bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a modified pre‐lysis sample preparation technique for flow cytometric minimal residual disease assessment in multiple myeloma, chronic lymphocytic leukemia, and B‐non Hodgkin lymphoma
Authors: Bayly Emma , Nguyen Vuong , Binek Adrian , Piggin Anna , Baldwin Kylie , Westerman David , Came Neil 
Published: June 2020

AbstractBackgroundMinimal residual disease (MRD) assessment of hematopoietic neoplasia below 10−4 requires more leukocytes than is usually attainable by post‐lysis preparation. However, not all laboratories are resourced for consensus Euroflow pre‐lysis methodology. Our study aim was to validate a modified pre‐lysis protocol against our standard post‐lysis method for MRD detection of multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and B‐non Hodgkin lymphoma (B‐NHL), to meet demand for deeper MRD assessment by flow cytometry.MethodClinical samples for MRD assessment of MM, CLL, and B‐NHL (50, 30, and 30 cases, respectively) were prepared in parallel by pre and post‐lysis methods for the initial validation. Total leukocytes, MRD, and median fluorescence intensity of antigen expression were compared as measures of sensitivity and antigen stability. Lymphocyte and granulocyte composition were compared, assessing relative sample processing stability. Sensitivity of the pre‐lysis assay was monitored post validation for a further 18 months.ResultsPre‐lysis achieved at least 10−4 sensitivity in 85% MM, 81% CLL, and 90% B‐NHL samples versus 24%, 48%, and 26% by post‐lysis, respectively, with stable antigen expression and leukocyte composition. Post validation over 18 months with technical expertise improving, pre‐lysis permitted 10−5 MRD assessment in 69%, 86%, and 82% of the respective patient groups.ConclusionThis modified pre‐lysis procedure provides a sensitive, robust, time efficient, and relatively cost‐effective alternative for MRD testing by MFC at 10−5, facilitating clinically meaningful deeper response assessment for MM, CLL, and B‐NHL. This method adaptation may facilitate more widespread adoption of highly sensitive flow cytometry‐based MRD assessment.
DNA methylation patterns of RAR‐β2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions
Authors: Kougioumtsidou Niki , Vavoulidis Eleftherios , Nasioutziki Maria , Symeonidou Marianthi , Pratilas Georgios Chrysostomos , Mareti Evangelia , Petousis Stamatios , Chatzikyriakidou Anthoula , Grimbizis Gregorios , Theodoridis Theodoros , Miliaras Dimosthenis , Dinas Konstantinos , Zepiridis Leonidas 
Published: June 2020

AbstractBackgroundPromoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR‐β2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population.MethodsFNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation‐specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels.ResultsFrom 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR‐β2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR‐β2, respectively. Methylated RASSF1A and RAR‐β2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR‐β2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy.ConclusionTo optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.
Predators can influence the host‐parasite dynamics of their prey via nonconsumptive effects
Authors: Zukowski Nicolette , Kirk Devin , Wadhawan Kiran , Shea Dylan , Start Denon , Krkošek Martin 
Published: June 2020

AbstractEcological communities are partly structured by indirect interactions, where one species can indirectly affect another by altering its interactions with a third species. In the absence of direct predation, nonconsumptive effects of predators on prey have important implications for subsequent community interactions. To better understand these interactions, we used a Daphnia‐parasite‐predator cue system to evaluate if predation risk affects Daphnia responses to a parasite. We investigated the effects of predator cues on two aspects of host–parasite interactions (susceptibility to infection and infection intensity), and whether or not these effects differed between sexes. Our results show that changes in response to predator cues caused an increase in the prevalence and intensity of parasite infections in female predator‐exposed Daphnia. Importantly, the magnitude of infection risk depended on how long Daphnia were exposed to the cues. Additionally, heavily infected Daphnia that were constantly exposed to cues produced relatively more offspring. While males were ~5× less likely to become infected compared to females, we were unable to detect effects of predator cues on male Daphnia–parasite interactions. In sum, predators, prey, and their parasites can form complex subnetworks in food webs, necessitating a nuanced understanding of how nonconsumptive effects may mediate these interactions.
Distinct responses of antagonistic and mutualistic networks to agricultural intensification
Authors: Morrison Beth M. L. , Dirzo Rodolfo 
Published: June 2020

AbstractSpecies interaction networks, which govern the maintenance of biodiversity and ecosystem processes within ecological communities, are being rapidly altered by anthropogenic activities worldwide. Studies on the response of species interaction networks to anthropogenic disturbance have almost exclusively focused on one interaction type at a time, such as mutualistic or antagonistic interactions, making it challenging to decipher how networks of different interaction types respond to the same anthropogenic disturbance. Moreover, few studies have simultaneously focused on the two main components of network structure: network topology (i.e., architecture) and network ecology (i.e., species identities and interaction turnover), thereby limiting our understanding of the ecological drivers underlying changes in network topology in response to anthropogenic disturbance. Here, we used 16,400 plant–pollinator and plant–herbivore interaction observations from 16 sites along an agricultural intensification gradient to compare changes in network topology and ecology between mutualistic and antagonistic networks. We measured two aspects of network topology—nestedness and modularity—and found that although the mutualistic networks were consistently more nested than antagonistic networks and antagonistic networks were consistently more modular, the rate of change in nestedness and modularity along the gradient was comparable between the two network types. Change in network ecology, however, was distinct between mutualistic and antagonistic networks, with partner switching making a significantly larger contribution to interaction turnover in the mutualistic networks than in the antagonistic networks, and species turnover being a strong contributor to interaction turnover in the antagonistic networks. The ecological and topological changes we observed in the antagonistic and mutualistic networks have different implications for pollinator and herbivore communities in agricultural landscapes, and support the idea that pollinators are more labile in their interaction partner choice, whereas herbivores form more reciprocally specialized, and therefore more vulnerable, interactions. Our results also demonstrate that studying both topological and ecological network structure can help to elucidate the effects of anthropogenic disturbance on ecological communities, with applications for conservation and restoration of species interactions and the ecosystem processes they maintain.
Lixisenatide in type 1 diabetes: A randomised control trial of the effect of lixisenatide on post‐meal glucose excursions and glucagon in type 1 diabetes patients
Authors: Ballav Chitrabhanu , Dhere Archana , Kennedy Irene , Agbaje Olorunsola F. , White Sarah , Franklin Rachel , Hartmann Bolette , Holst Jens J. , Holman Rury R. , Owen Katharine R. 
Published: June 2020

AbstractAimsThe GLP1 agonist lixisenatide is glucagonostatic and reduces post‐prandial blood glucose (PPBG) in type 2 diabetes. This study investigates its impact in type 1 diabetes (T1D).MethodsIn a blinded, crossover trial, 25 patients with T1D were randomised to 4 weeks adjunctive treatment with lixisenatide (L) or placebo (P), with a 4‐week washout period. The primary outcome was percentage of 3 hours PPBG in target (4‐10 mmol/L) assessed by CGM before and after treatment. Participants also underwent post‐treatment standardised mixed meal test (MMT, n = 25) and hyperinsulinaemic hypoglycaemic clamp (n = 15).ResultsPPBG CGM readings in target were similar between L vs P (Mean % ± SE, breakfast 45.4 ± 6.0 vs 44.3 ± 6.0, P = .48, lunch 45.5 ± 5.8 vs 50.6 ± 5.3, P = .27 and dinner 43.0 ± 6.7 vs 47.7 ± 5.6, P = .30). HbA1C was similar between L vs P (64.7 ± 1.6 vs 64.1 ± 1.6 mmol/mol, P = .30). Prandial insulin fell after lixisenatide (dose change −0.7 ± 0.6 vs +2.4 ± 0.7 units/d, P = .004), but basal insulin dose was similar between groups. The post‐MMT glucose area under the curve (AUC) was lower with L than P (392.0 ± 167.7 vs 628.1 ± 132.5 mmol/L × min, P < .001), as was the corresponding glucagon AUC (140.0 ± 110.0 vs 304.2 ± 148.2 nmol/L × min, P < .001). Glucagon and counter‐regulatory hormone values at a blood glucose of 2.4 mmol/L during the hypoglycaemic clamp were similar between L and P.ConclusionIn T1D, PPBG values were not altered by adjunctive lixisenatide although prandial insulin dose fell. Glucose and glucagon level during an MMT were significantly lower after lixisenatide, without affecting counter‐regulatory response during hypoglycaemia.
Propagermanium administration for patients with type 2 diabetes and nephropathy: A randomized pilot trial
Authors: Hara Akinori , Shimizu Miho , Hamaguchi Erika , Kakuda Hirokazu , Ikeda Kenzo , Okumura Toshiya , Kitagawa Kiyoki , Koshino Yoshitaka , Kobayashi Motoo , Takasawa Kazuya , Hisada Yukimasa , Toyama Tadashi , Iwata Yasunori , Sakai Norihiko , Wada Takashi 
Published: June 2020

SummaryAimsWe assessed the potential efficacy and safety of propagermanium (PG), an organic compound that inhibits the C–C chemokine receptor type 2, administration in patients with type 2 diabetes and nephropathy. Furthermore, we assessed the feasibility of future studies.Materials and methodsWe recruited patients from nine medical institutions in Japan for this randomized, open‐label, parallel two‐arm pilot trial. Inclusion criteria were diagnosis of type 2 diabetes, age 30‐75 years, dipstick proteinuria of ≥1+ or urinary albumin‐to‐creatinine ratio (UACR) of ≥30 mg/g and estimated glomerular filtration rate of ≥30 mL/min/1.73 m2. Patients were randomly assigned (1:2) using a minimization algorithm to either continuing usual care or concomitant administration of 30 mg PG per day for 12 months. The primary outcome was the change in UACR from baseline to 12 months. We also collected safety information for all patients who received at least one dose of PG.ResultsWe enrolled 29 patients, 10 were assigned to continue usual care and 19 to receive PG. Changes in UACR by PG in addition to the usual care were 25.0% (95% CI −20.4%, 96.5%, P = .33). No severe adverse events or renal events were observed during the study.ConclusionAlthough the treatment with PG was generally well tolerated, the dosage of 30 mg/d for 12 months did not reduce albuminuria when used in addition to usual care in patients with type 2 diabetes and nephropathy. Efficacy of PG should be verified in future definitive trials.
18F‐FDG PET/CT brain glucose metabolism as a marker of different types of depression comorbidity in chronic heart failure patients with impaired systolic function
Authors: Lyra Vassiliki , Parissis John , Kallergi Maria , Rizos Emmanouil , Filippatos Gerasimos , Kremastinos Dimitrios , Chatziioannou Sofia 
Published: June 2020

AbstractAimsDepression is an important issue in heart failure (HF). The study investigated whole‐brain and regional brain glucose metabolism in HF patients and its association with depression comorbidity.Methods and resultsTwenty‐nine hospitalized patients with symptomatic systolic HF (left ventricular ejection fraction <40%), New York Heart Association (NYHA) class II–IV and mean age of 55.5 ± 12.0 years, had psychometric questionnaires before discharge and an 18F‐FDG PET/CT brain scan after discharge. Semi‐automated image analysis was performed on all cases and 30 matched controls. The metabolic parameter mean standardized uptake value (SUVmean) was calculated for the whole brain and three brain regions implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing regional brain SUVmean with whole‐brain SUVmean. Cases had lower average whole‐brain SUVmean (3.90 ± 1.49 vs. 5.10 ± 1.35, P = 0.001) and average regional brain SUVmean (4.57 ± 2.31 vs. 9.96 ± 3.58, P < 0.001) compared to controls. Whole‐brain SUVmean had a significant correlation with patient age, NYHA class, diabetes, creatinine levels, depression, and cognitive impairment. Regional brain SUVmean was correlated with whole‐brain SUVmean and depression. The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with ‘epiphenomenal’ (>0.93) or ‘real’ (≤0.93) depression.ConclusionHeart failure patients with more severe disease showed whole‐brain and regional brain hypometabolism in 18F‐FDG PET/CT. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between ‘epiphenomenal’ and ‘real’ depression. Namely, presence of whole‐brain hypometabolism suggested ‘epiphenomenal’ depression, whereas absence suggested ‘real’ depression. Presence of significant relative regional brain hypometabolism enhanced the likelihood of ‘real’ depression diagnosis.
Homocyclic o‐dicarboxaldehydes: Derivatization reagents for sensitive analysis of amino acids and related compounds by capillary and microchip electrophoresis
Authors: Celá Andrea , Glatz Zdeněk 
Published: June 2020

AbstractAmino acids are essential compounds for living organisms, and their determination in biological fluids is crucial for the clinical analysis and diagnosis of many diseases. However, the detection of most amino acids is hindered by the lack of a strong chromophore/fluorophore or electrochemically active group in their chemical structures. The highly sensitive determination of amino acids often requires derivatization. Capillary electrophoresis is a separation technique with excellent characteristics for the analysis of amino acids in biological fluids. Moreover, it offers the possibility of precapillary, on‐capillary, or postcapillary derivatization. Each derivatization approach has specific demands in terms of the chemistry involved in the derivatization, which is discussed in this review. The family of homocyclic o‐dicarboxaldehyde compounds, namely o‐phthalaldehyde, naphthalene‐2,3‐dicarboxaldehyde, and anthracene‐2,3‐dicarboxaldehyde, are powerful derivatization reagents for the determination of amino acids and related compounds. In the presence of suitable nucleophiles they react with the primary amino group to form both fluorescent and electroactive derivatives. Moreover, the reaction rate enables all of the derivatization approaches mentioned above. This review focuses on articles that deal with using these reagents for the derivatization of amino acids and related compounds for ultraviolet‐visible spectrometry, fluorescence, or electrochemical detection. Applications in capillary and microchip electrophoresis are summarized and discussed.
Bladder cancer hunting: A microfluidic paper‐based analytical device
Authors: Jiang Qingyun , Han Tingting , Ren Haijun , Aziz Aziz Ur Rehman , Li Na , Zhang Hangyu , Zhang Zhengyao , Liu Bo 
Published: June 2020

AbstractBladder cancer is the fourth most common cancer in men, and it is becoming a prevalent malignancy. Most of the regular clinical examinations are prompt evaluations with cystoscopy, renal function testing, which require high‐precision instrument, well‐trained operators, and high cost. In this study, a microfluidic paper‐based analytical device (μPAD) was fabricated to detect nuclear matrix protein 22 (NMP22) and bladder cancer antigen (BTA) from the urine samples. Urine samples were collected from 11 bladder cancer patients and 10 well‐beings as experiment and control groups, respectively, to verify the working efficiency of μPAD. A remarkable checkout efficiency of up to 90.91% was found from the results. Meanwhile, this method is feasible for home‐based self‐detection from urine samples within 10 min for the total process, which provides a new way for quick, economical, and convenient tumor diagnosis, prognosis evaluation, and drug response.
Analysis and design of low‐power and high‐gain complementary metal oxide semi‐conductor low noise amplifier operating at 28 GHz frequency for millimeter wave LEOS, local multiport distribution system and radar application
Authors: Suganthi K , Malarvizhi S 
Published: June 2020

AbstractLow‐noise amplifier supports broadband standards with the advantage of low‐power, high‐gain, and low noise figure (NF). The low‐frequency design of this low‐noise amplifier (LNA) is used for multistandard wireless applications and the high‐frequency design of this LNA can be used in millimeter wave radar applications. This LNA is designed at the front‐end for amplification in the receiver side, so that signal to noise is adjusted on the multistandard receivers. LNA permits performance of the design with various parameters like NF, power efficiency, gain of the LNA, figure of merits, and linearity of the low‐noise amplifier. In 28 GHz, millimeter wave (mmW) circuits' design and analysis with high gain, low power, low NF, and wide bandwidth are preferred for radio frequency front end. This paper discusses, the Cascode design of CMOS LNA circuit at 28 GHz, and the novelty of the design is that it can operate at two different set of frequency bands (21 and 28 GHz) and it is multiband and multitunable. The design's conversion gain (S21) of 17.4 dB, NF of 4 dB, stability of 1, power optimized to 22.3 mW, and area of 0.399mm2 are reported. The input and output reflection coefficients are S11 ≤ −10 dB and S22 ≤ −10 dB. Electromagnetic simulation is performed using advanced design system tool. Output power of the proposed design is 2 dBm, transition frequency (fT) is 64GHz, and maximum operating frequency (fmax) is 96GHz. The observed results show that the proposed CMOS LNA design finds its suitability in mmW cloud radar application of mono‐pulse radar system and radar front‐end receiver circuits.
Clinical Decision‐Making for Dental Caries Management
Authors: White B. Alex , Maupomé Gerardo 
Published: June 2020

Scientific information on diagnosis, prevention, and management of dental caries and associated indicators of risk continues to increase rapidly. Patients vary in clinically important ways, however, and uncertainty affects our understanding of risk; diagnostic and prognostic information; efficacy and effectiveness of many preventive, diagnostic, and treatment alternatives; and outcomes associated with clinical strategies. Consequently, challenges abound for clinicians to identify, evaluate, and incorporate new information, patient preferences, and uncertainties into clinical practice.Clinical decision‐making—an analytical approach that makes explicit use of information to quantify probabilities and outcomes to analyze decisions under conditions of uncertainty—can provide a framework to analyze the impact of uncertainty of clinical information. Diagnostic, effectiveness, and outcome information is quantified and combined in an explicit way to serve as a tool for clinicians, not as a replacement for clinical judgment or experience. Such an approach has the potential to improve clinical practice and help dentists do their jobs better by structuring the decision problem and assessing probabilities and utilities. Clinical decision‐making also helps dentists communicate with each other by identifying clinical controversies, thereby characterizing how and why disagreements may arise and what additional data may be needed to address a clinical question.
Confronting Shibboleths of Dental Education
Authors: Masella Richard S. 
Published: June 2020

AbstractShibboleths are common expressions presented as indisputable truths. When used in educational discussions, they reflect “motherhood and apple pie” viewpoints and tend to bring debate to a halt. Use of shibboleths may precede a desired imposition of “locksteps” in educational programming and are easily perceived as paternalistic by recipients. Nine shibboleths are presented as common beliefs of dental faculty and administrators. Evidence contradicting the veracity of the “obvious truths” is offered. The traditional “splendid isolation” of dentistry contributes to parochialism and belief in false shibboleths. Sound principles of higher and health professions education, student learning, and dental practice apply to dental education as to all health disciplines. Student passivity in dental education is not the best preparation for proficiency in dental practice. The master teacher possesses a repertoire of methodologies specific to meeting defined educational objectives. Active learning experiences bear close resemblances to professional duties and responsibilities and internally motivate future doctors of dental medicine. The difficulty in achieving curricular change leads to curricular entrenchment. Dentistry and dental education should not trade their ethical high ground for the relatively low ethical standards of the business world. Principles of professional ethics should govern relationships between dentists, whether within the dental school workplace or in practice. Suggestions are made on how to confront shibboleths in dental school settings.