bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simulation-Based Optimization Model to Study the Impact of Multiple-Region Listing and Information Sharing on Kidney Transplant Outcomes
Authors: Gharibi Zahra , Hahsler Michael
Published: January 2021

More than 8000 patients on the waiting list for kidney transplantation die or become ineligible to receive transplants due to health deterioration. At the same time, more than 4000 recovered kidneys from deceased donors are discarded each year in the United States. This paper develops a simulation-based optimization model that considers several crucial factors for a kidney transplantation to improve kidney utilization. Unlike most proposed models, the presented optimization model incorporates details of the offering process, the deterioration of patient health and kidney quality over time, the correlation between patients’ health and acceptance decisions, and the probability of kidney acceptance. We estimate model parameters using data obtained from the United Network of Organ Sharing (UNOS) and the Scientific Registry of Transplant Recipients (SRTR). Using these parameters, we illustrate the power of the simulation-based optimization model using two related applications. The former explores the effects of encouraging patients to pursue multiple-region waitlisting on post-transplant outcomes. Here, a simulation-based optimization model lets the patient select the best regions to be waitlisted in, given their demand-to-supply ratios. The second application focuses on a system-level aspect of transplantation, namely the contribution of information sharing on improving kidney discard rates and social welfare. We investigate the effects of using modern information technology to accelerate finding a matching patient to an available donor organ on waitlist mortality, kidney discard, and transplant rates. We show that modern information technology support currently developed by the United Network for Organ Sharing (UNOS) is essential and can significantly improve kidney utilization.
A Two-in-One Strategy: Target and Nontarget Site Mechanisms Both Play Important Role in IMI-Resistant Weedy Rice
Authors: Yean Ru-Ann , Dilipkumar Masilamany , Rahman Sadequr , Song Beng-Kah
Published: January 2021

The introduction of Clearfield technology allows the use of imidazolinone (IMI) herbicides to control weedy rice. Imidazolinone herbicides stop the acetolactate synthase (ALS) enzyme from synthesizing branched-chain amino acids, resulting in the death of the plant. Since the launch of Clearfield technology in Malaysia in 2010, many farmers have replaced traditional cultivars with Clearfield (CL) rice lines (MR220-CL1 and MR220-CL2). This technology was initially effective; however, in recent years, local farmers have reported the reduced efficacy of IMI herbicides in controlling the spread of weedy rice. Under IMI herbicide treatment, in previous weedy rice studies, the target-site resistance (TSR) mechanism of the ALS gene has been suggested as a key factor conferring herbicide resistance. In our study, a combination of ALS gene sequencing, enzyme colorimetric assay, and a genome-wide association study (GWAS) highlighted that a non-target-site resistance (NTSR) can be an alternative molecular mechanism in IMI-resistant weedy rice. This is supported by a series of evidence, including a weak correlation between single nucleotide polymorphisms (SNPs) within the ALS exonic region and ALS enzyme activity. Our findings suggest that the adaptability of weedy rice in Clearfield rice fields can be more complicated than previously found in other rice strains.
Identification of Sortilin Alternatively Spliced Variants in Mouse 3T3L1 Adipocytes
Authors: Lui Ashley , Sparks Robert , Patel Rekha , Patel Niketa A.
Published: January 2021

Type 2 diabetes mellitus is a metabolic disorder defined by systemic insulin resistance. Insulin resistance in adipocytes, an important regulator of glucose metabolism, results in impaired glucose uptake. The trafficking protein, sortilin, regulates major glucose transporter 4 (Glut4) movement, thereby promoting glucose uptake in adipocytes. Here, we demonstrate the presence of an alternatively spliced sortilin variant (Sort17b), whose levels increase with insulin resistance in mouse 3T3L1 adipocytes. Using a splicing minigene, we show that inclusion of alternative exon 17b results in the expression of Sort17b splice variant. Bioinformatic analysis indicated a novel intrinsic disorder region (IDR) encoded by exon 17b of Sort17b. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) measurements using molecular dynamics demonstrated increased flexibility of the protein backbone within the IDR. Using protein–protein docking and co-immunoprecipitation assays, we show robust binding of Glut4 to Sort17b. Further, results demonstrate that over-expression of Sort17b correlates with reduced Glut4 translocation and decreased glucose uptake in adipocytes. The study demonstrates that insulin resistance in 3T3L1 adipocytes promotes expression of a novel sortilin splice variant with thus far unknown implications in glucose metabolism. This knowledge may be used to develop therapeutics targeting sortilin variants in the management of type 2 diabetes and metabolic syndrome.
Importance of Cx43 for Right Ventricular Function
Authors: Boengler Kerstin , Rohrbach Susanne , Weissmann Norbert , Schulz Rainer
Published: January 2021

In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart. Furthermore, we discuss the expression and localization of Cx43 in the diseased RV, i.e., in the tetralogy of Fallot and in pulmonary hypertension, in which the RV is affected, and RV hypertrophy and failure occur. We will also introduce other Cx molecules that are expressed in RV and surrounding tissues and have been reported to be involved in RV pathophysiology. Finally, we highlight therapeutic strategies aiming to improve RV function in pulmonary hypertension that are associated with alterations of Cx43 expression and function.
Studies of Sol-Gel Evolution and Distribution of Eu3+ Ions in Glass–Ceramics Containing LaF3 Nanocrystals Depending on Initial Sols Composition
Authors: Pawlik Natalia , Szpikowska-Sroka Barbara , Goryczka Tomasz , Pisarski Wojciech A.
Published: January 2021

In this work, we performed a systematic analysis of the impact of selected chemical reagents used in sol-gel synthesis (i.e., N,N-dimethylformamide) and different catalyst agents (i.e., CH3COOH, HNO3) on the formation and luminescence of Eu3+-doped SiO2–LaF3 nano-glass–ceramics. Due to the characteristic nature of intra-configurational electronic transitions of Eu3+ ions within the 4f6 manifold (5D0 → 7FJ, J = 0–4), they are frequently used as a spectral probe. Thus, the changes in the photoluminescence profile of Eu3+ ions could identify the general tendency of rare earth materials to segregate inside low-phonon energy fluoride nanocrystals, which allows us to assess their application potential in optoelectronics. Fabricated sol-gel materials, from sols to gels and xerogels to nano-glass–ceramics, were examined using several experimental techniques: X-ray diffraction (XRD), transmission electron microscopy (TEM), infrared spectroscopy (IR), and luminescence measurements. It was found that the distribution of Eu3+ ions between the amorphous silicate sol-gel host and LaF3 nanocrystals is strictly dependent on the initial composition of the obtained sols, and the lack of N,N-dimethylformamide significantly promotes the segregation of Eu3+ ions inside LaF3 nanocrystals. As a result, we detected long-lived luminescence from the 5D0 excited state equal to 6.21 ms, which predisposes the obtained glass–ceramic material for use as an optical element in reddish-orange emitting devices.
Mechanisms Applied by Protein Inhibitors to Inhibit Cysteine Proteases
Authors: Tušar Livija , Usenik Aleksandra , Turk Boris , Turk Dušan
Published: January 2021

Protein inhibitors of proteases are an important tool of nature to regulate and control proteolysis in living organisms under physiological and pathological conditions. In this review, we analyzed the mechanisms of inhibition of cysteine proteases on the basis of structural information and compiled kinetic data. The gathered structural data indicate that the protein fold is not a major obstacle for the evolution of a protease inhibitor. It appears that nature can convert almost any starting fold into an inhibitor of a protease. In addition, there appears to be no general rule governing the inhibitory mechanism. The structural data make it clear that the “lock and key” mechanism is a historical concept with limited validity. However, the analysis suggests that the shape of the active site cleft of proteases imposes some restraints. When the S1 binding site is shaped as a pocket buried in the structure of protease, inhibitors can apply substrate-like binding mechanisms. In contrast, when the S1 binding site is in part exposed to solvent, the substrate-like inhibition cannot be employed. It appears that all proteases, with the exception of papain-like proteases, belong to the first group of proteases. Finally, we show a number of examples and provide hints on how to engineer protein inhibitors.
MST3 Involvement in Na+ and K+ Homeostasis with Increasing Dietary Potassium Intake
Authors: Chan Chee-Hong , Wu Sheng-Nan , Bao Bo-Ying , Li Houng-Wei , Lu Te-Ling
Published: January 2021

K+ loading inhibits NKCC2 (Na-K-Cl cotransporter) and NCC (Na-Cl cotransporter) in the early distal tubules, resulting in Na+ delivery to the late distal convoluted tubules (DCTs). In the DCTs, Na+ entry through ENaC (epithelial Na channel) drives K+ secretion through ROMK (renal outer medullary potassium channel). WNK4 (with-no-lysine 4) regulates the NCC/NKCC2 through SAPK (Ste20-related proline-alanine-rich kinase)/OSR1 (oxidative stress responsive). K+ loading increases intracellular Cl−, which binds to the WNK4, thereby inhibiting autophosphorylation and downstream signals. Acute K+ loading-deactivated NCC was not observed in Cl−-insensitive WNK4 mice, indicating that WNK4 was involved in K+ loading-inhibited NCC activity. However, chronic K+ loading deactivated NCC in Cl−-insensitive WNK4 mice, indicating that other mechanisms may be involved. We previously reported that mammalian Ste20-like protein kinase 3 (MST3/STK24) was expressed mainly in the medullary TAL (thick ascending tubule) and at lower levels in the DCTs. MST3−/− mice exhibited higher ENaC activity, causing hypernatremia and hypertension. To investigate MST3 function in maintaining Na+/K+ homeostasis in kidneys, mice were fed diets containing various concentrations of Na+ and K+. The 2% KCl diets induced less MST3 expression in MST3−/− mice than that in wild-type (WT) mice. The MST3−/− mice had higher WNK4, NKCC2-S130 phosphorylation, and ENaC expression, resulting in lower urinary Na+ and K+ excretion than those of WT mice. Lower urinary Na+ excretion was associated with elevated plasma [Na+] and hypertension. These results suggest that MST3 maintains Na+/K+ homeostasis in response to K+ loading by regulation of WNK4 expression and NKCC2 and ENaC activity.
Importance of Both Imprinted Genes and Functional Heterogeneity in Pancreatic Beta Cells: Is There a Link?
Authors: Chabosseau Pauline , Rutter Guy A. , Millership Steven J.
Published: January 2021

Diabetes mellitus now affects more than 400 million individuals worldwide, with significant impacts on the lives of those affected and associated socio-economic costs. Although defects in insulin secretion underlie all forms of the disease, the molecular mechanisms which drive them are still poorly understood. Subsets of specialised beta cells have, in recent years, been suggested to play critical roles in “pacing” overall islet activity. The molecular nature of these cells, the means through which their identity is established and the changes which may contribute to their functional demise and “loss of influence” in both type 1 and type 2 diabetes are largely unknown. Genomic imprinting involves the selective silencing of one of the two parental alleles through DNA methylation and modified imprinted gene expression is involved in a number of diseases. Loss of expression, or loss of imprinting, can be shown in mouse models to lead to defects in beta cell function and abnormal insulin secretion. In the present review we survey the evidence that altered expression of imprinted genes contribute to loss of beta cell function, the importance of beta cell heterogeneity in normal and disease states, and hypothesise whether there is a direct link between the two.
Cargo Recognition and Function of Selective Autophagy Receptors in Plants
Authors: Luo Shuwei , Li Xifeng , Zhang Yan , Fu Yunting , Fan Baofang , Zhu Cheng , Chen Zhixiang
Published: January 2021

Autophagy is a major quality control system for degradation of unwanted or damaged cytoplasmic components to promote cellular homeostasis. Although non-selective bulk degradation of cytoplasm by autophagy plays a role during cellular response to nutrient deprivation, the broad roles of autophagy are primarily mediated by selective clearance of specifically targeted components. Selective autophagy relies on cargo receptors that recognize targeted components and recruit them to autophagosomes through interaction with lapidated autophagy-related protein 8 (ATG8) family proteins anchored in the membrane of the forming autophagosomes. In mammals and yeast, a large collection of selective autophagy receptors have been identified that mediate the selective autophagic degradation of organelles, aggregation-prone misfolded proteins and other unwanted or nonnative proteins. A substantial number of selective autophagy receptors have also been identified and functionally characterized in plants. Some of the autophagy receptors in plants are evolutionarily conserved with homologs in other types of organisms, while a majority of them are plant-specific or plant species-specific. Plant selective autophagy receptors mediate autophagic degradation of not only misfolded, nonactive and otherwise unwanted cellular components but also regulatory and signaling factors and play critical roles in plant responses to a broad spectrum of biotic and abiotic stresses. In this review, we summarize the research on selective autophagy in plants, with an emphasis on the cargo recognition and the biological functions of plant selective autophagy receptors.
Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression
Authors: Makalish Tatyana P. , Golovkin Ilya O. , Oberemok Volodymyr V. , Laikova Kateryna V. , Temirova Zenure Z. , Serdyukova Olesya A. , Novikov Ilya A. , Rosovskyi Roman A. , Gordienko Andrey I. , Zyablitskaya Evgeniya Yu. , Gafarova Elvina A. , Yurchenko Kseniya A. , Fomochkina Iryna I. , Kubyshkin Anatoly V.
Published: January 2021

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.
Conformational Landscape of Cytochrome P450 Reductase Interactions
Authors: Sellner Manuel , Fischer André , Don Charleen G. , Smieško Martin
Published: January 2021

Oxidative reactions catalyzed by Cytochrome P450 enzymes (CYPs), which constitute the most relevant group of drug-metabolizing enzymes, are enabled by their redox partner Cytochrome P450 reductase (CPR). Both proteins are anchored to the membrane of the endoplasmic reticulum and the CPR undergoes a conformational change in order to interact with the respective CYP and transfer electrons. Here, we conducted over 22 microseconds of molecular dynamics (MD) simulations in combination with protein–protein docking to investigate the conformational changes necessary for the formation of the CPR–CYP complex. While some structural features of the CPR and the CPR–CYP2D6 complex that we highlighted confirmed previous observations, our simulations revealed additional mechanisms for the conformational transition of the CPR. Unbiased simulations exposed a movement of the whole protein relative to the membrane, potentially to facilitate interactions with its diverse set of redox partners. Further, we present a structural mechanism for the susceptibility of the CPR to different redox states based on the flip of a glycine residue disrupting the local interaction network that maintains inter-domain proximity. Simulations of the CPR–CYP2D6 complex pointed toward an additional interaction surface of the FAD domain and the proximal side of CYP2D6. Altogether, this study provides novel structural insight into the mechanism of CPR–CYP interactions and underlying conformational changes, improving our understanding of this complex machinery relevant for drug metabolism.
First Complete Mitochondrial Genome of Melyridae(Coleoptera, Cleroidea): Genome Description and Phylogenetic Implications
Authors: Yuan Lilan , Ge Xueying , Xie Guanglin , Liu Haoyu , Yang Yuxia
Published: January 2021

To explore the characteristics of the mitogenome of Melyridae and reveal phylogenetic relationships, the mitogenome of Cordylepherus sp. was sequenced and annotated. This is the first time a complete mitochondrial genome has been generated in this family. Consistent with previous observations of Cleroidea species, the mitogenome of Cordylepherus sp. is highly conserved in gene size, organization and codon usage, and secondary structures of tRNAs. All protein-coding genes (PCGs) initiate with the standard start codon ATN, except ND1, which starts with TTG, and terminate with the complete stop codons of TAA and TAG, or incomplete forms, TA- and T-. Most tRNAs have the typical clover-leaf structure, except trnS1 (Ser, AGN), whose dihydrouridine (DHU) arm is reduced. In the A+T-rich region, three types of tandem repeat sequence units are found, including a 115 bp sequence tandemly repeated twice, a 16 bp sequence tandemly repeated three times with a partial third repeat and a 10 bp sequence tandemly repeated seven times. Phylogenetic analyses based on 13 protein-coding genes by both Bayesian inference (BI) and maximum likelihood (ML) methods suggest that Melyridae sensu lato is polyphyletic, and Dasytinae and Malchiinae are supported as independent families.
Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience
Authors: Vallianou Kalliopi , Marinaki Smaragdi , Skalioti Chrysanthi , Lionaki Sophia , Darema Maria , Melexopoulou Christina , Boletis Ioannis
Published: January 2021

Focal Segmental Glomerulosclerosis (FSGS) recurrence after kidney transplantation (KTx) is relatively frequent and is associated with poor graft survival. The aim of this study was to investigate which management strategies were associated with better outcomes in our cohort of KTx recipients with primary FSGS. We retrospectively collected data on patients with primary FSGS who received a KTx between 1993 and 2019. A history of biopsy proven FSGS in native kidneys and new onset of significant proteinuria early post-KTx led to the diagnosis of recurrence, which was confirmed by graft biopsy. From 1993 to 2019 we performed 46 KTxs in patients with primary FSGS. We identified 26 episodes of recurrence in 25 patients, 67% of them occurring in males. They were younger at the time of KTx (33.8 vs. 41.1 years old, p = 0.067) and had progressed to end stage renal disease (ESRD) faster after FSGS diagnosis (61.4 vs. 111.2 months, p = 0.038), while they were less likely to have received prophylactic plasmapheresis (61.5% vs. 90%, p = 0.029). 76.7% of recurrences were found early, after a median of 0.5 months (IQR 0.1–1) with a median proteinuria was 8.5 (IQR 4.9–11.9) g/day. All patients with recurrence were treated with plasmapheresis, while 8 (30.7%) additionally received rituximab, 1 (3.8%) abatacept, and 4 (15.4%) ACTH. 7 (27%) patients experienced complete and 11 (42.3%) partial remission after a mean time of 3 (±1.79) and 4.4 (±2.25) months, respectively. Prognosis was worse for patients who experienced a recurrence. Eleven (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5–43.3) months. In this series of patients, primary FSGS recurred frequently after KTx. Prophylacic plasmapheresis was shown efficacious in avoiding FSGS recurrence, while timely diagnosis and plasmapheresis-based regimens induced remission in more than half of the patients.
The Shift from Multiport to Single Port Increases the Amount of Bleeding in Laparoscopic Major Hepatectomy
Authors: Mittermair Christof , Weiss Michael , Schirnhofer Jan , Brunner Eberhard , Fischer Katharina , Obrist Christian , de Cillia Michael , Kemmetinger Vanessa , Gollegger Emanuel , Hell Tobias , Weiss Helmut
Published: January 2021

Background: Bleeding is a negative outcome predictor in liver surgery. Reduction in the abdominal wall trauma in major hepatectomy is challenging but might offer possible benefits for the patient. This study was conducted to assess hemostasis techniques in single-port major hepatectomies (SP-MajH) as compared to multiport major hepatectomies (MP-MajH). Methods: The non-randomized study comprised 34 SP-MajH in selected patients; 14 MP-MajH served as the control group. Intraoperative blood loss and number of blood units transfused served as the primary endpoints. Secondary endpoints were complications and oncologic five-year outcome. Results: All resections were completed without converting to open surgery. Time for hepatectomy did not differ between SP-MajH and MP-MajH. Blood loss and number of patients with blood loss > 25 mL were significantly larger in MP-MajH (p = 0.001). In contrast, bleeding control was more difficult in SP-MajH, resulting in more transfusions (p = 0.008). One intestinal laceration (SP-MajH) accounted for the only intraoperative complication; 90-day mortality was zero. Postoperative complications were noted in total in 20.6% and 21.4% of patients for SP-MajH and MP-MajH, respectively. No incisional hernia occurred. During a median oncologic follow-up at 61 and 56 months (SP-MajH and MP-MajH), no local tumor recurrence was observed. Conclusions: SP-MajH requires sophisticated techniques to ensure operative safety. Substantial blood loss requiring transfusion is more likely to occur in SP-MajH than in MP-MajH.
Predictive Value of Measures of Vascular Calcification Burden and Progression for Risk of Death in Incident to Dialysis Patients
Authors: Bellasi Antonio , Di Lullo Luca , Russo Domenico , Ciarcia Roberto , Magnocavallo Michele , Lavalle Carlo , Ratti Carlo , Fusaro Maria , Cozzolino Mario , Di Iorio Biagio Raffaele
Published: January 2021

Background: Vascular calcification (VC) is a marker of cardiovascular (CV) disease and various methods allow for presence and extension assessment in different arterial districts. Nevertheless, it is currently unclear which one of these methods for VC evaluation best predict outcome and if this piece of information adds to the predictive value of traditional CV risk factors in patients receiving hemodialysis (HD). Methods: data of 184 of the 466 patients followed in the Independent study (NCT00710788) were post hoc examined to assess the association three concurrent measures of vascular calcification and all-cause survival. Specifically, coronary artery calcification (CAC) was determined by the Agatston and the volume score while abdominal aorta calcification was determined by plain X-ray of the lumbar spine (Kauppila score (KS)). Survival and regression models as well as metrics of risk recalculation were used to test the association of VC and outcome beyond the Framingham risk score. Results: Middle-age (62.6(15.8) years) men (51%) and women (49%) starting HD were analyzed. Over 36 (median 36; interquartile range: 8–36) months of follow-up 69 patients expired. Each measure of VC (CAC or KS) predicted all-cause mortality independently factors commonly associated with all-cause survival (p < 0.001). Far more importantly, each measurement of VC significantly improved risk prediction and patient reclassification (p < 0.001) beyond traditional cardiovascular risk factors. Conclusions: Overall, presence and extension of VC, irrespective of the arterial site, predict risk of all-cause of death in patients starting hemodialysis. Of note, both CAC and KS increase risk stratification beyond traditional CV risk factors. However, future efforts are needed to assess whether a risk-based approach encompassing VC screening to guide HD patient management improves survival.
Using Salivary MMP-9 to Successfully Quantify Periodontal Inflammation during Orthodontic Treatment
Authors: Luchian Ionut , Moscalu Mihaela , Goriuc Ancuta , Nucci Ludovica , Tatarciuc Monica , Martu Ioana , Covasa Mihai
Published: January 2021

Periodontitis is one of the most common immune-mediated inflammatory conditions resulting in progressive destruction of periodontium. Metalloproteinase-9 (MMP-9), an enzyme that is involved in the degradation of gelatin and collagen and present in the gingival crevicular fluid, is markedly increased in periodontitis. The aim of the study is to evaluate the effects of periodontal treatment either alone or in combination with orthodontic treatment on MMP-9 levels. In this study, 60 individuals were subjected to periodontal treatment (PD) or periodontal treatment combined with orthodontic treatment (POD). Both periodontal and periodontal plus orthodontic treatments significantly improved clinical parameters and lowered MMP-9 levels compared to control group. However, the combination of periodontal with orthodontic treatment further improved clinical parameters and enhanced the lowering effect on MMP-9 levels compared to periodontal or control groups alone. Finally, the degree of malocclusion significantly affected the effect of the treatment on MPP-9 levels with PD treatment having the most pronounced effect. We concluded that salivary MMP-9 can serve to accurately predict the level of inflammation in affected periodontal tissues during orthodontic treatment that is also associated with the type of malocclusion, making it a viable diagnosis tool in monitoring the progression of the periodontium during orthodontic treatment.
Treatment of Hepatic Artery Stenosis in Liver Transplant Patients Using Drug-Eluting versus Bare-Metal Stents
Authors: Naidu Sailendra , Alzubaidi Sadeer , Knuttinen Grace , Patel Indravadan , Fleck Andrew , Sweeney John , Aqel Bashar , Larsen Brandon , Buras Matthew , Golafshar Michael , Oklu Rahmi
Published: January 2021

Hepatic artery stenosis after liver transplant is often treated with endovascular stent placement. Our institution has adopted use of drug-eluting stents, particularly in small-caliber arteries. We aimed to compare patency rates of drug-eluting stents vs. traditional bare-metal stents. This was a single-institution, retrospective study of liver transplant hepatic artery stenosis treated with stents. Primary patency was defined as time from stent placement to resistive index on Doppler ultrasonography (<0.5), hepatic artery thrombosis, or any intervention including surgery. Fifty-two patients were treated with stents (31 men; mean age, 57 years): 15, drug-eluting stents; 37, bare-metal stents. Mean arterial diameters were 4.1 mm and 5.1 mm, respectively. Technical success was 100% (52/52). At 6 months, 1, 2, and 3 years, primary patency for drug-eluting stents was 80%, 71%, 71%, and 71%; bare-metal stents: 76%, 65%, 53%, and 46% (p = 0.41). Primary patency for small-caliber arteries (3.5–4.5 mm) with drug-eluting stents was 93%, 75%, 75%, and 75%; bare-metal stents: 60%, 60%, 50%, and 38% (p = 0.19). Overall survival was 100%, 100%, 94%, and 91%. Graft survival was 100%, 98%, 96%, and 90%. Stenting for hepatic artery stenosis was safe and effective. While not statistically significant, patency improved with drug-eluting stents compared with bare-metal stents, especially in arteries < 4.5 mm in diameter. Drug-eluting stents can be considered for liver transplant hepatic artery stenosis, particularly in small-caliber arteries.
Improvement of Overall Survival Using TKIs as Salvage Therapy in Advanced Thyroid Carcinoma: Real-Life Data on a Single Center Experience
Authors: Brilli Lucia , Dalmiglio Cristina , Pilli Tania , Barbato Filomena , Maino Fabio , Capezzone Marco , Cartocci Alessandra , Castagna Maria Grazia
Published: January 2021

Background: Tyrosine kinase inhibitors (TKIs) have improved progression-free survival in patients with advanced thyroid cancer. So far, few studies have investigated the efficacy of TKIs in a second-line setting. The purpose of our study was to explore the salvage therapy efficacy in patients with advanced thyroid cancer. Methods: We retrospectively evaluated 63 patients with progressive advanced thyroid carcinoma treated with TKIs divided into a Study group (23 patients) treated with salvage therapy, and a Control group (40 patients) treated with only one TKI. Results: Similar clinical benefits (stable disease + partial response) and progression free survival between the first and the second line TKI were observed in the Study group (p > 0.99 and p = 0.5, respectively). Median overall survival (OS) was 67.7 months in the Study group and 22.6 months in the Control group (HR 2.46; 95% CI 1.34–4.52, p = 0.004). After stratifying the whole population by age (<65 and ≥65 years), OS was significantly different (p < 0.001) with the best survival curve in younger patients, treated with salvage therapy and the worst in older subjects, treated with only one TKI. Conclusions: Salvage therapy showed a significant improvement of OS in patients with advanced thyroid cancer who experienced disease progression during prior TKI therapies.
Hepatokines as a Molecular Transducer of Exercise
Authors: Seo Dae Yun , Park Se Hwan , Marquez Jubert , Kwak Hyo-Bum , Kim Tae Nyun , Bae Jun Hyun , Koh Jin-Ho , Han Jin
Published: January 2021

Exercise has health benefits and prevents a range of chronic diseases caused by physiological and biological changes in the whole body. Generally, the metabolic regulation of skeletal muscle through exercise is known to have a protective effect on the pathogenesis of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cardiovascular disease (CVD). Besides this, the importance of the liver as an endocrine organ is a hot research topic. Hepatocytes also secrete many hepatokines in response to nutritional conditions and/or physical activity. In particular, certain hepatokines play a major role in the regulation of whole-body metabolic homeostasis. In this review, we summarize the recent research findings on the exercise-mediated regulation of hepatokines, including fibroblast growth factor 21, fetuin-A, angiopoietin-like protein 4, and follistatin. These hepatokines serve as molecular transducers of the metabolic benefits of physical activity in chronic metabolic diseases, including NAFLD, T2D, and CVDs, in various tissues.
Gan-Lu-Yin (Kanroin), Traditional Chinese Herbal Extracts, Reduces Osteoclast Differentiation In Vitro and Prevents Alveolar Bone Resorption in Rat Experimental Periodontitis
Authors: Inagaki Yuji , Kido Jun-ichi , Nishikawa Yasufumi , Kido Rie , Sakamoto Eijiro , Bando Mika , Naruishi Koji , Nagata Toshihiko , Yumoto Hiromichi
Published: January 2021

Gan-Lu-Yin (GLY), a traditional Chinese herbal medicine, shows therapeutic effects on periodontitis, but that mechanism is not well known. This study aims to clarify the precise mechanism by investigating the inhibitory effects of GLY extracts on osteoclastogenesis in vitro and on bone resorption in periodontitis in vivo. RAW264.7 cells are cultured with soluble receptor activator of nuclear factor-kappa B (sRANKL) and GLY extracts (0.01–1.0 mg/mL), and stained for tartrate-resistant acid phosphatase (TRAP) to evaluate osteoclast differentiation. Experimental periodontitis is induced by placing a nylon ligature around the second maxillary molar in rats, and rats are administered GLY extracts (60 mg/kg) daily for 20 days. Their maxillae are collected on day 4 and 20, and the levels of alveolar bone resorption and osteoclast differentiation are estimated using micro-computed tomography (CT) and histological analysis, respectively. In RAW264.7 cells, GLY extracts significantly inhibit sRANKL-induced osteoclast differentiation at a concentration of more than 0.05 mg/mL. In experimental periodontitis, administering GLY extracts significantly decreases the number of TRAP-positive osteoclasts in the alveolar bone on day 4, and significantly inhibits the ligature-induced bone resorption on day 20. These results show that GLY extracts suppress bone resorption by inhibiting osteoclast differentiation in experimental periodontitis, suggesting that GLY extracts are potentially useful for oral care in periodontitis.
Hormonal Treatment of Men with Nonobstructive Azoospermia: What Does the Evidence Suggest?
Authors: Caroppo Ettore , Colpi Giovanni M.
Published: January 2021

Hormonal stimulation of spermatogenesis prior to surgery has been tested by some authors to maximize the sperm retrieval yield in patients with nonobstructive azoospermia. Although the rationale of such an approach is theoretically sound, studies have provided conflicting results, and there are unmet questions that need to be addressed. In the present narrative review, we reviewed the current knowledge about the hormonal control of spermatogenesis, the relationship between presurgical serum hormones levels and sperm retrieval rates, and the results of studies investigating the effect of hormonal treatments prior to microdissection testicular sperm extraction. We pooled the available data about sperm retrieval rate in patients with low vs. normal testosterone levels, and found that patients with normal testosterone levels had a significantly higher chance of successful sperm retrieval compared to those with subnormal T levels (OR 1.63, 95% CI 1.08–2.45, p = 0.02). These data suggest that hormonal treatment may be justified in patients with hypogonadism; on the other hand, the available evidence is insufficient to recommend hormonal therapy as standard clinical practice to improve the sperm retrieval rate in patients with nonobstructive azoospermia.
The Revised Mood Rhythm Instrument: A Large Multicultural Psychometric Study
Authors: Alves Braga de Oliveira Melissa , de Mendonça Filho Euclides , Carissimi Alicia , Lima dos Santos Garay Luciene , Scop Marina , Ruschel Bandeira Denise , Gutiérrez Carvalho Felipe , Mathur Salina , Epifano Kristina , Adan Ana , Frey Benicio N. , Hidalgo Maria
Published: January 2021

Background: Recent studies with the mood rhythm instrument (MRhI) have shown that the presence of recurrent daily peaks in specific mood symptoms are significantly associated with increased risk of psychiatric disorders. Using a large sample collected in Brazil, Spain, and Canada, we aimed to analyze which MRhI items maintained good psychometric properties across cultures. As a secondary aim, we used network analysis to visualize the strength of the association between the MRhI items. Methods: Adults (n = 1275) between 18–60 years old from Spain (n = 458), Brazil (n = 415), and Canada (n = 401) completed the MRhI and the self-reporting questionnaire (SRQ-20). Psychometric analyses followed three steps: Factor analysis, item response theory, and network analysis. Results: The factor analysis indicated the retention of three factors that grouped the MRhI items into cognitive, somatic, and affective domains. The item response theory analysis suggested the exclusion of items that displayed a significant divergence in difficulty measures between countries. Finally, the network analysis revealed a structure where sleepiness plays a central role in connecting the three domains. These psychometric analyses enabled a psychometric-based refinement of the MRhI, where the 11 items with good properties across cultures were kept in a shorter, revised MRhI version (MRhI-r). Limitations: Participants were mainly university students and, as we did not conduct a formal clinical assessment, any potential correlations (beyond the validated SRQ) cannot be ascertained. Conclusions: The MRhI-r is a novel tool to investigate self-perceived rhythmicity of mood-related symptoms and behaviors, with good psychometric properties across multiple cultures.
The Role of Hepatic Fat Accumulation in Glucose and Insulin Homeostasis—Dysregulation by the Liver
Authors: London Amalie , Lundsgaard Anne-Marie , Kiens Bente , Bojsen-Møller Kirstine Nyvold
Published: January 2021

Accumulation of hepatic triacylglycerol (TG) is associated with obesity and metabolic syndrome, which are important pathogenic factors in the development of type 2 diabetes. In this narrative review, we summarize the effects of hepatic TG accumulation on hepatic glucose and insulin metabolism and the underlying molecular regulation in order to highlight the importance of hepatic TG accumulation for whole-body glucose metabolism. We find that liver fat accumulation is closely linked to impaired insulin-mediated suppression of hepatic glucose production and reduced hepatic insulin clearance. The resulting systemic hyperinsulinemia has a major impact on whole-body glucose metabolism and may be an important pathogenic step in the development of type 2 diabetes.
Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study
Authors: Nkeh-Chungag Benedicta N. , Goswami Nandu , Engwa Godwill A. , Sewani-Rusike Constance R. , Mbombela Vuyolwethu , Webster Ingrid , De Boever Patrick , Kessler Harald H. , Stelzl Evelyn , Strijdom Hans
Published: January 2021

Limited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIV-positive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART−) and 171 individuals without HIV (HIV−) in Mthatha, Eastern Cape Province of South Africa. Flow-mediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART− and HIV− participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV− and HIV+ART− participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART.
Olympic Games Event Recognition via Transfer Learning with Photobombing Guided Data Augmentation
Authors: Mohamad Yousef I. , Baraheem Samah S. , Nguyen Tam V.
Published: January 2021

Automatic event recognition in sports photos is both an interesting and valuable research topic in the field of computer vision and deep learning. With the rapid increase and the explosive spread of data, which is being captured momentarily, the need for fast and precise access to the right information has become a challenging task with considerable importance for multiple practical applications, i.e., sports image and video search, sport data analysis, healthcare monitoring applications, monitoring and surveillance systems for indoor and outdoor activities, and video captioning. In this paper, we evaluate different deep learning models in recognizing and interpreting the sport events in the Olympic Games. To this end, we collect a dataset dubbed Olympic Games Event Image Dataset (OGED) including 10 different sport events scheduled for the Olympic Games Tokyo 2020. Then, the transfer learning is applied on three popular deep convolutional neural network architectures, namely, AlexNet, VGG-16 and ResNet-50 along with various data augmentation methods. Extensive experiments show that ResNet-50 with the proposed photobombing guided data augmentation achieves 90% in terms of accuracy.
Influence of Impeller Gap Drainage Width on the Performance of Low Specific Speed Centrifugal Pump
Authors: Wei Yangyang , Yang Yang , Zhou Ling , Jiang Lei , Shi Weidong , Huang Gaoyang
Published: January 2021

The centrifugal pump is one of the most important pieces of energy-consuming equipment in various hydraulic engineering applications. This paper takes a low specific speed centrifugal pump as the research object. Based on the research method combining numerical calculation and experimental verification, the influence of the gap drainage structure on the performance of the low specific speed centrifugal pump and its internal flow field distribution were investigated. The flow field inside the low specific speed centrifugal pump impeller under different gap widths was studied. The comparison between the numerical calculation results and the experimental results confirms that the numerical calculations in this paper have high accuracy. It was found that the gap drainage will reduce the head of the low specific speed centrifugal pump, but increase its hydraulic efficiency. Using a smaller gap width could greatly improve the performance of the low specific speed centrifugal pump on the basis of a slight reduction in the head. The high-pressure leakage flow at the gap flows from the blade pressure surface to the suction surface can effectively suppress the low-pressure area at the impeller inlet. The flow rate of the high-pressure leakage flow increases with the gap width. Excessive gap width may cause a low-pressure zone at the inlet of the previous flow passage. These results could serve as a reference for the subsequent gap design to further improve the operating stability of the low specific speed centrifugal pump.
Directed Mutational Strategies Reveal Drug Binding and Transport by the MDR Transporters of Candida albicans
Authors: Banerjee Atanu , Pata Jorgaq , Sharma Suman , Monk Brian C. , Falson Pierre , Prasad Rajendra
Published: January 2021

Multidrug resistance (MDR) transporters belonging to either the ATP-Binding Cassette (ABC) or Major Facilitator Superfamily (MFS) groups are major determinants of clinical drug resistance in fungi. The overproduction of these proteins enables the extrusion of incoming drugs at rates that prevent lethal effects. The promiscuity of these proteins is intriguing because they export a wide range of structurally unrelated molecules. Research in the last two decades has used multiple approaches to dissect the molecular basis of the polyspecificity of multidrug transporters. With large numbers of drug transporters potentially involved in clinical drug resistance in pathogenic yeasts, this review focuses on the drug transporters of the important pathogen Candida albicans. This organism harbors many such proteins, several of which have been shown to actively export antifungal drugs. Of these, the ABC protein CaCdr1 and the MFS protein CaMdr1 are the two most prominent and have thus been subjected to intense site-directed mutagenesis and suppressor genetics-based analysis. Numerous results point to a common theme underlying the strategy of promiscuity adopted by both CaCdr1 and CaMdr1. This review summarizes the body of research that has provided insight into how multidrug transporters function and deliver their remarkable polyspecificity.
Morphogenesis of Emerging Settlements: Mapping Incremental Urbanism
Authors: Kamalipour Hesam , Iranmanesh Aminreza
Published: January 2021

Informal urbanism has become a widespread form of urbanisation, particularly in the context of the global South. While there is an emerging body of knowledge focusing on the morphologies of informal settlements, the incremental transformations of emerging settlements have remained underexplored. Drawing on a case study of an emerging settlement in Nigeria, we map the emergence and incremental transformation of access networks and buildings. This is an exploratory study focusing on the morphogenesis of emerging settlements to explore how the incremental production of space works. We adopt urban mapping and typology as key methods. Following the analysis of emerging access networks, this paper identifies three primary types of change, namely add, alter, and remove, and further develops a typology of emerging junctions by specifying four types of T, Y, X, and Mixed shape junctions. The incremental transformations of buildings primarily incorporate practices of addition and removal, among others. We also identify three forms of relation between the emerging access networks and buildings: access network first, building first, and co-production. We argue that moving towards developing adaptive design interventions relies on a sophisticated understanding of the process of morphogenesis in emerging settlements.
Pertechnetate/Perrhenate Surface Complexation on Bamboo Engineered Biochar
Authors: Daňo Martin , Viglašová Eva , Štamberg Karel , Galamboš Michal , Galanda Dušan
Published: January 2021

The work deals with the evaluation of biochar samples prepared from Phyllostachys Viridiglaucescens bamboo. This evaluation consists of the characterization of prepared materials’ structural properties, batch and dynamic sorption experiments, and potentiometric titrations. The batch technique was focused on obtaining basic sorption data of 99mTcO4− on biochar samples including influence of pH, contact time, and Freundlich isotherm. ReO4−, which has very similar chemical properties to 99mTcO4−, was used as a carrier in the experiments. Theoretical modeling of titration curves of biochar samples was based on the application of surface complexation models, namely, so called Chemical Equilibrium Model (CEM) and Ion Exchange Model (IExM). In this case it is assumed that there are two types of surface groups, namely, the so-called layer and edge sites. The dynamic experimental data of sorption curves were fitted by a model based on complementary error function erfc(x).