bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ dynamics
Authors: Saadati Maryam , Jamali Yousef 
Published: May 2021

AbstractType 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of $$\beta $$
β
-cell mass and alteration of $$\beta $$
β
-cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in $$\beta $$
β
-cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of $$\beta $$
β
-cell mass to $$\beta $$
β
-cell function in T2D, we make use of a comprehensive electrophysiological model of human $$\beta $$
β
-cell clusters. We find that defect in $$\beta $$
β
-cell mass causes a functional decline in single $$\beta $$
β
-cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular $${\text {Ca}}^{2+}$$

Ca

2
+

concentration, which can lead to changes in insulin secretion dynamics and in insulin levels. The model demonstrates a good correspondence between suppression of synchronizing electrical activity and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both $$\beta $$
β
-cell synchronization and metabolic coupling in the behavior of $${\text {Ca}}^{2+}$$

Ca

2
+

concentration dynamics within human islets. Our results indicate that inter-$$\beta $$
β
-cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the whole-cell conductance of delayed rectifier $$\text {K}^{+}$$

K
+

channels modifies oscillatory activity patterns of $$\beta $$
β
-cell population lacking intercellular coupling, which significantly affect $${\text {Ca}}^{2+}$$

Ca

2
+

concentration and insulin secretion.
Gender differences in health-related quality of life measured by the Sarcoidosis Health Questionnaire
Authors: Gwadera Łukasz , Białas Adam J. , Górski Witold , Iwański Mikołaj A. , Miłkowska-Dymanowska Joanna , Górski Paweł , Piotrowski Wojciech J. 
Published: May 2021

AbstractSarcoidosis is granulomatous disease, which complex etiology is yet to be fully discovered. In the majority of cases its course is self-limiting. However it can have different clinical manifestations and can be debilitating condition with great impact on health-related quality of life (HRQL). The aim of our study was to assess if there are any differences in HRQL dependent to gender. We examined a group of 33 males and 42 females (with no differences in mean age, disease activity, TLCO, FEV1, FVC, FEV1/FVC) with a use of Sarcoidosis Health Questionnaire. We revealed lower total and daily functioning score in female group. Further analyses stratified by sex and activity of the disease presented many significant differences between the groups, revealing important issues for the discussion about gender specific differences in the HRQL of patients with sarcoidosis. In spite of clinical presentation may be similar, expectations and main concerns of sarcoidosis patient can vary between females and males. Therefore, it appears that in terms of education and symptomatic treatment accents should be put differently depending on the gender of the patient. Our results may also point to a need for more gender-oriented patient-physician communication which could enable better understanding, potentially improve adherence to therapy and decrease the risk of possible complications.
Simultaneous quantitative profiling of clinically relevant immune markers in neonatal stool swabs to reveal inflammation
Authors: Vidova Veronika , Benesova Eliska , Klanova Jana , Thon Vojtech , Spacil Zdenek 
Published: May 2021

AbstractAn aberrant immune response developed early in life may trigger inflammatory bowel disease (IBD) and food allergies (e.g., celiac disease). Fecal levels of immune markers categorize an inflammatory response (e.g., food allergy, autoimmune) paralleled with the initial microbial colonization. The immunoaffinity assays are routinely applied to quantify circulating immune protein markers in blood/serum. However, a reliable, multiplex assay to quantify fecal levels of immune proteins is unavailable. We developed mass spectrometry assays to simultaneously quantify fecal calprotectin, myeloperoxidase, eosinophil-derived neurotoxin, eosinophil cationic protein, alpha-1-antitrypsin 1, and adaptive immunity effectors in 134 neonatal stool swabs. We optimized extraction and proteolytic protocol and validated the multiplex assay in terms of linearity of response (> 100; typically 0.04 to 14.77 µg/mg of total protein), coefficient of determination (R2; > 0.99), the limit of detection (LOD; 0.003 to 0.04 µg/mg of total protein), the limit of quantification (LOQ; 0.009 to 0.122 µg/mg of total protein) and robustness. The median CV of intra- and interday precision was 9.8% and 14.1%, respectively. We quantified breast milk-derived IGHA2 to differentiate meconium from feces samples and to detect the first food intake. An early life profiling of immune markers reflects disrupted intestinal homeostasis, and it is perhaps suitable for pre-symptomatic interception of IBD and food allergies.
Cement bridging phenomenon in percutaneous vertebroplasty for adjacent vertebral compression fracture
Authors: Li Yun-Da , Tsai Tsung-Ting , Niu Chi-Chien , Lai Po-Liang 
Published: May 2021

AbstractIn some cases of vertebroplasty for adjacent fractures, we observed a cement bridging phenomenon, in which the injected cement flowed from the newly fractured vertebra to the previously cement-augmented vertebra through the space between the abutting anterior longitudinal ligament and the vertebral column. The purpose of this retrospective study was to investigate this phenomenon. From January 2012 to December 2014, patients who sustained new-onset adjacent vertebral compression fracture and who were again treated with vertebroplasty were enrolled. We divided the patients into two groups, the bridging group and the nonbridging group, to analyze the difference between them. Results showed that the cement bridging phenomenon occurred in 18 (22.8%) of the 79 patients. Significant differences between the bridging and nonbridging groups were identified in the following 3 imaging features: severe loss of the anterior vertebral body height at the new-onset adjacent vertebra on plain film (odds ratio [OR] = 4.46, p = 0.014), fluid accumulation (OR = 36.27, p < 0.001) and hypointense signaling (OR = 15.67, p < 0.001) around the space anterior to the abutting vertebral bodies and the corresponding intervertebral disc on MRI. After a 2-year follow-up, both the mean value of the focal kyphotic angle and anterior body height ratio were significantly better in the cement bridging group than in the nonbridging group. The cement bridging phenomenon, which has never been reported in the literature, is not rare in clinical practice. This phenomenon was associated with better maintenance of focal kyphotic angle and anterior body height ratio during the 2-year follow-up.
Effects of positive end-expiratory pressure on the predictability of fluid responsiveness in acute respiratory distress syndrome patients
Authors: Chen Yen-Huey , Lai Ying-Ju , Huang Ching-Ying , Lin Hui-Ling , Huang Chung-Chi 
Published: May 2021

AbstractThe prediction accuracy of pulse pressure variation (PPV) for fluid responsiveness was suggested to be unreliable in low tidal volume (VT) ventilation. However, high PEEP can cause ARDS patients relatively hypovolemic and more fluid responsive. We hypothesized that high PEEP 15 cmH2O can offset the disadvantage of low VT and improve the predictive performance of PPV. We prospectively enrolled 27 hypovolemic ARDS patients ventilated with low VT 6 ml/kg and three levels of PEEP (5, 10, 15 cmH2O) randomly. Each stage lasted for at least 5 min to allow for equilibration of hemodynamics and pulmonary mechanics. Then, fluid expansion was given with 500 ml hydroxyethyl starch (Voluven 130/70). The hemodynamics and PPV were automatically measured with a PiCCO2 monitor. The PPV values were significantly higher during PEEP15 than those during PEEP5 and PEEP10. PPV during PEEP15 precisely predicts fluid responsiveness with a cutoff value 8.8% and AUC (area under the ROC curve) of ROC (receiver operating characteristic curve) 0.847, higher than the AUC during PEEP5 (0.81) and PEEP10 (0.668). Normalizing PPV with driving pressure (PPV/Driving-P) increased the AUC of PPV to 0.875 during PEEP15. In conclusions, high PEEP 15 cmH2O can counteract the drawback of low VT and preserve the predicting accuracy of PPV in ARDS patients.
Thymic transcriptome analysis after Newcastle disease virus inoculation in chickens and the influence of host small RNAs on NDV replication
Authors: Guo Liangxing , Mu Zhaokun , Nie Furong , Chang Xuanniu , Duan Haitao , Li Haoyan , Zhang Jingfeng , Zhou Jia , Ji Yudan , Li Mengyun 
Published: May 2021

AbstractNewcastle disease (ND), caused by virulent Newcastle disease virus (NDV), is a contagious viral disease affecting various birds and poultry worldwide. In this project, differentially expressed (DE) circRNAs, miRNAs and mRNAs were identified by high-throughput RNA sequencing (RNA-Seq) in chicken thymus at 24, 48, 72 or 96 h post LaSota NDV vaccine injection versus pre-inoculation group. The vital terms or pathways enriched by vaccine-influenced genes were tested through KEGG and GO analysis. DE genes implicated in innate immunity were preliminarily screened out through GO, InnateDB and Reactome Pathway databases. The interaction networks of DE innate immune genes were established by STRING website. Considering the high expression of gga-miR-6631-5p across all the four time points, DE circRNAs or mRNAs with the possibility to bind to gga-miR-6631-5p were screened out. Among DE genes that had the probability to interact with gga-miR-6631-5p, 7 genes were found to be related to innate immunity. Furthermore, gga-miR-6631-5p promoted LaSota NDV replication by targeting insulin induced gene 1 (INSIG1) in DF-1 chicken fibroblast cells. Taken together, our data provided the comprehensive information about molecular responses to NDV LaSota vaccine in Chinese Partridge Shank Chickens and elucidated the vital roles of gga-miR-6631-5p/INSIG1 axis in LaSota NDV replication.
Sunshine, temperature and suicidal behaviour in patients treated with antidepressants: an explorative nested case–control study
Authors: Makris Georgios D. , White Richard A. , Reutfors Johan , Ekselius Lisa , Andersen Morten , Papadopoulos Fotios C. 
Published: May 2021

AbstractOur aim was to explore if different exposure windows for sunshine or temperature are associated with increased suicidal behaviour among people starting antidepressant treatment. 307 completed and 1674 attempted suicides were included as cases in the conditional logistic regression analyses, while controlling for potential confounders, including season, as well as temperature and hours of sunshine when these variables were not the main exposure variable. Ten controls were matched to each case using risk-set sampling. The role of season, age, and sex was examined with likelihood ratio tests (LRTs) with and without the respective interaction terms and with stratified analyses. There was no overall association between temperature or sunshine with suicidal behaviour. Age was a significant effect modifier for suicide and suicide attempt for both sunshine and temperature exposure. In stratified analyses, an increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated, in the unadjusted model, with a 3% increase in the rate of suicide (p = 0.023) amongst older patients (65+). In the same age group, an increase of 1 h in the average daily sunshine during the last 4 weeks was associated with an 8% increase in the rate of suicide attempt (p = 0.002), while the respective increase for the exposure period of 5–8 weeks was 7% (p = 0.007). An increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated with a 3% increase in the rate of suicide attempt (p = 0.007). These associations did not retain statistical significance in the adjusted models. No associations were found in the other age groups. Our results point to a possible effect modification by age, with higher risk of suicidal behavior associated with an increase in sunshine and temperature found in the older age groups.
Urinary miRNA profiles discriminate between obstruction-induced bladder dysfunction and healthy controls
Authors: von Siebenthal Michelle , Besic Mustafa , Gheinani Ali Hashemi , Akshay Akshay , Lizun-Platoni Salomé , Kunz Nadine , Burkhard Fiona C. , Monastyrskaya Katia 
Published: May 2021

AbstractUrgency, frequency and incomplete emptying are the troublesome symptoms often shared between benign prostatic obstruction-induced (BLUTD) and neurogenic (NLUTD) lower urinary tract dysfunction. Previously, using bladder biopsies, we suggested a panel of miRNA biomarkers for different functional phenotypes of the bladder. Urine is a good source of circulating miRNAs, but sex- and age-matched controls are important for urinary metabolite comparison. In two groups of healthy subjects (average age 32 and 57 years old, respectively) the total protein and RNA content was very similar between age groups, but the number of secreted extracellular vesicles (uEVs) and expression of several miRNAs were higher in the young healthy male volunteers. Timing of urine collection was not important for these parameters. We also evaluated the suitability of urinary miRNAs for non-invasive diagnosis of bladder outlet obstruction (BOO). A three urinary miRNA signature (miR-10a-5p, miR-301b-3p and miR-363-3p) could discriminate between controls and patients with LUTD (BLUTD and NLUTD). This panel of representative miRNAs can be further explored to develop a non-invasive diagnostic test for BOO. The age-related discrepancy in the urinary miRNA content observed in this study points to the importance of selecting appropriate, age-matched controls.
IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
Authors: Razawy Wida , Alves Celso H. , Koedam Marijke , Asmawidjaja Patrick S. , Mus Adriana M. C. , Oukka Mohamed , Leenen Pieter J. M. , Visser Jenny A. , van der Eerden Bram C. J. , Lubberts Erik 
Published: May 2021

AbstractThe IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R−/− mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R−/− mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R−/− mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R−/− mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R−/− mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.
Computational design of biopolymer aerogels and predictive modelling of their nanostructure and mechanical behaviour
Authors: Chandrasekaran Rajesh , Hillgärtner Markus , Ganesan Kathirvel , Milow Barbara , Itskov Mikhail , Rege Ameya 
Published: May 2021

AbstractTo address the challenge of reconstructing or designing the three-dimensional microstructure of nanoporous materials, we develop a computational approach by combining the random closed packing of polydisperse spheres together with the Laguerre–Voronoi tessellation. Open-porous cellular network structures that adhere to the real pore-size distributions of the nanoporous materials are generated. As an example, κ-carrageenan aerogels are considered. The mechanical structure–property relationships are further explored by means of finite elements. Here we show that one can predict the macroscopic stress–strain curve of the bulk porous material if only the pore-size distributions, solid fractions, and Young’s modulus of the pore-wall fibres are known a priori. The objective of such reconstruction and predictive modelling is to reverse engineer the parameters of their synthesis process for tailored applications. Structural and mechanical property predictions of the proposed modelling approach are shown to be in good agreement with the available experimental data. The presented approach is free of parameter-fitting and is capable of generating dispersed Voronoi structures.
Elevated levels of urine isocitrate, hydroxymethylglutarate, and formiminoglutamate are associated with arterial stiffness in Korean adults
Authors: Haam Ji-Hee , Kim Young-Sang , Cho Doo-Yeoun , Chun Hyejin , Choi Sang-Woon , Lee Yun Kyong , Lim Sang Wook , Koo Hyung Suk , Kim Moon Jong 
Published: May 2021

AbstractRecent evidence suggests that cellular perturbations play an important role in the pathogenesis of cardiovascular diseases. Therefore, we analyzed the association between the levels of urinary metabolites and arterial stiffness. Our cross-sectional study included 330 Korean men and women. The brachial-ankle pulse wave velocity was measured as a marker of arterial stiffness. Urinary metabolites were evaluated using a high-performance liquid chromatograph-mass spectrometer. The brachial-ankle pulse wave velocity was found to be positively correlated with l-lactate, citrate, isocitrate, succinate, malate, hydroxymethylglutarate, α-ketoisovalerate, α-keto-β-methylvalerate, methylmalonate, and formiminoglutamate among men. Whereas, among women, the brachial-ankle pulse wave velocity was positively correlated with cis-aconitate, isocitrate, hydroxymethylglutarate, and formiminoglutamate. In the multivariable regression models adjusted for conventional cardiovascular risk factors, three metabolite concentrations (urine isocitrate, hydroxymethylglutarate, and formiminoglutamate) were independently and positively associated with brachial-ankle pulse wave velocity. Increased urine isocitrate, hydroxymethylglutarate, and formiminoglutamate concentrations were associated with brachial-ankle pulse wave velocity and independent of conventional cardiovascular risk factors. Our findings suggest that metabolic disturbances in cells may be related to arterial stiffness.
A material stress test study on occurrence of leakage and material failure of peritoneal dialysis (PD) catheters
Authors: Klingele Matthias , Carstens Martin , Baerens Lea , Laschke Matthias W. , Metzger Wolfgang , Fliser Danilo , Meier Clemens M. 
Published: May 2021

AbstractPeritonitis is a common complication of peritoneal dialysis (PD). Our root cause analysis allowed to attribute some cases to leakage of the PD catheter. Accordingly, a clinically based stress test study on potential material damage issues of PD catheters was performed, focusing on material damage caused by cleaning, de- and attachment procedures during dialysate changes and on the individual storage methods of PD catheters between dialysate changes. PD catheters were exposed to both chemical stress by repeating dialysate-flow and physical stress simulating de- and connecting, fixation, pressure, flexing, folding etc.—simulating standard clinical daily routine of 8–10 years PD catheter usage. Potentially by normal usage caused damages should be then detected by intraluminal pressure, light- and electron microscopy. The multi-step visual control showed no obvious damages on PD catheters nor any leakage or barrier indulgence. Our tests simulating daily routine usage of PD catheters for several years could not detect any material defects under chemical or physical stress. Hence, we presume that most PD catheter damages, as identified cause for peritonitis in some of our patients, may be due to accidental, unnoticed external damage (e.g. through scissors, while changing dressings) or neglecting PD catheter handling specifications.
Cross-modal orienting of exogenous attention results in visual-cortical facilitation, not suppression
Authors: Keefe Jonathan M. , Pokta Emilia , Störmer Viola S. 
Published: May 2021

AbstractAttention may be oriented exogenously (i.e., involuntarily) to the location of salient stimuli, resulting in improved perception. However, it is unknown whether exogenous attention improves perception by facilitating processing of attended information, suppressing processing of unattended information, or both. To test this question, we measured behavioral performance and cue-elicited neural changes in the electroencephalogram as participants (N = 19) performed a task in which a spatially non-predictive auditory cue preceded a visual target. Critically, this cue was either presented at a peripheral target location or from the center of the screen, allowing us to isolate spatially specific attentional activity. We find that both behavior and attention-mediated changes in visual-cortical activity are enhanced at the location of a cue prior to the onset of a target, but that behavior and neural activity at an unattended target location is equivalent to that following a central cue that does not direct attention (i.e., baseline). These results suggest that exogenous attention operates via facilitation of information at an attended location.
A screen of FDA-approved drugs identifies inhibitors of protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3)
Authors: Rivas Dylan R. , Dela Cerna Mark Vincent C. , Smith Caroline N. , Sampathi Shilpa , Patty Blaine G. , Lee Donghan , Blackburn Jessica S. 
Published: May 2021

AbstractProtein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, small molecule inhibitors of PRL-3 are lacking. Here, we screened 1443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad-spectrum PRL inhibitors, Salirasib and Candesartan, blocked PRL-3-induced migration in human embryonic kidney cells with no impact on cell viability. Both drugs prevented migration of human colorectal cancer cells in a PRL-3 dependent manner and were selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX5R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.