bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of COVID‐19 on autism research: A cross‐sectional analysis of discontinued or suspended clinical trials
Authors: Neale Monika , Landers Elizabeth , Sajjadi Nicholas B. , Mazur‐Mosiewicz Anya , Hartwell Micah
Published: June 2022

Due to uncertainties associated with the COVID‐19 public health crisis, several clinical trials had to be withdrawn or postponed. Our investigation aimed to assess the rate of discontinuation of clinical trials focusing on Autism Spectrum Disorder. Of the 197 registered trials included in our systematic review, 15 (7.6%) were discontinued, with nearly half of these explicitly citing COVID‐19 as their reason for discontinuation. Pharmacological trials were six times more likely to be discontinued during the pandemic than non‐pharmacological studies. The difference between the likelihood of discontinuation was statistically significant (OR: 6.13; 95% CI: 1.22–30.71). There was no evidence of association between funding source and reasons for discontinuation. Limitations, along with implications for future trials are discussed.

Lay Summary

We investigated the impact of the COVID‐19 pandemic on the discontinuation rate of autism clinical trials. We found that drug trials were six times more likely to be discontinued during the pandemic compared to behavioral, diagnostic, and nutritional trials. The overall discontinuation rate was notably lower in autism clinical trials than in other areas of medical research. We recommend an examination of the methodology of the continued autism trials to assess their applicability in other fields.
Bioinformatics‐based and molecular docking study on the mechanism of action of Galla chinensis in the treatment of diabetic foot ulcers
Authors: Fan Shuyuan , Xu Yue , Qiu Feng , Liu Jing , Pan Taowen , Li Kun , Li Bin , Diao Yunpeng
Published: June 2022

Based on transcriptome sequencing and molecular biology, the active ingredient of Galla chinensis in the treatment of diabetic foot ulcers was identified, and its mechanism of action was analyzed.
A study of the THP‐1 cell line as the potential biologics production platform with the emphasis on serum‐free media substitution for economic expediency
Authors: Kimiz‐Gebologlu Ilgin , Demirden S. Furkan , Oncel Suphi S.
Published: June 2022

Cell cultures are frequently preferred in the industrial production of high value‐added biopharmaceuticals on a large scale. In the production of biopharmaceuticals, the selection of the appropriate cell line, the cell culture medium, and the culture conditions are very important. In medical products to be offered for human use, authorized institutions do not allow the use of serum which increases the culture yield, added to the culture. For this reason, the cell lines to be used must be adapted to the serum‐free medium. In this study, first, the direct and gradual adaptation of the THP‐1 cell line, which has a high potential for use in biopharmaceutical production, to a locally produced chemically defined serum‐free medium was carried out. Then, a comparison of the production efficiency in the shake flasks with the commercially available two different serum‐free media was performed. Finally, for the first time, THP‐1 cells were produced in spinner flasks and stirring tank bioreactor to simulate the large scale within the scope of this work.
Proposition of a structural model for business value creation based on circular business models, innovation, and resource recovery in the pet industry
Authors: Kuzma Edson , Sehnem Simone
Published: June 2022

Based on the assumptions of circular economy, resource recovery, and innovation, the aim of this research is to analyze the relationship between innovation constructs, resource recovery practices, Circular Economy Business Models (CEBMs), and value creation in a fast‐growing emerging economy. A set of empirical data from 443 companies in the pet industry were used. In terms of methodology, the study was processed using the SPSS software, using Structural Equation Modeling, with manipulation of primary data. CEBMs demand greater engagement, internalization of initiatives, and synergy with the operating ecosystem of the pet industry. Innovation is present but has the potential for expansion through adherence to the innovation ecosystem and its technological package, partnerships, and relationships so that companies can scale up and create value with the support of resource recovery practices. The results of this study can be useful for companies in the pet industry, as it allows the identification of areas and practices that require their attention to improve organizational performance and create value for the business based on initiatives supported by the assumptions of circular economy and sustainability.
Advancing engineering education: Using the three‐phase methodology to teach IoT
Authors: Assumpção Raphael M. , Chaves Pedro R. , Ferreira Luiz C. , Cardieri Paulo , Branquinho Omar C. , Fruett Fabiano
Published: June 2022

The multidisciplinary aspect of Internet of Things (IoT) requires teaching approaches that can support this characteristic. Research has shown that inductive teaching methods can contribute to deeper learning. The development of the three‐phase methodology (TpM), an approach that guides the many disciplines involved in the creation of IoT solutions, precipitated the development of strategies for its implementation. To test these strategies, we propose a new learning environment that uses the TpM in a postgraduate course in IoT where students are introduced to the concepts required to design, build, and test IoT solutions. The adoption of the TpM combined with extensive experimentation can produce a learning environment that encourages students’ active participation in the activities and facilitate the retention of the concepts learned. To evaluate the effectiveness of the proposed approach, we compared the results of an earlier edition of the course (2019), when the approach was not used, to two more recent ones (2020 and 2021) when it was. The same syllabus and rubrics were used in all three editions of the course. The final group projects’ grades and satisfaction surveys were used to evaluate the students’ performance and motivation. Findings indicate that the 2020 and 2021 classes performed better than the 2019's, as their final group project grades were considerably higher, indicating that the approach has an impact on the development of students’ transversal skills. The proposed learning environment encourages active participation in the activities and facilitates the retention of the concepts learned.
DPEP1 promotes drug resistance in colon cancer cells by forming a positive feedback loop with ASCL2
Authors: Zeng Cheng , Qi Guoping , Shen Ying , Li Wenjing , Zhu Qi , Yang Chunxia , Deng Jianzhong , Lu Wenbin , Liu Qian , Jin Jianhua
Published: June 2022

Background

Drug resistance is an important factor affecting the efficacy of chemotherapy in patients with colon cancer. However, clinical markers for diagnosing drug resistance of tumor cells are not only a few in number, but also low in specificity, and the mechanism of action of tumor cell drug resistance remains unclear.

Methods

Dipeptidase 1 (DPEP1) expression was analyzed using the cancer genome atlas (TCGA) and genotype‐Tissue Expression pan‐cancer data. Survival analysis was performed using the survival package in R software to assess the prognostic value of DPEP1 expression in colon cancer. Correlation and Venn analyses were adopted to identify key genes. Immunohistochemistry, western blot, qRT–PCR, Co‐immunoprecipitation, and dual‐luciferase reporter experiments were carried out to explore the underlying associations between DPEP1 and Achaete scute‐like 2 (ASCL2). MTT assays were used to evaluate the role of DPEP1 and ASCL2 in colon cancer drug resistance.

Results

DPEP1 was highly expressed in colon cancer tissues. DPEP1 expression correlated negatively with disease‐specific survival but not with overall survival. Bioinformatics analysis and experiments showed that the expressions of DPEP1 and ASCL2 in colon cancer tissues were markedly positively correlated. Mechanistic research indicated that DPEP1 enhanced the stability of protein ASCL2 by inhibiting its ubiquitination‐mediated degradation. In turn, ASCL2 functioned as a transcription factor to activate the transcriptional activity of the DPEP1 gene and boost its expression. Furthermore, DPEP1 also could enhance the expression of colon cancer stem cell markers (LGR5, CD133, and CD44), which strengthened the tolerance of colon cancer cells to chemotherapy drugs.

Conclusions

Our findings reveal that the DPEP1 enhances the stemness of tumor cells by forming a positive feedback loop with ASCL2 to improve resistance to chemotherapy drugs.
Anti‐inflammatory and immune‐mediated therapy for a case of febrile infection‐related epilepsy syndrome with rapid recurrence
Authors: Kurimoto Tomonori , Matsuoka Tsuyoshi , Ami Yuki , Kanno Koji , Fujii Takashi , Fujiwara Naoki , Matsuoka Takashi
Published: June 2022

Febrile infection‐related epilepsy syndrome (FIRES) is a disease of unknown etiology, characterized by refractory frequent focal seizures, which require prolonged intensive care. We successfully treated a boy with FIRES with anti‐inflammatory and immunosuppressive therapy. This case suggests that an autoimmune mechanism may play a role in the development of FIRES.
Chiral Gold Clusters with Crosslinking Ligands: Geometric Structures and Chiroptical Activities
Authors: Shichibu Yukatsu , Konishi Katsuaki
Published: June 2022

The geometric diversity of ligand‐protected metal clusters has greatly provoked the interest in the chirality of gold clusters bearing crosslinking ligands, which are a subject of active investigations. This review introduces recent geometric and computational studies on chiral gold clusters whose metal core is covered by intramolecular crosslinking moieties. Following an overview of the structural constructions, the geometric features of the ligand shells and metal cores of chiral gold clusters are elucidated, where an emphasis is placed on the importance of helical patterns of the crosslinking ligands arranged around the gold cores. In addition, insights into the atomic‐level origin of chiroptical activity, which cannot be accessed solely through experiments, are presented from computational studies using numerical and theoretical approaches, thereby providing a novel methodology based on transition‐moment and transition‐density analyses.
Population Pharmacokinetics of Tralokinumab in Adult Subjects With Moderate to Severe Atopic Dermatitis
Authors: Soehoel Anders , Larsen Malte Selch , Timmermann Stine
Published: June 2022

Tralokinumab is the first biologic therapy for moderate‐to‐severe atopic dermatitis (AD) that specifically neutralizes interleukin‐13 activity, a key driver of AD signs and symptoms. Tralokinumab is a human immunoglobulin G4 monoclonal antibody administered subcutaneously every 2 weeks (with possibility of maintenance dosing every 4 weeks). This population pharmacokinetic (PK) analysis aimed to identify sources of PK variability and relevant predictors of tralokinumab exposure in adults with moderate to severe AD. Nonlinear mixed‐effect modeling, including covariate analysis, was used on a data set including 2561 subjects (AD, asthma, healthy) from 10 clinical trials. A 2‐compartment model with first‐order absorption and elimination adequately described the tralokinumab PK. Body weight was identified as a relevant predictor of tralokinumab exposure; other covariates including age, sex, race, ethnicity, disease type, AD severity, and renal and hepatic impairment were not. For body weight, the difference in exposure between the upper‐ and lower‐weight quartiles in patients with AD was <2‐fold, supporting the appropriateness of flat dosing (300 mg). Given the reduced exposure associated with higher body weight, coupled with the reduced exposure provided by dosing every 4 weeks, it is uncertain whether higher‐weight patients will achieve sufficient exposure to maintain efficacy if dosed every 4 weeks instead of the standard every 2 weeks.
Detection of resistance loci to English grain aphid in common wheat
Authors: Zhankui Zeng , Zhipeng Han , Chunping Wang , Zhenghong Wang , Cheng Guo , Liming Wang , Li Gao
Published: June 2022

The English grain aphid (Sitobion avenae F.) causes significant yield and quality losses in wheat (Triticum aestivum L.) worldwide, and the use of insect‐resistant wheat cultivars reduces the loss level. The present study aimed to identify quantitative trait loci (QTL) and perform putative candidate gene evolutionary analysis for English grain aphid resistance in 261 F2:5 recombinant inbred lines (RILs) derived from the cross Amigo/XN1376. The RIL population and parents were genotyped with the Wheat 55K single nucleotide polymorphism (SNP) array. A total of 14,694 polymorphic SNPs were used to construct a genetic linkage map. One major effect of QTL was detected in F2:5 RILs and was located on chromosome 3DL, explained 19.33% phenotypic variance, temporarily designated as QSa3.haust‐3D. It was located in a 2.73 Mb, flanked by markers AX‐109429351 and AX‐110834100, from 550.25 to 552.98 Mb according to Chinese Spring reference genome. This region contained 39 annotated genes. Eight putative candidate genes for resistance to English grain aphid were identified among these genes. The QTL with closely linked SNP markers could be useful for marker‐assisted selection for resistance to English grain aphid for wheat breeding.
How and when does perceived greenwashing affect employees' job performance? Evidence from China
Authors: Li Wei , Li Weining , Seppänen Veikko , Koivumäki Timo
Published: June 2022

Despite increasing interest in the implications of greenwashing, few studies have examined the underlying mechanism and contingency of how greenwashing affects employee outcomes. In this study, we develop a mediated moderation model to analyze the impact of perceived greenwashing on employee job performance (i.e., task performance and organizational citizenship behavior). Using a questionnaire survey of 400 employees in 20 Chinese companies, the results reveal that perceived greenwashing negatively affects job performance and that the relationship is mediated by organizational cynicism. Furthermore, employees' green values strengthen the indirect negative relationship between perceived greenwashing practices and job performance through organizational cynicism. The study contributes to addressing the long‐discussed problem of whether greenwashing pays vis‐à‐vis a human resource management perspective and micro‐level approach. The findings indicate that a close cooperation between the human resources and corporate environmental responsibility management departments is required to achieve the sustainable development of businesses.
Higher BCG‐induced trained immunity prevalence predicts protection from COVID‐19: Implications for ongoing BCG trials
Authors: Singh Samer , Kishore Dhiraj , Singh Rakesh K. , Pathak Chandramani , Ranjan Kishu
Published: June 2022

Endeavors to identify potentially protective variables for COVID‐19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID‐19 impact on populations to their Bacillus–Calmette–Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID‐19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ‘trained immunity’ (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID‐19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase‐matched COVID‐19 incidences (r(24): −0.79 to −0.57; p‐value < .004), mortality (r(24): −0.63 to −0.45; p‐value < .03), and interim case fatality rates (i‐CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID‐19, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.
Disease‐related population declines in bats demonstrate non‐exchangeability in generalist predators
Authors: Wray Amy K. , Gratton Claudio , Jusino Michelle A. , Wang Jing Jamie , Kochanski Jade M. , Palmer Jonathan M. , Banik Mark T. , Lindner Daniel L. , Peery M. Zachariah
Published: June 2022

The extent to which persisting species may fill the functional role of extirpated or declining species has profound implications for the structure of biological communities and ecosystem functioning. In North America, arthropodivorous bats are threatened on a continent‐wide scale by the spread of white‐nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans. We tested whether bat species that display lower mortality from this disease can partially fill the functional role of other bat species experiencing population declines. Specifically, we performed high‐throughput amplicon sequencing of guano from two generalist predators: the little brown bat (Myotis lucifugus) and big brown bat (Eptesicus fuscus). We then compared changes in prey consumption before versus after population declines related to WNS. Dietary niches contracted for both species after large and abrupt declines in little brown bats and smaller declines in big brown bats, but interspecific dietary overlap did not change. Furthermore, the incidence and taxonomic richness of agricultural pest taxa detected in diet samples decreased following bat population declines. Our results suggest that persisting generalist predators do not necessarily expand their dietary niches following population declines in other predators, providing further evidence that the functional roles of different generalist predators are ecologically distinct.
A comparison in species distribution model performance of succulents using key species and subsets of environmental predictors
Authors: Buckland Catherine E. , Smith Andrew J. A. C. , Thomas David S. G.
Published: June 2022

Identifying the environmental drivers of the global distribution of succulent plants using the Crassulacean acid metabolism pathway of photosynthesis has previously been investigated through ensemble‐modeling of species delimiting the realized niche of the natural succulent biome. An alternative approach, which may provide further insight into the fundamental niche of succulent plants in the absence of dispersal limitation, is to model the distribution of selected species that are globally widespread and have become naturalized far beyond their native habitats. This could be of interest, for example, in defining areas that may be suitable for cultivation of alternative crops resilient to future climate change. We therefore explored the performance of climate‐only species distribution models (SDMs) in predicting the drivers and distribution of two widespread CAM plants, Opuntia ficus‐indica and Euphorbia tirucalli. Using two different algorithms and five predictor sets, we created distribution models for these exemplar species and produced an updated map of global inter‐annual rainfall predictability. No single predictor set produced markedly more accurate models, with the basic bioclim‐only predictor set marginally out‐performing combinations with additional predictors. Minimum temperature of the coldest month was the single most important variable in determining spatial distribution, but additional predictors such as precipitation and inter‐annual precipitation variability were also important in explaining the differences in spatial predictions between SDMs. When compared against previous projections, an a posteriori approach correctly does not predict distributions in areas of ecophysiological tolerance yet known absence (e.g., due to biotic competition). An updated map of inter‐annual rainfall predictability has successfully identified regions known to be depauperate in succulent plants. High model performance metrics suggest that the majority of potentially suitable regions for these species are predicted by these models with a limited number of climate predictors, and there is no benefit in expanding model complexity and increasing the potential for overfitting.
Collaborative governance or state regulation? Endless efforts but little capacity for sustainability transformation of the German textile sector
Authors: Beyers Felix , Leventon Julia , Heinrichs Harald
Published: June 2022

Collaborative governance is increasingly demanded in multiple sectors and considered promising to address wicked sustainability challenges. Whether it meets these expectations remains uncertain, particularly as such initiatives take place within a broader landscape of public and private policies and projects. We explore how collaborative governance initiative is shaped by its broader landscape to deliver on its goals. To do so, we provide a framework for analysing governance modes and social interactions in collaborative governance. We use an exploratory case study of the German Partnership for Sustainable Textiles (hereafter: Textiles Partnership). The partnership is a multi‐stakeholder, collaborative governance initiative that links to a variety of different initiatives, and highlights barriers and transformation potential both within and outside its boundaries. Based on qualitative interviews, analysis of policy documents and a focus group discussion, we show that the complexity of the landscape field is accompanied by capacity constraints for all actors involved. Such complexity raises questions about whether this governance mode influences actual change on the ground, or diverts energies into navigating and proliferating complexity with low levels of meaningful outcomes. There is a growing call from actors within the partnership towards more state‐centred regulation, resulting in a Due Diligence Act in 2021, to regulate corporate action across national borders. The evidence we present shows the need to reconsider the balance between state regulation and collaborative governance arrangements.
A Sensor for Selective Dopamine Determination Based on Overoxidized Poly‐1,5‐Diaminonaphthalene on Graphene Nanosheets
Authors: Abdelwahab Adel A. , Naggar Ahmed H. , Abd‐Elmottaleb M. , Abdel‐Hakim Mohamed
Published: June 2022

An effective nanocomposite sensor for selective electroanalytical dopamine (DA) determination using overoxidized conducting polymer of poly‐1,5‐diaminonaphthalene (OPoly‐1,5‐DAN) functionalized graphene nanosheets (GNS) was achieved. The OPoly‐1,5‐DAN/GNS nanocomposite polymer was prepared via an electropolymerization of 1,5‐DAN on GNS/GCE after 7 cycles of potential scan (−0.2 V to +0.9 V), followed by an electrooveroxidation of the nanocomposite Poly‐1,5‐DAN/GNS by the potential cycle (0.0 V to +1.8 V) for 2 scans. The OPoly‐1,5‐DAN was effectively designed by GNS as a uniformly distribution of nanocomposite that caused more accumulations of analyte due to large electrocatalytic active positions created on electrode surface. The high specific and sensitive performance of the OPoly‐1,5‐DAN/GNS nanocomposite polymer was conducted to greater effective electrons transferring behavior for DA with copresent of vitamin C (VC). The stable and suitable formation of OPoly‐1,5‐DAN/GNS nanocomposite polymer showed rapid charge transport voltammogram and obvious electrocatalytic activity to DA and eliminated VC response. Moreover, the OPoly‐1,5‐DAN/GNS displays an excellent responses to DA determination with wide linear range (LR) 1.0–150 μM and lower detection limit (DL) 8.82±0.1 nM as comparing with other studies. Additionally, the excellent reproducibility of OPoly‐1,5‐DAN/GNS as well as long‐term stability indicated that it is an excellent and effective electrochemical DA sensor. Finally, the electroanalytical application of the OPoly‐1,5‐DAN/GNS nanocomposite polymer was employed for the electroanalysis of DA in human urine.
Joint steepest descent and non‐stationary Richardson method for low‐complexity detection in massive MIMO systems
Authors: Khoso Imran A. , Zhang Xiaofei , Dai Xiaoming , Ahmed Adeel , Dayo Zaheer Ahmed
Published: June 2022

Signal detection is a major challenge in massive multiple‐input multiple‐output (MIMO) wireless systems due to array of hundreds of antennas. Linear minimum mean square error (MMSE) enables near‐optimal detection performance in massive MIMO but suffers from unbearable computational complexity due to complicated matrix inversions. To address this problem, we propose a novel low‐complexity signal detector based on joint steepest descent (SD) and non‐stationary Richardson (NSR) iteration method. The SD is applied to get an efficient searching direction for the following NSR method to enhance the performance. The key idea of the proposed algorithm is to utilize a combination of the scaled‐diagonal initialization and the system‐ and iteration‐dependent acceleration mechanism, so that the convergence can be significantly speeded up. An antenna‐ and eigenvalue‐based scaling parameter is introduced for the proposed detector to further improve the error‐rate performance. We also provide convergence guarantees for the proposed technique. Numerical results demonstrate that the proposed joint detection approach attains superior performance compared to existing iterative approaches and provides a lower computational complexity than the conventional MMSE detector.
A weights direct determination neuronet for time‐series with applications in the industrial indices of the Federal Reserve Bank of St. Louis
Authors: Mourtas Spyridon D.
Published: June 2022

The shortcomings of conventional back‐propagation neuronets, such as slow training speed and local minimum, are known to be addressed by neuronets trained under the weights‐and‐structure‐determination (WASD) algorithm. Derived from power activation feed‐forward neuronets, a multi‐input WASD for time‐series neuronet (MI‐WASDTSN) model is presented in this paper. The MI‐WASDTSN is equipped with a novel WASD for time‐series (WASDTS) algorithm, for handling time‐series modeling and forecasting problems. Employing a power sigmoid activation function, the WASDTS algorithm handles the model fitting and validation by determining the optimal input variables number and the weights of the MI‐WASDTSN. More specifically, the WASDTS algorithm finds and holds only the activation function powers that reduce the model's error during validation. Applications on Federal Reserve Bank of St. Louis (FRED) industrial indices under three different patterns of time‐series validate our MI‐WASDTSN model in order to demonstrate its outstanding learning and forecasting performance. In addition, to support and advance the findings of this work, we created a MATLAB repository for interested users, which is freely available via GitHub.
Carer burden and psychological distress in young‐onset dementia: An Australian perspective
Authors: Kang Matthew , Farrand Sarah , Walterfang Mark , Velakoulis Dennis , Loi Samantha M. , Evans Andrew
Published: June 2022

Objectives

Carer burden in dementia is associated with poor outcomes, including early nursing home placement for people with dementia and psychological distress for their carers. Carers of people with young‐onset dementia (YOD) are particularly vulnerable to carer burden. Yet they are often overlooked by clinicians as dementia services are generally designed for older people. We sought to estimate the rate of burden and psychological distress in carers of YOD at a state‐wide tertiary service based in Australia.

Methods

We conducted a cross‐sectional study examining 71 dyads from a Neuropsychiatry service. We collected patient demographic and clinical data including the Neuropsychiatry Unit Cognitive Assessment tool (NUCOG) and Mini‐Mental State Examination (MMSE). Carer data, such as demographics and psychological distress, were obtained using Depression Anxiety Stress Scale 21 (DASS‐21). Carer burden was rated using the Zarit Burden Inventory‐short version (ZBI).

Results

Higher carer burden, measured using ZBI, was associated with longer duration of dementia and greater severity of overall cognitive impairment. Carers who felt burdened reported higher levels of stress, depression, and anxiety measured using DASS‐21. Multiple linear regression analysis found carer burden was independently predicted by duration of dementia, total cognition score and carers experiencing psychological stress.

Discussion

We found that patient variables of dementia duration and cognitive impairment and carer variable of carer stress to be associated with carer burden. Poor executive function was associated with carer stress. Early identification and management of carer burden and psychological distress is important for outcomes. Ideally, this should be provided by a specialist YOD service.
Elevated liver enzymes predict morbidity and mortality despite antiviral cure in patients with chronic hepatitis C: Data from the German Hepatitis C‐Registry
Authors: Tacke Frank , Klinker Hartwig , Boeker Klaus H. W. , Merle Uta , Link Ralph , Buggisch Peter , Hüppe Dietrich , Cornberg Markus , Sarrazin Christoph , Wedemeyer Heiner , Berg Thomas , Mauss Stefan ,   DHC‐R
Published: June 2022

While direct‐acting antivirals (DAAs) cure chronic hepatitis C virus (HCV) infection in almost all patients, some patients remain at risk of liver disease despite HCV cure. In order to identify risk factors indicating liver‐related morbidity and death after viral cure, we included 6982 patients from the national multicenter real‐world German Hepatitis C Registry with regular follow‐up visits for up to 7 years after DAA therapy. Definitions for normal liver function tests (in women/men) were alanine aminotransferase (ALT; ≤35/≤50 U/L), ALT according to American Association for the Study of Liver Diseases (AASLD; ≤19/≤30 U/L), and gamma‐glutamyltransferase (GGT; ≤40/≤60 U/L). In our cohort, 97.4% of patients achieved sustained virologic response (SVR). At 24 weeks after SVR (SVR24), elevated ALT occurred in 657/6982 (9.4%), elevated ALT (AASLD) in 2609/6982 (37.4%), and elevated GGT in 1777/6982 (25.5%) patients. Risk factors for increased ALT at SVR24 were obesity, alcohol, cirrhosis, elevated baseline ALT, and non‐SVR. Increased GGT at SVR24 was significantly (p < 0.05) and independently associated with male sex (odds ratio [OR], 2.12), higher body mass index (OR, 1.04), age >50 years (OR, 1.60), liver cirrhosis (OR, 3.97), alcohol consumption (OR, 2.99), diabetes (OR, 1.63), non‐SVR (OR, 8.00), and elevated GGT at baseline (OR, 17.12). In multivariate regression analysis, elevated GGT at SVR24, particularly in combination with cirrhosis, was the best predictor for hepatic decompensation, hepatocellular carcinoma development, and death, followed by elevated ALT (AASLD) and standard ALT, which predicted hepatic decompensation. Despite successful HCV therapy, elevated GGT at SVR24 and to a lesser extent ALT are predictive of the future clinical outcome and linked with liver‐associated comorbidities. This may highlight the relevance of nonalcoholic fatty liver disease, diabetes mellitus, alcohol, and cirrhosis for the clinical outcome in a vulnerable population, even after HCV cure.
Latin American Attachment studies: A narrative review
Authors: Fourment Katherine , Espinoza Camila , Ribeiro Ana Carla Lima , Mesman Judi
Published: June 2022

Attachment theory´s core hypotheses (universality, normativity, sensitivity, and competence) are assumed to be applicable worldwide. However, the majority of studies on attachment theory have been conducted in Western countries, and the extent to which these core hypotheses are supported by research conducted in Latin America has never been systematically addressed. The purpose of this systematic narrative literature review is to provide an integrative discussion of the current body of empirical studies concerning attachment theory conducted in Latin American countries. For that purpose, a search was conducted in four electronic databases (Web of Science, PsycInfo, SciELO, and Redalyc) and 82 publications on attachment and/or sensitivity met inclusion criteria. None of the studies reported cases in which an attachment relationship was absent, and a predominance of secure attachment patterns was found, mainly for non‐risk samples (NRS). Sensitivity levels were generally deemed adequate in NRS, and related to attachment quality. Attachment security and caregivers’ sensitivity were positively associated with child outcomes. Attachment‐based intervention studies mostly showed efficacy. In conclusion, Latin American research supports the key theoretical assumptions of attachment theory, mainly in samples of urban middle‐class NRS. However, the field of attachment‐related research would be enriched by also investing in Latin American studies on caregiving rooted in local concepts and theories.
Actinium coordination chemistry: A density functional theory study with monodentate and bidentate ligands
Authors: Tomeček Josef , Li Cen , Schreckenbach Georg
Published: June 2022

In the current study, the coordination chemistry of nine‐coordinate Ac(III) complexes with 35 monodentate and bidentate ligands was investigated using density functional theory (DFT) in terms of their geometries, charges, reaction energies, and bonding interactions. The energy decomposition analysis with naturals orbitals for chemical valence (EDA‐NOCV) and the quantum theory of atoms in molecules (QTAIM) were employed as analysis methods. Trivalent Ac exhibits the highest affinities toward hard acids (such as charged oxophilic donors, fluoride), so its classification as a hard acid is justified. Natural population analysis quantified the involvement of 5f orbitals on Ac to be about 30% of total valence electron natural configuration indicating that Ac is a member of the actinide series. Pearson correlation coefficients were used to study the pairwise correlations among the bond lengths, ΔGreaction energies, charges on Ac and donor atoms, and data from EDA‐NOCV and QTAIM. Strong correlations and anticorrelations were found between Voronoi charges on donor atoms with ΔG, EDA‐NOCV interaction energies and QTAIM bond critical point densities.
Immunophenotyping of lymphocytes and monocytes and the status of cytokines in the clinical course of Covid‐19 patients
Authors: Idiz Ufuk O. , Yurttas Tahir T. , Degirmencioglu Serife , Orhan Bagnu , Erdogan Emre , Sevik Husnu , Sevinc Mert M.
Published: June 2022

Lymphopenia, T cell subgroup changes, and cytokine level differences are important in the early diagnosis and treatment of Covid‐19 cases and similar pandemics. We aimed to investigate the T cell, monocyte subgroups, and cytokine differences according to disease severity. A total of 46 volunteers were included in the study. According to disease status, there were three groups (control, mild, and severe). The age, gender, smoking status, temperature, heart rate and oxygen saturation, complete blood count, C‐reactive protein (CRP) was noted, and flow cytometric analyses were performed for T cell and monocyte subgroups, and cytokine levels. Temperature, heart rate, SPO2, white blood cell (WBC), lympocyte count, trombocyte count, neutrophil/lymphocyte ratio, D‐dimer and CRP levels, lymphocyte %, lymphocyte/monocyte rate, monocyte subtypes (%), CD3+, CD4+, CD8+ cell counts, interleukin (IL)‐1β, TNF‐alpha, monocyte chemoattractant protein (MCP)‐1, IL‐6, IL‐8, IL‐10, IL‐18, IL‐23 were significantly different between groups. CRP, IL‐8, neutrophil/lymphocyte ratio, NK cells (%) have positive correlation and negative correlation was observed at lymphocyte (count), lymphocyte (%), lymphocyte/monocyte, classical monocyte (%), lymphocyte (count), CD3+ (count), CD4+ (count). As conclusion, lymphocyte (%), Lymphocyte (count), CRP levels, CD3+ and CD4+ cell counts strongly correlate with disease severity are valuable parameters for determining the prognoses of Covid‐19.
Evaluation of periodontal status and cytokine levels in saliva and gingival crevicular fluid of patients with inflammatory bowel diseases
Authors: Enver Ayaz , Ozmeric Nurdan , Isler Sila Cagri , Toruner Murat , Fidan Cigdem , Demirci Gulsah , Elgun Serenay , Silva Andre Paes B. da
Published: June 2022

Background

Periodontal diseases and inflammatory bowel diseases (IBD, ulcerative colitis [UC] and Crohn disease [CD]) have been reported to present with increased salivary and gingival crevicular fluid (GCF) concentrations of cytokines. The aim of this study was to evaluate the salivary and GCF levels of TNF‐α, IL‐1β, IL‐10, and IL‐17A and their associations with the periodontal statuses of UC, CD, and non‐IBD patients, and to analyze the interrelationships among these cytokines, IBD conditions, and periodontal diseases.

Methods

This cross‐sectional study was performed with a total of 131 patients (62 women and 69 men, mean age 42.96±13.02 years). Patients were divided into three groups: UC, CD, and non‐IBD. Periodontal status was defined according to the 2017 World Workshop Disease Classification. Salivary and GCF cytokine levels were analyzed using ELISA.

Results

UC and CD patients diagnosed as having periodontitis and gingivitis presented with significantly higher levels of TNF‐α and lower levels of IL‐10 as compared with non‐IBD patients (p<0.05). UC patients diagnosed with periodontitis exhibited significantly higher scores of bleeding on probing (p = 0.011) and increased salivary and GCF IL‐1β levels as compared with CD patients (p = 0.005, and 0.012, respectively). Considering the active and remission status of IBD, salivary IL‐1β was found to be correlated with the parameters representing the severity of periodontal diseases in active UC and CD patients.

Conclusion

In the presence of periodontal diseases, UC and CD patients showed different expression levels of TNF‐α, IL‐1β, and IL‐10 in oral secretions as compared with non‐IBD patients.
Hyperthermic intraperitoneal chemotherapy does not increase risk of major complication or failure to rescue in cytoreductive surgery
Authors: Macfie Rebekah C. , Cha Da Eun , Gleeson Elizabeth , Yu Allen , Cohen Noah , Sarpel Umut , Golas Benjamin , Hiotis Spiros , Labow Daniel
Published: June 2022

Introduction

Failure to rescue (FTR) is defined as death after a major complication. We evaluated FTR after cytoreductive surgery (CRS) with and without hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

The ACS NSQIP database 2005–2018 was reviewed for all cases of CRS. Propensity score matching was used to compare outcomes between those undergoing CRS alone and those undergoing CRS/HIPEC. Patients were matched on age, sex, ascites, diabetes, hypertension and resection of liver, pancreas, colon/rectum, diaphragm, stomach, small bowel, and/or spleen.

Results

Thirty nine thousand one hundred and twenty‐six patients underwent CRS; 38,387 underwent CRS alone; 739 underwent CRS/HIPEC. After matching there were 726 patients in each arm. Patients undergoing CRS/HIPEC had higher risk of reintubation (25 [3.4%] vs. 13 [1.8%] p = 0.049), urinary tract infection UTI (44 [6.1%] vs. 25 [3.4%] p = 0.019) and sepsis (73 [10.1%] vs. 44 [6.1%] p = 0.005). Patients in the CRS arm required more transfusions (229 [31.5%] vs. 176 [24.2%] p = 0.002).

There was no significant difference in FTR between the CRS and CRS/HIPEC groups (11 [4.0%] vs. 6 [2.3%] p = 0.258), nor in the pooled incidence of major complications (275 [37.9%] vs. 262 [36.1%] p = 0.48).

Conclusion

CRS/HIPEC is associated with increased rates of reintubation, UTI, and sepsis while CRS alone was associated with increased transfusion. However, the addition HIPEC to CRS did not increase the risk of pooled major complication or FTR.
Comparative pharmacokinetic studies of five C‐glycosylflavones in normal and urolithiasis model rats following administration of total flavonoids from Desmodium styracifolium by liquid chromatography‐tandem mass spectrometry
Authors: Li Xue , Chen Chao , Zhang Tianjiao , Ding Nan , Zheng Peiyong , Yang Ming
Published: June 2022

The total flavonoids of Desmodium styracifolium are the flavonoid extracts purified from Desmodii Styracifolii Herba, which has conventionally been used for treating urolithiasis in China. In this study, a sensitive and simple liquid chromatography‐tandem mass spectrometry method was developed to simultaneously determine five active components of the extracts in rat plasma. Chromatographic separation of the analytes (schaftoside, vicenin‐1, vicenin‐2, vicenin‐3, and isovitexin) was performed on an ACQUITY UPLC HSS T3 Column under gradient elution conditions. The calibration curves were linear over ranges from 0.5 to 100 ng/ml for schaftoside, vicenin‐1, vicenin‐2, and vicenin‐3, and 0.2–20 ng/ml for isovitexin. The relative standard deviation of intra‐ and inter‐day precisions were ≤6.8% and ≤8.3%, respectively, and the accuracies (relative error) were within ±7.6%. The recoveries of the analytes ranged between 97.3% and 100.3%, and the matrix effects ranged from 98.6% to 113.8%. The method was successfully applied to the pharmacokinetic studies of the five active ingredients of Desmodium styracifolium, for the first time, in both normal and urolithiasis model rats. Results revealed that the plasma levels of these components were significantly increased under the pathological state. This study provided valuable information facilitating the clinical investigation of this medicine.
Trace determination of perchlorate in drinking water by capillary zone electrophoresis with isotachophoresis sample cleanup and conductivity detection
Authors: Žabenský Branislav , Bodor Róbert , Makata Dávid , Szucs Roman , Masár Marián
Published: June 2022

An analytical test procedure for the direct determination of trace levels of perchlorate in drinking water by isotachophoresis combined with capillary zone electrophoresis was developed. A capillary electrophoresis analyzer with column coupling technology, capable of combining capillaries with different internal diameters, was employed in combination with conductivity detection. This combination of the capillary electrophoresis techniques facilitated preconcentration of the trace analytes and elimination of potentially interfering macro‐components. To eliminate the influence of weak and moderately strong acids on the migration of perchlorate, acidic leading electrolyte (pH 3.2) in the isotachophoresis step and acidic background electrolyte (pH 3.9) in the zone electrophoresis step were chosen. The addition of polyvinylpyrrolidone into the electrolytes enhanced the resolution of perchlorate from other anions, especially remaining anionic macro‐components. The developed method is characterized by good repeatability of migration time (relative standard deviation less than 0.2%) as well as peak area (relative standard deviation less than 5.9%), linearity (R = 0.9996), recoveries (100–112%), and sample throughput (90 samples/24 h). The limit of quantitation for perchlorate in drinking water was achieved at 12.5 nmol/L (1.25 μg/L). This approach is more sensitive and more robust than transient isotachophoresis and offers advantages over some more established analytical techniques such as ion chromatography.
Thinning effects on forest production and rainfall redistribution: Reduced soil water deficit and improved sustainability of semiarid plantation forestlands
Authors: Meng Ling‐Chao , Cui Zeng , Huang Ze , Lucas‐Borja Manuel Esteban , Dunkerley David , Wu Gao‐Lin
Published: June 2022

Large‐scale planted afforestation worldwide has exacerbated soil desiccation and led to a serious shortage of water resources for forests sustainability in semiarid areas. Consequently, thinning is discussed as an important management approach to conserve water resources and to maintain plantation forestland sustainability. Here, we explored the effects of thinning intensity on semiarid forest production and soil water supply. Three artificial forests of Populus cathayana with an age of 15 yr were selected and thinned with different intensities [1/3 amount of trees removed (T1/3), 2/3 amount of trees removed (T2/3), and using no thinning (NT) as a control]. Results showed that thinning presented a significant impact on the above‐ground three‐dimensional structure of planted forests and increased forest gaps. Meanwhile, the rainfall redistribution pattern changed significantly. Thinning increased throughfall (T1/3, 43% ± 9%; T2/3, 79% ± 18%), reduced stemflow (T1/3, −44 ± 2%; T2/3, −71% ± 2%), and increased the soil water replenishment (T1/3, 34% ± 7%; T2/3, 64% ± 19%) of forest land. Meanwhile, the dead root channel caused by thinning effectively increased the water infiltration rate and groundwater replenishment, and effectively reduced soil water deficit (T1/3, 41% ± 33%; T2/3, 57% ± 33%). Through trade‐off analysis, we found that non‐thinning aboveground biomass yields were the highest, and T2/3 yields higher water yield, while T1/3 can maintain acceptable aboveground biomass while keeping better soil water. We conclude that thinning increased soil water supply, reduced soil water deficit and maintained forestland sustainability, and there are synergies of thinning on forest production and soil water supply through rainfall redistribution for maintaining the sustainability of semiarid plantation forestlands.
Burden of early hospitalization after simultaneous liver–kidney transplantation: Results from the US Multicenter SLKT Consortium
Authors: Sharma Pratima , Xie Jiaheng , Wang Leyi , Zhang Min , Magee John , Answine Adeline , Barman Pranab , Jo Jennifer , Sinha Jasmine , Schluger Aaron , Perreault Gabriel J. , Walters Kara E. , Cullaro Giuseppe , Wong Randi , Filipek Natalia , Biggins Scott W. , Lai Jennifer C. , VanWagner Lisa B. , Verna Elizabeth C. , Patel Yuval A.
Published: June 2022

The burden of early hospitalization (within 6 months) following simultaneous liver–kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6‐month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6–63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non–alcohol‐associated fatty liver disease, 23% alcohol‐associated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End‐Stage Liver Disease–sodium scores were 27.2 kg/m2 (IQR, 23.6–32.2 kg/m2) and 28 (IQR, 23–34), respectively. Two‐thirds of the cohort had at least one hospitalization within the first 6 months of SLKT. Age, race, hospitalization at SLKT, diabetes mellitus, BMI, and discharge to subacute rehabilitation (SAR) facility after SLKT were independently associated with a high incidence rate ratio of early hospitalization. Number of hospitalizations within the first 6 months did not affect conditional survival. Early hospitalizations after SLKT were very common but did not affect conditional survival. Although most of the risk factors for early hospitalization were nonmodifiable, discharge to SAR after initial SLKT was associated with a significantly higher incidence rate of early hospitalization. Efforts and resources should be focused on identifying SLKT recipients at high risk for early hospitalization to optimize their predischarge care, discharge planning, and long‐term follow‐up.