bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multicentric Comparison of Apparent Diffusion Coefficient Mapping and the Kaiser Score in the Assessment of Breast Lesions
Authors: Dietzel Matthias , Krug Barbara , Clauser Paola , Burke Christina , Hellmich Martin , Maintz David , Uder Michael , Bickel Hubert , Helbich Thomas , Baltzer Pascal A.T. 
Published: October 2020

Objective
We sought to compare the diagnostic performance of apparent diffusion coefficient (ADC) mapping with the Kaiser score (KS) to distinguish benign from malignant breast lesions and to assess the potential of this approach to help avoid unnecessary biopsies.

Materials and Methods
In this multicentric study, individual patient data from 3 different centers were analyzed. Consecutive patients receiving standardized multiparametric breast magnetic resonance imaging for standard nonscreening indications were included. At each center, 2 experienced radiologists with more than 5 years of experience retrospectively interpreted the examinations in consensus and applied the KS to every histologically verified lesion. The corresponding mean ADC of each lesion was measured using a Wielema type 4 region of interest. According to established methods, the KS and ADC were combined, yielding the KS+ score. Diagnostic accuracy was evaluated by the area under the receiver operating characteristics curve (AUROC) and compared between the KS, ADC, and KS+ (DeLong test). Likewise, the potential to help avoid unnecessary biopsies was compared between the KS, ADC, and KS+ based on established high sensitivity thresholds (McNemar test).

Results
A total of 450 lesions in 414 patients (mean age, 51.5 years; interquartile range, 42–60.8 years) were included, with 219 lesions being malignant (48.7%; 95% confidence interval [CI], 44%–53.4%). The performance of the KS (AUROC, 0.915; CI, 0.886–0.939) was significantly better than that of the ADC (AUROC, 0.848; CI, 0.811–0.880; P < 0.001). The largest difference between these parameters was observed when assessing subcentimeter lesions (AUROC, 0.909 for KS; CI, 0.849–0.950 vs 0.811 for ADC; CI, 0.737–0.871; P = 0.02).
The use of the KS+ (AUROC, 0.918; CI, 0.889–0.942) improved the performance slightly, but without any significant difference relative to a single KS or ADC reading (P = 0.64).
When applying high sensitivity thresholds for avoiding unnecessary biopsies, the KS and ADC achieved equal sensitivity (97.7% for both; cutoff values, >4 for KS and ≤1.4 × 10−3 mm2/s for ADC). However, the rate of potentially avoidable biopsies was higher when using the KS (specificity: 65.4% for KS vs 32.9% for ADC; P < 0.0001). The KS was superior to the KS+ in avoiding unnecessary biopsies.

Conclusions
Both the KS and ADC may be used to distinguish benign from malignant breast lesions. However, KS proved superior in this task including, most of all, when assessing small lesions less than 1 cm. Using the KS may avoid twice as many unnecessary biopsies, and the combination of both the KS and ADS does not improve diagnostic performance.
A Gratifying Step forward for the Application of Artificial Intelligence in the Field of Endoscopy: A Narrative Review
Authors: Xu Yixin , Tan Yulin , Wang Yibo , Gao Jie , Wu Dapeng , Xu Xuezhong 
Published: October 2020

Background:
Endoscopy is the optimal choice of diagnosis of gastrointestinal (GI) diseases. Following the advancements made in medical technology, different kinds of novel endoscopy-methods have emerged. Although the significant progress in the penetration of endoscopic tools that have markedly improved the diagnostic rate of GI diseases, there are still some limitations, including instability of human diagnostic performance caused by intensive labor burden and high missed diagnosis rate of subtle lesions. Recently, artificial intelligence (AI) has been applied gradually to assist endoscopists in addressing these issues.

Methods and Results:
In this study, we provide an overview of the application of the AI technology in the field of endoscopy, as well as its current limitations and prospects. The result suggested that AI had a significantly higher diagnostic accuracy compared with human endoscopists in the diagnosis of GI diseases. With the help of AI technology, the diagnostic performances of nonexpert endoscopists had been improved considerably.

Conclusion:
AI technology still has several limitations, and there are still plenty of opportunities for improvement.
Real world hypertension treatment patterns analysis identifies putative gaps and risk-associated patterns
Authors: Bandhakavi Sricharan , McCammon Jasmine M. , Karigowde Sunil , Liu Zhipeng , Ni Xianglian , Rahmanian Farbod 
Published: October 2020

ABSTRACTObjectiveAlthough treatment patterns’ analyses at scale can provide insights into associated health outcomes, they remain relatively uncharacterized for most chronic diseases, including hypertension (HTN). To address this gap, we analyzed HTN treatment patterns among US health-insured patients.Materials and MethodsNew (n = 200,786) or all (n = 4.1 million) HTN patients were identified from 2015, 2016 enrollments in a nationwide administrative claims’ database and compared for HTN-specific treatment (Rx) choices, Rx count, and distinct roundsof treatmentoptions (ROTO), respectively. Selected treatment patterns were risk-assessed using predictive modeling and/or literature-based recommendations.ResultsFor 2016, ACE inhibitors/ARBs were most frequent choices in new HTN patients’ vs more diverse Rx-choices among all HTN patients. All HTN patients had ∼3-fold and ∼5-fold-higher prevalence of (same-year) polytherapy and Rx interventions, respectively.New HTN patients with ≥2 rounds of treatment options (vs single/initial round) were associated with ∼5-fold or higher predicted HTN complications’ risk (p-value < 0.0001). All HTN patients with ≥3 rounds of treatment options (vs single/initial round) had 3.8-fold higher next-year HTN complications’ risk (p-value < 0.0001). Co-morbidities/persistence of ≥3 rounds of treatment options over 2 years further increased these odds and total medications/chronic disease score correlated with ROTO counts.Discussion∼95% of new HTN patients in 2016 did not start treatment with current literature-recommended first option, Thiazides. Assuming “sticky” prescription patterns, opportunity exists to improve (current) initial HTN treatments. Additionally, ROTO counts can inform HTN complications’ risk/management thereof.ConclusionWe highlight opportunities to improve initial HTN treatments and treatment patterns associated with higher risk among HTN patients.
Durable SARS-CoV-2 B cell immunity after mild or severe disease
Authors: Ogega Clinton O. , Skinner Nicole E. , Blair Paul W. , Park Han-Sol , Littlefield Kirsten , Ganesan Abhinaya , Ladiwala Pranay , Antar Annukka AR , Ray Stuart C. , Betenbaugh Michael J. , Pekosz Andrew , Klein Sabra L. , Manabe Yukari C. , Cox Andrea L. , Bailey Justin R. 
Published: October 2020

AbstractMultiple studies have shown loss of SARS-CoV-2 specific antibodies over time after infection, raising concern that humoral immunity against the virus is not durable. If immunity wanes quickly, millions of people may be at risk for reinfection after recovery from COVID-19. However, memory B cells (MBC) could provide durable humoral immunity even if serum neutralizing antibody titers decline. We performed multi-dimensional flow cytometric analysis of S protein receptor binding domain (S-RBD)-specific MBC in cohorts of ambulatory COVID-19 patients with mild disease, and hospitalized patients with moderate to severe disease, at a median of 54 (39-104) days after onset of symptoms. We detected S-RBD-specific class-switched MBC in 13 out of 14 participants, including 4 of the 5 participants with lowest plasma levels of anti-S-RBD IgG and neutralizing antibodies. Resting MBC (rMBC) made up the largest proportion of S-RBD-specific class-switched MBC in both cohorts. FCRL5, a marker of functional memory when expressed on rMBC, was dramatically upregulated on S-RBD-specific rMBC. These data indicate that most SARS-CoV-2-infected individuals develop S-RBD-specific, class-switched MBC that phenotypically resemble germinal center-derived B cells induced by effective vaccination against other pathogens, providing evidence for durable B cell-mediated immunity against SARS-CoV-2 after recovery from mild or severe COVID-19 disease.Graphical Abstract
Predicting the Disposition of the Antimalarial Drug Artesunate and its Active Metabolite Dihydroartemisinin Using Physiologically-Based Pharmacokinetic Modeling
Authors: Arey Ryan , Reisfeld Brad 
Published: October 2020

AbstractArtemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required, and one approach to predict these pharmacokinetic characteristics is physiologically-based pharmacokinetic (PBPK) modeling. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite, dihydroartemisinin (DHA). The model was developed for both rats and humans and incorporated drug metabolism of the parent compound and major metabolite. Model calibration was conducted using data from the literature in a Bayesian framework, and model verification was assessed using separate sets of data. Results showed good agreement between model predictions and the validation data, demonstrating the capability of the model in predicting the blood, plasma, and tissue pharmacokinetics of AS and DHA. It is expected that such a tool will be useful in characterizing the disposition of these chemicals and ultimately improve dosing regimens by enabling a quantitative assessment of the tissue-specific drug levels critical in the evaluation of efficacy and toxicity.
Addition of Daptomycin to Levofloxacin Increased the Efficacy of Levofloxacin Monotherapy against a Methicillin-SusceptibleStaphylococcus aureusStrain in Experimental Meningitis and Prevented Development of Resistance
Authors: Cottagnoud Philippe , Sprenker Frederike , Cottagnoud Marianne , Collaud Alexandra , Ashkbus Reza , Perreten Vincent 
Published: October 2020

AbstractDaptomycin and levofloxacin were tested as monotherapies and in combination against the antibiotic-susceptibleS. aureusstrain MSSA 1112 in a rabbit meningitis model and the effect of the combination on induction of resistance was determined in vitro. Changes of the susceptibility to fluoroquinolones and daptomycin was determined by the measurement of the MIC and mutations were detected by whole genome sequence comparison of the mutants with the parent strain MSSA 1112. Meningitis was induced by intracisternal inoculation of 105CFU of MSSA 1112 and treatment was started 10 h later by injection of daptomycin (15 mg/kg) and levofloxacin (10 mg/kg) standard doses. Cerebrospinal fluid (CSF) samples were repeatedly collected during therapy in order to determine killing rates and results of bactericidal activity were expressed in Δlog10CFU/ml over 8 h. The combination of daptomycin with levofloxacin was significantly (p< 0.001) superior to levofloxacin monotherapy and increased the antibacterial activity of daptomycin. In vitro, MSSA 1112 was cycled over six days with either increasing concentrations of levofloxacin or daptomycin or with a combination of levofloxacin with half of the MIC of daptomycin or daptomycin with half of the MIC of levofloxacin leading to mutations in target genes as identified by whole genome sequence analysis. Addition of low concentration of daptomycin (0.25 mg/L) reduced levofloxacin-induced resistance in vitro. Addition of levofloxacin in low concentration (0.125 mg/L) did not influence daptomycin-induced resistance.These findings highlight the lack of reciprocal interference of antibiotics in combination with regard to the development of resistance.
Projecting the impact of behaviour and isolation interventions and super spreader events from mass gatherings and international travel on Malaysia’s COVID-19 epidemic trajectories using an augmented SEIR model
Authors: Ayub Aidonna Jan , Wai Son Gregory Ho , Hanafiah Khayriyyah Mohd 
Published: October 2020

AbstractBackgroundVarious levels of lockdown implemented to contain the rapid spread of COVID-19 are not long-term solutions due to socioeconomic implications.MethodsTo inform safe reopening, we used an augmented SEIR model to project the impact of 1) interventions and potential new epidemic trajectories arising from super spreader (SS) events and/or international travel and 2) re-introducing strong behavioural interventions on resurgence trajectories.ResultsOur model suggests that 50% behaviour intervention effectiveness (BIE) (from enforced social distancing during lockdown, early in the epidemic), along with 50% isolation intervention effectiveness (IIE) (from increased testing and isolating infected individuals) was achieved during lockdown, which curbed COVID-19 transmission in Malaysia. Post-lockdown, BIE plays a minimal role if IIE reaches or exceeds 46.9% when other variables are held constant. At IIE of 30% and BIE of 21.3%, SS events of 5,000 active cases risks COVID-19 resurgence, with 4-year projected 12.9mn cumulative cases and 1.1mn deaths. Earlier action to increase BIE to 50% on day 98 compared to day 111, prevented an additional 21,401 recovered cases and 257 deaths.ConclusionUntil a safe and effective vaccine is widely available, the risk of COVID-19 resurgence from large SS events warrants caution in decisions to allow for mass gatherings and regular international travel.
Repulsive electrostatic interactions modulate dense and dilute phase properties of biomolecular condensates
Authors: Crabtree Michael D. , Holland Jack , Kompella Purnima , Babl Leon , Turner Noah , Baldwin Andrew J. , Nott Timothy J. 
Published: October 2020

AbstractLiquid-like membraneless organelles form via multiple, weak interactions between biomolecules. The resulting condensed states constitute novel solvent environments inside eukaryotic cells that partition biomolecules and may favour particular biochemical reactions. Here we demonstrate that, in addition to attractive interactions, repulsive electrostatic interactions modulate condensate properties. We find that net charge modulates the formation, morphology and solvent properties of model Ddx4 condensates in cells and in vitro and that a net negative charge is conserved across germ cell-specific Ddx4 orthologues. This conserved net charge provides a sensitivity to multivalent cations that is not observed in somatic paralogues. The disfavouring effect of a net negative charge in Ddx4 orthologues appears to be offset by increased charge patterning, indicating that fine tuning of both attractive and repulsive interactions can create responsive solvent environments inside biomolecular condensates.
Separable neural mechanisms support intentional forgetting and thought substitution
Authors: Hubbard Ryan J. , Sahakyan Lili 
Published: October 2020

AbstractPsychological and neuroscientific experiments have established that people can intentionally forget information via different strategies: direct suppression and thought substitution. However, few studies have directly compared the effectiveness of these strategies in forgetting specific items, and it remains an open question if the neural mechanisms supporting these strategies differ. Here, we developed a novel item-method directed forgetting paradigm with Remember, Forget, and Imagine cues, and recorded EEG to directly compare these strategies. Behaviorally, Forget and Imagine cues produced similar forgetting compared to Remember cues, but through separable neural processes; Forget cues elicited frontal oscillatory power changes that were predictive of future forgetting, whereas item-cue representational similarity was predictive of later accuracy for Imagine cues. These results suggest that both strategies can lead to intentional forgetting, but directed forgetting may rely on frontally-mediated suppression, while thought substitution may lead to contextual shifting, impairing successful retrieval.
Sexual selection theory meets disease vector control: Testing harmonic convergence as a “good genes” signal inAedes aegyptimosquitoes
Authors: League Garrett P. , Harrington Laura C. , Pitcher Sylvie A. , Geyer Julie K. , Baxter Lindsay L. , Montijo Julian , Rowland John G. , Johnson Lynn M. , Murdock Courtney C. , Cator Lauren J. 
Published: October 2020

AbstractThe mosquitoAedes aegyptiis a medically important, globally distributed vector of the viruses that cause dengue, yellow fever, chikungunya, and Zika. Although reproduction and mate choice are key components of vector population dynamics and control, our understanding of the mechanisms of sexual selection in mosquitoes remains poor. In “good genes” models of sexual selection, females use male cues as an indicator of both mate and offspring inherent genetic quality. Recent studies inAe. aegyptiprovide evidence that male wingbeat acoustics signal aspects of offspring quality and performance during mate selection in a process known as harmonic convergence. However, the extent to which harmonic convergence may signal overall inherent quality of mates and their offspring remains unknown. To examine this, we measured the potential acoustic signaling and heritability of a broad panel of parent and offspring fitness traits in two generations of field-derivedAe. aegyptioriginating from dengue endemic field sites in Thailand. Our data show that in this population of mosquitoes, harmonic convergence does not signal male fertility, female fecundity, and male flight performance traits, which despite displaying robust variability in both parents and their offspring were only weakly heritable. Together with previous work, our findings suggest that vector reproductive control programs should treat harmonic convergence as an indicator of some, but not all aspects of inherent quality, and that multiple forms of sexual selection are likely at play inAe. aegyptiin a trait, population, and environment dependent manner.
Oocyte Aging is Controlled by Mitogen Activated Protein Kinase Signaling
Authors: Achache Hanna , Falk Roni , Lerner Noam , Beatus Tsevi , Tzur Yonatan B. 
Published: October 2020

AbstractOogenesis is one of the first processes to fail during aging. In women, most oocytes cannot successfully complete meiotic divisions during the fourth decade of life. Studies of the nematodeCaenorhabditis eleganshave uncovered conserved genetic pathways that control lifespan, but our knowledge regarding reproductive aging in worms and humans is limited. Specifically, little is known about germline internal signals that dictate the oogonial biological clock. Here, we report a thorough characterization of the changes in the worm germline during aging. We found that shortly after ovulation halts, germline proliferation declines, while apoptosis continues, leading to a gradual reduction in germ-cell numbers. In late aging stages, we observed that meiotic progression is disturbed and crossover designation and DNA double-strand break repair decrease. In addition, we detected a decline in the quality of mature oocytes during aging, as reflected by decreasing size and elongation of interhomolog distance, a phenotype also observed in human oocytes. Many of these altered processes were previously attributed to MAPK signaling variations in young worms. In support of this, we observed changes in activation dynamics of MPK-1 during aging. We therefore tested the hypothesis that MAPK controls oocyte quality in aged worms using both genetic and pharmacological tools. We found that in mutants with high levels of activated MPK-1, oocyte quality deteriorates more rapidly than in wild-type worms, whereas reduction of MPK-1 levels enhances quality. Thus, our data indicate that MAPK signaling controls germline aging and could be used to attenuate the rate of oogenesis quality decline.
Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms
Authors: Aksoy-Aksel Ayla , Gall Andrea , Seewald Anna , Ferraguti Francesco , Ehrlich Ingrid 
Published: October 2020

AbstractDopaminergic signaling plays an important role in associative learning including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial cluster ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct mechanisms how mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1-receptors. Early extinction training augments both, GABA co-release onto dorso-medial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior.
Phytochemical characterization andin vitroantibacterial activity ofXeroderris stuhlmannii(Taub.) Mendonca & E.P. Sousa bark extracts
Authors: Selemani Major A. , Kazingizi Luckmore F. , Manzombe Emily , Bishi Lorraine Y. , Mureya Cleopas , Gwata Tichaziwa T. , Rwere Freeborn 
Published: October 2020

ABSTRACTThe use of herbal medicine is common in many rural communities in Zimbabwe because generic drugs are expensive and not readily available. In this work, we documented the important phytochemicals fromXeroderris stuhlmannii(Taub.) Mendonca & E.P. Sousa (Murumanyama in Shona), bark extracts and tested their antibacterial activity in order to demonstrate its potential as an antimicrobial agent. Qualitative screening of secondary metabolites confirmed the presence of alkaloids, flavonoids, terpenoids, steroids and polyphenols in the crude bark extracts. The MICs values for the crude extracts on six bacterial strains ranged from 0.23–0.80 mg/mL. Antimicrobial tests showed higher potency for crude bark extracts onE. Coli(MIC, 0.232 mg/mL) and lower potency oncoliform(MIC, 0.798 mg/mL). LC-MS/MS analysis of various fractions confirmed the presence of twenty-eight phytochemicals whereas, twelve phytochemicals were identified using GC-MS. Both techniques confirmed the presence of ursolic acid, roburic acid, reticuline, rotenone and p-coumaric acid glucoside in hexane and methanol extracts. In summary, our findings show thatXeroderris stuhlmannii(Taub.) Mendonca & E.P. Sousa contain many phytochemical compounds that have antimicrobial activity. Moreover, some of the compounds in the bark extract have been shown to possess antioxidant, antiviral, antitumor and anti-inflammatory properties. Thus,Xeroderris stuhlmannii(Taub.) Mendonca & E.P. Sousa barks can act as a useful herbal supplement for treatment of a number of diseases in rural communities where modern drugs are expensive and not readily available.