bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic strain, parental education and psychotic experiences among college students in the United States: Findings from the Healthy Minds Study 2020
Authors: Oh Hans , Nagendra Arundati , Besecker Megan , Smith Lee , Koyanagi Ai , Wang Julia Shu‐Huah
Published: September 2021

Aim

Socioeconomic status (SES) is linked to psychosis, and much can be learned by examining how various indicators of SES—specifically economic strain and intergenerational transfer of resources—are related to sub‐threshold psychotic experiences among college students.

Methods

Using data from the Healthy Minds Survey (September 2020–December 2020), we used multivariable logistic regression models to examine the associations between five SES indicators and 12‐month psychotic experiences, adjusting for age, gender and race/ethnicity. We also examined the count of predictors and psychotic experiences.

Results

Each indicator of economic strain was associated with greater odds of psychotic experiences. In particular, increasing levels of financial stress (current, childhood and pandemic‐related) were associated with greater odds of psychotic experiences in a dose–response fashion. Food insecurity was associated with double the odds of psychotic experiences. In terms of intergenerational transfer of resources, having either one or no parents who attended college was associated with significantly greater odds of having psychotic experiences, when compared with having both parents who attended college. Examining all predictors in the same model, only childhood and current financial stress and food insecurity were significantly associated with psychotic experiences. The count of predictors was significantly associated with greater odds of having psychotic experiences in a dose‐dependent fashion.

Conclusions

Among college students, economic strain and intergenerational transfer of resources were associated with recent psychotic experiences, highlighting the importance of economic interventions targeting young adults to influence risk for psychosis.
RNF170 mutation causes autosomal dominant sensory ataxia with variable pyramidal involvement
Authors: Van Daele Sien H. , Moisse Matthieu , Race Valérie , Van Eesbeeck Amélie , Keldermans Liesbeth , Vermeer Sascha , Van Esch Hilde , Claeys Kristl G. , Van Damme Philip
Published: September 2021

Background

Although hereditary ataxias are a group of clinically and genetically heterogeneous disorders, specific clinical clues can sometimes incriminate certain genes. This can trigger genetic testing in sporadic patients or prompt dissecting certain genes more thoroughly when initial genetic testing is negative. Also for the assembly of gene panels and interpretation of the results, genotype−phenotype correlations remain important to establish.

Methods

We clinically evaluated a Belgian family with autosomal dominant inherited sensory ataxia and variable pyramidal involvement and performed targeted clinical exome sequencing. Secondly, we retrospectively screened sequencing data of an in‐house cohort of 404 patients with neuromuscular disorders for variants in the identified gene RNF170.

Results

All affected family members showed sensory ataxia on examination. Pyramidal involvement, and sometimes slow‐pursuit abnormalities and/or a sensory neuropathy, were more variable findings. We identified the heterozygous variant p.Arg199Cys in RNF170 in all three affected siblings of our family. We did not find additional pathogenic variants in RNF170 in our in‐house neuromuscular cohort.

Conclusions

We confirm the heterozygous variant p.Arg199Cys in RNF170 in a Belgian family with autosomal dominant sensory ataxia and variable pyramidal involvement. This constitutes a rare but clinically recognizable phenotype that warrants testing of RNF170. Unlike the distinctive bi‐allelic loss of function variants in RNF170 associated with hereditary spastic paraplegia (HSP), the p.Arg199Cys variant is the only one reported in sensory ataxia. It is important for neurologists to be aware of this characteristic phenotype and to include this gene in gene panels for ataxia and HSP.
Size effect in creep–fatigue crack growth interaction in P2M steel
Authors: Shlyannikov Valery , Kosov Dmitry , Fedorenkov Dmitry , Zhang Xian‐Chen , Tu Shan‐Tung
Published: September 2021

An investigation of the crack propagation under the creep–fatigue interaction in C(T) specimens of P2M steel was carried out. Numerical calculations included the determination of the stress–strain state fields for the viscoelastic material, as well as the distributions of stress triaxiality, nonlinear stress intensity factors, and the C‐integral along the crack front in specimen with different thickness. The interpretation of the experimental results under fatigue–creep interaction is given by the elastic and nonlinear stress intensity factors in terms of the traditional and new normalized cyclic fracture diagrams. Considering the size effects through the creep‐dominated stress intensity factors caused differences in the crack growth behavior. In specimens with the same geometry, the crack growth rate under the creep–fatigue interaction increased monotonically compared with harmonic fatigue, and the superposition of fatigue and creep contributions shows an order of magnitude increase in the total crack growth rate with respect to the pure creep.
Using Expectancy Value Theory to understand motivation, persistence, and achievement in university‐level foreign language learning
Authors: Nagle Charles
Published: September 2021

Most students take language courses at university, but only a fraction go beyond the introductory and intermediate levels despite the fact that continued study is likely necessary to achieve full communicative competence in the target language. By shedding light on the motivational pathways that predict language learning effort, persistence, and achievement, motivation research can provide actionable data that can guide strategies to help students generate and maintain motivation, leading to better learning outcomes and a stronger and healthier language program for educators and administrators. This survey‐based study applied Expectancy Value Theory to understand links between motivation, persistence, and achievement in a fourth‐semester Spanish course, a critical transition point in the language curriculum. Expectancy Value Theory subcomponents showed differential relationships to willingness to communicate, enrollment choices, and final course grade. Based on this data, suggestions are offered for supporting university students' language learning interest and achievement.
Lianas and trees exhibit divergent intrinsic water‐use efficiency along elevational gradients in South American and African tropical forests
Authors: Mumbanza Francis M. , Bauters Marijn , Meunier Félicien , Boeckx Pascal , Cernusak Lucas A. , De Deurwaerder Hannes P. T. , Demol Miro , Meeussen Camille , Sercu Bram , Verryckt Lore T. , Pauwels Jana , Cizungu Landry N. , Báez Selene , Lubini Constantin A. , Verbeeck Hans
Published: September 2021

Aim

Elevational gradients provide excellent opportunities to explore long‐term morphological and physiological responses of plants to environmental change. We determined the difference in the elevational pattern of foliar carbon isotope composition (δ13C) between lianas and trees, and assessed whether this difference arises from changes in photosynthesis or stomatal conductance. We also explored the pattern of nutrient limitations with the elevation of these two growth forms.

Location

The study was conducted in two mountain forests situated in the Neotropics and Palaeotropics.

Time period

August–September 2015 and August–October 2016.

Major taxa studied

Lianas and trees.

Methods

We conducted inventories of lianas and trees using standardized techniques along elevational gradients in Ecuador and Rwanda. We determined the values of several foliar traits including δ13C and chemical traits in dominant liana and tree species. We set up Bayesian linear mixed‐effect models to quantify the effects of elevation and growth form on each of the foliar traits , and the difference of the effect of elevation between the two growth forms (lianas and trees).

Results

We found consistent growth form specific divergences in foliar δ13C and carbon to nitrogen ratio (C : N) responses to elevation. While we noted a meaningful increase in foliar δ13C and C : N with elevation for trees, lianas did not exhibit such a trend. Foliar δ13C and C : N remained relatively constant for lianas along the transects.

Main conclusions

Lianas operate at relatively constant intrinsic water‐ and nitrogen‐use efficiencies with elevation compared with trees. Altogether, the study suggests the existence of a functional divergence of water and nutrient use strategies between lianas and trees along tropical elevational transects.
Spatial network analysis as a tool for measuring change in accessibility over time: Limits of transport investment as a driver for UK regional development
Authors: Hossain Md. Anwar , Cooper Crispin H. V.
Published: September 2021

This paper develops spatial network metrics that contribute to analysis of regional development. We use the sDNA software to derive longitudinal road network density and efficiency measures based on the network within a 1‐hr travel time buffer. We estimate this travel time itself from network shape and show it to be comparable to Google Maps travel time data. Economic analysis of 374 Local Administrative Units in the UK mainland shows cross‐sectional association between our network density and efficiency measures and Gross Value Added per capita (GVApc), whether measured in bivariate correlation or in multiple regression controlling for population, education, economic activity rate and rail stations. This is however both mediated and moderated by the proportion of knowledge‐based businesses; regions lacking a strong knowledge‐based sector show only weak correspondence between GVApc and accessibility. Looking at change over time, increase in network accessibility is linked to growth in the knowledge‐based sector, but inversely linked to economic performance during the 8‐year period studied, a finding which remains unexplained. Although further substantiation is needed, results suggest that the policy of transport investment as a driver of UK economic growth may be less effective in areas lacking potential to develop a strong knowledge‐based sector.
The impact of knowledge depth and breadth on the geography of analytical industry technological networks: Evidence from China’s biotechnology industry
Authors: Ye Qin
Published: September 2021

The debate on the role of knowledge specialization compared to diversification as a driver of regional innovation has been conflicting for a long time. This article contributes to this framework by exploring the effect of knowledge bases of analytical industry represented by China’s biotechnology industry on regional innovation from the perspective of networks. The network connecting the industry’s patented technology to the cities where the inventors are located depicts the geography of innovation in this industry. The more patents that a city generates in the core technology fields, the greater its centrality in the network, and the greater its relative importance to the industry innovation. Knowledge depth and breadth, two distinct dimensions of the knowledge bases on behalf of specialization and diversification, affect a city’s centrality in the technological network. In the analytical industry, both the knowledge depth and breadth of the city have negative curvilinear effects on its centrality in the network. The influence of knowledge depth is greater than that of knowledge breadth, but the synergy between the two is not significant. To promote the innovation performance of analytical industries, peripheral cities are more likely to increase knowledge breadth, while core cities are more likely to increase knowledge depth.
Improving healthcare for patients with HIV, tuberculosis and hepatitis C in eastern Europe: a review of current challenges and important next steps
Authors: Kraef Christian , Bentzon Adrian , Skrahina Alena , Mocroft Amanda , Peters Lars , Lundgren Jens D. , Chkhartishvili Nikoloz , Podlekareva Daria , Kirk Ole
Published: September 2021

Objectives

In some eastern European countries, serious challenges exist to meet the HIV‐, tuberculosis (TB)‐ and hepatitis‐related target of the United Nations Sustainable Development Goals. Some of the highest incidence rates for HIV and the highest proportion of multi‐drug‐resistant (MDR) tuberculosis worldwide are found in the region. The purpose of this article is to review the challenges and important next steps to improve healthcare for people living with TB, HIV and hepatitis C (HCV) in eastern Europe.

Methods

References for this narrative review were identified through systematic searches of PubMed using pre‐idientified key word for articles published in English from January 2000 to August 2020. After screening of titles and abstracts 37 articles were identified as relevant for this review. Thirty‐eight further articles and sources were identified through searches in the authors’ personal files and in Google Scholar.

Results

Up to 50% of HIV/MDR‐TB‐coinfected individuals in the region die within 2 years of treatment initiation. Antiretroviral therapy (ART) coverage for people living with HIV (PLHIV) and the proportion virological suppressed are far below the UNAIDS 90% targets. In theory, access to various diagnostic tests and treatment of drug‐resistant TB exists, but real‐life data point towards inadequate testing and treatment. New treatments could provide elimination of viral HCV in high‐risk populations but few countries have national programmes.

Conclusion

Some eastern European countries face serious challenges to achieve the sustainable development goal‐related target of 3.3 by 2030, among others, to end the epidemics of AIDS and tuberculosis. Better integration of healthcare systems, standardization of health care, unrestricted substitution therapy for all people who inject drugs, widespread access to drug susceptibility testing, affordable medicines and a sufficiently sized, well‐trained health workforce could address some of those challenges.
Clustering analysis and punishment‐driven consensus‐reaching process for probabilistic linguistic large‐group decision‐making with application to car‐sharing platform selection
Authors: Yu Su‐min , Du Zhi‐jiao , Zhang Xue‐yang
Published: September 2021

Probabilistic linguistic large‐group decision‐making (LGDM) is becoming a hot topic in the field of decision science. In general, clustering and consensus‐reaching are the two important processes to deal with LGDM problems. Traditional clustering methods are mainly based on opinion similarity measures and cannot directly control the number of decision makers (DMs) that can be contained in a cluster. Situations of noncooperative behavior toward consensus may be encountered during the consensus‐reaching process. This paper first proposes a distance‐to‐center clustering algorithm to classify the large group. The most important characteristic of the algorithm is that it is based on similarity measures of probabilistic linguistic information, and specifies the upper and lower limits on the number of DMs in the cluster. Then, a novel weight‐determining method is developed that considers the size, external consensus level, and inner consensus level of a cluster. A punishment‐driven consensus model is designed to manage opinion differences and noncooperative behaviors. Finally, the proposed clustering algorithm and consensus model are applied to a case study of car‐sharing platform selection. The results and comparative analysis reveal the potential application and effectiveness of this study.
Bibliometric analysis of the Doctor of Nursing Practice dissertations in the ProQuest Dissertations and Theses database
Authors: Shi Xiuxiu , Zhou Ying , Li Zheng
Published: September 2021

Aims

To examine the distributed characteristics and explore the research themes of Doctor of Nursing Practice (DNP) dissertations during the past two decades.

Design

A descriptive statistical and visualization bibliometric analysis was conducted.

Methods

Doctor of Nursing Practice dissertations submitted between January 2005 and June 2021 were collected from the ProQuest Dissertations and Theses database. A descriptive statistical analysis was conducted to calculate the distribution of the DNP dissertations by granting institution and the published year of publications. The VOSviewer 1.6.13 was used to explore the bibliometric networks and research priorities of the DNP dissertations.

Results

A total of 4989 DNP dissertations from 90 universities were included in this study, all from the United States. The number of DNP dissertations showed an upward trend, with steady growth from 2005 to 2014 and rapid growth after 2015. The DNP studies focused on five areas: health care management in clinical nursing, advanced practice in nursing education and health education, public health problems, mental health care for adolescents and nurses and the older people care and long‐term care.

Conclusion

Parallel to the numerical increase in DNP dissertations is a steady expansion in the range of research topics and scopes, which is aligned with specific specializations of the DNP. Many are interdisciplinary and employ techniques imported from the fields of public health, psychology and social sciences, resulting in nursing educators and practitioners continually broaden their subject perspectives.

Impact

Knowing where, when and why DNP research trends developed will help nursing educators to further develop DNP education and optimize DNP programs in the future, such as paying more attention to the nursing practice. Moreover, this study will inspire DNP students and researchers to expand their subject perspectives and broaden the research scope to solve nursing practice problems based on interdisciplinary theories and methods.
Non‐generally accepted accounting principles disclosures and audit committee chairs’ external directorships
Authors: Lee Cheng‐Hsun
Published: September 2021

I examine the relation between the quality of non‐generally accepted accounting principles (GAAP) earnings disclosures and the number of external directorships held by a firm's independent audit committee chair (ACC). I find that firms with ACCs holding more external directorships provide higher quality non‐GAAP disclosures than those who do not hold outside board positions. When the ACC has at least one external directorship, the firm's non‐GAAP exclusions are more transitory, indicating that they are of higher quality. In addition, when the ACC has at least one external directorship, non‐GAAP exclusions that are incremental to those excluded by analysts are smaller in magnitude and therefore are less aggressive. Overall, the results suggest that the number of external directorships ACCs holds plays an important role in firms’ non‐GAAP disclosures. The results are consistent with a reputation cost perspective, where ACCs with more external directorships face higher reputation concerns from having more to lose, resulting in stronger monitoring and thus higher quality non‐GAAP disclosures.
Imipramine impedes glioma progression by inhibiting YAP as a Hippo pathway independent manner and synergizes with temozolomide
Authors: Wang Yan , Wang Xiang , Wang Xu , Wu Di , Qi Ji , Zhang Yu , Wang Kai , Zhou Ding , Meng Qing‐Ming , Nie Er , Wang Qiang , Yu Ru‐Tong , Zhou Xiu‐Ping
Published: September 2021

Patients with malignant glioma often suffered from depression, which leads to an increased risk of detrimental outcomes. Imipramine, an FDA‐approved tricyclic antidepressant, has been commonly used to relieve depressive symptoms in the clinic. Recently, imipramine has been reported to participate in the suppression of tumour progression in several human cancers, including prostate cancer, colon cancer and lymphomas. However, the effect of imipramine on malignant glioma is largely unclear. Here, we show that imipramine significantly retarded proliferation of immortalized and primary glioma cells. Mechanistically, imipramine suppressed tumour proliferation by inhibiting yes‐associated protein (YAP), a recognized oncogene in glioma, independent of Hippo pathway. In addition to inhibiting YAP transcription, imipramine also promoted the subcellular translocation of YAP from nucleus into cytoplasm. Consistently, imipramine administration significantly reduced orthotopic tumour progression and prolonged survival of tumour‐bearing mice. Moreover, exogenous overexpression of YAP partially restored the inhibitory effect of imipramine on glioma progression. Most importantly, compared with imipramine or temozolomide (TMZ) monotherapy, combination therapy with imipramine and TMZ exhibited enhanced inhibitory effect on glioma growth both in vitro and in vivo, suggesting the synergism of both agents. In conclusion, we found that tricyclic antidepressant imipramine impedes glioma progression by inhibiting YAP. In addition, combination therapy with imipramine and TMZ may potentially serve as promising anti‐glioma regimens, thus predicting a broad prospect of clinical application.
Percutaneous trigeminal tractotomy for trigeminal neuralgia: Postoperative MRI findings
Authors: Gurbani Saumya S. , Brandman David M. , Reeves Christopher , Boulis Nicholas M. , Weinberg Brent D.
Published: September 2021

Background and Purpose

Percutaneous trigeminal tractotomy is an ablative procedure that can be used to treat trigeminal neuralgia in patients who have failed prior pharmacologic and surgical treatments. Using perioperative computed tomography (CT) guidance, ablation of the descending spinal trigeminal nucleus and trigeminal tract can be performed precisely to mitigate damage to surrounding structures. These patients are subsequently followed with postoperative imaging and clinical visits to assess long‐term pain relief.

Methods

In this report, we present a series of four patients with trigeminal neuralgia who were had refractory disease after prior medical and surgical interventions. These patients underwent CT‐guided percutaneous trigeminal tractotomy for pain relief. The patients underwent postoperative MRI and were followed for up to 6 months for long‐term clinical outcomes.

Results

For intraoperative CT, we find that preprocedure lumbar contrast injection enables better visualization of the cord during placement of the ablation probe. On postoperative imaging, we find that all four patients have hyperintense lesions on T2‐weighted MRI that correspond with the location of the trigeminal nucleus and tract. Three patients had short‐term pain relief, one of which continued to have long‐term relief.

Conclusion

Intraoperative CT and postoperative MRI serve as useful modalities for confirming localization, evaluating complications, and can be used as a metric for quality control.
Admissions due to vaccine preventable diseases in a large paediatric intensive care unit in Greece over a 10‐year period
Authors: Kazantzi Maria , Prapa Marilena , Christakou Eleni , Paraschou Dimitra , Kalabalikis Panagiotis , Barbaressou Charikleia , Papaevangelou Vassiliki
Published: September 2021

Aim

Childhood immunisation is an important preventive measure. However, care givers may delay routine immunisations or seek exemptions from state vaccine mandates. Vaccine refusal creates barriers on vaccine coverage and leads to morbidity and mortality.

Methods

Our study reviews morbidity and mortality from vaccine preventable diseases (VPDs) in a large paediatric intensive care unit in Greece over a 10‐year period.

Results

During the study period, 73 cases of VPDs were recorded, corresponding to 3.5% of total paediatric intensive care unit admissions. Influenza was the most prevalent VPD, followed by pneumococcal disease, measles, pertussis and meningococcal disease. Most patients (83.3%) were unvaccinated for the admission's VPD. Outcome was unfavourable for 31.9% of the patients (17 children died, 6 developed chronic impairment).

Conclusion

Absent or incomplete vaccination may result in serious morbidity and mortality from preventable diseases. Strengthening vaccination strategies are needed to improve individual protection as well as herd immunity.
Skin masses in dogs under one year of age
Authors: Kim D. , Dobromylskyj M. J. , O'Neill D. , Smith K. C.
Published: September 2021

Objectives

To utilise a large histopathology database to ascertain the incidence and nature of skin masses in young dogs from 0 to 12 months of age.

Materials and Methods

A total of 2554 submissions received for histopathology from dogs 0 to 12 months of age, clinically diagnosed with a skin mass between 2006 and 2013, were retrieved from the database of a large commercial diagnostic laboratory. The histological diagnosis and site of the lesion, together with age, breed and sex of the dog were recorded.

Results

The most common skin mass found in this study was histiocytoma (n=2212, 86.6%). The majority of all submissions were neoplastic (n=2408, 94.3%), and most of those were benign (n=2372, 98.5%). Almost all of the benign neoplastic lesions were of round cell origin (n=2229, 94.0%) whereas most of the non‐neoplastic lesions were derived from the epithelium (n=136, 93.8%). The five most commonly diagnosed skin masses in young dogs were histiocytoma, papilloma, dermoid cyst, follicular cyst and mast cell tumour. A male predisposition was shown for histiocytoma (odds ratio 1.72) and mast cell tumour (odds ratio 2.18) with a strong site predilection for the limb region (30.8% and 27.8% respectively). Dermoid cysts and follicular cysts were most commonly found in the skin of the abdomen (64.7% and 52.3% respectively) with boxers being predisposed (25.9% of dermoid cyst and 25.0% of follicular cyst).

Clinical Significance

A large proportion of skin mass submissions in young dogs were neoplastic and benign. Also, the most common skin mass in young dogs was found to be histiocytoma. Tumours can occur in this age group and should be considered as a potential differential diagnosis also in young patients presenting with a skin mass.
Mycobacterium avium infection associated with sterile polyarthritis in a dog
Authors: Gelendi S. , Taylor S. , D'Aout C. , Pitchford C. , Coldrick O. , Sanchez‐Jimenez C. , O'Halloran C.
Published: September 2021

A 1‐year‐old male neutered Portuguese Podengo dog was presented for lameness, inappetence, pyrexia, diarrhoea and abdominal moderate to severe lymphadenomegaly. Cytology of synovial fluid revealed neutrophilic inflammation in multiple joints suggestive of immune‐mediated polyarthritis. Cytology of fine‐needle‐aspiration material obtained from lymph nodes revealed macrophages with intracytoplasmic, rod‐like Ziehl‐Neelsen positive staining structures, indicative of mycobacteria. Four‐month treatment with enrofloxacin, rifampicin and clarithromycin resulted in clinical improvement and resolution of polyarthritis as evidenced on repeat synoviocentesis, but diarrhoea recurred, Ziehl‐Neelsen positive organisms were again found on lymph node cytology and analysis of the 16S rRNA‐gene using the Basic Local Alignment Search Tool facility resulted in a match to Mycobacterium avium with 100% sequence identity. Treatment was adjusted to include pradofloxacin, doxycycline, rifampicin and ethambutol and 3 months later the dog is clinically normal. Based on the literature search, this is the first time canine Mycobacterium avium infection associated with immune‐mediated polyarthritis is reported. Based on scoping searches, this is the first report of canine Mycobacterium avium infection associated with immune‐mediated polyarthritis.
Animal source foods, rich in essential amino acids, are important for linear growth and development of young children in low‐ and middle‐income countries
Authors: Parikh Panam , Semba Richard , Manary Mark , Swaminathan Sumathi , Udomkesmalee Emorn , Bos Rolf , Poh Bee Koon , Rojroongwasinkul Nipa , Geurts Jan , Sekartini Rini , Nga Tran Thuy
Published: September 2021

Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and delayed neurocognitive developments are most common. Fortunately, this is also the period when diet exercises its greatest influence. Growing up in an adverse environment, with a deficient diet, as typically seen in low‐ and middle‐income countries (LMICs), hampers growth and development of children and prevents them from realising their full developmental and economic future potential. Sufficient nutrient availability and utilisation are paramount to a child's growth and development trajectory, especially in the period after breastfeeding. This review highlights the importance of essential amino acids (EAAs) in early life for linear growth and, likely, neurocognitive development. The paper further discusses signalling through mammalian target of rapamycin complex 1 (mTORC1) as one of the main amino acid (AA)‐sensing hubs and the master regulator of both growth and neurocognitive development. Children in LMICs, despite consuming sufficient total protein, do not meet their EAA requirements due to poor diet diversity and low‐quality dietary protein. AA deficiencies in early life can cause reductions in linear growth and cognition. Ensuring AA adequacy in diets, particularly through inclusion of nutrient‐dense animal source foods from 6 to 23 months, is strongly encouraged in LMICs in order to compensate for less than optimal growth during complementary feeding.
Amino acid divergence in the ligand‐binding pocket of Vibrio LuxR/HapR proteins determines the efficacy of thiophenesulfonamide inhibitors
Authors: Newman Jane D. , Chopra Jay , Shah Priyanka , Shi Eda , McFadden Molly E. , Horness Rachel E. , Brown Laura C. , van Kessel Julia C.
Published: September 2021

The quorum‐sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2‐thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure–activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3‐phenyl‐1‐(thiophen‐2‐ylsulfonyl)‐1H‐pyrazole), inhibits quorum sensing in multiple strains of V. vulnificus, V. parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand‐binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfonamides from less‐effective derivatives. Our results revealed the previously unknown differences in LuxR/HapR proteins that control quorum sensing in Vibrio species and underscore the potential for developing thiophenesulfonamides as specific quorum sensing‐directed treatments for Vibrio infections.
A new avirulence gene of Leptosphaeria maculans, AvrLm14, identifies a resistance source in American broccoli (Brassica oleracea) genotypes
Authors: Degrave Alexandre , Wagner Marine , George Pierre , Coudard Laurent , Pinochet Xavier , Ermel Magali , Gay Elise J. , Fudal Isabelle , Moreno‐Rico Onesimo , Rouxel Thierry , Balesdent Marie‐Hélène
Published: September 2021

In many cultivated crops, sources of resistance to diseases are sparse and rely on introgression from wild relatives. Agricultural crops often are allopolyploids resulting from interspecific crosses between related species, which are sources of diversity for resistance genes. This is the case for Brassica napus (oilseed rape, canola), an interspecific hybrid between Brassica rapa (turnip) and Brassica oleracea (cabbage). B. napus has a narrow genetic basis and few effective resistance genes against stem canker (blackleg) disease, caused by the fungus Leptosphaeria maculans, are currently available. B. rapa diversity has proven to be a valuable source of resistance (Rlm, LepR) genes, while B. oleracea genotypes were mostly considered susceptible. Here we identified a new resistance source in B. oleracea genotypes from America, potentially effective against French L. maculans isolates under both controlled and field conditions. Genetic analysis of fungal avirulence and subsequent cloning and validation identified a new avirulence gene termed AvrLm14 and suggested a typical gene‐for‐gene interaction between AvrLm14 and the postulated Rlm14 gene. AvrLm14 shares all the usual characteristics of L. maculans avirulence genes: it is hosted in a genomic region enriched in transposable elements and heterochromatin marks H3K9me3, its expression is repressed during vegetative growth but shows a strong overexpression 5–9 days following cotyledon infection, and it encodes a small secreted protein enriched in cysteine residues with few matches in databases. Similar to the previously cloned AvrLm10‐A, AvrLm14 contributes to reduce lesion size on susceptible cotyledons, pointing to a complex interplay between effectors promoting or reducing lesion development.
Experience of patients with COVID‐19 in hospital isolation in Taiwan
Authors: Hsiao Chun‐Ting , Sun Jia‐Jing , Chiang Yi‐Hsuan , Chen Hsiu‐Lien , Liu Tsui‐Yao
Published: September 2021

The COVID‐19 pandemic has significantly impacted everyone's lives, challenging us in ways that can be frustrating, daunting, and intensely emotive. This qualitative study explored the isolation experiences of patients with COVID‐19 in a hospital in northern Taiwan. We collected data from nine patients in June–July 2020, conducting semi‐structured, virtual face‐to‐face, in‐depth interviews to gather input on two topics: (1) the psychological effect of hospital isolation on patients, including the psychological burden, stress response, support, disease stigma, and fear of returning to society; and (2) the patients' cognition and behaviors, which included tracking epidemic information, monitoring disease progression, soliciting suggestions about hospital isolation, and gauging comprehension after recovery. The results confirmed that hospital isolation significantly impacts patients physically, psychologically, spiritually, and socially. Thus, the isolated patients faced the dual challenges of fighting, adapting to, and recovering from the disease itself and struggling in isolation to maintain positive beliefs, independently assess their condition, and gain strength from the knowledge of continuing social support.
Three Basic Issues that Arise when Using Informational Restrictions in SVARs*
Authors: Ouliaris Sam , Pagan Adrian
Published: September 2021

When sign or other informational restrictions are used in SVARs, impulse responses are only set identified. Three issues need to be addressed when finding such sets. One is that the restrictions must be sufficient to separate the shocks. Failure to do so can result in unacceptable structural equations, for example two supply curves in the SVAR. Another is the need to adjust the identified set so that the responses are to the same size shock. Otherwise the range of responses that are being found may simply reflect different shock sizes. The third issue is estimation of the SVAR when all the shocks are not separated. Researchers are often unwilling to set out sign restrictions to separate all shocks and so we describe what can be done to accommodate that attitude by using a triangular SVAR that parallels what is used with exact restrictions.
Early‐life cytomegalovirus infection is associated with gut microbiota perturbations and increased risk of atopy
Authors: Sbihi Hind , Simmons Karen E. , Sears Malcolm R. , Moraes Theo J. , Becker Allan B. , Mandhane Piush J. , Subbarao Padmaja , Dai Darlene L. Y. , Finlay B. Brett , Turvey Stuart E. , Gantt Soren
Published: September 2021

Background

The “old friends” hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the “old friends” hypothesized to help prevent allergic diseases. We sought to elucidate whether early‐life CMV infection is associated with childhood atopy via perturbations of the gut microbiota.

Methods

Participants were recruited from a population‐based birth cohort (CHILD study) and followed prospectively until age 5 years in four Canadian cities. A total of 928 participants provided stool microbiome data, urine for CMV testing, skin prick tests, and questionnaire‐based detailed environmental exposures. Cytomegalovirus infection was assessed in the first year of life while the main outcome was defined by persistent sensitization to any allergen at ages 1, 3, and 5 years.

Results

Early CMV infection was associated with increased beta and decreased alpha diversity of the gut microbiota. Both changes in diversity measures and early CMV infection were associated with persistent allergic sensitization at age 5 years (aOR = 2.08; 95% CI: 1, 4.33). Mediation analysis demonstrated that perturbation of gut microbial composition explains 30% of the association.

Conclusions

Early‐life CMV infection is associated with an alteration in the intestinal microbiota, which mediates the effect of the infection on childhood atopy. This work indicates that preventing CMV infection would not put children at increased risk of developing atopy. Rather, a CMV vaccine, in addition to preventing CMV‐associated morbidity and mortality, might reduce the risk of childhood allergic diseases.
Decreased levels of endocytic collagen receptor Endo180 in dermal fibroblasts lead to decreased production of type I collagen and increased expression of matrix metalloproteinase‐1
Authors: Iwahashi Hiroyasu , Kawashima Yoshihito , Masaki Hitoshi
Published: September 2021

Background

Endo180 is involved in collagen remodeling by incorporating extracellular degraded collagen. Ultraviolet irradiation of dermal fibroblasts reduces Endo180 expression, which affects collagen fiber remodeling. However, it is unclear whether the decrease in Endo180 is directly related to the decrease in type I collagen fibers during photoaging. We aimed to clarify the relationship between Endo180 reduction and the decrease in type I collagen fibers observed in photoaged dermis.

Methods

Endo180 was reduced in normal human dermal fibroblasts using RNAi. Endo180 knockdown cells were inoculated into collagen gels. The influence of Endo180 knockdown was evaluated by measuring mRNA expression of collagen fiber remodeling‐related factors and collagen gel contraction. The collagen state and oxidative stress in the collagen gels were also measured.

Results

Endo180 knockdown cells, which were confirmed by gelatin uptake inhibition, showed upregulation of matrix metalloproteinase‐1 and downregulation of type I collagen mRNA expression when cultured in collagen gels. The contractility of the collagen gel was reduced by Endo180 knockdown. The collagen state in the extracellular matrix of the collagen gels containing Endo180 knockdown fibroblasts showed increased amounts of 3/4 fragmented collagen and denatured collagen and decreased type I collagen synthesis. In addition, an increase in intracellular oxidative stress was observed.

Conclusions

This study confirmed that the decrease in Endo180 caused a failure in collagen fiber formation and a decrease in collagen production, reproducing the photoaging dermal structural changes. This suggests that the decrease in Endo180 may be involved in wrinkle formation, which is a characteristic of photoaged skin.
Diversifying the medical curriculum as part of the wider decolonising effort: A proposed framework and self‐assessment resource toolbox
Authors: Mbaki Yvonne , Todorova Eli , Hagan Pamela
Published: September 2021

The narrative of decolonisation has recently amassed momentum, with the student and public voice providing the greatest advocacy, resulting in medical schools and universities embarking on a broader range of initiatives in response to the wider decolonisation agenda. Part of this wider effort is the diversification of the curriculum to create a more culturally responsive and equity focussed experience and training. Diversifying the curriculum poses considerable challenges due to limited expertise and/or relevant resources. It is from identification of this deficit, as well as our own experience in a UK medical school of diversifying our medical curriculum in the context of our decolonising efforts and the nature of the work required, that we developed a framework and created a toolbox of reflective questions, examples and resources to aid this work. As authors, we acknowledge that this process will be ongoing as we educate ourselves and reframe perceptions of the world, learn from lived experiences and incorporate advice from experts. The aspiration of this toolbox is to support those involved in efforts and initiatives to undo the effects of colonialism in medical education and research, and more specifically those who seek to diversify their curriculum within this context. This will ultimately benefit the education of our students, with the objective of equipping them with the knowledge, understanding and skills to provide equitable care to their patients.
When is Psychology Research Useful in Artificial Intelligence? A Case for Reducing Computational Complexity in Problem Solving
Authors: Hélie Sébastien , Pizlo Zygmunt
Published: September 2021

A problem is a situation in which an agent seeks to attain a given goal without knowing how to achieve it. Human problem solving is typically studied as a search in a problem space composed of states (information about the environment) and operators (to move between states). A problem such as playing a game of chess has possible states, and a traveling salesperson problem with as little as 82 cities already has more than different tours (similar to chess). Biological neurons are slower than the digital switches in computers. An exhaustive search of the problem space exceeds the capacity of current computers for most interesting problems, and it is fairly clear that humans cannot in their lifetime exhaustively search even small fractions of these problem spaces. Yet, humans play chess and solve logistical problems of similar complexity on a daily basis. Even for simple problems humans do not typically engage in exploring even a small fraction of the problem space. This begs the question: How do humans solve problems on a daily basis in a fast and efficient way? Recent work suggests that humans build a problem representation and solve the represented problem—not the problem that is out there. The problem representation that is built and the process used to solve it are constrained by limits of cognitive capacity and a cost–benefit analysis discounting effort and reward. In this article, we argue that better understanding the way humans represent and solve problems using heuristics can help inform how simpler algorithms and representations can be used in artificial intelligence to lower computational complexity, reduce computation time, and facilitate real‐time computation in complex problem solving.
The MdMEK2–MdMPK6–MdWRKY17 pathway stabilizes chlorophyll levels by directly regulating MdSUFB in apple under drought stress
Authors: Shan Dongqian , Wang Chanyu , Song Handong , Bai Yixue , Zhang Haixia , Hu Zehui , Wang Lin , Shi Kun , Zheng Xiaodong , Yan Tianci , Sun Yanzhao , Zhu Yunpeng , Zhang Tong , Zhou Zhaoyang , Guo Yan , Kong Jin
Published: September 2021

Drought stress severely limits plant growth and production in apple (Malus domestica Borkh.). To breed water‐deficit‐tolerant apple cultivars that maintain high yields under slight or moderate drought stress, it is important to uncover the mechanisms underlying the transcriptional regulation of chlorophyll metabolism in apple. To explore this mechanism, we generated transgenic ‘Gala3’ apple plants with overexpression or knockdown of MdWRKY17, which encodes a transcription factor whose expression is significantly induced by water deficit. Under moderate drought stress, we observed significantly higher chlorophyll contents and photosynthesis rates in overexpression transgenic plants than in controls, whereas these were dramatically lower in the knockdown lines. MdWRKY17 directly regulates MdSUFB expression, as demonstrated by in vitro and in vivo experiments. MdSUFB, a key component of the sulfur mobilization (SUF) system that assembles Fe‐S clusters, is essential for inhibiting chlorophyll degradation and stabilizing electron transport during photosynthesis, leading to higher chlorophyll levels in transgenic apple plants overexpressing MdWRKY17. The activated MdMEK2–MdMPK6 cascade by water‐deficit stress fine‐tunes the MdWRKY17–MdSUFB pathway by phosphorylating MdWRKY17 under water‐deficit stress. This fine‐tuning of the MdWRKY17–MdSUFB regulatory pathway is important for balancing plant survival and yield losses (chlorophyll degradation and reduced photosynthesis) under slight or moderate drought stress. The phosphorylation by MdMEK2–MdMPK6 activates the MdWRKY17–MdSUFB pathway at S66 (identified by LC‐MS), as demonstrated by in vitro and in vivo experiments. Our findings reveal that the MdMEK2–MdMPK6–MdWRKY17–MdSUFB pathway stabilizes chlorophyll levels under moderate drought stress, which could facilitate the breeding of apple varieties that maintain high yields under drought stress.
Algunas modificaciones del régimen del seguro de responsabilidad civil en una nueva ley española de contrato de seguro
Authors: Peñas Moyano María Jesús
Published: September 2021

La Ley española de contrato de seguro acaba de celebrar su cuarenta aniversario. El tiempo transcurrido desde su entrada en vigor motiva el debate de la elaboración de un nuevo texto que incluya modificaciones también en el régimen del seguro de responsabilidad civil. Algunas de las reformas que deben abordarse en este ámbito se refieren a una correcta delimitación temporal del riesgo, a través de las cláusulas correspondientes para evitar confusiones con una posible limitación de derechos de los asegurados. Ha de reconsiderarse igualmente ejercicio de la acción directa por parte de los terceros perjudicados y el ámbito de las posibles excepciones que se pueden oponer, así como la oportunidad de contemplar en el régimen contractual los seguros de naturaleza obligatoria.