscale cellular surface structures.
Exploration of Root-associated Bacteria from the Medicinal Plant Platycodon grandiflorum

The present study was performed to investigate root-associated bacteria from Platycodon grandiflorum, a medicinal plant commonly grown in East Asia. Isolates were obtained from the rhizosphere or root interior with various culture media, and phylogenetic analyses were performed based on their 16S rDNA sequences. In consideration of practical applications, traits related to plant growth promotion and niche adaptation were assessed in several endophytic strains with fewer biosafety concerns. The effects of a bacterial inoculation on seedling and mature plant growth were evaluated. Seventeen genera that encompassed more than 30 bacterial lineages were successfully retrieved from the roots, the majority of which have not been reported as P. grandiflorum-associated bacteria, particularly for non-negligible Proteobacteria. Although nitrogen-fixing or phosphate-solubilizing and indole acetic acid-producing activities were recorded in all of the strains selected, these strains were beneficial or detrimental to plant growth as evidenced by their influence on the length of seedlings and biomass of mature plants. Among the 4 endophytic Rhizobium species tested in the present study, the potentially novel Rhizobium sp. BF-E16, which was more compatible with the non-leguminous medicinal plant P. grandiflorum, was identified. Other than plant growth-promoting traits, characteristics such as plant constituent-hydrolyzing activities need to be taken into consideration and their roles clarified when investigating plant growth-promoting rhizobacteria.
Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes

Significance High-grade neuroendocrine tumors (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are recalcitrant cancers for which more effective treatments and follow-up detection systems are urgently needed. Moreover, the relationship between LCNEC and SCLC is largely unknown and a current matter of debate. Human material is scarcely available, making animal models of pivotal importance. Here we report 2 robust models of LCNEC and SCLC remarkably similar to their human counterparts. We show that SCLC can arise from basal cells, which determines the evolution of the high malignant neuroendocrine lung tumor type. Besides, we provide a noninvasive imaging method based on Ga-DOTATOC to monitor changes and assess evaluation of the diseases. High-grade neuroendocrine lung malignancies (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are among the most deadly lung cancer conditions with no optimal clinical management. The biological relationships between SCLC and LCNEC are still largely unknown and a current matter of debate as growing molecular data reveal high heterogeneity with potential therapeutic consequences. Here we describe murine models of high-grade neuroendocrine lung carcinomas generated by the loss of 4 tumor suppressors. In an Rbl1-null background, deletion of Rb1, Pten, and Trp53 floxed alleles after Ad-CMVcre infection in a wide variety of lung epithelial cells produces LCNEC. Meanwhile, inactivation of these genes using Ad-K5cre in basal cells leads to the development of SCLC, thus differentially influencing the lung cancer type developed. So far, a defined model of LCNEC has not been reported. Molecular and transcriptomic analyses of both models revealed strong similarities to their human counterparts. In addition, a 68Ga-DOTATOC–based molecular-imaging method provides a tool for detection and monitoring the progression of the cancer. These data offer insight into the biology of SCLC and LCNEC, providing a useful framework for development of compounds and preclinical investigations in accurate immunocompetent models.
A Biohistorical Perspective of Typhoid and Antimicrobial Resistance

Abstract We combine methodology from history and genetics to reconstruct the biosocial history of antimicrobial resistance (AMR) in the bacterium Salmonella enterica serovar Typhi (S. Typhi). We show how evolutionary divergence in S. Typhi was driven by rising global antibiotic use and by the neglect of typhoid outside of high-income countries. Although high-income countries pioneered 1960s precautionary antibiotic regulations to prevent selection for multidrug resistance, new antibiotic classes, typhoid’s cultural status as a supposedly ancient disease of “undeveloped” countries, limited international funding, and narrow biosecurity agendas helped fragment effective global collective action for typhoid control. Antibiotic-intensive compensation for weak water and healthcare systems subsequently fueled AMR selection in low- and middle-income countries but often remained invisible due to lacking surveillance capabilities. The recent rise of extensively drug-resistant typhoid bears the biosocial footprint of more than half a century of antibiotic-intensive international neglect.
A mesophilic cysteine-less split intein for protein trans-splicing applications under oxidizing conditions

Significance Protein trans-splicing catalyzed by split inteins is a powerful tool for traceless posttranslational protein modification. For example, it can be used to reconstitute a protein from 2 fragments, append a peptide tag to a protein, or cyclize a polypeptide. We report the first cysteine-less (CL) split intein that is high yielding under native and physiological conditions. In contrast to cysteine-containing inteins, the split CL intein is fully operational under oxidizing conditions, i.e., in the absence of reducing agents. Leveraging this property, we utilize the CL intein to selectively conjugate fluorophores to disulfide-containing antibody fragments, and to target membrane receptors on living cells. Carrying out the experimental protocol under oxidizing conditions avoids protein damage due to reduction of disulfide bonds. Split intein-mediated protein trans-splicing has found extensive applications in chemical biology, protein chemistry, and biotechnology. However, an enduring limitation of all well-established split inteins has been the requirement to carry out the reaction in a reducing environment due to the presence of 1 or 2 catalytic cysteines that need to be in a reduced state for splicing to occur. The concomitant exposure of the fused proteins to reducing agents severely limits the scope of protein trans-splicing by excluding proteins sensitive to reducing conditions, such as those containing critical disulfide bonds. Here we report the discovery, characterization, and engineering of a completely cysteine-less split intein (CL intein) that is capable of efficient trans-splicing at ambient temperatures, without a denaturation step, and in the absence of reducing agents. We demonstrate its utility for the site-specific chemical modification of nanobodies and an antibody Fc fragment by N- and C-terminal trans-splicing with short peptide tags (CysTag) that consist of only a few amino acids and have been prelabeled on a single cysteine using classical cysteine bioconjugation. We also synthesized the short N-terminal fragment of the atypically split CL intein by solid-phase peptide synthesis. Furthermore, using the CL intein in combination with a nanobody–epitope pair as a high-affinity mediator, we showed chemical labeling of the extracellular domain of a cell surface receptor on living mammalian cells with a short CysTag containing a synthetic fluorophore. The CL intein thus greatly expands the scope of applications for protein trans-splicing.
Setting boundaries: Utilization of time to boundary for objective evaluation of the balance error scoring system

ABSTRACT Subjective evaluations of balance performance, like the modified Balance Error Scoring System (mBESS), are highly popular. Alternatively, quantitative measures may offer additional clarity in identifying balance dysfunction. A novel measure to define balance impairments is time to boundary (TTB), which represents the amount of time available to make corrective postural adjustments prior to the centre of pressure (CoP) reaching the edge of the base of support. The purpose of this investigation was to assess TTB and traditional measures of CoP displacement of young adults performing the mBESS on a BTrackS balance plate. Path length and TTB were calculated in anterior-posterior (AP) and medio-lateral (ML) directions, respectively. AP and ML path lengths were largest in Single stance (109.2 & 118.1 cm, respectively) and smallest in Dual stance (27.1 & 36.4 cm, respectively). The average AP and ML TTBs were higher in Dual (10.67 & 7.27 s, respectively) compared to Single (3.54 & 1.20 s, respectively) or Tandem (10.11 & 1.94 s, respectively) stances, and lower in Single stance compared to Tandem. Given the effect sizes for TTB were greater than those of path length in both directions, TTB more adequately differentiates these stance conditions than path length or subjective scores.
A Single Inductor-based Cascaded H-Bridge PFC Converter with CM Noise Elimination

Cascaded H-Bridge (CHB) power factor correction (PFC) converter is an attractive approach to achieve high efficiency and high-power density in various applications. However, severe common-mode (CM) noise might be caused by the high dv/dt through parasitic capacitances and multiple floating dc links in the circuit. In this paper, a novel single-phase single inductor-based three-level totem-pole CHB PFC converter is proposed. By deriving the equivalent CM circuit model, it is found that the proposed converter eliminates the CM noise through parasitic capacitances and multiple dc links without the impedance balancing dependency. Finally, experimental prototype is developed to verify the effectiveness of the proposed topology.
Brain size affects responsiveness in mating behaviour to variation in predation pressure and sex ratio

Despite ongoing advances in sexual selection theory, the evolution of mating decisions remains enigmatic. Cognitive processes often require simultaneous processing of multiple sources of information from environmental and social cues. However, little experimental data exist on how cognitive ability affects such fitness‐associated aspects of behaviour. Using advanced tracking techniques, we studied mating behaviours of guppies artificially selected for divergence in relative brain size, with known differences in cognitive ability, when predation threat and sex ratio was varied. In females, we found a general increase in copulation behaviour in when the sex ratio was female biased, but only large‐brained females responded with greater willingness to copulate under a low predation threat. In males, we found that small‐brained individuals courted more intensively and displayed more aggressive behaviours than large‐brained individuals. However, there were no differences in female response to males with different brain size. These results provide further evidence of a role for female brain size in optimal decision‐making in a mating context. In addition, our results indicate that brain size may affect mating display skill in male guppies. We suggest that it is important to consider the association between brain size, cognitive ability and sexual behaviour when studying how morphological and behavioural traits evolve in wild populations.
Dynamics of electroencephalogram oscillations underlie right-eye preferences in predatory behavior of the music frog

ABSTRACT Visual lateralization is a typical characteristic of many vertebrates; however, its underlying dynamic neural mechanism is unclear. In this study, predatory responses and dynamic brain activities were evaluated in the Emei music frog (Nidirana daunchina) to assess the potential eye preferences and their underlying dynamic neural mechanism, using behavioral and electrophysiological experiments, respectively. To do this, when the prey stimulus (live cricket and leaf as control) was moved around the frogs in both clockwise and anticlockwise directions at constant velocity, the number of predatory responses were counted and electroencephalogram (EEG) absolute power spectra for each band were measured for the telencephalon, diencephalon and mesencephalon. The results showed that: (1) no significant differences in the number of predatory responses could be found for the control (leaf), but the number of predatory responses for the right visual field (RVF) was significantly greater than that for the left visual field (LVF) when the live cricket was moved into the RVF clockwise; (2) compared with no stimulus in the visual field and stimulus in the LVF, the power spectra of each EEG band were greater when the prey stimulus was moved into the RVF clockwise; and (3) the power spectra of the theta, alpha and beta bands in the left diencephalon were significantly greater than those of the right counterpart for the clockwise direction, but similar significant differences presented for the delta, theta and alpha bands in the anticlockwise direction. Together, the results suggested that right-eye preferences for predatory behaviors exist in music frogs, and that the dynamics of EEG oscillations might underlie this right eye/left hemisphere advantage. Summary: Predatory responses in the music frog (Nidirana daunchina) indicate that EEG oscillations at higher frequency may play important roles in right-eye preference.
Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses

ABSTRACT Objective There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm. Methods Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered. Results On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88, p < .001) and remained increased from 5 to 20 (B = −10.42, SE = 5.81, p = .071) and 50 minutes (B = −0.70, SE = 3.37, p = .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B = 15.22, SE = 8.14, p = .062). No placebo effect was found on evocation day 3 (B = 3.57, SE = 3.26, p = .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks. Conclusions Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications. Trial Registration: The study was registered as a clinical trial on www.trialregister. nl (number NTR5596).
Health economics of dementia

GENERAL ASPECTS. Classification and Diagnostics (L. Fratiglioni). Epidemiology (L. Fratiglioni). Symptomatology: Functional Capacity and Behaviour (H. Brodaty D. Lie). Care Options and Service Innovations in Dementia Care (L. Johansson). Different Ways of Organizing and Financing Health Care (S. Ha"! nsson). Cultural Concepts of Care for the Demented (B. Ineichen). Interaction with People Suffering Severe Dementia (A. Norberg). Distress and Burden for Family Caregivers (C. Whitlatch). HEALTH ECONOMICS APPROACHES TO DEMENTIA. Principles of Pharmacoeconomics (M. Drummond). Methodological Issues in Health Economic Studies of Dementia (G. Karlsson, et al.). Modeling Disease Progression with Markov Models (F. Sonnenberg E. Leventhal). Cost of Illness of Dementia (W. Max). Costs of Dementia in the Netherlands (M. Koopmanschap, et al.). Cost of Treatment and Care of Alzheimera s Disease in Germany (J.--M. Schulenburg, et al.). Costing Community Care of People with Dementia (M. Knapp R. Wigglesworth). Indirect Costs and Costing Informal Care (M. Koopmanschap W. Brouwer). The Resident Assessment Instrument (RAI) and Resource Use in Dementia Care (G. Ljunggren J. Morris). Costs of Diagnostic Procedures (S. Gauthier). How Will Japan Cope with the Impending Surge of Dementia? (Y. Arai N. Ikegami). Drug Costs in Dementia Care (J. Fastbom M. Giron). Costs of Dementia--Specific Care Approaches (A. Wimo, et al.). OUTCOME MEASUREMENTS. Test Scores in Clinical Trials vs Performance in Real Life: Can Clinical Global Assessments Bridge the Gap? (R. Doody). Severity Scales (B. Reisberg, et al.). Measuring QALYs in Dementia (P. Neumann, et al.). Assessing ADL/IADL in Persons with Dementia (L. Nyga ). Assessment of Cognitive Functioning (O. Almkvist). Measurements of Quality of Life in Dementia (P. Whitehouse). Assessment of Behavioral and Psychiatric Symptoms in Patients with Dementia Disorders (S. Eriksson A. Wimo). Instruments to Measure the Family Caregiver Burden (M. Grafstr? . Sandman). PHARMACOECONOMIC ASPECTS. Drug Authoritiesa Policy on the Assessment of Drugs for Dementia (S. Hill P. McGettigan). Designing Phase III Trials of Anti--dementia Drugs with a View Towards Pharmacoeconomic Considerations (L. Schneider). Evaluation of the Healthcare Resource Utilization and Caregiver Time in Anti--dementia Drug Trials (A. Wimo, et al.). Clinical and Economic Considerations of Anti--Dementia Drug Treatment: Efficacy, Effectiveness, Efficiency (H. Feldman B. Prigent). Ethical Considerations in Pharmacoeconomic Trials in Dementia (S. Post). Issues in Cross--Cultural Assessment of Economic Outcomes in Dementia (E. Witthaus). Nursing Home Placement and Mortality as Outcomes in Clinical Trials of Anti--Dementia Drugs: Methodological Issues (S. Gracon F. Smith). Outcomes Research and Alzheimera s Disease: A Pharmaceutical Industry Perspective (V. Mastey). FINAL REMARKS. A Proposed Health Economics Research Agenda for Dementia (B. Winblad, et al.). Index.
Effect of beta-blockers on survival of lung cancer patients: a systematic review and meta-analysis

Supplemental Digital Content is available in the text. The recent interest in beta-blockers as possible agents for drug repurposing in oncology arises from many pre-clinical and epidemiologic studies suggesting a possible clinically relevant antitumour effect. In lung cancer, given the contradictory results obtained, it is crucial to further study its effects. A systematic review of the literature was planned to evaluate a possible beneficial effect of beta-blocker on overall survival in lung cancer patients. Medline and Embase databases were searched from inception until 1 May 2018 to identify published studies that assessed the effect beta-blocker use on overall survival in lung cancer patients. Risk of bias was evaluated by Newcastle-Ottawa scale. Hazard ratios and 95% confidence intervals for overall survival were estimated using a random-effects model. Of 920 studies, seven (all retrospective and observational, six cohort and one case-control), including 7448 patients, met the inclusion criteria. Beta-blocker users with lung cancer had no increased overall survival compared to non-users (hazard ratio = 1.00; 95% confidence interval = 0.91–1.10; I2 = 45%). Similarly, beta-blocker users with non-small cell lung cancer had no increased overall survival compared to beta-blocker non-users (hazard ratio = 0.96; 95% confidence interval = 0.80–1.17; I2 = 56%). Our findings do not suggest an overall survival advantage in patients with lung cancer using beta-blocker therapy when compared to non-users. Further prospective cohort studies, designed to overcome the intrinsic limitations of retrospective observational studies are warranted to definitively clarify any possible beneficial effect of beta-blockers on lung cancer overall survival.