bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertebrate keratinization evolved into cornification mainly due to transglutaminase and sulfhydryl oxidase activities on epidermal proteins: An immunohistochemical survey
Authors: Alibardi Lorenzo
Published: July 2021

The epidermis of vertebrates forms an extended organ to protect and exchange gas, water, and organic molecules with aquatic and terrestrial environments. Herein, the processes of keratinization and cornification in aquatic and terrestrial vertebrates were compared using immunohistochemistry. Keratins with low cysteine and glycine contents form the main bulk of proteins in the anamniote epidermis, which undergoes keratinization. In contrast, specialized keratins rich in cysteine‐glycine and keratin associated corneous proteins rich in cysteine, glycine, and tyrosine form the bulk of proteins of amniote soft cornification in the epidermis and hard cornification in scales, claws, beak, feathers, hairs, and horns. Transglutaminase (TGase) and sulfhydryl oxidase (SOXase) are the main enzymes involved in cornification. Their evolution was fundamental for the terrestrial adaptation of vertebrates. Immunohistochemistry results revealed that TGase and SOXase were low to absent in fish and amphibian epidermis, while they increased in the epidermis of amniotes with the evolution of the stratum corneum and skin appendages. TGase aids the formation of isopeptide bonds, while SOXase forms disulfide bonds that generate numerous cross‐links between keratins and associated corneous proteins, likely increasing the mechanical resistance and durability of the amniote epidermis and its appendages. TGase is low to absent in the beta‐corneous layers of sauropsids but is detected in the softer but pliable alpha‐layers of sauropsids, mammalian epidermis, medulla, and inner root sheath of hairs. SOXase is present in hard and soft corneous appendages of reptiles, birds, and mammals, and determines cross‐linking among corneous proteins of scales, claws, beaks, hairs, and feathers.
Persistent fibrosis and decreased cardiac function following cardiac injury in the Ctenopharyngodon idella (grass carp)
Authors: Long Daniel W , Webb Charles H , Wang Yadong
Published: July 2021

Following the discovery of heart regeneration in zebrafish, several more species within the Cyprinidae family have been found to have the same capability, suggesting heart regeneration may be conserved within this family. Although gonad regeneration has been observed in grass carp (Ctenopharyngodon idella), one of the largest cyprinid fish, the species' response to cardiac injury has not been characterized. Surprisingly, we found cardiomyocytes do not repopulate the injured region following cryoinjury to the ventricle, instead exhibiting unresolved fibrosis and decreased cardiac function that persists for the 8‐week duration of this study. Additionally, fibroblasts are likely depleted following injury, a phenomenon not previously described in any cardiac model. The data collected in this study indicate that heart regeneration is unlikely in grass carp (C. idella). It is possible that not all members of the Cyprinidae family possesses regenerative capability observed in zebrafish. Further study of these phenomenon may reveal the underlying differences between regeneration versus unresolved fibrosis in heart disease.
Temporal preparation in adults with autistic spectrum disorder: The variable foreperiod effect
Authors: Girardi Giovanna , Fernandez Laura Gabriela , Leboyer Marion , Latimier Alice , Chokron Sylvie , Zalla Tiziana
Published: July 2021

Research suggested the possibility that temporal cognition may be different in autistic spectrum disorder (ASD). Although there are some empirical studies examining timing ability in these individuals, to our knowledge, no one directly assessed the ability to predict when an event will occur. Here, we report a study on implicit temporal preparation in individuals with ASD as indexed by the variable foreperiod (FP) effect. We compared a group of adult ASD participants to a group of typically‐developed (TD) controls, for their respective abilities to utilize implicit temporal information in a simple detection task with three different preparatory intervals (FP, short, middle and long). Participants were given a warning tone to signal an imminent stimulus, and asked to press a key as quickly as they could upon detection of the stimulus. Both groups were able to use implicit temporal information, as revealed by both the variable‐FP effect (i.e., faster response for targets appearing after a long FP) and asymmetric sequential effects (i.e., slower response in short‐FP trials following a previous long‐FP trial). The TD group exhibited a faster response in a long‐FP trial that was preceded by short‐FP one, whereas the ASD group did not, as reflected in their higher percentage of response omissions for a target that appeared later than in the previous trial. The reduced ability of ASD participants to modulate their responses under these conditions might reflect a difficulty in time‐based monitoring of stimulus occurrence.

Lay Summary

Time‐processing may be different in autistic spectrum disorder (ASD). This study addressed the ability to anticipate a relevant stimulus's onset according to predictable interstimulus intervals comparing adults with ASD and typically developed controls. We found that ASD participants did not benefit from temporal preparation when stimulus appeared later than previously attended. This suggests a reduced ability in detecting implicit temporal regularities between events.
Impact of age, hypercholesterolemia, and the vitamin D receptor on brain endogenous β‐amyloid peptide accumulation in mice
Authors: Peng H. Benson , Bukuroshi Paola , Durk Matthew R. , Grootendorst Paul , Yan Xiaoyu , Pan Sophie R. , de Lannoy Ines A. M. , Pang K. Sandy
Published: July 2021

Age, hypercholesterolemia, and vitamin D deficiency are risk factors that increase the brain accumulation of pathogenic β‐amyloid peptides (40 and 42), precursors leading to Alzheimer's disease (AD) in humans. The relative changes accompanying aging, high cholesterol, and/or treatment of calcitriol, active vitamin D receptor (VDR) ligand, under normal physiology are unknown. We examined these relative changes in C57BL/6 mice of ages 2, 4–8, and more than 10 months old, which were fed a normal or high fat / high cholesterol diet and treated with calcitriol, active ligand of the vitamin D receptor (0 or 2.5 μg/kg ×4, intraperitoneally, every other day to elicit cholesterol lowering in liver). Aβ40 but not Aβ42 accumulation in brain and lower P‐glycoprotein (P‐gp) and neprilysin protein expressions for Aβ efflux and degradation, respectively, were found to be associated with aging. But there was no trend for BACE1 (β‐secretase 1, a cholesterol‐sensitive enzyme) toward Aβ synthesis with age. In response to calcitriol treatment, P‐gp was elevated, mitigating partially the age‐related changes. Although age‐dependent decreasing trends in mRNA expression levels existed for Cyp46a1, the brain cholesterol processing enzyme, whose inhibition increases BACE1 and ApoE to facilitate microglia Aβ degradation, mRNA changes for other cholesterol transporters: Acat1 and Abca1, and brain cholesterol levels remained unchanged. There was no observable change in the mRNA expression of amyloid precursor protein (APP) and the influx (RAGE) and efflux (LRP1) transporters with respect to age, diet, or calcitriol treatment. Overall, aging poses as a risk factor contributing to Aβ accumulation in brain, and VDR‐mediated P‐gp activation partially alleviates the outcome.
The synergistic effect of coronary artery bifurcations and calcifications on the adverse outcomes after PCI: Is 1+1>1?
Authors: Dai Yuxiang , Ge Junbo
Published: July 2021

Key Points

A prospective registry data from 21,165 patients who underwent percutaneous coronary intervention (PCI) with DES showed that the combined presence of bifurcation and moderate to severe calcification was uncommon, with a rate of approximately 5% in this cohort.

The presence of combined bifurcating target vessel with moderate/severe calcification is associated with a higher risk of adverse outcomes than either attribute alone.

Further study is needed to identify new approaches and new treatment to reduce ischemic risk in this subset of patients at particularly high risk.
Evaluation of 4‐(4‐Fluorobenzyl)piperazin‐1‐yl]‐Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects
Authors: Mirabile Salvatore , Vittorio Serena , Paola Germanò Maria , Adornato Ilenia , Ielo Laura , Rapisarda Antonio , Gitto Rosaria , Pintus Francesca , Fais Antonella , De Luca Laura
Published: July 2021

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4‐fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4‐(4‐fluorobenzyl)piperazin‐1‐yl]‐(3‐chloro‐2‐nitro‐phenyl)methanone 26 (IC50=0.18 μM) that proved to be ∼100‐fold more active than reference compound kojic acid (IC50=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.
A personalized self‐learning system based on knowledge graph and differential evolution algorithm
Authors: Wang Feng , Zhang Lingling , Chen Xingchen , Wang Ziming , Xu Xin
Published: July 2021

Discovering the most adaptive learning path and content is an urgent issue for nowadays e‐learning environment, for achieving learning goals efficiently and effectively. The main challenge of building this system is to provide appropriate educational guide and resource for different learners with respective interests and knowledge base. In order to reduce people's cognitive overload and fulfill their self‐learning requirements, this article proposes a framework for a self‐learning system. The system is design to be closed and updated automatically, in which learning path is discovered based on differential evolution (DE) algorithm and knowledge graph. The output of the system includes: (1) the personalized learning path adapted to learner's specific needs; (2) learning resource recommendation matching the learning path; (3) test results of learners' learning effect after following the learning path and resources recommendation; (4) revised learning path and resources recommendation according to learner's evaluation. Experimental results show that the system based on DE algorithm and disciplinary knowledge graph is feasible in optimal learning path discovery and further learning resources recommendation.
Self‐adaptation and distributed knowledge‐based service ecosystem evolution
Authors: Wang Xianghui , Feng Zhiyong , Huang Keman , Chen Shizhan
Published: July 2021

Web services (or Web APIs) on the Internet tends to encounter various unexpected runtime failures because of their dynamicity and distribution. Self‐adaptation technologies for the service‐based business process can effectively repair runtime failures and improve its success rate. However, the same failures may occur on subsequent invocations because relevant processes do not evolve after failures. This makes the response time of the business processes too long. We proposed a self‐adaptation and distributed knowledge‐based evolution model (SDKEM) to guarantee business processes' stabilities, that is, low failure rates and stable response time. SDKEM adopts a service knowledge base (SKB) to organize services from a provider and uses bridge rules to eliminate semantic conflicts among multiple distributed SKBs. It can automatically trigger the evolution of a service ecosystem through the designed self‐adaptation mechanism. We adopt the “survival of the fittest” principle for crucial elements in the ecosystem during evolution so that ultimately, service‐based processes and services with high stability remain. Experiments show that, with the developed evolution mechanism, runtime failures of business processes significantly reduce. In most cases, their response time and success rates are comparable to those under the running situation where no runtime failure occurs, meaning the runtime failures within a service‐based process are automatically repaired.
Grain yield performance and stability of winter wheat and triticale cultivars in a temperate climate
Authors: Derejko Adriana , Studnicki Marcin , Wójcik‐Gront Elżbieta
Published: July 2021

The productivity of modern triticale (× Triticosecale Wittm. ex A. Camus) cultivars makes them more viable as an alternative to wheat (Triticum aestivum L.) grains in many environments. We tested 51 winter wheat and 18 winter triticale cultivars in 52 locations nested in six regions in Poland. The aim of the study was to check whether the yield of triticale is comparable with the yield of wheat, especially under unfavorable soil and climatic conditions. The grain yield of winter wheat ranged from 9.22 to 15.72 t ha–1 depending on the region, and the yield of triticale ranged from 9.24 to 14.82 t ha–1. The analysis showed that triticale is well adapted to the temperate environment, and its yield is more stable and less dependent on the weather conditions of the year than that of winter wheat. The results indicated that triticale and wheat grown in lower quality soils will obtain a very similar yield. We also recommend that triticale cultivar selection should be based on specific end use requirements. So far, a similar comparison has been made for Mediterranean and temperate climates, but this is the first work for a transitional temperate climate.
In vitro metabolism of the REV‐ERB agonist SR‐9009 and subsequent detection of metabolites in associated routine equine plasma and urine doping control samples
Authors: Cutler Charlotte , White Daniel Leigh , Viljanto Marjaana
Published: July 2021

SR‐9009 is a synthetic compound widely available to purchase online as ‘supplement’ products due to its potential performance‐enhancing effects, presenting a significant threat with regard to doping control in sport. In vitro metabolism with equine liver microsomes was performed to identify potential targets for detection of SR‐9009. Six metabolites were identified, with the most abundant consisting of N‐dealkylated metabolites (M1–M3). The addition of the identified metabolites to high‐resolution accurate mass databases resulted in a positive finding for the N‐dealkylated metabolite M1 of SR‐9009 in an associated plasma and urine doping sample. Liquid chromatography–high‐resolution mass spectrometry was used to verify the presence of the N‐dealkylated metabolite (M1) in both matrices, with a low concentration of the parent compound and additional N‐desalkyl metabolites (M2 and M3) detected in the plasma sample as supporting evidence of administration. To the best of the authors' knowledge, this is the first report of an adverse analytical finding in an equine sample for SR‐9009 or its metabolites in equine doping control.
Phylogenetic restriction of plant invasion in drought‐stressed environments: Implications for insect‐pollinated plant communities in water‐limited ecosystems
Authors: Simon Andrew D. F. , Marx Hannah E. , Starzomski Brian M.
Published: July 2021

Background

Plant–pollinator community diversity has been found to decrease under conditions of drought stress; however, research into the temporal dimensions of this phenomenon remains limited. In this study, we investigated the effect of seasonal drought on the temporal niche dynamics of entomophilous flowering plants in a water‐limited ecosystem. We hypothesized that closely related native and exotic plants would tend to share similar life history and that peak flowering events would therefore coincide with phylogenetic clustering in plant communities based on expected phenological responses of plant functional types to limitations in soil moisture availability.

Location

Galiano Island, British Columbia, Canada.

Methods

Combining methods from pollinator research and phylogenetic community ecology, we tested the influence of environmental filtering over plant community phenology across gradients of landscape disturbance and soil moisture. Floral resource availability and community structure were quantified by counts of flowering shoots. We constructed a robust phylogeny to analyze spatial and temporal variation in phylogenetic patterns across the landscape, testing the significance of the observed patterns against a randomly generated community phylogeny. Phylogenetic metrics were then regressed against factors of disturbance and soil moisture availability.

Results

Critical seasonal fluctuations in floral resources coincided with significant phylogenetic clustering in plant communities, with decreasing plant diversity observed under conditions of increasing drought stress. Exotic plant species in the Asteraceae became increasingly pervasive across the landscape, occupying a late season temporal niche in drought‐stressed environments.

Main conclusion

Results suggest that environmental filtering is the dominant assembly process structuring the temporal niche of plant communities in this water‐limited ecosystem. Based on these results, and trends seen elsewhere, the overall diversity of plant–pollinator communities may be expected to decline with the increasing drought stress predicted under future climate scenarios.
Wolbachiain the spittlebugProsapia ignipectus: Variable infection frequencies, but no apparent effect on host reproductive isolation
Authors: Wheeler Timothy B. , Thompson Vinton , Conner William R. , Cooper Brandon S.
Published: July 2021

Animals serve as hosts for complex communities of microorganisms, including endosymbionts that live inside their cells.Wolbachiabacteria are perhaps the most common endosymbionts, manipulating host reproduction to propagate. ManyWolbachiacause cytoplasmic incompatibility (CI), which results in reduced egg hatch when uninfected females mate with infected males.Wolbachiathat cause intense CI spread to high and relatively stable frequencies, while strains that cause weak or no CI tend to persist at intermediate, often variable, frequencies.Wolbachiacould also contribute to host reproductive isolation (RI), although current support for such contributions is limited to a few systems. To test forWolbachiafrequency variation and effects on host RI, we sampled several localProsapia ignipectus(Fitch) (Hemiptera: Cercopidae) spittlebug populations in the northeastern United States over two years, including closely juxtaposed Maine populations with different monomorphic color forms, “black” and “lined.” We discovered a group‐BWolbachia(wPig) infectingP. ignipectusthat diverged from group‐AWolbachia—like modelwMel andwRi strains inDrosophila—6 to 46 MYA. Populations of the sister speciesProsapia bicincta(Say) from Hawaii and Florida are uninfected, suggesting thatP. ignipectusacquiredwPig after their initial divergence.wPig frequencies were generally high and variable among sites and between years. While phenotypingwPig effects on host reproduction is not currently feasible, thewPig genome contains three divergent sets of CI loci, consistent with highwPig frequencies. Finally, Maine monomorphic black and monomorphic lined populations ofP. ignipectusshare bothwPig and mtDNA haplotypes, implying no apparent effect ofwPig on the maintenance of this morphological contact zone. We hypothesizeP. ignipectusacquiredwPig horizontally as observed for manyDrosophilaspecies, and that significant CI and variable transmission produce high but variablewPig frequencies.
Sodium‐glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review
Authors: Rasalam Roy , Atherton John J. , Deed Gary , Molloy‐Bland Michael , Cohen Neale , Sindone Andrew
Published: July 2021

Aims

To systematically review randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)‐derived evidence for SGLT2i efficacy mechanisms in heart failure (HF).

Methods and results

Systematic searches of Medline and Embase were performed. In seven trials [3730–17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type‐2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56–105 patients; low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N‐terminal pro B‐type natriuretic peptide levels; significant reductions vs. placebo were reported after 8–12 months (two studies; 3730–4744 patients) but not ≤12 weeks (three studies; 80–263 patients). Limited available RCT‐derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics.

Conclusions

Sodium–glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis‐driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.
Evolved to protect, designed to destroy: IL‐17‐producing γδ T cells in infection, inflammation, and cancer
Authors: Agerholm Rasmus , Bekiaris Vasileios
Published: July 2021

T cells of the gamma delta (γδ) lineage are evolutionary conserved from jawless to cartilaginous and bony fish to mammals and represent the “swiss army knife” of the immune system capable of antigen‐dependent or independent responses, memory, antigen presentation, regulation of other lymphocytes, tissue homeostasis, and mucosal barrier maintenance, to list a few. Over the last 10 years, γδ T cells that produce the cytokine IL‐17 (γδT17) have taken a leading position in our understanding of how our immune system battles infection, inflicts tissue damage during inflammation, and gets rewired by the tumor microenvironment. A lot of what we know about γδT17 cells stems from mouse models, however, increasing evidence implicates these cells in numerous human diseases. Herein, we aim to give an overview of the most common mouse models that have been used to study the role of γδT17 cells in infection, inflammation, and cancer, while at the same time we will evaluate evidence for their importance in humans. We hope and believe that in the next 10 years, means to take advantage of the protective and destructive properties of γδ T and in particular γδT17 cells will be part of our standard immunotherapy toolkit.
Wind quality designation concept and application
Authors: Şen Zekâi , Serencam Uğur
Published: July 2021

Generally, wind energy production is based on the average wind speed without any classification. This article proposes a classification system on the basis of wind speed durations greater than a given threshold value. For this purpose, the wind quality designation (WQD) concept is defined based on the wind potential duration, amount, and intensity on a threshold level. Its classifications are depicted on five risk percentage classes as “excellent,” “very good,” “good,” “fair,” and “weak. Apart from the classification, the change of WQD with wind speed threshold provides qualitative and quantitative wind speed energy production assessment. The specific objective of the article is to present theoretical WQD explanations on the basis of the most frequently employed two‐parameter Weibull probability distribution function (PDF). The application is provided for Adiyaman City, Kahta meteorology station wind speed records from the Southeastern province of Turkey. It is noticed that there is no “Weak” category at this station and the most effective quality class is “Excellent” from 14 m/s to almost 27 m/s wind speeds. The average wind speed corresponds to about 62% WQD. Finally, the wind speed potential durations PDF abides by the logarithmic‐normal PDF, whereas amount and intensity accord with the Weibull PDFs.
Standards for electric vehicle charging stations in India: A review
Authors: Kumar K Jeykishan , Kumar Sudhir , V.S Nandakumar
Published: July 2021

This review paper examines the types of electric vehicle charging station (EVCS), its charging methods, connector guns, modes of charging, and testing and certification standards, and the current status of Indian standards with respect to international standards. The paper also discusses key challenges in the standardization of EVCS worldwide and provides recommendations. It is recommended to use the combined charging system (CCS) charging methodology which will cater to the electric vehicle (EV) market in the country as well as abroad and help promote faster adoption of EVs. With many advantages with CCS charging methodology such as single connector, both AC and DC charging, high power capacity, promoted by a large number of EV manufacturers across the globe, etc., it is recommended to use CCS charging methodology. CHArge de MOve (CHAdeMO) is the only charging methodology having a vehicle to grid (V2G) functionality that can be made compatible with local grid codes which can support the grid during peak load demand using the combination of bidirectional EVCS and EV batteries acting as energy storage equipment. Finally, a comparative analysis is provided between the Indian standards and international standards from Europe, China, Japan, Germany, North America, and International Organization for Standardization (ISO).
Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low‐, intermediate‐1‐, intermediate‐2‐, and high‐risk myelofibrosis in JUMP, a Phase 3b, expanded‐access study
Authors: Passamonti Francesco , Gupta Vikas , Martino Bruno , Foltz Lynda , Zaritskey Andrey , Al‐Ali Haifa Kathrin , Tavares Renato , Maffioli Margherita , Raanani Pia , Giraldo Pilar , Griesshammer Martin , Guglielmelli Paola , Bouard Catherine , Paley Carole , Tiwari Ranjan , Vannucchi Alessandro M.
Published: July 2021

Ruxolitinib, a potent Janus kinase 1/2 inhibitor, has demonstrated durable improvements in patients with myelofibrosis. In this analysis of the Phase 3b JUMP study, which included patients aged ≥18 years with a diagnosis of primary or secondary myelofibrosis, we assessed the safety and efficacy of ruxolitinib in patients stratified by Dynamic International Prognostic Scoring System (DIPSS) risk categories. Baseline characteristic data were available to assess DIPSS status for 1844 of the 2233 enrolled patients; 60, 835, 755, and 194 in the low‐, intermediate (Int)‐1‐, Int‐2‐, and high‐risk groups, respectively. Ruxolitinib was generally well tolerated across all risk groups, with an adverse‐event (AE) profile consistent with previous reports. The most common hematologic AEs were thrombocytopenia and anemia, with highest rates of Grade ≥3 events in high‐risk patients. Approximately, 73% of patients experienced ≥50% reductions in palpable spleen length at any point in the ≤24‐month treatment period, with highest rates in lower‐risk categories (low, 82.1%; Int‐1, 79.3%; Int‐2, 67.1%; high risk, 61.6%). Median time to spleen length reduction was 5.1 weeks and was shortest in lower‐risk patients. Across measures, 40%–57% of patients showed clinically meaningful symptom improvements, which were observed from 4 weeks after treatment initiation and maintained throughout the study. Overall survival (OS) was 92% at Week 72 and 75% at Week 240 (4.6 years). Median OS was longer for Int‐2‐risk than high‐risk patients (253.6 vs. 147.3 weeks), but not evaluable in low‐/Int‐1‐risk patients. By Week 240, progression‐free survival (PFS) and leukemia‐free survival (LFS) rates were higher in lower‐risk patients (PFS: low, 90%; Int‐1, 82%; Int‐2, 46%; high risk, 15%; LFS: low, 92%; Int‐1, 86%; Int‐2, 58%; high risk, 19%). Clinical benefit was seen across risk groups, with more rapid improvements in lower risk patients. Overall, this analysis indicates that ruxolitinib benefits lower‐risk DIPSS patients in addition to higher risk.
Surface water–groundwater interactions of Xiluodu Reservoir based on the dynamic evolution of seepage, temperature, and hydrochemistry due to impoundment
Authors: Zhou Ziwen , Zhou Zhifang , Xu Haiyang , Li Mingwei
Published: July 2021

Reservoir construction greatly affects the regional ecological environment, particularly surface water–groundwater interactions around the reservoir. Xiluodu Reservoir, a representative large‐scale reservoir in China, has had substantial impacts on surface water–groundwater interactions at the dam site since impoundment. This study analysed the dynamic characteristics of surface water–groundwater level, temperature, and hydrochemistry to determine the evolution of surface water–groundwater interaction before and after the impoundment. The levels of groundwater and some surface water rose by more than 100 m after impoundment and the water level of saturated limestone gradually stabilized, whereas basalt saturation in the affected area continued to expand. The groundwater temperature did not decrease significantly, whereas the hydrochemical types and ion contents of both surface water and groundwater experienced significant changes. Calculation of the saturation index indicated spatiotemporal changes in the saturation state of minerals. The replenishment source of each type of water and their mutual relationships were determined using cluster analysis and isotope characteristics. The results confirmed continuous, significant, and variable surface water–groundwater interactions at the dam site, which were partially reversed after impoundment. Changes in surface water–groundwater interactions were due to impoundment, the impact of which decreases with distance from the dam, as well as the unique geological conditions and artificial construction.
Sequential acquisition of human papillomavirus infection between genital and oral anatomic sites in males
Authors: Dickey Brittney L. , Fan Wenyi , Bettampadi Deepti , Reich Richard R. , Sirak Bradley , Abrahamsen Martha , Baggio Maria Luiza , Galan Lenice , Silva Roberto Carvalho , Salmerón Jorge , Villa Luisa L. , Lazcano‐Ponce Eduardo , Giuliano Anna R.
Published: July 2021

Oral human papillomavirus (HPV) is associated with increasing rates of HPV‐associated oropharyngeal cancer (OPC) in men. Sequential infection from one site to another has been demonstrated at the cervix and anus. Thus, risk of an oral HPV infection after a genital infection of the same type in the HPV infection in men study was investigated. Samples from 3140 men enrolled in a longitudinal cohort were assessed for sequential genital to oral infection with one of nine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58); and then also sequential, same‐type oral to genital infection. Incidence rate ratios (IRRs) compared rates of oral HPV among men with and without prior genital infection of the same type. Risk of sequential HPV infections were assessed using Cox proportional hazards model. Incidence of an oral HPV infection was significantly higher among men with a prior genital infection of the same type for any of the 9 HPV types (IRR: 2.3; 95% CI: 1.7‐3.0). Hazard ratio of a sequential genital to oral HPV infection was 2.3 (95% CI: 1.7‐3.1) and 3.5 (95% CI: 1.9‐6.4) for oral to genital infection. Both changed minimally after adjustment for age, country, circumcision, alcohol use, lifetime sexual partners and recent oral sex partners. HPV infections at one site could elevate risk of a subsequent genital or oral HPV infection of the same type in men, emphasizing the importance of vaccination to prevent all HPV infections.
Particle swarm optimization approach to portfolio construction
Authors: Chen Ren‐Raw , Huang Wiliam Kaihua , Yeh Shih‐Kuo
Published: July 2021

Particle swarm optimization (PSO) is an artificial intelligence technique that can be used to find approximate solutions to extremely difficult or impossible numeric optimization problems. Recently, PSO algorithms have been widely used in solving complex financial optimization problems. This paper presents a PSO approach to solve a portfolio construction problem, since this methodology is a population‐based heuristic algorithm that is suitable for solving high‐dimensional constrained optimization problems. The computational results show that PSO algorithms have advantages in optimizing the Sortino ratio, especially in speed, when the size of the portfolio is large.
Forecast uncertainty, disagreement, and the linear pool
Authors: Knüppel Malte , Krüger Fabian
Published: July 2021

The linear pool is the most popular method for combining density forecasts. We analyze its implications concerning forecast uncertainty, using a new framework that focuses on the means and variances of the individual and combined forecasts. Our results show that, if the variance predictions of the individual forecasts are unbiased, the well‐known “disagreement” component of the linear pool exacerbates the upward bias of its variance prediction. This finding suggests the removal of the disagreement component from the linear pool. The resulting centered linear pool outperforms the linear pool in simulations and an empirical application to inflation.
The double‐edged sword of global integration: Robustness, fragility, and contagion in the international firm network
Authors: Grant Everett , Yung Julieta
Published: July 2021

Increased global integration of firm, production, and financial networks has the potential to benefit growth but also amplify the transmission of crises. We test whether higher global connectedness is associated with robust (beneficial) or fragile (harmful) behavior using networks derived from firm equity returns across all industries (1991–2016). More globally connected firms are less likely to be in distress, with higher profit, revenue, and equity price growth; however, they are more exposed to direct contagion from distressed neighboring firms. Our analysis reveals the centrality of finance, increased globalization, and greater potential for crises to spread globally when they do occur.
Novel use of a midline catheter for therapeutic and donor apheresis in children and adults
Authors: Casacchia Colleen , Lozano Maria , Schomberg John , Barrows Jennifer , Salcedo Tamara , Puthenveetil Geetha
Published: July 2021

Background

Apheresis procedures require adequate vascular access to achieve optimal inlet flow rates. While central lines provide such access, their placement and use are associated with risks; some of these risks are minimized if peripheral intravenous access can be established. However, peripheral intravenous access is associated with challenges in the pediatric setting. Research indicates that midline catheters reduce the use of CVADs and their associated risks. The use of midline catheters for apheresis has been reported recently in adults, but no studies have been published on their use in children. Thus, the purpose of this study was to evaluate the use of midline catheters for apheresis in the pediatric setting.

Methods

A retrospective observational study was conducted to evaluate the safety and efficacy of midline catheters in subjects who underwent apheresis at a pediatric hospital from April 2018 to August 2020. Demographic data, clinical data (diagnosis, procedure, catheter size, body mass), and outcome data (inlet flow rate, total blood volume [TBV] processed, procedure time, and cell counts) were collected.

Results

Eighteen subjects received a total of 100 midline catheters for 73 apheresis procedures. Inlet flow rates ranged from 45 to 80 mL/min, TBV ranged from 2872 to 20 000 mL, and procedure time ranged from 1.25 to 7 hours. Inlet flow rates met or exceeded the recommended inlet flow rates for apheresis in children and adults (P < .0001). No adverse events occurred.

Conclusion

Midline catheters provide safe and effective vascular access for apheresis. Future research should include younger patients with lower body mass.
Matrisome, innervation and oxidative metabolism affected in older compared with younger males with similar physical activity
Authors: Lagerwaard Bart , Nieuwenhuizen Arie G. , Bunschoten Annelies , de Boer Vincent C.J. , Keijer Jaap
Published: July 2021

Background

Due to the interaction between skeletal muscle ageing and lifestyle factors, it is often challenging to attribute the decline in muscle mass and quality to either changes in lifestyle or to advancing age itself. Because many of the physiological factors affecting muscle mass and quality are modulated by physical activity and physical activity declines with age, the aim of this study is to better understand the effects of early ageing on muscle function by comparing a population of healthy older and young males with similar physical activity patterns.

Methods

Eighteen older (69 ± 2.0 years) and 20 young (22 ± 2.0 years) males were recruited based on similar self‐reported physical activity, which was verified using accelerometry measurements. Gene expression profiles ofvastus lateralisbiopsies obtained by RNA sequencing were compared, and key results were validated using quantitative polymerase chain reaction and western blot.

Results

Total physical activity energy expenditure was similar between the young and old group (404 ± 215 vs. 411 ± 189 kcal/day,P = 0.11). Three thousand seven hundred ninety‐seven differentially expressed coding genes (DEGs) were identified (adjustedP‐value cut‐off of <0.05), of which 1891 were higher and 1906 were lower expressed in the older muscle. The matrisome, innervation and inflammation were the main upregulated processes, and oxidative metabolism was the main downregulated process in old compared with young muscle. Lower protein levels of mitochondrial transcription factor A (TFAM,P = 0.030) and mitochondrial respiratory Complexes IV and II (P = 0.011 andP = 0.0009, respectively) were observed, whereas a trend was observed for Complex I (P = 0.062), in older compared with young muscle. Protein expression of Complexes I and IV was significantly correlated to mitochondrial capacity in thevastus lateralisas measuredin vivo(P = 0.017,R2 = 0.42 andP = 0.030,R2 = 0.36). A trend for higher muscle‐specific receptor kinase (MUSK) protein levels in the older group was observed (P = 0.08).

Conclusions

There are clear differences in the transcriptome signatures of thevastus lateralismuscle of healthy older and young males with similar physical activity levels, including significant differences at the protein level. By disentangling physical activity and ageing, we appoint early skeletal muscle ageing processes that occur despite similar physical activity. Improved understanding of these processes will be key to design targeted anti‐ageing therapies.
Sperm motility analysis of Cobitis hankugensis, Iksookimia longicorpa (Teleostei, Cypriniformes, Cobitidae) and their unisexual natural hybrids
Authors: Yun Seung Woon , Kim Hyun Tae , Park Jong Young
Published: July 2021

Hybrid sterility is an inevitable phenomenon in the speciation process to avoid indiscriminate increases in species, but it is not always unconditional. We used computer assisted sperm analysis (CASA) to analyze sperm motility of Cobitis hankugensis, Iksookimia longicorpa, and their unisexual natural hybrids. In parental species, the sperm concentrations of C. hankugensis and I. longicorpa were 11.6 ± 4.8 × 109 and 16.5 ± 6.8 × 109, respectively. For sperm motility, the total motility was higher in the parental species (C. hankugensis, 91.3%; I. longicorpa, 87.5%) than other hybrids. After 1 min, the motility duration was reduced to 14% in C. hankugensis and 3.3% in I. longicorpa. This result could indicate that the duration of sperm motility of C. hankugensis is longer than that of I. longicorpa up to 1 min after spermatozoa activation. All of the hybrids had a low concentration and it was distinct from their parent species. Total motility and other velocity parameters also showed significantly lower values except for the HHL (one from the C. hankugensis genome with two from the I. longicorpa genome) type motility measurement (13.6%). These results suggest that the hybrids derived from C. hankugensis and I. longicorpa, are not completely infertile, contrary to histological observations.
Interest in and uptake of genetic counseling for preconception carrier screening when offered to predominantly white reproductive‐age persons seeking gynecologic care at a single U.S. academic medical center
Authors: Nesbit Carleigh B. , Pollack Catherine C. , Mascia Nicolina S. , LaCroix Valerie H. , Applebee Devin M. , Bosco Amy W. , Wilkinson‐Ryan Ivy , Erekson Elisabeth D. , Evans Rebecca H.
Published: July 2021

The objective of this study was to assess the level of interest in preconception carrier screening among reproductive‐aged persons presenting for gynecologic care and to identify demographic factors predictive of pursuing screening. Patients aged 18–40 who were presenting for gynecologic care at a single U.S. academic medical center were provided with information about current options for preconception carrier screening and were offered genetic counseling referral with the possibility to undergo screening. Outcomes of interest were desire for genetic counseling referral and attendance at genetic counseling visit. Statistical analyses were performed as appropriate using R version 3.6.1 with variables significant at 0.1 included in a multivariable logistic regression. Of 193 participants, 79 (41%) desired genetic counseling referral. Participants aged 25–34 (OR 3.39, 95% CI 1.47–8.10) and nulliparas (OR 2.69, 95% CI 1.23–6.03) were more likely to desire referral. Thirty‐five participants (44.3% of those who desired referral) attended a visit with genetic counseling. Having an advanced degree (OR 3.27, 95% CI 1.06–10.4) was associated with visit attendance. Thirteen participants underwent screening, and five were found to be a carrier of at least one X‐linked or autosomal recessive condition. Surprisingly, presenting for a gynecologic visit directly related to planning a pregnancy was not associated with increased interest in preconception carrier screening. Nulliparas and those aged 25–34 likely expressed greater interest in referral due to high potential for future childbearing in these groups. The increased level of visit attendance in participants with advanced degrees is likely confounded by the high level of health literacy and financial resources in this group.
Reflections of parents of children with 22q11.2 Deletion Syndrome on the experience of receiving psychiatric genetic counseling: ‘Awareness to Act’
Authors: Carrion Prescilla , Semaka Alicia , Batallones Rolan , Slomp Caitlin , Morris Emily , Inglis Angela , Moretti Marlene , Austin Jehannine
Published: July 2021

Individuals with 22q11.2 deletion syndrome (22qDS) have a 25%–41% risk for a psychotic disorder. Although early intervention for psychiatric conditions leads to the best long‐term outcomes, healthcare providers often provide inadequate information about these issues and psychiatric services are underused by this population. We conducted semi‐structured interviews with parents of children with 22qDS a month after they received psychiatric genetic counseling (pGC), to evaluate outcomes and perceived value of pGC with respect to parents’ needs. Using grounded theory, we generated a theoretical framework of the process of building parental awareness of psychiatric risks associated with 22qDS and protective and management strategies for mental health (MH). Parents described how after their child's diagnosis with 22qDS, a variety of barriers stalled their building awareness of psychiatric risk and protective/management strategies: dealing with the immediate symptoms of 22qDS; child's young age; parental fear and stigma; and missing MH guidance. These barriers led them to carry the burden of worrying over missing emerging psychiatric symptoms and the stress over advocating for their child's MH. Parents indicated pGC was beneficial in that led them to achieve an ‘awareness to act,’ feeling confident in being alert and equipped to protect and/or manage their child's MH.
Concentration of Gallbladder Phosphatidylcholine in Cholangiopathies: A Phosphorus‐31 Magnetic Resonance Spectroscopy Pilot Study
Authors: Pfleger Lorenz , Halilbasic Emina , Gajdošík Martin , Benčíková Diana , Chmelík Marek , Scherer Thomas , Trattnig Siegfried , Krebs Michael , Trauner Michael , Krššák Martin
Published: July 2021

Background

Biliary phosphatidylcholine (PtdC) concentration plays a role in the pathogenesis of bile duct diseases. In vivo phosphorus‐31 magnetic resonance spectroscopy (31P‐MRS) at 7 T offers the possibility to assess this concentration noninvasively with high spectral resolution and signal intensity.

Purpose

Comparison of PtdC levels of cholangiopathic patient groups to a control group using a measured T1 relaxation time of PtdC in healthy subjects.

Study Type

Case control.

Subjects

Two patient groups with primary sclerosing cholangitis (PSC, 2f/3 m; age: 43 ± 7 years) and primary biliary cholangitis (PBC, 4f/2 m; age: 57 ± 6 years), and a healthy control group (CON, 2f/3 m; age: 38 ± 7 years). Ten healthy subjects for the assessment of the T1 relaxation time of PtdC.

Field Strength/Sequence

A 3D phase‐encoded pulse‐acquire 31P‐MRSI sequence for PtdC quantification and a 1D image‐selected in vivo 31P spectroscopy for T1 estimation at 7 T, and a T2‐weighted half‐Fourier single‐shot turbo spin echo MRI sequence for volumetry at 3 T.

Assessment

Calculation of gallbladder volumes and PtdC concentration in groups using hepatic gamma‐adenosine triphosphate signal as an internal reference and correction for insufficient relaxation of PtdC with a T1 value assessed in healthy subjects.

Statistical Tests

Group comparison of PtdC content and gallbladder volumes of the PSC/PBC and CON group using Student's t‐tests with a significance level of 5%.

Results

PtdC T1 value of 357 ± 85 msec in the gallbladder. Significant lower PtdC content for the PSC group, and for the female subgroup of the PBC group compared to the CON group (PSC/CON: 5.74 ± 0.73 mM vs. 9.64 ± 0.97 mM, PBC(f)/CON: 5.77 ± 1.44 mM vs. 9.64 ± 0.97 mM). Significant higher gallbladder volumes of the patient groups compared to the CON group (PSC/CON: 66.3 ± 15.8 mL vs. 20.9 ± 2.2 mL, PBC/CON: 49.8 ± 18.2 mL vs. 20.9 ± 2.2 mL).

Data Conclusion

This study demonstrated the application of a 31P‐MRSI protocol for the quantification of PtdC in the human gallbladder at 7 T. Observed differences in PtdC concentration suggest that this metabolite could serve as a biomarker for specific hepatobiliary disorders.

Level of Evidence

2

Technical Efficacy Stage

3