bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated in silico Approach and in vitro Study for the Discovery of Small‐Molecule USP7 Inhibitors as Potential Cancer Therapies
Authors: Kanan Duaa , Kanan Tarek , Dogan Berna , Orhan Muge Didem , Avsar Timucin , Durdagi Serdar
Published: October 2020

The ubiquitin‐specific protease 7 (USP7) is a highly promising well‐validated target for a variety of malignancies. USP7 is critical in regulating the tumor suppressor p53 along with numerous epigenetic modifiers and transcription factors. Previous studies showed that USP7 inhibitors led to increased levels of p53 and anti‐proliferative effects in hematological and solid tumor cell lines. Thus, this study aimed to identify potent and safe USP7 hit inhibitors as potential anti‐cancer therapeutics via an integrated computational approach that combines pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations and post‐MD free energy calculations. In this study, the crystal structure of USP7 has been extensively investigated using a combination of three different chemical pharmacophore modeling approaches. We then screened ∼220.000 drug‐like small molecule library and the hit ligands predicted to be nontoxic were evaluated further. The identified hits from each pharmacophore modeling study were further examined by 1‐ns short MD simulations and MM/GBSA free energy analysis. In total, we ran 1 ns MD simulations for 1137 selected on small compounds. Based on their average MM/GBSA scores, 18 ligands were selected for 50 ns MD simulations along with one highly potent USP7 inhibitor used as a positive control. The in vitro enzymatic inhibition assay testing of our lead 18 molecules confirmed that 7 of these molecules were successful in USP7 inhibition. Screening results showed that within the used screening approaches, the most successful one was structure‐based pharmacophore modeling with the success rate of 75 %. The identification of potent and safe USP7 small molecules as potential inhibitors is a step closer to finding appropriate effective therapies for cancer. Our lead ligands can be used as a scaffold for further structural optimization and development, enabling further research in this promising field.
Multiple‐Dose Pharmacokinetics, Safety, and Tolerability of Aprocitentan, a Dual Endothelin Receptor Antagonist, in Healthy Japanese and Caucasian Subjects
Authors: Fontes Magda S.C. , Dingemanse Jasper , Sidharta Patricia N.
Published: October 2020

Aprocitentan is an orally active dual endothelin receptor antagonist currently in development for treatment of difficult‐to‐control (resistant) hypertension. In phase 1 and 2 studies, aprocitentan has been characterized predominantly in Caucasian subjects. In this bridging, double‐blind study, 20 healthy Japanese and Caucasian male and female subjects received 25 mg of aprocitentan or placebo once daily for 10 days and were monitored until 216 hours after the last dosing. The pharmacokinetics of aprocitentan were similar between ethnicities. At steady state, maximum plasma concentration was reached at 4 and 3 hours, and elimination half‐life was 49.1 and 48.8 hours for Japanese and Caucasian subjects, respectively. The accumulation index was around 3 for both populations. Geometric means ratios for maximum plasma concentration and area under the plasma concentration–time curve during 1 dosing interval were around 1, with 90% confidence interval ranging from 0.87 to 1.30. Aprocitentan was safe and well tolerated in both groups. As no clinically relevant differences were found between Japanese and Caucasian subjects, it is unlikely that the pharmacokinetics of aprocitentan would differ significantly between Caucasian subjects and other ethnicities. Aprocitentan can therefore be administered at a dose level of up to 25 mg in any ethnicity without dose adjustment.
Genetics of robustness under nitrogen‐ and water‐deficient conditions in field‐grown lettuce
Authors: Macias‐González M. , Truco M. J. , Smith R. , Cahn M. , Simko I. , Hayes R. , Michelmore R. W.
Published: October 2020

Robustness is the measure of the ability to perform well across multiple environments. The genetics of robustness in lettuce (Lactuca sativaL.) under changing nitrogen (N) application was studied by two parameters obtained from linear regression analysis. Robustness in changing water application was assessed by two parameters: relative efficiency component (REC) and susceptibility component (SC). The efficiency, sensitivity, and the effect of reduced irrigation on these parameters was assessed for 50 lines of lettuce in 2011. Efficiency, sensitivity, and plant N uptake and utilization were important traits in robustness under changing N application. Eight cultivars were re‐evaluated in 2012, 2014, and 2016 under high‐ and low‐N treatments in order to estimate the repeatability of efficiency and sensitivity. Repeatability was greater for efficiency than sensitivity. In addition, the genetics of efficiency, sensitivity, REC, SC, nutrient concentration, nutrient content, dry‐to‐fresh biomass percentage, bolting, and shoot biomass production were studied by quantitative trait locus (QTL) analysis of a recombinant inbred line (RIL) population derived from the cultivars Grand Rapids and Iceberg. The population was phenotyped in three experiments and genotyped by sequencing. Major clusters of QTL for these traits were identified in linkage groups (LGs) 3, 7, and 9. Minor‐effect QTL for sensitivity were identified in LGs 3 and 4. Intermediate‐effect QTL for SC were identified in LGs 4 and 7. These results provide evidence that the components of robustness under changing N (efficiency and sensitivity) and water (REC and SC) availability are genetically independent and can be improved through breeding.
Narrowband UVB phototherapy reduces TNF production by B‐cell subsets stimulated via TLR7 from individuals with early multiple sclerosis
Authors: Trend Stephanie , Leffler Jonatan , Cooper Matthew N , Byrne Scott N , Kermode Allan G , French Martyn A , Hart Prue H
Published: October 2020

Objectives

At the end of a 60‐day course of narrowband UVB phototherapy, administered to individuals with early multiple sclerosis, there were changes in the relative proportions of circulating B‐cell subsets. This study investigated phototherapy‐associated changes to cytokine responses of B cells when exposed to a TLR7 ligand.

Methods

PBMCs from participants of the PhoCIS (Phototherapy for Clinically Isolated Syndrome) trial taken before (day 1) and after phototherapy for 8 weeks (day 60) were incubated with, or without, the TLR7 ligand, R848, for 18 h. Production of TNF and IL‐10 in seven B‐cell subsets was examined, with cytokine responses in each individual at day 60, adjusted for responses at day 1. Paired PBMCs were from participants administered phototherapy (n = 7) or controls (n = 6).

Results

At day 60, significantly fewer B cells, particularly marginal zone‐like B cells (CD27+/IgD+), from participants administered phototherapy produced TNF in response to TLR7 stimulation. When responses by seven B‐cell subsets were analysed together using multivariate methods, a phototherapy‐specific signature was observed. An increased responsiveness from day 1 to day 60 in IgM‐only memory B cells (CD27+/IgD−/IgM+) after TLR7 stimulation also predicted slower progression from CIS to MS. Phototherapy was without significant effect on B‐cell IL‐10 production.

Conclusions

Reduced TNF responses after TLR7 stimulation in marginal zone‐like B cells from participants administered phototherapy suggested treatment‐associated priming effects that were detected upon subsequent polyclonal B‐cell activation. Changes in responsiveness to TLR7 stimulation also suggested that IgM‐only memory B cells may be important in conversion from CIS to MS.
Understanding the interpretation and implementation of social and emotional learning in physical education
Authors: Wright Paul M. , Gray Shirley , Richards K. Andrew R.
Published: October 2020

Social and emotional learning (SEL) competencies such as self‐management and relationship skills are associated with positive outcomes for youth. Therefore, educational policies in many countries emphasise the integration of these competencies throughout the curriculum and specifically in physical education (PE). However, little research has examined the impact of such policy in the context of practice. Drawing upon occupational socialisation theory, this study assessed how secondary teachers interpret and implement this aspect of the Scottish national curriculum. Data sources included teacher interviews (n = 14), pupil focus groups (n = 32) and systematic observations of 23 lessons. Quantitative data were analysed using descriptive statistics while qualitative data were analysed using constant comparison and thematic analysis. The trustworthiness of findings was supported through triangulation, peer debriefing and member check. Findings indicate the curriculum is interpreted at several levels driven largely by teachers’ background experience and organisational influences. Generally, SEL is viewed favourably, but ambiguity and lack of support are challenges to implementation. Common practice involves creating a positive learning environment as well as implicit and reactive teaching approaches. More robust implementation involves the addition of explicit and empowering teaching approaches. Implications for practice, teacher education, policy development and research are discussed.
Axolotl liver regeneration is accomplished via compensatory congestion mechanisms regulated by ERK signaling after partial hepatectomy
Authors: Ohashi Ayaka , Saito Nanami , Kashimoto Rena , Furukawa Saya , Yamamoto Sakiya , Satoh Akira
Published: October 2020

Background

Axolotls have remarkable organ‐level regeneration capability. They can regenerate their limbs, tail, brain, gills, and heart. The liver had been considered to be a regenerative organ in these highly regeneration‐competent animals. Therefore, no research had been performed on liver regeneration in urodele amphibians. In the present study, we focused on axolotl liver regeneration and found a unique regeneration mechanism compared with other vertebrates.

Results

Partial hepatectomy (PH) was performed to assess axolotl liver regeneration. Regeneration was assessed using block‐face imaging (CoMBi), histology, cell proliferation, weight gain, and Albumin (Alb) + area. Axolotl liver histology was compared with other vertebrates. Axolotl liver consists of Glisson's capsule, sinusoids, and hepatic cord with no apparent lobule structures. Hepatocytes were mononucleated or multinucleated. PH increased the multinucleated hepatocytes and the Alb + area, but there was no apparent liver shape recovery even 40 days after PH. Gene expression pattern suggests that no epimorphic regeneration takes place. We also found that the increase in the number of proliferating hepatocytes was regulated by ERK‐signaling.

Conclusion

Our findings suggest that axolotls, which have epimorphic regeneration ability, regenerate their liver via unique mechanisms, compensatory congestion.
Stony coral populations are more sensitive to changes in vital rates in disturbed environments
Authors: Hall Tessa E. , Freedman Andrew S. , de Roos André M. , Edmunds Peter J. , Carpenter Robert C. , Gross Kevin
Published: October 2020

Reef‐building corals, like many long‐lived organisms, experience environmental change as a combination of separate but concurrent processes, some of which are gradual yet long‐lasting, while others are more acute but short‐lived. For corals, some chronic environmental stressors, such as rising temperature and ocean acidification, are thought to induce gradual changes in colonies' vital rates. Meanwhile, other environmental changes, such as the intensification of tropical cyclones, change the disturbance regime that corals experience. Here, we use a physiologically structured population model to explore how chronic environmental stressors that impact the vital rates of individual coral colonies interact with the intensity and magnitude of disturbance to affect coral population dynamics and cover. We find that, when disturbances are relatively benign, intraspecific density dependence driven by space competition partially buffers coral populations against gradual changes in vital rates. However, the impact of chronic stressors is amplified in more highly disturbed environments, because disturbance weakens the buffering effect of space competition. We also show that coral cover is more sensitive to changes in colony growth and mortality than to external recruitment, at least in open populations, and that space competition and size structure mediate the extent and pace of coral population recovery following a large‐scale mortality event. Understanding the complex interplay among chronic environmental stressors, mass‐mortality events, and population size structure sharpens our ability to manage and to restore coral‐reef ecosystems in an increasingly disturbed future.
Higher mortality rates for large‐ and medium‐sized mammals on plantation roads compared to highways in Peninsular Malaysia
Authors: Jamhuri Jamaluddin , Edinoor Mohd Anuar , Kamarudin Norizah , Lechner Alex M. , Ashton‐Butt Adham , Azhar Badrul
Published: October 2020

The fragmentation of forests by agricultural expansion, urbanization, and road networks is an ongoing global biodiversity crisis. In Southeast Asia and other tropical regions, wildlife populations are being isolated into pockets of natural habitat surrounded by road networks and monoculture plantations. Mortality from wildlife–vehicle collisions (WVCs) is contributing to a decline in many species of conservation priority in human‐modified landscapes. This study is the first in Malaysia to investigate factors affecting the occurrence of WVCs. We assessed roadkill data gathered by the Department of Wildlife and National Parks on small‐, medium‐, and large‐sized mammals in Peninsular Malaysia. We examined the relationship between wildlife road accidents and several environmental factors. We found a total of 605 roadkill animals, involving 21 species, which included three species classified as Endangered. Road type (plantation road or highway), year, and distance of the road from continuous and fragmented forests were significant in determining mammal mortality. Unexpectedly, the majority of road mortality occurred on palm oil plantation roads compared to highways. Mortality of small‐ and medium‐sized mammals was greater at locations further from continuous forest than those closer to fragmented forests. Segmentation of continuous forest by roads should be avoided wherever possible to reduce the threat of roads on crossing wildlife.
Infant cannibalism in wild white‐faced capuchin monkeys
Authors: Nishikawa Mari , Ferrero Nuria , Cheves Saul , Lopez Ronald , Kawamura Shoji , Fedigan Linda M. , Melin Amanda D. , Jack Katharine M.
Published: October 2020

Cannibalism has been observed in a variety of animal taxa; however, it is relatively uncommon in primates. Thus, we rely heavily on case reports of this behavior to advance our understanding of the contexts under which it occurs. Here, we report the first observation of cannibalism in a group of wild white‐faced capuchin monkeys (Cebus imitator). The subject was a dead infant, estimated to be 10 days old, and the probable victim of infanticide. Consumption of the corpse was initiated by a 2‐year‐old male (second cousin of the infant), though it was eventually taken over and monopolized by the group's alpha female (grandaunt of the infant). Although most group members expressed interest in the corpse (sniffing, touching, and threatening it), no others made an attempt to consume it. Given that this is the only observation of cannibalism recorded in over 37 years of study on this population, we consider it to be a rare behavior in this species. This detailed record contributes new data, which, when combined with other reports within and across species and contexts, enables the evaluation of adaptive explanations of cannibalism.
Which passengers are on your bus? A taxonomy of the barriers adolescents with chronic pain face in achieving functional recovery
Authors: Jacobs Konrad , Smith Alisha , Heathcote Lauren C. , Caes Line
Published: October 2020

Background

Despite evidence that intensive interdisciplinary pain treatment (IIPT) is effective in facilitating functional recovery in adolescents with chronic pain, engagement with IIPT is suboptimal among adolescents. A key aspect of IIPT is to support functional recovery via (re)engagement with age‐appropriate daily activities. The aim of this study was to gain a comprehensive insight into adolescents’ perceptions of the barriers they need to overcome to engage with age‐appropriate activities in order to achieve functional recovery.

Methods

Forty‐one adolescents who were starting an IIPT programme completed the ‘passenger‐on‐the‐bus metaphor’, an exercise in which they identify and describe their perceived barriers (i.e. ‘passengers’ on their bus) that prevent them from engaging with age‐appropriate activities. The responses were analysed using inductive thematic analyses to generate a taxonomy of perceived barriers to functional recovery.

Results

We generated a taxonomy of seven different barriers that participants described facing on their road to functional recovery: physical constraints, being ‘fed up’, low self‐confidence and self‐esteem, perfectionism, avoidance of engagement with pain, feelings (such as sadness, anger, guilt, anxiety) and social barriers (received from a range of sources such as parents, friends, school and wider society).

Conclusion

The findings reveal a variety of barriers that were perceived to hinder functional recovery through reduced engagement with age‐appropriate activities and thereby hamper progress within IIPT. The Passenger on the bus metaphor can be used to identify similar barriers faced by adolescents in an individualized treatment approach, thereby making it possible for clinicians to target their IIPT more precisely.
Medical cannabis treatment for chronic pain: Outcomes and prediction of response
Authors: Aviram Joshua , Pud Dorit , Gershoni Tamar , Schiff‐Keren Bareket , Ogintz Miriam , Vulfsons Simon , Yashar Tamar , Adahan Haim‐Moshe , Brill Silviu , Amital Howard , Goor‐Aryeh Itay , Robinson Dror , Green Leslie , Segal Refael , Fogelman Yacov , Tsvieli Oren , Yellin Ben , Vysotski Yelena , Morag Ofir , Tashlykov Vadim , Sheinfeld Roee , Goor Ruth , Meiri David , Eisenberg Elon
Published: October 2020

Background

Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire‐based prospective cohort was aimed to assess the long‐term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success.

Methods

Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity).

Results

A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12‐month follow‐up. At 1 year, average pain intensity declined from baseline by 20% [−1.97 points (95%CI = −2.13 to −1.81; p < 0.001)]. All other parameters improved by 10%–30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = −34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non‐serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite.

Conclusions

This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild‐to‐modest long‐term improvement of the tested measures and identifying possible predictors for treatment success.
New Amine/Phenylglycedyl Ether Adducts for Mild Steel Protection in 1 M HCl: Experimental and Computational Study
Authors: Akalezi C. O. , Onwumere F. C. , Alisa C. O. , Nnanyereugo M. N. , Oguzie E. E.
Published: October 2020

The key objective of this study is to ascertain the effect of structure and increased molecular size on the corrosion inhibition potential of two synthesized amines, when compared to their precursor compounds. The product amines were N‐(2‐hydroxy‐3‐phenoxy) ethanolamine (NHPE), N,N−Di‐(2‐hydroxy‐3‐phenoxypropyl) ethanolamine (NNHPE) synthesized from monoethanolamine (MEA) and phenyl glycidyl ether (PGE) as starting materials. Both starting and product amines were characterized using FTIR spectroscopy. The corrosion inhibition potentials were assessed using experimental and quantum theoretical modeling and calculations. Some key electronic properties such as highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies, gap energy, dipole moment and surface area, were calculated and discussed. The various approaches adopted in this study were in reasonable agreement and the following average inhibition efficiency trend was obtained: NNHPE (75.7 %)>NHPE (68.3 %)>PGE (64.2) >MEA (61.0).
Heritable hazards of smoking: Applying the “clean sheet” framework to further science and policy
Authors: Bline Abigail P. , Dearfield Kerry L. , DeMarini David M. , Marchetti Francesco , Yauk Carole L. , Escher Jill ,   Workshop Presenters
Published: October 2020

All the cells in our bodies are derived from the germ cells of our parents, just as our own germ cells become the bodies of our children. The integrity of the genetic information inherited from these germ cells is of paramount importance in establishing the health of each generation and perpetuating our species into the future. There is a large and growing body of evidence strongly suggesting the existence of substances that may threaten this integrity by acting as human germ cell mutagens. However, there generally are no absolute regulatory requirements to test agents for germ cell effects. In addition, the current regulatory testing paradigms do not evaluate the impacts of epigenetically mediated intergenerational effects, and there is no regulatory framework to apply new and emerging tests in regulatory decision making. At the 50th annual meeting of the Environmental Mutagenesis and Genomics Society held in Washington, DC, in September 2019, a workshop took place that examined the heritable effects of hazardous exposures to germ cells, using tobacco smoke as the example hazard. This synopsis provides a summary of areas of concern regarding heritable hazards from tobacco smoke exposures identified at the workshop and the value of the Clean Sheet framework in organizing information to address knowledge and testing gaps.
Climate sensitivity of water use by riparian woodlands at landscape scales
Authors: Mayes Marc , Caylor Kelly K. , Singer Michael Bliss , Stella John C. , Roberts Dar , Nagler Pamela
Published: October 2020

Semi‐arid riparian woodlands face threats from increasing extractive water demand and climate change in dryland landscapes worldwide. Improved landscape‐scale understanding of riparian woodland water use (evapotranspiration, ET) and its sensitivity to climate variables is needed to strategically manage water resources, as well as to create successful ecosystem conservation and restoration plans for potential climate futures. In this work, we assess the spatial and temporal variability of Cottonwood (Populus fremontii)‐Willow (Salix gooddingii) riparian gallery woodland ET and its relationships to vegetation structure and climate variables for 80 km of the San Pedro River corridor in southeastern Arizona, USA, between 2014 and 2019. We use a novel combination of publicly available remote sensing, climate and hydrological datasets: cloud‐based Landsat thermal remote sensing data products for ET (Google Earth Engine EEFlux), Landsat multispectral imagery and field data‐based calibrations to vegetation structure (leaf‐area index, LAI), and open‐source climate and hydrological data. We show that at landscape scales, daily ET rates (6–10 mm day−1) and growing season ET totals (400–1,400 mm) matched rates of published field data, and modelled reach‐scale average LAI (0.80–1.70) matched lower ranges of published field data. Over 6 years, the spatial variability of total growing season ET (CV = 0.18) exceeded that of temporal variability (CV = 0.10), indicating the importance of reach‐scale vegetation and hydrological conditions for controlling ET dynamics. Responses of ET to climate differed between perennial and intermittent‐flow stream reaches. At perennial‐flow reaches, ET correlated significantly with temperature, whilst at intermittent‐flow sites ET correlated significantly with rainfall and stream discharge. Amongst reaches studied in detail, we found positive but differing logarithmic relationships between LAI and ET. By documenting patterns of high spatial variability of ET at basin scales, these results underscore the importance of accurately accounting for differences in woodland vegetation structure and hydrological conditions for assessing water‐use requirements. Results also suggest that the climate sensitivity of ET may be used as a remote indicator of subsurface water resources relative to vegetation demand, and an indicator for informing conservation management priorities.
Quantifying groundwater sensitivity and resilience over peninsular India
Authors: Kumar Nikhil , Sinha Jhilam , Madramootoo Chandra A. , Goyal Manish Kumar
Published: October 2020

Groundwater in India plays an important role to support livelihoods and maintain ecosystems and the present rate of depletion of groundwater resources poses a serious threat to water security. Yet, the sensitivity of the hydrological processes governing groundwater recharge to climate variability remains unclear in the region. Here we assess the groundwater sensitivity (precipitation–recharge relationship) and its potential resilience towards climatic variability over peninsular India using a conceptual water balance model and a convex model, respectively in 54 catchments over peninsular India. Based on the model performance using a comprehensive approach (Nash Sutcliffe Efficiency [NSE], bias and variability), 24 out of 54 catchments are selected for assessment of groundwater sensitivity and its resilience. Further, a systematic approach is used to understand the changes in resilience on a temporal scale based upon the convex model and principle of critical slowing down theory. The results of the study indicate that the catchments with higher mean groundwater sensitivity (GWS) encompass high variability in GWS over the period (1988–2011), thus indicating the associated vulnerability towards hydroclimatic disturbances. Moreover, it was found that the catchments pertaining to a lower magnitude of mean resilience index incorporates a high variability in resilience index over the period (1993–2007), clearly illustrating the inherent vulnerability of these catchments. The resilience of groundwater towards climatic variability and hydroclimatic disturbances that is revealed by groundwater sensitivity is essential to understand the future impacts of changing climate on groundwater and can further facilitate effective adaptation strategies.
Breast cancer incidence in the regions of Belarus and Ukraine most contaminated by the Chernobyl accident: 1978 to 2016
Authors: Zupunski Ljubica , Yaumenenka Alesia , Ryzhov Anton , Veyalkin Ilya , Drozdovitch Vladimir , Masiuk Sergii , Ivanova Olha , Kesminiene Ausrele , Pukkala Eero , Moiseev Pavel , Prysyazhnyuk Anatoly , Schüz Joachim , Ostroumova Evgenia
Published: October 2020

Even 30 years after the accident, an association between breast cancer incidence and ionizing radiation exposure from Chernobyl fallout remains uncertain. We studied breast cancer incidence in the most contaminated regions of Belarus (Gomel and Mogilev) and Ukraine (Kyiv, Zhytomyr and Chernihiv) before (1978‐1986) and after (1987‐2016) the accident. Breast cancer cases and female population size data were received from the national cancer registries and the state departments of statistics. The study included 85 132 breast cancers with 150 million person‐years at risk. We estimated annual rayon (district)‐average absorbed doses to the breast from external and internal irradiation of the adult female population over the period of 1986‐2016. We studied an association between rayon‐average cumulative absorbed breast dose with 5‐year lag, that is, excluding the exposure in 5 years prior to breast cancer diagnosis, and breast cancer incidence using negative binomial regression models. Mean (median) cumulative breast dose in 2016 was 12.3 (5.0) milligray (mGy) in Belarus and 5.7 (2.3) mGy in Ukraine, with the maximum dose of 55 mGy and 54 mGy, respectively. Breast cancer incidence rates statistically significantly increased with calendar year and attained age, and were higher in urban than in rural residents. Adjusting for time, age and urbanicity effects, we found no evidence of increasing incidence with rayon‐average 5‐year lagged cumulative breast dose. Owing to ecological study design limitations, a case‐control study covering this area with individually reconstructed absorbed breast doses is needed testing for association between low‐dose protracted radiation exposure and breast cancer risk after Chernobyl.
Impact of bank capital on non‐performing loans: New evidence of concave capital from dynamic panel‐data and time series analysis in Malaysia
Authors: Hajja Yaman
Published: October 2020

Amid the steep expansion in Malaysia household debt, we investigate the role of bank capital in disciplining non‐performing loans (NPLs) after controlling for the macroeconomic environment. Utilizing generalized method of moments (GMM) on a dynamic panel‐data of 19 commercial banks and stress testing of NPLs using vector autoregression (VAR) on aggregated‐monthly time series of the banking system, we provide new evidence that the capital (in the past and in the future) is a concave function of NPLs implying that increasing the capital will initially increase the NPLs until NPLs reach a maximum threshold (under the moral hazard effect), after which more capital build ups will succeed in decreasing NPLs (under the disciplinary or regulatory effect). We also find that higher levels in GDP growth and lending interest rate and are associated with more NPLs, while higher inflation is associated with less NPLs. Monetary expansion, that is, higher money supply growth raises NPLs in banks, while competition between banks and higher liquidity of the stock market are NPLs reducing.
The use of alpha‐2‐macroglobulin as a novel treatment for patients with chronic pelvic pain syndrome
Authors: Brooks Brocha , Leishear Kim , Aronson Rebecca , Howell Melanie , Khakshooy Allen , Pico Michael , Shrikhande Allyson
Published: October 2020

Synopsis

Alpha‐2‐macroglobulin shows potential for use as an adjunctive treatment option for chronic pelvic pain syndrome when injected into Alcock’s canal using a hydrodissection technique.
Behavioral strategies for reducing disease transmission in the workplace
Authors: Gravina Nicole , Nastasi Jessica A. , Sleiman Andressa A. , Matey Nicholas , Simmons Davis E.
Published: October 2020

The coronavirus pandemic highlighted that workplaces may serve as a hub of disease transmission if proper precautions are not enacted. The Centers for Disease Control recommends several strategies for decreasing the spread of illnesses in the workplace, including a) promoting proper hand hygiene, b) cleaning and sanitizing the work area, c) encouraging sick employees to stay home, d) personal protective equipment, and, e) social distancing. Research suggests that instructions are often not sufficient to change work behaviors, and behavioral interventions may be needed. Thus, the present paper reviews existing research that informs the implementation of behavioral strategies to reduce the spread of disease in the workplace, and makes recommendations for organizations to protect employees, clients, and customers. Intervention components such as training, prompts, the reduction of response effort, clear workplace policies, feedback, and consequences are discussed, and practical recommendations and suggestions for future research are provided.
Quantitative assessment of dentine mineralization and tubule occlusion by NovaMin and stannous fluoride using serial block face scanning electron microscopy
Authors: Mahmoodi Behrad , Goggin Patricia , Fowler Christabel , Cook Richard B.
Published: October 2020

Dentine hypersensitivity (DH) is one of the most common dental conditions affecting most adults during their lifetime. Tubule occlusion is a widely accepted method for treating DH. Current in‐vitro techniques such as focused ion beam, scanning electron microscopy (SEM), or hydraulic conductance that are used to determine tubule occlusion do not provide the depth of occlusion, are time‐consuming, expensive and the volume of dentine tested is limited. The presented study aimed to assess the ability of serial block‐face SEM (SBF‐SEM) to section dentine, to quantify the number of occluded tubules including the depth of penetration by NovaMin and stannous fluoride (SnF2) and to compare mineral density between the control and treated dentine. Results demonstrated that NovaMin provided a better occlusion with 100% of the tubules blocked at the surface compared to 83% for SnF2. The grayscale value (230.42) was significantly higher (p ≤ 0.05) after treatment with NovaMin compared to SnF2 (222.06) and the control (196.37), indicating increased mineral density and dentine mineralization. SBF‐SEM has the potential to be used for large volume analysis of bone‐like materials at high resolution with minimal sample preparation over a short period. It can be significantly useful in the development and research of new biomaterials.
Bonding and metastability for Group 12 dications
Authors: Sadjadi SeyedAbdolreza , Matta Chérif F. , Hamilton Ian P.
Published: October 2020

Electronic structure and bonding properties of the Group 12 dications M22+(M = Zn, Cd, Hg) are investigated and electron density‐derived quantities are used to characterize the metastability of these species. Of particular interest are the complementary descriptions afforded by the Laplacian of the electron density∇2ρ(r)and the one‐electron Bohm quantum potential (Q= ) along the bond path. Further, properties derived from the pair density including the localization‐delocalization matrices (LDMs) and the interacting quantum atoms (IQA) energies are analyzed within the framework of the quantum theory of atoms in molecules (QTAIM). From the crossing points of the singlet (ground) and triplet (excited) potential energy curves, the barriers for dissociation (BFD) are estimated to be 25.2 kcal/mol (1.09 eV) for Zn22+, 22.8 kcal/mol (0.99 eV) for Cd22+, and 26.4 kcal/mol (1.14 eV) for Hg22+. For comparison and benchmarking purposes, the case of N22+is considered as a texbook example of metastability. At the equilibrium geometries, LDMs, which are used here as an electronic fingerprinting tool, discriminate and group together Group 12 M22+from its isoelectronic Group 11 M2. While “classical” bonding indices are inconclusive in establishing regions of metastability in the bonding, it is shown that the one‐electron Bohm quantum potential is promising in this regard.
Structure, stability and bonding of the leapfrogB240,±1,±2
Authors: Muya Jules Tshishimbi , Isamura Bienfait Kabuyaya , Patouossa Issofa , Nguyen Minh Tho , Ceulemans Arnout
Published: October 2020

Two new structural motifs of the B24clusters are constructed by use of the leapfrog transformation. The resulting leapfrog B24has either a bowl shape with a square vacancy or a quasi‐planar 2D close‐packed triangular boron sheet. The neutral and ionic forms of the latter are found to be more stable than their homologous leapfrog bowl clusters, with the exception of the dicationic B24+2. While the leapfrog isomer is less stable than the tubular double ring in the neutral state, it becomes competitive in some ionic states. The nucleus independent chemical shift, electron localization function, ring current maps and the electronic structure of leapfrog B24clusters reveal them to behave as aromatics.
Randomized controlled trial of a brief online self‐compassion intervention for mothers of infants: Effects on mental health outcomes
Authors: Lennard Georgina R. , Mitchell Amy E. , Whittingham Koa
Published: October 2020

Objective

To test the effectiveness of a brief self‐compassion intervention in improving mental health outcomes for mothers of infants.

Method

A randomized controlled trial study design was used. A community sample of mothers of infants (<2 years) completed measures of self‐compassion, fears of compassion, psychological flexibility, depression, anxiety, stress, symptoms of posttraumatic stress, and infant feeding experiences. Mothers randomized to intervention received access to online self‐compassion resources, and 248 mothers (intervention n = 94, waitlist‐control n = 154) completed postintervention assessment 8 weeks later.

Results

Overall, 62.8% (n = 59) of intervention participants accessed the resources per‐protocol, and lower fear of compassion scores predicted resource use. At postintervention, mothers who used the resources had improved scores for posttraumatic stress symptoms (95% confidence interval [CI] = 0.31–5.47, p = .028), depression (95% CI = 0.15–2.01, p = .023), self‐compassionate action (95% CI = 0.41–3.45, p = .012), and engagement with compassion from others (95% CI = 0.22–5.49, p = .034) compared to waitlist‐control. Fears of compassion moderated intervention effectiveness. There were no effects on other outcome variables.

Conclusions

Findings support the potential effectiveness of interventions based on compassion‐focused therapy to improve maternal mental health.
Respiratory quotient: Effects of fatty acid composition
Authors: Price Edwin R. , Mager Edward M.
Published: October 2020

Respiratory quotient (RQ) is commonly used to infer which substrates are oxidized, with glucose yielding RQ = 1 and fat normally thought to yield an average of RQ = 0.71. Because fat depot compositions differ among species, we examined how the various common fatty acids affect RQ. RQs ranged from less than 0.7 (e.g., stearic acid) to greater than 0.76 (e.g., docosahexaenoic acid). Furthermore, we conducted a survey of the fatty acid composition of fuel lipids of several vertebrate taxa to determine how the RQ for lipid oxidation during fasting should vary among species. Our survey indicates that most fasting vertebrates from terrestrial ecosystems oxidizing fat should have RQs equaling approximately 0.71, as normally expected. However, some fasting animals in aquatic or marine systems—particularly fish—should have RQs as high as 0.73 when oxidizing only fat. Selective mobilization of fatty acids increased the lipid RQ, but probably by a negligible amount. We conclude that researchers should take habitat and taxon into account when choosing a value for lipid RQ, and preferably should use fatty acid composition for their study species to determine an appropriate RQ for lipids. In the absence of species‐specific fatty acid composition data, we suggest assuming a lipid RQ of 0.725 for cold‐water fish.
Early radiological response evaluation with response evaluation criteria in solid tumors 1.1 stratifies survival in hepatocellular carcinoma patients treated with lenvatinib
Authors: Kaneko Shun , Tsuchiya Kaoru , Yasui Yutaka , Inada Kento , Kirino Sakura , Yamashita Koji , Osawa Leona , Hayakawa Yuka , Sekiguchi Shuhei , Higuchi Mayu , Takaura Kenta , Maeyashiki Chiaki , Tamaki Nobuharu , Takeguchi Takaya , Takeguchi Yuko , Nakanishi Hiroyuki , Itakura Jun , Takahashi Yuka , Himeno Yoshiro , Kurosaki Masayuki , Izumi Namiki
Published: October 2020

Background and Aim

Lenvatinib (LEN) has an antitumor effect with an early reduction in contrast enhancement for unresectable hepatocellular carcinoma (HCC). The aim of this study was to reveal the most useful radiological response evaluation for overall survival (OS) in patients treated with LEN.

Methods

Patients receiving LEN therapy (n = 80) were retrospectively recruited from April 2018 to January 2020. Enhanced computed tomography scans were performed at baseline and every 4–8 weeks. OS and radiological response were evaluated using response evaluation criteria in solid tumors (RECIST 1.1), modified RECIST (mRECIST), and Choi criteria. To be eligible for study, a minimal cumulative duration of LEN was 4 weeks. A total of 62 patients were included in the analysis.

Results

The median OS was 469 days. The RECIST 1.1, mRECIST, and Choi criteria identified 14 (22.5%), 30 (48.3%), and 33 (53.2%) patients with an objective response, respectively. In the univariate analysis, Child–Pugh class B, major vascular invasion, and high alpha‐fetoprotein (>200) were statistically significant poor prognostic factors. Radiological response was a significantly better prognostic factor in each criterion (RECIST, mRECIST, and Choi). In the multivariate analysis, radiological response evaluated by RECIST (hazard ratio, 0.259; 95% confidence interval, 0.0723–0.928; P = 0.038) was an independent factor. Furthermore, only RECIST significantly stratified prognosis (P = 0.041) when limited to the first evaluation.

Conclusion

RECIST 1.1 was useful even as early therapeutic evaluation for HCC patients treated with LEN. Understanding the characteristics of radiological response over time may contribute to improving the prognosis of patients with HCC.
Minimal braces
Authors: Fabres Phelipe A. , Kothari Nishad , de Carvalho Marcelo H.
Published: October 2020

McCuaig proved a generation theorem for braces, and used it as the principal induction tool to obtain a structural characterization of Pfaffian braces. A brace is minimal if deleting any edge results in a graph that is not a brace. From McCuaig's brace generation theorem, we derive our main theorem that may be viewed as an induction tool for minimal braces. As an application, we prove that a minimal brace of order has size at most , when , and we provide a complete characterization of minimal braces that meet this upper bound. A similar work has already been done in the context of minimal bricks by Norine and Thomas wherein they deduce the main result from the brick generation theorem due to the same authors.
Why psychiatry might cooperate with religion: The Michigan Society of Pastoral Care, 1945–1968
Authors: Hirshbein Laura
Published: October 2020

The early decades of the pastoral care movement were characterized by a remarkable collaboration with psychiatry. While historians of the religious aspects of this movement have noted the reliance of pastoral care on psychiatry and psychology, it has been less clear how and why mental health professionals elected to work with clergy. This paper uses the Michigan Society of Pastoral Care (MSPC), one of the early training programs for hospital chaplains on the model of the Boston‐based Institute for Pastoral Care, as a window to explore the interactions between psychiatry and religion at mid century. Raymond Waggoner, the nationally recognized and well‐connected chair of the psychiatry department at the University of Michigan, was instrumental in expanding the influential pastoral care program at his hospital and in his state as part of his bigger mission of emphasizing the fundamental role of psychiatry in American life. Waggoner played a key role within the MSPC, in conjunction with leaders within the medical departments of the major hospitals in the state. All of the members of the MSPC viewed psychiatry's insights as essential for pastoral care, with the caveat that chaplains should remain pupils, not practitioners of psychotherapy.
Behavioural profiles and offender characteristics: Typology based on the Personality Assessment Inventory (PAI) in homicide cases
Authors: Sea Jonghan , Beauregard Eric , Youngs Donna
Published: October 2020

This study used cluster analysis in 126 homicide cases based on Personality Assessment Inventory (PAI; Morey, 1999). PAI was implemented by 126 homicides and then dichotomously coded for the presence or absence of cut‐off PAI scale score in order to create criteria for analysis. These cases were input for the agglomerative hierarchical cluster using Ward's method as the clustering algorithm. The results of the analysis classified five clusters: “normal,” “antisocial,” “submissive‐depressive,” “soma‐anxiety” and “isolated.” The representative characteristics were explored and compared with five clusters. As a result, these five clusters significantly differed in various criminogenic variables, such as criminal record and imprisonment experience. But, other variables were not significantly discriminated.
Characterization of inulin‐type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities
Authors: Zou Yuan‐Feng , Zhang Yan‐Yun , Zhu Zhong‐Kai , Fu Yu‐Ping , Paulsen Berit S , Huang Chao , Feng Bin , Li Li‐Xia , Chen Xing‐Fu , Jia Ren‐Yong , Song Xu , He Chang‐Liang , Yin Li‐Zi , Ye Gang , Lv Cheng , Yin Zhong‐Qiong
Published: October 2020

BACKGROUND

Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE–Sepharose column and characterized.

RESULTS

It was confirmed that the neutral polymers CPPN and CTPN were β‐(2,1)‐linked inulin‐type fructans with non‐reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC‐J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN.

CONCLUSION

The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin‐containing health products. © 2020 Society of Chemical Industry