bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating performance of existing computational models in predicting CD8+ T cell pathogenic epitopes and cancer neoantigens
Authors: Buckley Paul R. , Lee Chloe H. , Ma Ruichong , Woodhouse Isaac , Woo Jeongmin , Tsvetkov Vasily O , Shcherbinin Dmitrii S , Antanaviciute Agne , Shughay Mikhail , Rei Margarida , Simmons Alison , Koohy Hashem
Published: December 2020

T cell recognition of a cognate peptide-MHC complex (pMHC) presented on the surface of infected or malignant cells, is of utmost importance for mediating robust and long-term immune responses. Accurate predictions of cognate pMHC targets for T Cell Receptors (TCR) would greatly facilitate identification of vaccine targets for both pathogenic diseases as well as personalized cancer immunotherapies. Predicting immunogenic peptides therefore has been at the centre of intensive research for the past decades but has proven challenging. Although numerous models have been proposed, performance of these models has not been systematically evaluated and their success rate in predicting epitopes in the context of human pathology, has not been measured and compared. In this study, we evaluated the performance of several publicly available models, in identifying immunogenic CD8+ T cell targets in the context of pathogens and cancers. We found that for predicting immunogenic peptides from an emerging virus such as SARS-CoV-2, none of the models perform substantially better than random or offer considerable improvement beyond HLA ligand prediction. We also observed suboptimal performance for predicting cancer neoantigens. Through investigation of potential factors associated with ill performance of models, we highlight several data- and model-associated issues. In particular, we observed that cross-HLA variation in the distribution of immunogenic and non-immunogenic peptides in training data of the models seem to substantially confound the predictions. We additionally compared key parameters associated with immunogenicity between pathogenic peptides and cancer neoantigens and observed evidence for differences in the thresholds of binding affinity and stability, which suggested the need to modulate different features in identifying immunogenic pathogen vs. cancer peptides. Overall, we demonstrate that accurate and reliable prediction of immunogenic CD8+ T cell targets remains unsolved, thus we hope our work will guide users and model developers regarding potential pitfalls and unsettled questions in existing immunogenicity predictors.
Assessment of age‐related morphological changes in the testes of post‐hatch light ecotype Nigerian indigenous chicken
Authors: Udoumoh Anietie Francis , Igwebuike Udensi Maduabuchi , Okoye Chidozie Nwabuisi , Ugwu Ugochukwu Michael , Oguejiofor Chike Fidelis
Published: December 2020

The age‐related morphological changes of the testes in light ecotype Nigerian indigenous chicken were evaluated in this study using gross anatomical, histological and histomorphometric techniques. The results showed that the testes of 3‐ to 9‐month‐old birds were light pink while testes of sexually mature chicken were creamy white in colour. The left and right testicular weight, length, diameter, circumference and the organosomatic indices increased significantly (p < .05) with increasing age across the groups. Although the mean tubular diameter and epithelial height of the left and right seminiferous tubules increased significantly (p < .05) with age, the tubular diameter, epithelial height and luminal diameter did not vary significantly (p > .05) between the left and right testes of all the groups. The one‐cell layer thick germinal epithelium of the left testes at 3 to 6 months old showed islands of cell proliferation that contained spermatogonia and spermatocytes. At 6 to 9 months, the left testes exhibited numerous early spermatids with occasional occurrence of late stage spermatids while the right testes showed scanty early stage spermatids. At 12 to 18 months, the germinal epithelia of both left and right testes were characterized by the presence of Sertoli cells, spermatogonia, primary spermatocytes, numerous early and late stage spermatids as well as spermatozoa. In conclusion, the morphological features highlighted in the present study show that at pre‐pubertal periods, the left testes may develop faster than the right testes. However, both left and right testes may participate actively in the production of spermatozoa during the post‐pubertal life.
TKI dose reduction can effectively maintain major molecular remission in patients with chronic myeloid leukaemia
Authors: Claudiani Simone , Apperley Jane F. , Szydlo Richard , Khan Afzal , Nesr George , Hayden Chloe , J. Innes Andrew , Dominy Kathy , Foskett Pierre , Foroni Letizia , Khorashad Jamshid , Milojkovic Dragana
Published: December 2020

Targeted therapy for chronic myeloid leukaemia (CML) has allowed for a near‐normal patient life‐expectancy; however, quality of life and aggravation of existing co‐morbidities have posed new treatment challenges. In clinical practice, TKI dose reduction occurs frequently, often on multiple occasions, because of intolerance. We conducted a retrospective ‘real‐world practice’ review of 246 patients receiving lower than standard dose (LD) TKI after the achievement of major molecular response (MR3), because of intolerable adverse events. In 274 of 298 cases of dose reduction (91·9%), MR3 was maintained at median follow‐up of 27·3 months. One patient progressed to blast crisis while on LD TKI. Two patients developed two new ABL kinase domain mutations (T315I and V299L), of whom one had achieved deep molecular response on an alternative LD TKI at last follow‐up. Seventy‐six patients eventually discontinued LD TKI and the two‐year treatment‐free remission (TFR) rate in these patients was 74·1%. The majority of patients with CML in at least MR3 appear to be safely managed with LD TKI, although three of 246 patients had new events (progression and new mutation), indicating that this approach requires vigilance. TKI LD does not prevent the achievement of TFR in this patient population.
Does self‐compassion help to deal with dietary lapses among overweight and obese adults who pursue weight‐loss goals?
Authors: Thøgersen‐Ntoumani Cecilie , Dodos Louisa A. , Stenling Andreas , Ntoumanis Nikos
Published: December 2020

Objectives

Self‐compassion can facilitate self‐improvement motivation. We examined the effects of self‐compassion in response to dietary lapses on outcomes relevant to weight‐loss strivings using a longitudinal design. The indirect effects of self‐compassion via guilt and shame were also explored.

Design

An Ecological Momentary Assessment methodology was employed with a sample of adults who were overweight or obese attempting to lose weight via dietary restriction (N = 56; Mage = 34.88; SD = 13.93; MBMI = 32.50; SD = 6.88) and who responded to brief surveys sent to their mobile phones twice daily for two weeks.

Methods

Dietary temptations and lapses were assessed at each diary entry, and self‐compassion in response to dietary lapses, intention to continue dieting, weight‐loss‐related self‐efficacy, negative reactions to the lapse, and self‐conscious emotions were surveyed on occasions when participants reported having experienced a dietary lapse. The participants were also weighed in a laboratory prior to the EMA phase and via self‐report straight after the EMA phase. Weight was measured again in the laboratory 12 weeks after the EMA period.

Results

Bayesian multilevel path analyses showed that self‐compassion did not predict weight loss. However, at the within‐person level, self‐compassion was positively related to intentions and self‐efficacy to continue dieting, and negatively related to negative affective reactions to the lapses. Guilt mediated the associations of self‐compassion with intention, self‐efficacy, and negative reactions.

Conclusion

Self‐compassion may be a powerful internal resource to cultivate when dieters experience inevitable setbacks during weight‐loss strivings which could facilitate weight‐loss perseverance.
Burrowing into the forest: Phylogeny of the Asian forest scorpions (Scorpionidae: Heterometrinae) and the evolution of ecomorphotypes
Authors: Loria Stephanie F. , Prendini Lorenzo
Published: December 2020

Asian forest scorpions (Scorpionidae Latreille, 1802: Heterometrinae Simon, 1879) are distributed across South and Southeast Asia. All are fossorial, constructing burrows under stones or in open ground, in habitats differing in precipitation and vegetation cover, from rainforests and tropical deciduous forests to savanna and scrubland. The systematics of these scorpions has long been confused due to bad taxonomy and the absence of a phylogenetic framework. Although the monophyly of the group was previously confirmed as part of broader phylogenetic analyses based on exemplar species, the only quantitative analysis of species‐level variation to date was based on overall similarity. This contribution presents the first species‐level phylogenetic analysis of Asian Scorpionidae, based on 186 morphological characters and 4188 aligned base‐pairs of DNA sequence data from two nuclear and three mitochondrial loci for 132 terminals including all 41 ingroup species and four outgroup species. Simultaneous analyses of the morphological and molecular datasets with parsimony, Maximum Likelihood and Bayesian Inference provided the framework for a revised classification presented elsewhere. In order to understand how adaptation following dispersal into new habitats has driven the morphological diversification of Asian forest scorpions, species were scored for 10 characters concerning morphology and burrow architecture, which contributed to an ensemble index of adaptation to habitat aridity. Species were classified into three ecomorphotypes based on the index, and ancestral state reconstruction of ecomorphotypes performed on the phylogeny. A pattern was recovered in which lineages and species occurring in different habitats on a continuum from wet (evergreen forest) to dry (savanna, scrubland) exhibited characters presumed to be adaptive and hence responsible for driving scorpion diversification.
Increased frequency of heart transplantation, shortened waitlist time and preserved post‐transplant survival in adults with congenital heart disease, on the new heart transplant allocation system
Authors: Jani Milena , Cook Stephen , Huang Si Hong , Boeve Theodore , Leacche Marzia , Manandhar‐Shrestha Nabin K. , Jovinge Stefan V. , Loyaga‐Rendon Renzo Y.
Published: December 2020

Historically, adult congenital patients have longer waitlist time and worse outcomes on the heart transplant waitlist as well as poorer early post‐transplant survival. A new heart transplantation allocation system was implemented in the United States on October 18, 2018. The effect of the new allocation system on adult congenital patients is unknown. Adult congenital patients listed for transplantation between November 1, 2015 and September 30, 2019 registered in the United Network for Organ Sharing were included in the study. October 18, 2018 was used as the limit to distribute listed and transplanted patients into old and new groups. A total of 399 patients were listed for heart transplant only, 284 in the old system and 115 in the new system. Clinical characteristics were similar between both groups. The cumulative incidence of poor outcome on the transplant list was similar in both groups (P = .23), but the cumulative incidence of transplant was higher in the new system group (P < .009) and was associated with a shorter waitlist time. The one‐year post‐transplant outcome was similar between old and new groups (P = .37). The new allocation system has benefited adult congenital patients with increased cumulative frequency of transplantation without worsening short‐term survival after transplantation.
Lack of neural evidence for implicit language learning in 9‐month‐old infants at high risk for autism
Authors: Liu Janelle , Tsang Tawny , Ponting Carolyn , Jackson Lisa , Jeste Shafali S. , Bookheimer Susan Y. , Dapretto Mirella
Published: December 2020

Word segmentation is a fundamental aspect of language learning, since identification of word boundaries in continuous speech must occur before the acquisition of word meanings can take place. We previously used functional magnetic resonance imaging (fMRI) to show that youth with autism spectrum disorder (ASD) are less sensitive to statistical and speech cues that guide implicit word segmentation. However, little is known about the neural mechanisms underlying this process during infancy and how this may be associated with ASD risk. Here, we examined early neural signatures of language‐related learning in 9‐month‐old infants at high (HR) and low familial risk (LR) for ASD. During natural sleep, infants underwent fMRI while passively listening to three speech streams containing strong statistical and prosodic cues, strong statistical cues only, or minimal statistical cues to word boundaries. Compared to HR infants, LR infants showed greater activity in the left amygdala for the speech stream containing statistical and prosodic cues. While listening to this same speech stream, LR infants also showed more learning‐related signal increases in left temporal regions as well as increasing functional connectivity between bilateral primary auditory cortex and right anterior insula. Importantly, learning‐related signal increases at 9 months positively correlated with expressive language outcome at 36 months in both groups. In the HR group, greater signal increases were additionally associated with less severe ASD symptomatology at 36 months. These findings suggest that early differences in the neural networks underlying language learning may predict subsequent language development and altered trajectories associated with ASD risk.
A pilot study on right ventricular longitudinal strain as a predictor of outcome in COVID‐19 patients with evidence of cardiac involvement
Authors: Stockenhuber Alexander , Vrettos Apostolos , Androshchuk Vitaliy , George Manju , Robertson Calum , Bowers Nicola , Clifford Piers , Firoozan Soroosh
Published: December 2020

Aims

The aim of this investigation was to evaluate echocardiographic parameters of cardiac function and in particular right ventricular (RV) function as a predictor of mortality in patients with coronavirus disease‐2019 (COVID‐19) pneumonia.

Methods and Results

This prospective observational study included 35 patients admitted to a UK district general hospital with COVID‐19 and evidence of cardiac involvement, that is, raised Troponin I levels or clinical evidence of heart failure during the first wave of the COVID‐19 pandemic (March–May 2020). All patients underwent echocardiography including speckle tracking for right ventricular longitudinal strain (RVLS) providing image quality was sufficient (30 out of 35 patients). Upon comparison of patients who survived COVID‐19 with non‐survivors, survivors had significantly smaller RVs (basal RV diameter 38.2 vs 43.5 mm P = .0295) with significantly better RV function (Tricuspid annular plane systolic excursion (TAPSE): 17.5 vs 15.3 mm P = .049; average RVLS: 24.3% vs 15.6%; P = .0018). Tricuspid regurgitation (TR) maximal velocity was higher in survivors (2.75 m/s vs 2.11 m/s; P = .0045) indicating that pressure overload was not the predominant driver of this effect and there was no significant difference in left ventricular (LV) ejection fraction. Kaplan–Meier and log‐rank analysis of patients split into groups according to average RVLS above or below 20% revealed significantly increased 30‐day mortality in patients with average RVLS under 20% (HR: 3.189; 95% CI: 1.297–12.91; P = .0195).

Conclusion

This study confirms that RVLS is a potent and independent predictor of outcome in COVID‐19 patients with evidence of cardiac involvement.
Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system
Authors: Grinspan Zachary M. , Patel Anup D. , Shellhaas Renée A. , Berg Anne T. , Axeen Erika T. , Bolton Jeffrey , Clarke David F. , Coryell Jason , Gaillard William D. , Goodkin Howard P. , Koh Sookyong , Kukla Alison , Mbwana Juma S. , Morgan Lindsey A. , Singhal Nilika S. , Storey Margaret M. , Yozawitz Elissa G. , Abend Nicholas S. , Fitzgerald Mark P. , Fridinger Sara E. , Helbig Ingo , Massey Shavonne L. , Prelack Marisa S. , Buchhalter Jeffrey ,   the Pediatric Epilepsy Learning Healthcare System
Published: December 2020

Objective

Common data elements (CDEs) are standardized questions and answer choices that allow aggregation, analysis, and comparison of observations from multiple sources. Clinical CDEs are foundational for learning health care systems, a data‐driven approach to health care focused on continuous improvement of outcomes. We aimed to create clinical CDEs for pediatric epilepsy.

Methods

A multiple stakeholder group (clinicians, researchers, parents, caregivers, advocates, and electronic health record [EHR] vendors) developed clinical CDEs for routine care of children with epilepsy. Initial drafts drew from clinical epilepsy note templates, CDEs created for clinical research, items in existing registries, consensus documents and guidelines, quality metrics, and outcomes needed for demonstration projects. The CDEs were refined through discussion and field testing. We describe the development process, rationale for CDE selection, findings from piloting, and the CDEs themselves. We also describe early implementation, including experience with EHR systems and compatibility with the International League Against Epilepsy classification of seizure types.

Results

Common data elements were drafted in August 2017 and finalized in January 2020. Prioritized outcomes included seizure control, seizure freedom, American Academy of Neurology quality measures, presence of common comorbidities, and quality of life. The CDEs were piloted at 224 visits at 10 centers. The final CDEs included 36 questions in nine sections (number of questions): diagnosis (1), seizure frequency (9), quality of life (2), epilepsy history (6), etiology (8), comorbidities (2), treatment (2), process measures (5), and longitudinal history notes (1). Seizures are categorized as generalized tonic‐clonic (regardless of onset), motor, nonmotor, and epileptic spasms. Focality is collected as epilepsy type rather than seizure type. Seizure frequency is measured in nine levels (all used during piloting). The CDEs were implemented in three vendor systems. Early clinical adoption included 1294 encounters at one center.

Significance

We created, piloted, refined, finalized, and implemented a novel set of clinical CDEs for pediatric epilepsy.
Healthy ageing in urban China: Governing the ageing population
Authors: Yu Yi
Published: December 2020

The Chinese government has promoted the concept of “healthy ageing” to meet the goals of Healthy China 2030. Thus, achieving healthy ageing has become the principal motivation behind community eldercare organisations’ activities and services for the elderly in Chinese cities. The principles of healthy ageing encourage older adults to participate in activities, conduct volunteer labour, and strive to improve or at least maintain their physical health. Based on six months of ethnographic fieldwork, this paper examines the discourses and practices surrounding the “healthy ageing” paradigm in urban China and its role in governing the ageing population. This paper argues that the concept of healthy ageing requires older adults to set health as their primary goal, which also entails their embodiment of the healthy ageing paradigm. This paper bridges the literature on governmentality and critical and cultural gerontology while also contributing to the understanding of population governance in China.
A feminist public sociology of the pandemic: Interviewing about a crisis, during a crisis
Authors: Averett Kate Henley
Published: December 2020

Widespread school closures due to the coronavirus‐2019 (COVID‐19) pandemic have left US parents—especially mothers—doing increasing amounts of family labor as they oversee their children's remote learning. In this article, I reflect on the process of interviewing 112 US parents, primarily mothers, about their experiences of pandemic‐related school closures, amidst the pandemic itself. These interviews were largely intensely emotional experiences. I reflect on the emotions of both respondents and researcher to argue that carrying out such interviews in the midst of a crisis can function as a form of care work. I propose the idea of a feminist public sociology of the pandemic that has three primary aims: bearing witness to the experiences of those impacted by the pandemic, making a record of those experiences, and helping scholars and the public to think about the pandemic sociologically, ideally in such a way that will aid in the creation of policy responses that address and reduce this suffering.
Micro‐ and nano‐emulsions based on soluble soy polysaccharide and octenyl succinic anhydride modified soluble soy polysaccharide
Authors: Qi Jun‐Ru , Zhang Dai‐Yu , Zhao Ru‐Xia , Liao Jin‐Song , Cao Yong , Xiao Jie
Published: December 2020

In this study, emulsion stabilised by soybean soluble polysaccharide (SSPS) and octenyl succinic anhydride modified SSPS (OSA‐SSPS) with high molecular weight (HMW) at concentrations (2%, 3%, 4%, 5%, 6%) was prepared. The droplet size of emulsion stabilised by OSA‐SSPS (HMW) was between 150 and 300 nm with a single distribution peak and increased by 0.1 μm after 4 weeks; that of emulsion stabilised by SSPS was between 1 and 5 μm with two distribution peaks and increased by more than 2 μm after 4 weeks. The viscosity of emulsion with OSA‐SSPS (HMW) was larger than that with SSPS, and the absolute value of zeta potential of microemulsion with SSPS was lower than 43 mV while that of nanoemulsion with OSA‐SSPS (HMW) was higher than 46 mV. The stability of nanoemulsion with OSA‐SSPS (HMW) slightly varied with the increase of storage time and concentration, which provided theoretical guidance for the application of OSA‐SSPS in nanoemulsion.
“We are part of this place, but I do not think I belong.” Temporariness, Social Inclusion and Belonging among Migrant Farmworkers in Southwestern Ontario
Authors: Basok Tanya , George Glynis
Published: December 2020

The Canadian temporary migration regime has been widely criticised for its failure to provide protections and address migrant needs. This article contributes to these critiques by analysing how temporariness impacts the sense of belonging and perceptions of social inclusion among farmworkers in Canada. The sense of inclusion and belonging is vital for individuals’ sense of well‐being, and therefore, a critique of temporariness is incomplete without it. Based on ethnographic research conducted in 2018–2019 in a rural community in Southwestern Ontario, Canada, it documents that, despite certain initiatives to make temporary migrant workers feel welcomed, migrants have not grown attached to this place. We situate farmworkers’ limited sense of belonging in the exclusionary architecture of this labour migration regime. We argue that two structural elements in particular make it impossible for most migrant farmworkers to feel connected to Canada—the forced separation from their families, and the lack of mobility within the labour force.
Macrophage reprogramming for therapy
Authors: Bart Valentina M. T. , Pickering Robert J. , Taylor Philip R. , Ipseiz Natacha
Published: December 2020

Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting‐edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage‐targeted approaches in human disease.
For a critical appraisal of artificial intelligence in healthcare: The problem of bias in mHealth
Authors: Brault Nicolas , Saxena Mohit
Published: December 2020

Rationale, aims and objectives

Artificial intelligence and big data are more and more used in medicine, either in prevention, diagnosis or treatment, and are clearly modifying the way medicine is thought and practiced. Some authors argue that the use of artificial intelligence techniques to analyze big data would even constitute a scientific revolution, in medicine as much as in other scientific disciplines. Moreover, artificial intelligence techniques, coupled with mobile health technologies, could furnish a personalized medicine, adapted to the individuality of each patient. In this paper we argue that this conception is largely a myth: what health professionals and patients need is not more data, but data that are critically appraised, especially to avoid bias.

Methods

In this historical and conceptual article, we focus on two main problems: first, the data and the problem of its validity; second, the inference drawn from the data by AI, and the establishment of correlations through the use of algorithms. We use examples from the contemporary use of mobile health (mHealth), i.e. the practice of medicine and public health supported by mobile or wearable devices such as mobile phones or smart watches.

Results

We show that the validity of the data and of the inferences drawn from these mHealth data are likely to be biased. As biases are insensitive to the size of the sample, even if the sample is the whole population, artificial intelligence and big data cannot avoid biases and even tend to increase them.

Conclusions

The large amount of data thus appears rather as a problem than a solution. What contemporary medicine needs is not more data or more algorithms, but a critical appraisal of the data and of the analysis of the data. Considering the history of epidemiology, we propose three research priorities concerning the use of artificial intelligence and big data in medicine.
PTSD Improvement Associated with Social Connectedness in Gerofit Veterans Exercise Program
Authors: Wilkins Stacy Schantz , Melrose Rebecca J. , Hall Katherine S. , Blanchard Erin , Castle Steven C. , Kopp Teresa , Katzel Leslie I. , Holder Alice , Alexander Neil , McDonald Michelle K.S. , Tayade Arti , Forman Daniel E. , Abbate Lauren M. , Harris Rebekah , Valencia Willy M. , Morey Miriam C. , Lee Cathy C.
Published: December 2020

Objective

Post‐traumatic stress disorder (PTSD) is common in Veterans. Symptoms can perpetuate into late life, negatively impacting physical and mental health. Exercise and social support are beneficial in treating anxiety disorders such as PTSD in the general population, although less is known about the impact on Veterans who have lived with PTSD for decades. This study assessed associations between social connectedness, physical function and self‐reported change in PTSD symptoms among older Veterans specifically participating in Gerofit.

Design

Prospective clinical intervention.

Setting

Twelve sites of Veterans Affairs (VA) Gerofit exercise program across the United States.

Participants

Three hundred and twenty one older Veteran Gerofit participants (mean age = 74) completed physical assessments and questionnaires regarding physical and emotional symptoms and their experience.

Measurements

Measures of physical function, including 30‐second chair stands, 10‐m and 6‐min walk were assessed at baseline and 3 months; change in PTSD symptoms based on the Diagnostic Statistical Manual—5 (DSM‐5) assessed by a self‐report questionnaire; and social connection measured by the Relatedness Subscale of the Psychological Need Satisfaction in Exercise scale (PNSE) were evaluated after 3 months of participation in Gerofit.

Results

Ninety five (29.6%) Veterans reported PTSD. Significant improvement was noted in self‐rated PTSD symptoms at 3 months (P < .05). Moderate correlation (r = .44) was found between social connectedness with other participants in Gerofit and PTSD symptom improvement for those Veterans who endorsed improvement (n = 59). All participants improved on measures of physical function. In Veterans who endorsed PTSD there were no significant associations between physical function improvement and PTSD symptoms.

Conclusion

Veterans with PTSD that participated in Gerofit group exercise reported symptom improvement, and social connectedness was significantly associated with this improvement. In addition to physical health benefits, the social context of Gerofit may offer a potential resource for improving PTSD symptoms in older Veterans that warrants further study.
Progression of Physical Frailty and the Risk of All‐Cause Mortality: Is There a Point of No Return?
Authors: Xue Qian‐Li , Bandeen‐Roche Karen , Tian Jing , Kasper Judith D. , Fried Linda P.
Published: December 2020

Objectives

To investigate the rate and patterns of accumulation of frailty manifestations in relationship to all‐cause mortality and whether there is a point in the progression of frailty beyond which the process becomes irreversible and death becomes imminent (a.k.a. point of no return).

Design

Longitudinal observational study.

Setting

Community or a non‐nursing home residential care setting.

Participants

Two thousand five hundred and fifty seven robust older adults identified at baseline in 2011 with follow‐up for all‐cause mortality between 2011 and 2018.

Measurements

Frailty was measured by the physical frailty phenotype. Cox models were used to study the relationships of the number of frailty criteria (0–5) at each point in time and its accumulation patterns with all‐cause mortality. Markov state‐transition models were used to study annual transitions between health states (i.e., frailty, recovery, and death) after becoming frail among those with frailty onset (n = 373).

Results

There was a nonlinear association between greater number of frailty criteria and increasing risk of mortality, with a notable risk acceleration after having accumulated all five criteria (hazard ratio (HR) = 32.6 vs none, 95% confidence interval (CI) = 15.7–67.5). In addition, the risk of one‐year mortality tripled, and the likelihood of recovery (i.e., reverting to be robust or pre‐frail) halved among those with five frailty criteria compared to those with three or four criteria. A 50% increase in mortality risk was also associated with frailty onset without (vs with) a prior history of pre‐frailty (HR = 1.51, 95% CI = 1.20–1.90).

Conclusion

Both the number and rate of accumulation of frailty criteria were associated with mortality risk. Although there was insufficient evidence to declare a point of no return, having all five‐frailty criteria signals the beginning of a transition toward a point of no return. Ongoing monitoring of frailty progression could aid clinical and personal decision‐making regarding timing of intervention and eventual transition from curative to palliative care.
Remnant oral biofilm and microorganisms after autoclaving sterilization of retrieved healing abutments
Authors: Barreiros Pedro , Braga João , Faria‐Almeida Ricardo , Coelho Cristina , Teughels Wim , Souza Júlio C. M.
Published: December 2020

Objective

The purpose of this study was to evaluate the sterilization effectiveness against biofilms on retrieved healing abutments used in implant dentistry.

Background

A large number of clinicians reuse healing abutments to decrease treatment costs although it can promote infection due to the presence of remnant biofilm biomass.

Methods

One hundred and eighty‐five titanium healing abutments previously used for 3 months in oral cavity were assessed in this study. Abutments were submitted to cleaning, chemical disinfection, and autoclave sterilization according to clinical guidelines. The abutments were aseptically placed into glass tubes containing specific bacterial growth medium and then incubated for 10 days. From glass tubes with bacterial growth, 100 µl medium was transferred to Schaedler's agar for morphological identification and counting of strict anaerobes and to Columbia blood agar for presumptive identification of facultative anaerobes after incubation. Isolated strains were then identified at species level by enzymatic and biochemical tests within API microorganism detection platform. Also, polymerase chain reaction (PCR) was performed for identification of undefined strains.

Results

After the standard cleaning and sterilization procedures, fifty‐six (approximately 30%) retrieved abutments showed the presence of remnant biofilm biomass. The bacteria identified into the remnant biofilms covering the abutments were representative of the commensal oral microbiota including Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Enterococcus faecalis.

Conclusion

Although some healing abutments did not reveal the existence of bacteria, organic components from biofilm biomass are still strongly adhered on the retentive micro‐regions and surfaces of abutments and therefore that would support the accumulation of biofilm including pathogenic species leading to patients’ cross‐infections. Further studies should be performed on the assessment of different materials, design, and connections of the healing abutments associated with clinical disinfection procedures in implant dentistry.
Collaborative Innovation in Labor Market Inclusion
Authors: Lindsay Colin , Pearson Sarah , Batty Elaine , Cullen Anne Marie , Eadson Will
Published: December 2020

This article deploys the concept of “collaborative innovation” to discuss key stakeholders’ and service users' experiences of innovative labor market inclusion services. We draw on work by Sørensen and Torfing (2011, 2016, 2017) to frame collaborative innovation as a distinctive approach to the coproduction of services that respond to user needs, and highlight the importance of governance and leadership practices that foster mutual learning and boundary spanning innovation. The article reports on 102 interviews with service users (in this case, unemployed lone parents) and 117 interviews with key stakeholders involved in local partnerships. We identify benefits from such collaborative approaches in terms of innovative service design and positive outcomes for service users. We conclude that policy makers should consider the potential added value of collaborative innovation in labor market inclusion.
Social‐Psychological Context Moderates Incentives to Co‐produce: Evidence from a Large‐Scale Survey Experiment on Park Upkeep in an Urban Setting
Authors: Letki Natalia , Steen Trui
Published: December 2020

This paper presents evidence that the relevance of incentives to co‐produce depends on the social‐psychological context under which actors operate. We propose that context (including community attachment, trust in local authorities, ethnic diversity, unemployment level, and population density) moderates effect of incentives (utility of the co‐produced service, monetary and reputational rewards, and social norms). Through a survey experiment carried out in 593 urban locations across 13 countries, we show that willingness to co‐produce increases with community attachment and decreases with ethnic diversity of the local area. The relevance of utility and social norms as determinants of willingness to co‐produce depends on the social‐psychological context. Reputational and monetary rewards have limited effect, and their relation to the context is less clear. All incentives are largely irrelevant when actors operate in cooperation‐conducive circumstances, where co‐production is a value in itself. However, their importance as “tools” to encourage co‐production arises under challenging contexts.
Prediction of tourist flow based on multi‐source traffic data in scenic spot
Authors: Lu Hao , Zhang Jianqin , Xu Zhijie , Shi Ruixuan , Wang Jiachuan , Xu Shishuo
Published: December 2020

At present, China's tourism industry has entered an era of rapid development. It is of great significance to predict the precise and real‐time tourist flow of the popular tourist areas with dense crowds, providing decision support for rational evacuation of tourist flow, activation of emergency plans, and prevention of security accidents. This article presents a long short‐term memory (LSTM) neural network model based on the global attention mechanism. The model first uses two LSTM layers to calculate attention weights using multi‐source data at different time steps to improve the model’s learning ability. Then the model predicts the tourist flow of the scenic spots in the next time period based on the weights and outputs previously obtained. At the final stage, the pre‐trained parameters of the network are used to initialize the model. To verify the validity of the model, we compared it with the LSTM model, back propagation neural network model, and autoregressive integrated moving average model based on the data of Beijing’s South Luogu Lane scenic spot. It turned out that the results of our solution were more in line with the true value, which proves that it is feasible for real‐time prediction of tourist flow in popular scenic spots.
OsmiR164‐targeted OsNAM, a boundary gene, plays important roles in rice leaf and panicle development
Authors: Chang Zhongyuan , Xu Ruihan , Xun Qian , Liu Jiajun , Zhong Tianhui , Ding Yanfeng , Ding Chengqiang
Published: December 2020

The CUP‐SHAPED COTYLEDON (CUC) genes (CUC1, CUC2 and CUC3) regulate organ boundary formation in Arabidopsis. However, the functions of their homologous genes in rice (Oryza sativa) are still unknown. Here, we have identified an orthologous gene of CUC1 and CUC2 in rice, named OsNAM. Subcellular localization and yeast two‐hybrid assay results have suggested that OsNAM encodes a conserved nuclear NAC (NAM/ATAF1/CUC2) protein with a transcriptional activator. The null mutant osnam‐1 presented a fused leaf structure, small panicles, reduced branches and aberrant floral organ identities when compared with those of the wild type. Beta‐glucuronidase staining and GFP reporter lines indicated that OsNAM was expressed in young tissues and that its boundary enrichment expression was regulated by OsmiR164. Loss‐of‐function mutants for OsCUC3 resulted in no obvious defects throughout rice development. The osnam oscuc3 double mutant, however, resulted in severe leaf fusion of the first two leaves, while the osnam single mutant showed a similar phenotype from the seventh leaf. These results indicated that OsNAM and OsCUC3 act redundantly for boundary specification during post‐embryonic development. Overall, we describe the biological functions of OsNAM and OsCUC3 in rice development and the expression characteristics of OsNAM. This work reveals the important role of CUC genes in rice.
A WHO tool for risk‐based decision making on blood safety interventions
Authors: Janssen Mart P. , Nuebling C. Micha , Lery François‐Xavier , Maryuningsih Yuyun S. , Epstein Jay S.
Published: December 2020

Background

Risk‐based decision making is increasingly recognized as key to support national blood policy makers and blood operators concerning the implementation of safety interventions, especially to address emerging infectious threats and new technology opportunities. There is an urgent need for practical decision support tools, especially for low‐ and middle‐income countries that may not have the financial or technical capability to develop risk models. WHO supported the development of such a tool for blood safety. The tool enables users to perform both a quantitative Multi‐Criteria Decision Assessment and a novel step‐by‐step qualitative assessment.

Study Design and Methods

This paper summarizes the content, functionalities, and added value of the new WHO tool. A fictitious case study of a safety intervention to reduce the risk of HIV transmission by transfusion was used to demonstrate the use and usefulness of the tool.

Results

Application of the tool highlighted strengths and weaknesses of both the quantitative and qualitative approaches. The quantitative approach facilitates assessment of the robustness of the decision but lacks nuances and interpretability especially when multiple constraints are taken into consideration. Conversely, while unable to provide an assessment of robustness, the step‐by‐step qualitative approach helps structuring the thought process and argumentation for a preferred intervention in a systematic manner.

Conclusion

The relative strengths and weaknesses of the quantitative and step‐by‐step qualitative approach to risk‐based decision making are complementary and mutually enhancing. A combination of the two approaches is therefore advisable to support the selection of appropriate blood safety interventions for a particular setting.
BASP1 Suppresses Cell Growth and Metastasis through Inhibiting Wnt/β‐Catenin Pathway in Gastric Cancer
Authors: Li Li , Meng Qinghua , Li Guoying , Zhao Limei
Published: December 2020

Objective. Our research is designed to explore the function of brain acid soluble protein 1 (BASP1) in the progression of gastric cancer (GC) and its underlying molecular mechanisms. Methods. In this study, the expression of BASP1 was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR) in both GC tissue and GC cells. The cell cloning, proliferation, apoptosis, migration, and invasion potential of AGS and HGC‐27 cells were, respectively, determined using colony formation assay, 5‐ethynyl‐20‐deoxyuridine (EDU) assay, flow cytometry, and Transwell assay. The protein expressions of Bax, caspase‐3, Bcl‐2, matrix metalloproteinases 2 (MMP‐2), MMP‐9, Wilms tumor 1 (WT1), Wnt, and β‐catenin in AGS and HGC‐27 cells were measured by western blot. In addition, the mRNA expressions of WT1, Wnt, and β‐catenin in AGS and HGC‐27 cells were detected by qRT‐PCR. Results. BASP1 expression was significantly downregulated in both GC tissue and GC cells. BASP1 overexpression markedly repressed proliferation, migration, and invasion and facilitated apoptosis in AGS and HGC‐27 cells. In addition, BASP1 overexpression notably promoted the protein expression of Bax and caspase‐3 in AGS and HGC‐27 cells and inhibited the expression of Bcl‐2, MMP‐2, and MMP‐9. Moreover, BASP1 overexpression significantly inhibited the mRNA and protein expression of WT1, Wnt, and β‐catenin in AGS and HGC‐27 cells. Conclusion. BASP1 could significantly suppress cell proliferation, migration, and invasion and promote apoptosis through inhibiting the activation of the Wnt/β‐catenin pathway in GC.
Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo‐Substituted Mixed Ester/Amide‐Based Derivatives as Jack Bean Urease Inhibitors
Authors: Rashid Muhammad , Rafique Hummera , Roshan Sadia , Shamas Shazia , Iqbal Zafar , Ashraf Zaman , Abbas Qamar , Hassan Mubashir , Qureshi Zia Ur Rahman , Asad Muhammad Hassham Hassan Bin
Published: December 2020

A series of halo‐substituted mixed ester/amide‐based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo‐substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl‐substituted anilines 1a–b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo‐substituted benzoic acids 3a–f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC501.6 ± 0.2 nM, better than the standard thiourea having IC50472.1 ± 135.1 nM. The 2‐chloro‐substituted phenyl ring on one side of compound 4b and 4‐isopropyl‐substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver–Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of −7.8 and −7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.
Associations of DASH Diet in Pregnancy With Blood Pressure Patterns, Placental Hemodynamics, and Gestational Hypertensive Disorders
Authors: Wiertsema Clarissa J. , Mensink‐Bout Sara M. , Duijts Liesbeth , Mulders Annemarie G. M. G. J. , Jaddoe Vincent W. V. , Gaillard Romy
Published: December 2020

Background

The Dietary Approaches to Stop Hypertension (DASH) diet improves blood pressure in nonpregnant populations. We hypothesized that adherence to the DASH diet during pregnancy improves hemodynamic adaptations, leading to a lower risk of gestational hypertensive disorders.

Methods and Results

We examined whether the DASH diet score was associated with blood pressure, placental hemodynamics, and gestational hypertensive disorders in a population‐based cohort study among 3414 Dutch women. We assessed DASH score using food‐frequency questionnaires. We measured blood pressure in early‐, mid‐, and late pregnancy (medians, 95% range: 12.9 [9.8–17.9], 20.4 [16.6–23.2], 30.2 [28.6–32.6] weeks gestation, respectively), and placental hemodynamics in mid‐ and late pregnancy (medians, 95% range: 20.5 [18.7–23.1], 30.4 [28.5–32.8] weeks gestation, respectively). Information on gestational hypertensive disorders was obtained from medical records. Lower DASH score quartiles were associated with a higher mid pregnancy diastolic blood pressure, compared with the highest quartile (
P
<0.05). No associations were present for early‐ and late pregnancy diastolic blood pressure and systolic blood pressure throughout pregnancy. Compared with the highest DASH score quartile, the lower DASH score quartiles were associated with a higher mid‐ and late pregnancy umbilical artery pulsatility index (
P
≤0.05) but not with uterine artery resistance index. No associations with gestational hypertensive disorders were present.

Conclusions

A higher DASH diet score is associated with lower mid pregnancy diastolic blood pressure and mid‐ and late pregnancy fetoplacental vascular function but not with uteroplacental vascular function or gestational hypertensive disorders within a low‐risk population. Further studies need to assess whether the effects of the DASH diet on gestational hemodynamic adaptations are more pronounced among higher‐risk populations.
Repositioning Xinxing 信行 (540–594) in the Chinese Meditation Tradition
Authors: Lin Pei-ying
Published: December 2020

This paper aims to bring out an alternative perspective on the life and work of the alleged founder of the Sanjiejiao 三階教 school, Xinxing. The current study discusses a different aspect of Xinxing’s influence, namely, his impact as a chan master. As the prominent Chan School went through different phases of development, the influence of Xinxing’s meditational teaching waxed and waned in the Chan cycle. Focusing on the texts titled Duigen qixingfa 對根起行法 and Zhizhongshi zhufa 制眾事諸法, I will explore the connotation of sanmei 三昧 (samādhi) in his teaching. In particular, I will explore the term “formless samādhi” (wuxiang sanmei 無相三昧) in Xinxing’s work and in other contemporary texts on meditation by meditation masters, such as Huisi 慧思 (515–577). In this way, this study situates Xinxing in the larger context of meditation teachings which emerged during the sixth century.