bluuebunny/crossref_metadata_2025 huggingface dataset:
Toward a theory‐based specification of non‐pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations
Authors: Sikkes Sietske A.M. , Tang Yi , Jutten Roos J. , Wesselman Linda M.P. , Turkstra Lyn S. , Brodaty Henry , Clare Linda , Cassidy‐Eagle Erin , Cox Kay L. , Chételat Gaël , Dautricourt Sophie , Dhana Klodian , Dodge Hiroko , Dröes Rose‐Marie , Hampstead Benjamin M. , Holland Thomas , Lampit Amit , Laver Kate , Lutz Antoine , Lautenschlager Nicola T. , McCurry Susan M. , Meiland Franka J. M. , Morris Martha Clare , Mueller Kimberly D. , Peters Ruth , Ridel Gemma , Spector Aimee , van der Steen Jenny T. , Tamplin Jeanette , Thompson Zara ,   ISTAART Non‐pharmacological Interventions Professional Interest Area, Bahar‐Fuchs Alex
Published: November 2020

Introduction

Non‐pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results.

Methods

In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System.

Results

Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols.

Discussion

We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.
Item response theory analysis of the Clinical Dementia Rating
Authors: Li Yan , Xiong Chengjie , Aschenbrenner Andrew J. , Chang Chih‐Hung , Weiner Michael W , Nosheny Rachel L , Mungas Dan , Bateman Randall J , Hassenstab Jason , Moulder Krista L , Morris John C
Published: November 2020

Introduction

The Clinical Dementia Rating (CDR) is widely used in Alzheimer's disease research studies and has well established reliability and validity. To facilitate the development of an online, electronic CDR (eCDR) for more efficient clinical applications, this study aims to produce a shortened version of the CDR, and to develop the statistical model for automatic scoring.

Methods

Item response theory (IRT) was used for item evaluation and model development. An automatic scoring algorithm was validated using existing CDR global and domain box scores as the reference standard.

Results

Most CDR items discriminate well at mild and very mild levels of cognitive impairment. The bi‐factor IRT model fits best and the shortened CDR still demonstrates very high classification accuracy (81%∼92%).

Discussion

The shortened version of the CDR and the automatic scoring algorithm has established a good foundation for developing an eCDR and will ultimately improve the efficiency of cognitive assessment.
The Autism‐Related lncRNA MSNP1AS Regulates Moesin Protein to Influence the RhoA, Rac1, and PI3K/Akt Pathways and Regulate the Structure and Survival of Neurons
Authors: Luo Ting , Ou Jin‐Nan , Cao Li‐Fang , Peng Xiao‐Qing , Li Ya‐Min , Tian Yong‐Quan
Published: November 2020

Autism spectrum disorder (ASD) is a complex disease involving multiple genes and multiple sites, and it is closely related to environmental factors. It has been gradually revealed that long noncoding RNAs (lncRNAs) may regulate the pathogenesis of ASD at the epigenetic level. In neuronal cells, the lncRNA moesin pseudogene 1 antisense (MSNP1AS) forms a double‐stranded RNA with moesin (MSN) to suppress moesin protein expression. MSNP1AS overexpression can activate the RhoA pathway and inhibit the Rac1 and PI3K/Akt pathways; however, the regulation of Rac1 by MSNP1AS is not associated with MSN, and the effect on the RhoA pathway may also be associated with other factors. MSNP1AS can decrease the number and length of neurites, inhibit neuronal cell viability and migration, and promote apoptosis. Downregulation of MSN expression functions similarly to MSNP1AS, and its overexpression can block the above functions of MSNP1AS. In addition, in vivo experiments show that MSN improves social interactions and reduces repetitive behaviors in BTBR mice, decreases the activity of RhoA and restores the activity of PI3K/Akt pathway. Therefore, the abnormal expression of MSNP1AS in ASD patients might influence the structure and survival of neuronal cells through the regulation of moesin protein expression to facilitate the development and progression of ASD. These findings provide new evidence for studying the mechanisms of lncRNAs in ASD.

Lay Summary

Autism spectrum disorder (ASD) is a common neurodevelopmental disease and its neurodevelopmental mechanisms have not been elucidated. More and more studies have found that long noncoding RNAs (lncRNAs) can regulate the development of central nervous system in many ways and affect the pathogenic process of ASD. Moesin pseudogene 1 antisense (MSNP1AS) is an up‐regulated lncRNA in ASD patients. In‐depth functional experiments showed that MSNP1AS inhibited moesin protein expression and regulated the activation of multiple signaling pathways, thus decreasing the number and length of neurites, inhibiting neuronal cell viability and migration, and promoting apoptosis. Therefore, MSNP1AS is an important lncRNA related to ASD and can regulate the biological function of neurons.
Association between arterial stiffness and the presence of cerebral small vessel disease markers
Authors: Bae Jae‐Han , Kim Jeong‐Min , Park Kwang‐Yeol , Han Su‐Hyun
Published: November 2020

Objective

We investigated the effect of arterial stiffness on the severity of enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) at different brain locations.

Methods

A total of 854 stroke patients underwent both brachial‐ankle pulse wave velocity (baPWV) measurement and brain MRI. The extent of EPVS was separately rated at the levels of the basal ganglia (BG) and centrum semiovale (CS). The CMBs were categorized as strictly lobar CMB and deep CMB. The patients were categorized according to baPWV quartiles, and multivariable logistic regressions were performed to evaluate whether the baPWV increment was independently associated with each cerebral SVD marker at different locations. The odds ratio (OR) with 95% confidence interval (CI) was derived on the reference of the first quartile.

Results

Severe EPVSs at BG and CS were detected in 243 (28.5%) and 353 patients (41.3%), respectively. The increment of baPWV quartiles was associated with both severe BG EPVS burden (Q4: OR = 2.58, CI = 1.45–4.60) and severe CS EPVS burden (Q4: OR = 2.06, CI = 1.24–3.42). Deep CMBs were found in 259 patients (30.3%), and strictly lobar CMBs were found in 170 patients (19.9%). Multivariable logistic regression model revealed deep CMB was independently associated with the baPWV increment (Q4: OR = 2.52, CI = 1.62–3.94). However, strictly lobar CMB had a neutral relationship with baPWV.

Conclusion

Increased arterial stiffness is consistently associated with the presence of deep CMB and severe EPVS burden at the BG and CS, suggesting a common pathophysiologic mechanism.
Clinical characteristics and management of immune checkpoint inhibitor‐related pneumonitis: A single‐institution retrospective study
Authors: Wang Hanping , Zhao Yanwei , Zhang Xiaotong , Si Xiaoyan , Song Peng , Xiao Yi , Yang Xu , Song Lan , Shi Juhong , Zhao Haitao , Zhang Li
Published: November 2020

Introduction

The increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization.

Methods

Patients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections.

Results

In total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP.

Conclusions

The clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored.
Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low‐molecular‐weight heparin
Authors: Patel Sandip H. , George Tiffany L. , Wang Tzu‐Fei , Vogt Sherry M. , Folefac Edmund , Xu Menglin , Yang Yuanquan , Parikh Anish B. , Verschraegen Claire F. , Clinton Steven K. , Yin Ming
Published: November 2020

Background

Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low‐molecular‐weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized.

Methods

Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups.

Results

Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow‐up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28‐4.69 [P = .007]) and first‐onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13‐4.42 [P = .02]). Analysis of 6‐month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone.

Conclusions

Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone.
A hybrid indicator many‐objective optimization algorithm for the selection and delivery of disaster relief materials problem
Authors: Zhu Zhuanghua
Published: November 2020

Traditional methods fail to comprehensively consider the selection and delivery of disaster relief materials (SDDM) problem. To solve the problem, the SDDM will be comprehensively considered in this article, which will be built into a many‐objective disaster relief materials selection and delivery model with four objectives to be optimized in the last kilometer of the disaster relief organization. Meanwhile, a many‐objective optimization algorithm is designed to solve the proposed disaster relief materials model by employing the different excellent indicators. Two extensive simulation experiments are carried out. On the one hand, the performance of the designed many‐objective is tested on DTLZ and WFG benchmark functions. On the other hand, the proposed many‐objective model is solved by employing the designed algorithm. In addition, the simulation result shows that the designed algorithm is effective in solving the SDDMs problem.
Recent Progress of Transition Metal Phosphides for Photocatalytic Hydrogen Evolution
Authors: Hong Long‐fei , Guo Rui‐tang , Yuan Ye , Ji Xiang‐yin , Lin Zhi‐dong , Li Zheng‐sheng , Pan Wei‐guo
Published: November 2020

Photocatalytic hydrogen evolution can effectively alleviate the troublesome global energy crisis by converting solar energy into the chemical energy of hydrogen. In order to realize efficient hydrogen generation, a variety of semiconductor materials have been extensively investigated, including TiO2, CdS, g‐C3N4, metal‐organic frameworks (MOFs), and others. In recent years, to achieve higher photocatalytic performance and reach the level of large‐scale industrial applications, photocatalysts decorated with transition metal phosphides (TMPs) have shone brightly because of their low cost, stable physical and chemical properties, and substitution for precious metals of TMPs. This Review highlights the preparation methods and properties associated with photocatalysis of TMPs. Moreover, the H2 generation efficiency of photocatalysts loaded with TMPs and the roles of TMPs in catalytic systems are also studied systematically. Apart from being co‐catalysts, several TMPs can also serve as host catalysts to boost the activity of photocatalytic composites. Finally, the development prospects and challenges of TMPs are put forward, which is valuable for future researchers to expand the application of TMPs in photocatalytic directions and to develop more active photocatalytic systems.
Assessment of cytological features of glandular lesions of the cervix on conventional smear preparations—a comprehensive study from a tertiary care hospital
Authors: Mantri Shweta , Ravikumar Gayatri , Crasta Julian
Published: November 2020

Background

Atypical glandular cells (AGC) as a diagnostic category in cervicovaginal cytology remains as a challenge to cytopathologists.

Aims

The aim of the present study is to identify the cytological features helpful in categorizing AGC as reactive or neoplastic upon correlation with histology.

Materials and Methods

The study was a retrospective review of cervical smears, with histopathological follow up, reported as glandular lesions for a period of 9 years. The architectural and nuclear features studied were adapted from The Bethesda System (TBS) to stratify the lesions as AGC, AGC‐FN (atypical glandular cells favour neoplasia) and adenocarcinoma. The cytological categories were correlated with histology.

Results

A total of 89 cases of which 67 (AGC NOS = 34, AGC FN = 19, adenocarcinoma = 14) with histology were reviewed. Neoplastic lesions were encountered in 14 cases (34.6%). Of the cases diagnosed as AGC‐NOS, AGC‐FN and adenocarcinoma, 26.5%, 68.4% and 100% respectively were neoplastic on histopathology. Squamous lesions accounted for 14.9% of all the glandular lesions. Rosette or acinar formation and loss of polarity frequently observed in neoplastic lesions as compared to reactive changes (p = 0.0004, p = 0.001). Of the nuclear features, nuclear hyperchromasia or coarse clumping of chromatin along with nuclear membrane irregularity and nuclear pleomorphism was frequently associated with neoplastic lesions as compared to reactive conditions (p = 0.007, p = 0.001, p = 0.0002).

Conclusion

A diagnosis of AGC at cytology harbors significant number of malignant lesions when confirmed on biopsy. Architectural features complemented with nuclear characteristics helps in differentiating between reactive and neoplastic conditions. Hence stratifying glandular lesions at cytology according to TBS helps in the management.
Proposal to optimize evaluation and treatment of Febrile infection‐related epilepsy syndrome (FIRES): A Report from FIRES workshop
Authors: Koh Sookyong , Wirrell Elaine , Vezzani Annamaria , Nabbout Rima , Muscal Eyal , Kaliakatsos Marios , Wickström Ronny , Riviello James J. , Brunklaus Andreas , Payne Eric , Valentin Antonio , Wells Elizabeth , Carpenter Jessica L. , Lee Kihyeong , Lai Yi‐Chen , Eschbach Krista , Press Craig A. , Gorman Mark , Stredny Coral M. , Roche William , Mangum Tara
Published: November 2020

Febrile infection‐related epilepsy syndrome (FIRES) is a rare catastrophic epileptic encephalopathy that presents suddenly in otherwise normal children and young adults causing significant neurological disability, chronic epilepsy, and high rates of mortality. To suggest a therapy protocol to improve outcome of FIRES, workshops were held in conjunction with American Epilepsy Society annual meeting between 2017 and 2019. An international group of pediatric epileptologists, pediatric neurointensivists, rheumatologists and basic scientists with interest and expertise in FIRES convened to propose an algorithm for a standardized approach to the diagnosis and treatment of FIRES. The broad differential for refractory status epilepticus (RSE) should include FIRES, to allow empiric therapies to be started early in the clinical course. FIRES should be considered in all previously healthy patients older than two years of age who present with explosive onset of seizures rapidly progressing to RSE, following a febrile illness in the preceding two weeks. Once FIRES is suspected, early administrations of ketogenic diet and anakinra (the IL‐1 receptor antagonist that blocks biologic activity of IL‐1β) are recommended.
Efficacy and safety of adjunctive perampanel in patients with focal seizures or generalized tonic‐clonic seizures: Post hoc analysis of Phase II and Phase III double‐blind and open‐label extension studies in India
Authors: Mehndiratta Man M. , Gulhane Manoj , Jabeen Shaik A. , Patten Anna , Dash Amitabh , Malhotra Manoj
Published: November 2020

Objective

This post hoc analysis assessed the efficacy and safety of adjunctive perampanel in patients (aged ≥ 12 years) with focal seizures (FS), with/without focal to bilateral tonic‐clonic seizures (FBTCS), or generalized tonic‐clonic seizures (GTCS) in India.

Methods

Centers in India were identified from six double‐blind, randomized, Phase II and Phase III studies of adjunctive perampanel (2–12 mg/day) and their open‐label extensions (OLEx). Efficacy assessments included median percent change in seizure frequency per 28 days, 50% and 75% responder and seizure‐freedom rates. Treatment‐emergent adverse events (TEAEs) were monitored.

Results

Overall, 128 patients (placebo, n = 39; perampanel, n = 89) were included in the double‐blind Safety Analysis Set and 126 (FS, n = 113 [placebo, n = 32; perampanel, n = 81]; FBTCS, n = 35 [placebo, n = 14; perampanel, n = 21]; GTCS, n = 13 [placebo, n = 6; perampanel, n = 7]) comprised the Full Analysis Set. Median percent reductions in seizure frequency per 28 days for placebo vs perampanel for Indian patients were as follows: 34.8% vs 49.8% (FS; not significant [NS]) and 43.1% vs 60.5% (FBTCS; NS) at 4–12 mg/day, respectively, and −22.4% vs 8.2% (GTCS; NS) at 8 mg/day, respectively. Fifty‐percent responder rates were 37.5% vs 55.1% (FS; NS), 42.9% vs 60.0% (FBTCS; NS), and 16.7% vs 42.9% (GTCS; NS), respectively; seizure‐freedom rates were 0.0% vs 5.8%, 7.1% vs 10.0%, and 0.0% vs 14.3%, respectively (all NS). Overall, 110 patients entered OLEx studies (FS, n = 99; GTCS, n = 11). Perampanel was efficacious for up to four years for FS and FBTCS and two years for GTCS. Across double‐blind and OLEx studies, TEAEs occurred in 58.4% and 83.6% of Indian perampanel‐treated patients, respectively; dizziness was most common. Efficacy and safety outcomes were generally similar overall between Indian and non‐Indian patients.

Significance

These data suggest adjunctive perampanel (up to 12 mg/day) may be a suitable anti‐seizure medication for patients (aged ≥ 12 years) with FS, with/without FBTCS, or GTCS in India.
Gene expression profile unveils diverse biological effect of serum vitamin D in Hodgkin's and diffuse large B‐cell lymphoma
Authors: Donati Benedetta , Ferrari Angela , Ruffini Alessia , Manzotti Gloria , Fragliasso Valentina , Merli Francesco , Zanelli Magda , Valli Riccardo , Luminari Stefano , Ciarrocchi Alessia
Published: November 2020

The primary function of 25(OH)Vitamin D (VitD) is to control calcium; however, recent evidence associated serum VitD deficiency to high aggressiveness and worse outcome in different type of malignancies including lymphomas, and the reasons of such effect are to be defined. In this study, we investigated the association of VitD blood levels with gene expression in a retrospective cohort of 181 lymphomas (104 diffuse large B‐cell lymphomas [DLBCLs] and 77 classical Hodgkin's lymphomas [cHLs]) of whom 116 with available gene expression profiles (52 DLBCLs and 64 cHLs, respectively). In DLBCL, VitD deficiency did not cause significant alteration in gene expression suggesting different mechanisms of action including a possible systemic effect or an effect on pharmacokinetics. By contrast, in cHLs, VitD deficiency induced profound changes in the transcriptional program leading to the NF‐κB‐mediated activation of stress‐protective and pro‐survival pathways. Coherently, VitD signaling defined by vitamin D Receptor (VDR) expression analysis, resulted highly activated in cHLs but not in DLBCLs. Even if preliminary, these data represent the first evidence of a direct role of VitD in the biology of cHL and suggest a multimodality and disease‐specific activity of this vitamin in lymphomas.
A δ18O and δ2H stable water isotope analysis of subalpine forest water sources under seasonal and hydrological stress in the Canadian Rocky Mountains
Authors: Langs Lindsey E. , Petrone Richard M. , Pomeroy John W.
Published: November 2020

Subalpine forests are hydrologically important to the function and health of mountain basins. Identifying the specific water sources and the proportions used by subalpine forests is necessary to understand potential impacts to these forests under a changing climate. The recent “Two Water Worlds” hypothesis suggests that trees can favour tightly bound soil water instead of readily available free‐flowing soil water. Little is known about the specific sources of water used by subalpine trees Abies lasiocarpa (Subalpine fir) and Picea engelmannii (Engelmann spruce) in the Canadian Rocky Mountains. In this study, stable water isotope (δ18O and δ2H) samples were obtained from S. fir and Engelmann spruce trees at three points of the growing season in combination with water sources available at time of sampling (snow, vadose zone water, saturated zone water, precipitation). Using the Bayesian Mixing Model, MixSIAR, relative source water proportions were calculated. In the drought summer examined, there was a net loss of water via evapotranspiration from the system. Results highlighted the importance of tightly vadose zone, or bound soil water, to subalpine forests, providing insights of future health under sustained years of drought and net loss in summer growing seasons. This work builds upon concepts from the “Two Water Worlds” hypothesis, showing that subalpine trees can draw from different water sources depending on season and availability. In our case, water use was largely driven by a tension gradient within the soil allowing trees to utilize vadose zone water and saturated zone water at differing points of the growing season.
Hurricane Katrina and the Gulf Oil Spill: Lessons learned about short‐term and long‐term effects
Authors: Osofsky Joy D. , Osofsky Howard J.
Published: November 2020

The impact and lessons learned from Hurricane Katrina and the Gulf Oil Spill are described as an example of work done reflecting best practices and theory to gain a better understanding of risk and resilience for children and families. Hurricane Katrina, described as the worst natural disaster in the US history, resulted in traumatic separations of children and families and devastation of communities and schools. The impact was greater on families with fewer resources before the hurricane who were provided limited support to return and rebuild. Insufficient community support and economic resources contributed to prolonged traumatiaation and slow recovery. Many were still recovering from Hurricane Katrina when impacted by the Gulf Oil Spill. For families with multigenerational ties to the fishing and oil industries, the Gulf Oil Spill resulted in both cumulative trauma and increased risk. In implementing the behavioural health response, much was learned about promotive and protective factors for individual and community resilience. Services provided following the disasters were based on precepts of individual, family, and community resilience. To enhance recovery and support resilience, the development of regional coalitions across at risk areas provides important coordination before disasters occur for better preparation and response.
Depressive Anhedonia and Creative Self‐concepts, Behaviors, and Achievements
Authors: Silvia Paul J. , Eddington Kari M. , Harper Kelly L. , Burgin Chris J. , Kwapil Thomas R.
Published: November 2020

In the large literature on creativity and mental illness, relatively few studies have explored anhedonia—impairments in anticipating, seeking, and experiencing rewards. This project explored self‐reported creativity in a sample of adults who differed in depressive anhedonia, determined via face‐to‐face structured clinical interviews. Participants completed measures of everyday creativity (engaging in common creative behaviors and hobbies), creative self‐concepts (creative self‐efficacy, creative personal identity, and self‐rated creativity in different domains), and creative achievements. Compared to the control group (n = 52), people in the anhedonia group (n = 22) had significantly higher engagement in little‐c creative activities (medium effect size). Effect sizes for self‐rated creativity and creative achievement were either small or near‐zero. Taken together, the findings suggest that anhedonia deserves more attention in future research on motivational aspects of creativity.
New function of polysaccharide from Rubus chingii Hu: protective effect against ethyl carbamate induced cytotoxicity
Authors: Ke Huihui , Bao Tao , Chen Wei
Published: November 2020

BACKGROUND

Rubus chingii Hu is a widely cultivated fruit in China and has declared multiple bioactivities including antioxidative activity. Ethyl carbamate (EC), mostly found in fermented food and alcoholic beverages, is a recognized human carcinogen, and researchers have proposed the correlation between oxidative stress and its toxicity. This study acquired the polysaccharide from R. chingii (RP) and explored its effect on EC‐induced cytotoxicity using Caco‐2 cells as the cell model.

RESULTS

Results showed that RP exhibited protection against EC‐induced toxicity by repairing redox imbalance as indicative of mitigated mitochondrial membrane potential collapse, attenuated reactive oxygen species overproduction, and impeded glutathione depletion. Moreover, the structural features of RP were characterized and revealed that it was mainly constituted by galacturonic acid and arabinose, with an average molecular weight of 7.039 × 105 g mol−1.

CONCLUSION

Overall, our results provided a new approach dealing with the toxicity caused by EC from the perspective of oxidative stress and described a new potential healthy value of R. chingii Hu, which could contribute to the development of a promising dietary supplement and functional food. © 2020 Society of Chemical Industry
The diverse functional genes of maize rhizosphere microbiota assessed using shotgun metagenomics
Authors: Akinola Saheed Adekunle , Ayangbenro Ayansina Segun , Babalola Olubukola Oluranti
Published: November 2020

Background

The geographical diversification in chemical, biological and physical properties of plant biospheres instigates heterogenicity in the proliferation of important soil microbiome. Controlling functions and structure of plant rhizosphere from a better understanding and prediction of a plantʼs immediate environment will help assess plant–microbe interplay, improve the productivity of plant ecosystems and improve plant response to adverse soil conditions. Here we characterized functional genes of the microbial community of maize rhizosphere using a culture‐independent method.

Results

Our metadata showed microbial genes involved in nitrogen fixation, phosphate solubilization, quorum sensing molecules, trehalose, siderophore production, phenazine biosynthesis protein, daunorubicin resistance, acetoin, 1‐aminocyclopropane‐1‐carboxylate deaminase, 4‐hydroxybenzoate, disease control and stress‐reducing genes (superoxidase dismutase, catalase, peroxidase, etc.). β‐Diversity showed that there is a highly significant difference between most of the genes mined from rhizosphere soil samples and surrounding soils.

Conclusions

The high relative abundance of stress‐reducing genes mined from this study showed that the sampling sites harbor not only important plant‐beneficial organisms but also a hotspot for developing bio‐fertilizers. Nevertheless, since most of these organisms are unculturable, mapping cultivation strategies for their growth could make them readily available as bio‐inoculants and possible biotechnological applications in the future. © 2020 Society of Chemical Industry
Generalized fractional integral operators on Orlicz–Hardy spaces
Authors: Arai Ryutaro , Nakai Eiichi , Sawano Yoshihiro
Published: November 2020

The generalized fractional integral operators are shown to be bounded from an Orlicz–Hardy space to another Orlicz–Hardy space , where Φ and Ψ are generalized Young functions. The result extends the boundedness of the usual fractional integral operator from to for and , which was proved by Stein and Weiss in 1960.
A high‐efficiency design for 5‐W 2.4/5.8 GHz concurrent dual‐band class‐E power amplifier
Authors: Nguyen Dang‐An , Seo Chulhun
Published: November 2020

In this letter, a distributed element‐based load network is proposed for designing a high‐efficiency dual‐band (DB) 5‐W Class‐E power amplifier (PA), at two widely spaced frequencies of 2.4 and 5.8 GHz. This network consists of two different stages. The first stage deploys a flexible network configuration with crossed transmission lines (TLINs) to provide concurrent DB fundamental matching in a closed‐form derivation, which transforms the standard resistance of 50 Ω directly to the optimal complex impedances. By tolerating the combination of the up‐side and down‐side TLINs, the size of the overall circuit as well as the implementation complexity are reduced. The second stage uses a DB TLIN‐based resonator preceded by a series 50 Ω stub to control the harmonic impedances without altering the fundamental impedances, ensuring high efficiency at the fundamental frequencies. The measured prototype shows highest power added efficiency (PAE) of around 62.9% and 61.7% with output power of about 39 and 35 dBm at 2.45 and 5.76 GHz, respectively.
Synthesis, properties, and molecular simulations of high‐barrier polyimide containing carbazole moiety and amide group in the main chain
Authors: Liu Yiwu , Tang Ao , Tan Jinghua , He Pan , Chen Chengliang , Wu Ding , Li Yuhui , Zhao Xianqing , Zhang Hailiang
Published: November 2020

An intrinsic high‐barrier polyimide (2,7‐CPAPPI) containing rigid planar carbazole moiety and amide group in main chain was prepared. The 2,7‐CPAPPI shows very attractive barrier performances, possessing water vapor transmission rate (WVTR) and oxygen transmission rate (OTR) low to 0.04 g m−2 day−1 and 0.11 cm3 m−2 day−1, respectively. Meanwhile, 2,7‐CPAPPI also displays exceptional thermal stability with a glass transition temperature (Tg) of 552°C and coefficient of thermal expansion (CTE) of 15.48 ppm/K. The barrier performances of 2,7‐CPAPPI are compared with those of a structural analog (2,7‐CPPI, containing only carbazole moiety in the main chain) and a typical polyimide (Kapton). The structure–barrier performances relationship was investigated by molecular simulations, wide angle X‐ray diffraction (WAXD), and positron annihilation lifetime spectroscopy (PALS). The results show that 2,7‐CPAPPI has more number of intermolecular hydrogen bonds among the three PIs, which leads to close chain packing and thereby high crystallinity, low free volume, and poor chains mobility. That is, the high crystallinity and low free volume of 2,7‐CPAPPI decrease the diffusion and solubility of gases. Meanwhile, the poor chains mobility further reduces the gases diffusion. The decreased diffusion and solubility of gases consequently promote the improvement of barrier properties for 2,7‐CPAPPI.
NOx synthesis by atmospheric‐pressure N2/O2 filamentary DBD plasma over water: Physicochemical mechanisms of plasma–liquid interactions
Authors: Roy Nepal C. , Pattyn Cédric , Remy Antoine , Maira Nicolas , Reniers François
Published: November 2020

In this study, an atmospheric‐pressure filamentary dielectric barrier discharge plasma is produced over a deionized (DI) water surface to study the physicochemical mechanisms of plasma–liquid surface interactions for NOx synthesis. The gas‐phase plasma diagnostics are performed using optical emission spectroscopy, Fourier‐transform infrared spectroscopy, and by recording voltage–current curves, and liquid‐phase species are analyzed using ion chromatography and UV−visible spectrophotometer. The investigations indicate that the reaction pathways for reactive oxygen and nitrogen species (H2O2, , ) formation in DI water depend on different experimental conditions. It is observed that the conversion of nitrites into nitrates is significantly influenced by reactive oxygen species. The energy yield for the total amount of NOx synthesized ranges from 1.3 × 10−4 to 3.4 × 10−3 mol/MJ.
Bayesian methods to compare dose levels with placebo in a small n, sequential, multiple assignment, randomized trial
Authors: Fang Fang , Hochstedler Kimberly A. , Tamura Roy N. , Braun Thomas M. , Kidwell Kelley M.
Published: November 2020

Clinical trials studying treatments for rare diseases are challenging to design and conduct due to the limited number of patients eligible for the trial. One design used to address this challenge is the small n, sequential, multiple assignment, randomized trial (snSMART). We propose a new snSMART design that investigates the response rates of a drug tested at a low and high dose compared with placebo. Patients are randomized to an initial treatment (stage 1). In stage 2, patients are rerandomized, depending on their initial treatment and their response to that treatment in stage 1, to either the same or a different dose of treatment. Data from both stages are used to determine the efficacy of the active treatment. We present a Bayesian approach where information is borrowed between stage 1 and stage 2. We compare our approach to standard methods using only stage 1 data and a log‐linear Poisson model that uses data from both stages where parameters are estimated using generalized estimating equations. We observe that the Bayesian method has smaller root‐mean‐square‐error and 95% credible interval widths than standard methods in the tested scenarios. We conclude that it is advantageous to utilize data from both stages for a primary efficacy analysis and that the specific snSMART design shown here can be used in the registration of a drug for the treatment of rare diseases.
LHC signals for KK graviton from an extended warped extra dimension
Authors: Agashe Kaustubh , Ekhterachian Majid , Kim Doojin , Sathyan Deepak
Published: November 2020

Abstract

We analyze signals at the Large Hadron Collider (LHC) from production and decay of Kaluza-Klein (KK) gravitons in the context of “extended” warped extra-dimensional models, where the standard model (SM) Higgs and fermion fields are restricted to be in-between the usual ultraviolet/Planck brane and a ∼ O(10) TeV (new, “intermediate”) brane, whereas the SM gauge fields (and gravity) propagate further down to the ∼ O(TeV) infrared brane. Such a framework suppresses flavor violation stemming from KK particle effects, while keeping the KK gauge bosons and gravitons accessible to the LHC. We find that the signals from KK graviton are significantly different than in the standard warped model. This is because the usually dominant decay modes of KK gravitons into top quark, Higgs and longitudinal W/Z particles are suppressed by the above spatial separation between these two sets of particles, thus other decay channels are allowed to shine themselves. In particular, we focus on two novel decay channels of the KK graviton. The first one is the decay into a pair of radions, each of which decays (dominantly) into a pair of SM gluons, resulting in a resonant 4-jet final state consisting of two pairs of dijet resonance. On the other hand, if the radion is heavier and/or KK gluon is lighter, then the KK graviton mostly decays into a KK gluon and a SM gluon. The resulting KK gluon has a significant decay branching fraction into radion and SM gluon, thereby generating (again) a 4-jet signature, but with a different underlying event topology, i.e., featuring now three different resonances. We demonstrate that the High-Luminosity LHC (HL-LHC) has sensitivity to KK graviton of (up to) ∼ 4 TeV in both channels, in the specific model with only gluon field (and gravity) propagating in the extended bulk, whereas it is unlikely to have sensitivity in the standard dijet resonance search channel from KK graviton decay into two gluons.
Purinergic Receptors Crosstalk with CCR5 to Amplify Ca2+ Signaling
Authors: Horioka Mizuho , Ceraudo Emilie , Lorenzen Emily , Sakmar Thomas P. , Huber Thomas
Published: November 2020

Many G protein-coupled receptors (GPCRs) signal through more than one subtype of heterotrimeric G proteins. For example, the C–C chemokine receptor type 5 (CCR5), which serves as a co-receptor to facilitate cellular entry of human immunodeficiency virus 1 (HIV-1), normally signals through the heterotrimeric G protein, Gi. However, CCR5 also exhibits G protein signaling bias and certain chemokine analogs can cause a switch to Gq pathways to induce Ca2+ signaling. We want to understand how much of the Ca2+ signaling from Gi-coupled receptors is due to G protein promiscuity and how much is due to transactivation and crosstalk with other receptors. We propose a possible mechanism underlying the apparent switching between different G protein signaling pathways. We show that chemokine-mediated Ca2+ flux in HEK293T cells expressing CCR5 can be primed and enhanced by ATP pretreatment. In addition, agonist-dependent lysosomal exocytosis results in the release of ATP to the extracellular milieu, which amplifies cellular signaling networks. ATP is quickly degraded via ADP and AMP to adenosine. ATP, ADP and adenosine activate different cell surface purinergic receptors. Endogenous Gq-coupled purinergic P2Y receptors amplify Ca2+ signaling and allow for Gi- and Gq-coupled receptor signaling pathways to converge. Associated secretory release of GPCR ligands, such as chemokines, opioids, and monoamines, should also lead to concomitant release of ATP with a synergistic effect on Ca2+ signaling. Our results suggest that crosstalk between ATP-activated purinergic receptors and other Gi-coupled GPCRs is an important cooperative mechanism to amplify the intracellular Ca2+ signaling response.
Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing’s syndrome
Authors: Geer Eliza B. , Salvatori Roberto , Elenkova Atanaska , Fleseriu Maria , Pivonello Rosario , Witek Przemyslaw , Feelders Richard A. , Bex Marie , Borresen Stina W. , Puglisi Soraya , Biller Beverly M. K. , Cohen Fredric , Pecori Giraldi Francesca
Published: November 2020

Purpose

The efficacy of levoketoconazole in treating hypercortisolism was demonstrated in an open-label phase 3 study (SONICS) of adults with endogenous Cushing’s syndrome (CS) and baseline mean urinary free cortisol (mUFC) ≥  1.5× ULN. Clinical signs and symptoms and patient-reported outcomes from the SONICS trial were evaluated in the current manuscript.

Methods

Patients titrated to an individualized therapeutic dose entered a 6-month maintenance phase. Secondary endpoints included investigator-graded clinical signs and symptoms of CS during the maintenance phase, and patient-reported quality of life (CushingQoL questionnaire) and depression symptoms (Beck Depression Inventory II [BDI-II]).

Results

Of 94 enrolled patients, 77 entered the maintenance phase following individualized dose titration. Significant mean improvements from baseline were noted at end of maintenance (Month 6) for acne, hirsutism (females only), and peripheral edema. These improvements were observed as early as Day 1 of maintenance for hirsutism (mean baseline score, 7.8; ∆ − 1.9; P < 0.0001), end of Month 1 for acne (mean baseline score, 2.8; ∆ − 1.2; P = 0.0481), and Month 4 for peripheral edema (mean baseline score, 1.0; ∆ − 0.5; P = 0.0052). Significant mean improvements from baseline were observed by Month 3 of maintenance for CushingQoL (mean baseline score, 44.3; ∆ + 6.9; P = 0.0018) and at Month 6 for BDI-II (mean baseline score, 17.1; ∆ − 4.3; P = 0.0043) scores. No significant mean improvement was identified in a composite score of 7 other clinical signs and symptoms.

Conclusions

Treatment with levoketoconazole was associated with sustained, meaningful improvements in QoL, depression, and certain clinical signs and symptoms characteristic of CS.

ClinialTrials.gov identifier: NCT01838551.
Improving Clairvoyant: reduction algorithm resilient to imbalanced process arrival patterns
Authors: Proficz Jerzy , Ocetkiewicz Krzysztof M.
Published: November 2020

The Clairvoyant algorithm proposed in “A novel MPI reduction algorithm resilient to imbalances in process arrival times” was analyzed, commented and improved. The comments concern handling certain edge cases in the original pseudocode and description, i.e., adding another state of a process, improved cache friendliness more precise complexity estimations and some other issues improving the robustness of the algorithm implementation. The proposed improvements include skipping of idle loop rounds, simplifying generation of the ready set and management of the state array and an about 90-fold reduction in memory usage. Finally an extension enabling process arrival times (PATs) prediction was added: an additional background thread used to exchange the data with the PAT estimations. The performed tests, with a dedicated mini-benchmark executed in an HPC environment, showed correctness and improved performance of the solution, with comparison to the original or other state-of-the-art algorithms.
Correction to: Disagreement lost
Authors: Abreu Zavaleta Martín
Published: November 2020

The article Disagreement lost, written by Martín Abreu Zavaleta, was originally published electronically on the publisher’s internet portal on 16 September 2020 without open access. The copyright of the article changed on 18 September 2020 to © The Author(s) 2020 and the article is forthwith distributed under a Creative Commons Attribution.
Review of Ultimate Strength Assessment of Ageing and Damaged Ship Structures
Authors: Tekgoz M. , Garbatov Y. , Soares C. Guedes
Published: November 2020

The objective of this work is to provide an overview of the ultimate strength assessment of ageing and damaged ship structures in the last decades. Particular attention is paid to the ultimate strength of plates, stiffened panels, box girders, and entire ship hull structures subjected to corrosion degradation, fatigue cracking, and mechanical damage caused by accidental loading or impact. A discussion on the effect of the cyclic load on the plate rigidity, re-yielding, and ultimate load capacity on the ship hull girder is also part of the present study. Finally, some conclusions and discussions about potential future work are provided, identifying that more studies about the impact of corrosion degradation on the structural behaviour of the stiffened panels and the overall hull girders are needed. Studies related to the dynamic collapse behaviour of corroded and damaged ship structures under time-variant load also requires additional attention.
Vitamin D in Head and Neck Cancer: a Systematic Review
Authors: Mäkitie Antti , Tuokkola Iida , Laurell Göran , Mäkitie Outi , Olsen Kerry , Takes Robert P. , Florek Ewa , Szyfter Krzysztof , Sier Cornelis F. M. , Ferlito Alfio
Published: November 2020

Purpose of review

Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome.

Recent findings

The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable.

The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.
Exploring customers’ likeliness to use e-service touchpoints in brick and mortar retail
Authors: Barann Benjamin , Betzing Jan H. , Niemann Marco , Hoffmeister Benedikt , Becker Jörg
Published: November 2020

E-commerce has embraced the digital transformation and innovated with e-service touchpoints to improve customers’ experiences. Now some traditional, less-digitalized brick and mortar (BaM) retailers are starting to counteract the increasing competition by adopting digital touchpoints. However, the academic literature offers little in terms of what determines customers’ behavioral intentions toward e-service touchpoints. Therefore, drawing from the dominant design theory, this article first conceptually adapts selected dominant touchpoints of leading e-commerce solutions to BaM retail. Then 250 shoppers are surveyed regarding the likeliness that they will use the selected touchpoints, followed by an exploratory factor analysis to determine the touchpoints’ characteristics that lead to the shoppers’ assessments. The results suggest that customers prefer touchpoints that support product search and selection, provide information, and increase shopping efficiency. The likeliness that surveyed shoppers will use the touchpoints was affected by the functionality provided, the content conveyed, and the mediating device. The results provide a foundation for further research on customers’ behavioral intentions toward BaM e-service touchpoints and provide useful information for BaM retailers.