bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Childhood Experiences and Associated Mental Distress and Suicide Risk: Results From the Zambia Violence Against Children Survey
Authors: Lee NaeHyung , Massetti Greta M. , Perry Elizabeth W. , Self-Brown Shannon
Published: December 2021

Purpose: Adverse childhood experiences (ACEs) are a global public health concern. Little research exists on the prevalence and health consequences of ACEs in Zambia. The current study examined associations between individual and cumulative ACEs, mental distress, and suicide risk among Zambian youth. Methods: Data from Zambia Violence Against Children and Youth Survey were used (18-24 years old, n=1034). Bivariate and adjusted logistic models were performed with independent variables (i.e., experienced physical violence (PV), sexual violence (SV), and emotional violence (EV); witnessed intimate partner violence (IPV) and community violence (CV); orphan status; cumulative ACE exposure) and dependent variables (i.e., mental distress and suicide risk). Adjusted models controlled for demographic and social characteristics. Results: 76.8% of Zambian youth experienced one or more ACEs, and more than 30% witnessed CV (38.4%) or IPV (30.2%), or experienced PV (35.1%), prior to age 18. 27.5% were orphans, and less than 20% experienced EV (17.3%) or SV (15.4%) in childhood. 42.4% experienced mental distress in the past 30 days, and 12.5% reported lifetime suicidal thoughts or suicide attempts. PV, EV, cumulative ACE exposure, older age, being single, and stronger friendships were significantly related to experiencing mental distress. Cumulative ACEs exposure was associated with significantly higher suicide risk. Conclusions: Preventing ACEs can reduce mental distress and suicide risk among Zambian youth. Youth with cumulative ACE exposure can be prioritized for mental health intervention. More research is warranted to investigate the broad-based prevention of ACEs, especially PV and EV, and protective factors that can promote resilience among youth who have experienced ACEs.
Literary dynamics in The.PowerBook by Jeanette Winterson and Oryx and Crake by Margaret Atwood
Authors: O’Leary Irene
Published: December 2021

Interaction between text and reader is a prominent concern in stylistics. This paper focusses on interactions among stylistic processes and subconscious microcognitive processes that generate changes to narrative and interpretation during reading. Drawing on process philosophy and recent neuroscientific research, I articulate this dynamism through analysis of a brief narrative moment from each of The.PowerBook by Jeanette Winterson and Oryx and Crake by Margaret Atwood. I argue that high densities of stylistic and microcognitive perturbations lead to frequent narrative and interpretive changes in the two moments. The analyses reinforce portrayals of reading as intensely complex, dynamic and changeable. Complexity, dynamism and mutability also characterise the stylistic changes in the two narrative moments. This paper advocates greater attention to the role of volatile stylistic and cognitive microdynamics in shaping the reading of prose fiction.
Round Table. From Lisbon to Porto: taking stock of developments in EU social policy: Social Europe 2.0? New prospects after the Porto Social Summit
Authors: Ferrera Maurizio
Published: December 2021

The sequence of crises in the 2010s entirely changed the socio-economic context that had inspired the Lisbon strategy in the year 2000. EU policy veered towards austerity and social policy became an ‘adjustment variable’. Since the mid-2010s, however, a slow process of rebalancing has gained ground, culminating in the adoption of the European Pillar of Social Rights (EPSR) in 2017. The Porto Summit has confirmed the centrality of the Pillar for a new Social Europe. To appreciate fully the EPSR’s potential, it is necessary to focus not only on binding measures but also on EU incentives and actions aimed at promoting (and partially funding) concrete access to social rights. Especially through the ‘guarantee’ instrument, the EU can play a bigger and more effective role in the sphere of social citizenship, without stumbling into the political obstacles associated with hard law.
Choose your own adventure: Vocal jazz improvisation, conceptual metaphor, and cognitive embodiment
Authors: Forbes Melissa , Cantrell Kate
Published: December 2021

Creativity in the form of musical improvisation has received growing attention from researchers informed by the literature on embodiment. To date, this research has focused on the embodied experiences of improvising instrumentalists rather than those of improvising singers. This article investigates the experience of embodiment during improvisation through a systematic analysis of the metaphorical language used by an artist-level jazz singer in her reflections on practice. Extensive interview data with the participant were analyzed to identify and reconstruct metaphorical expressions into conceptual metaphors. In this process, the metaphor of IMPROVISATION IS AN ADVENTURE was identified as the overarching conceptual structure that the participant used to make sense of her experiences of improvisation. This metaphor and its mappings illuminate the cognitively embodied dimension of vocal jazz improvisation. These findings will be of interest to jazz singers and vocal jazz educators who are encouraged to explore more fully the role of the body–mind’s interactions with its environment in order to establish expertise in improvisational ways of knowing. This research illuminates the multidimensional nature of an expert singer’s experiences of improvisation and is presented as a provocation for future research to include singers as participants when investigating musical improvisation and cognitive embodiment.
Thrombosis with Thrombocytopenia Syndrome After Administration of AZD1222 or Ad26.COV2.S Vaccine for COVID-19: A Systematic Review
Authors: Waqar Usama , Ahmed Shaheer , Gardezi Syed M.H.Ali , Tahir Muhammad Sarmad , Abidin Zain ul , Hussain Ali , Ali Natasha , Mahmood Syed Faisal
Published: December 2021

Background

Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS.

Methods

A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes.

Findings

Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered to 140 patients (87·5%). TTS onset occurred in a median of 9 (4) days after vaccination. Venous thrombosis was most common (61.0%). Most patients developed cerebral venous sinus thrombosis (CVST; 66.3%). CVST was significantly more common in female vs male patients (p = 0·001) and in patients aged <45 years vs ≥45 years (p = 0·004). The mortality rate was 36.2%, and patients with suspected TTS, venous thrombosis, CVST, pulmonary embolism, or intraneural complications, patients not managed with non-heparin anticoagulants or IVIG, patients receiving platelet transfusions, and patients requiring intensive care unit admission, mechanical ventilation, or inpatient neurosurgery were more likely to expire than recover.

Interpretation

These findings help to understand the pathophysiology of TTS while also recommending diagnostic and management approaches to improve prognosis in patients.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
“It’s Not Just the Right Thing . . . It’s a Survival Tactic”: Disentangling Leaders’ Motivations and Worries on Social Care
Authors: Fraze Taressa K. , Beidler Laura B. , Savitz Lucy A.
Published: December 2021

Health care organizations face growing pressure to improve their patients’ social conditions, such as housing, food, and economic insecurity. Little is known about the motivations and concerns of health care organizations when implementing activities aimed at improving patients’ social conditions. We used semi-structured interviews with 29 health care organizations to explore their motivations and tensions around social care. Administrators described an interwoven set of motivations for delivering social care: (a) doing the right thing for their patients, (b) improving health outcomes, and (c) making the business case. Administrators expressed tensions around the optimal role for health care in social care including uncertainty around (a) who should be responsible, (b) whether health care has the needed capacity/skills, and (c) sustainability of social care activities. Health care administrators could use guidance and support from policy makers on how to effectively prioritize social care activities, partner with other sectors, and build the needed workforce.
Child Maltreatment Prevention Service Cases are Significantly Reduced During the COVID-19 Pandemic: A Longitudinal Investigation Into Unintended Consequences of Quarantine
Authors: Whaling Kelly M. , Der Sarkissian Alissa , Larez Natalie , Sharkey Jill D. , Allen Michael A. , Nylund-Gibson Karen
Published: December 2021

Unprecedented financial and emotional stress, paired with measures to slow the spread of COVID-19 (e.g., school closures), place youth at risk for experiencing increased rates of abuse. We analyzed data from New York City’s Administration for Children’s Services to investigate the frequency of child maltreatment prevention service case openings during this time. Longitudinal counts of case openings were compiled for January through June of the years 2014–2020. An independent samples Kruskal–Wallis H-test suggested that pre-quarantine case openings were significantly larger than case openings during quarantine. To account for the possible influence of other historical events impacting data, a secondary Kruskal–Wallis H-test was conducted comparing only the 4 months of quarantine data available to the 4 months immediately preceding quarantine orders. The second independent samples Kruskal–Wallis H-test again suggested that pre-quarantine case openings were significantly larger than case openings during quarantine. A Poisson regression model further supported these findings, estimating that the odds of opening a new child maltreatment prevention case during quarantine declined by 49.17%. These findings highlight the severity of COVID-19 impacts on child maltreatment services and the gap between demand for services and service accessibility. We conclude with recommendations for local governments, community members, and practitioners.
Resuscitating criminal courts after Covid-19: Trialling a cure worse than the disease
Authors: McConville Mike , Marsh Luke
Published: December 2021

This article, focusing on the issue of custody time limits litigated under Covid-19 conditions, sets out how reasoned decisions to refuse to extend custody for unconvicted defendants excited the disapproval of senior judges such that fundamental changes were made to evidence, procedure and proof as well as effecting permanent manipulation of the composition of the adjudicating panels authorised to deal with such cases. This additionally raises fundamental questions about the administration and governance of the courts, the independence of the judiciary in decision-making and the basic utility of the presumption of innocence in such cases.
The reception of support in peer-to-peer online networks: Network position, support solicitation, and support provision in an online asthma caregivers group
Authors: Liu Yan , Huang Wensen , Luo Dan
Published: December 2021

This study applies social network analysis and quantitative content analysis to messages exchanged within an online support forum of caregivers of children with chronic asthma to examine how peer-to-peer network positions and personal communication styles (seeking and providing support) impact the reception of social support. Content analysis is used to determine rates of giving and receiving informational and emotional support. Network analysis assesses levels of individual betweenness and closeness centrality in the online network. Relationships between network positions, solicitation strategies, and the provision and reception of informational and emotional support are examined. Betweenness and closeness centrality are associated with improved informational and emotional support. The provision of informational support is also improved by providing descriptions of personal experience. Practical implications for the design and use of online support platforms are discussed.
Determination of a most representative cycle from cylinder pressure ensembles via statistical method using distribution skewness
Authors: Pulpeiro González Jorge , Hall Carrie M , Kolodziej Christopher P
Published: December 2021

In internal combustion engine research, cylinder pressure measurements provide valuable information about the underlying thermodynamic and combustion processes, and are typically collected in ensembles of several 100 traces. Although in some particular fields of combustion research all traces are analyzed, in most cases only one trace is studied because analyzing all the traces is impractical due to the large number of collected samples. Instead, an ensemble-averaged pressure trace is commonly calculated and used for analysis. However, this pressure trace is highly smoothed and dynamic information is lost during the averaging process. With the average trace, pressure rise rates are lower and pressure oscillations such as the ones resulting from combustion knock are lost. In this work, a statistical method was developed to determine the “most representative cycle,” which is the cycle from the ensemble that has the pressure trace most representative of the engine operating condition. Eleven characteristic parameters are computed from each pressure trace and probabilistic distributions are obtained for each of the parameters using all the traces in the ensemble. Finally, the most representative cycle is selected by means of a cost function minimization. The benefits of this method are illustrated using experimental data from four very different engine platforms, under four different combustion modes and over a range of operating conditions.
Effects of Research-Related Activities on Graduation at a Hispanic Serving Institution
Authors: Dong Winny , Eddy Rebecca M. , Mendelsohn David M. , Koletar Courtney , Matelski Monique , Barraza Everardo
Published: December 2021

This paper reports on the results of a study of 6,654 unique students on the type of research-related activities (e.g., undergraduate research and internships) they participated in while at California State Polytechnic University, Pomona (Cal Poly Pomona). Results indicate that the odds of graduating for students who participated in research-related activities were almost twice those of students who did not participate in research-related activities. These results differ from and complement studies on the impact of undergraduate research at liberal arts colleges and research-intensive universities. Study results indicate that non-first-generation students, non-low-income students, and non-underrepresented minority (non-URM) students were more likely to participate in research. Participation in internships with industry and with a professional were most predictive of graduation. Students who participated in multiple research-related activities were also more likely to graduate than those who participated in fewer activities; results indicate research participation is equally beneficial across groups with different demographic characteristics including major, sex, first generation and URM status.
Collective Reactions to Epidemic Threat: Attachment and Cultural Orientations Predict Early COVID-19 Infection and Mortality Rates and Trajectories
Authors: Kafetsios Konstantinos
Published: December 2021

Hypotheses on culture-level attachment and individualism/collectivism relationships with COVID-19 infection and death rates during a period at the beginning of the epidemic were tested in data from 53 countries and 50 U.S. states. Results from multilevel growth curve analyses showed group-average anxious attachment predicted a lower initial number of cases and deaths cross-culturally and in the United States, while avoidant attachment predicted a higher initial number of COVID-19 infections in the United States and a higher initial number of deaths in both studies. Yet, during this period, culture-level anxious attachment was associated with a higher growth rate of infections and deaths, while a lower growth rate of infections and deaths was observed in countries and U.S. states with higher individualism and avoidance. The research provides new insights into attachment and culture relationships and points to different mechanisms that may explain initial and growth rate trajectories at the beginning of the epidemic.
Gastric adenocarcinoma of the fundic gland: A review of clinicopathological characteristics, treatment and prognosis
Authors: Meng Xiang-yu , Yang Guang , Dong Cheng-ji , Zheng Ru-yi
Published: December 2021

Gastric adenocarcinoma of the fundic gland is a rare, well-differentiated gastric cancer entity, and very few patients transition to poorly differentiated tubular adenocarcinoma during progression. Gastric adenocarcinoma of the fundic gland originates from the mucosa of the gastric fundic gland, usually without chronic gastritis or intestinal metaplasia. Histologically, the tumor cells are closely arranged to form anastomosing tubular glands, and more than 95% of tumor cells differentiate towards chief cells. Most gastric adenocarcinoma of the fundic gland cases are characterized by submucosal involvement, but the tumor volume is usually small, with lymphatic and vascular invasion rarely observed. Therefore, endoscopic submucosal dissection can be an ideal treatment, leading to a favorable prognosis, and recurrence and metastasis of the disease are uncommon.
Associations between adverse childhood experiences and need and unmet need for care coordination
Authors: Anyigbo Chidiogo , Fuller Anne E. , Cheng Yao I , Fu Linda Y. , Belcher Harolyn M. , Tarini Beth A. , Brown Nicole M.
Published: December 2021

Introduction

Children exposed to adverse childhood experiences (ACEs) may access multiple systems of care to address medical and social complexities. Care coordination (CC) optimizes health outcomes for children with special health care needs who often use multiple systems of care. Little is known about whether ACEs are associated with the need and unmet need for CC.

Methods

Use of the 2016–2017 National Survey of Children’s Health to identify children who saw ≥1 health care provider in the last 12 months. The study team used weighted logistic regression analyses to examine associations between 9 ACE types, ACE score, and need and unmet need for CC.

Results

In the sample ( N  = 39,219, representing 38,316,004 US children), material hardship (adjusted odds ratio (aOR), 1.50; 95% confidence interval (CI), 1.29–1.75), parental mental illness (aOR, 1.31; 95% CI, 1.07–1.60), and neighborhood violence (aOR, 1.33; 95% CI, 1.01–1.74) were significantly associated with an increased need for CC. Material hardship was also associated with an unmet need for CC (aOR, 2.37; 95% CI, 1.80–3.11). Children with ACE scores of 1, 2, 3, and ≥4 had higher odds of need and unmet need for CC than children with 0 ACEs.

Discussion

Specific ACE types and higher ACE scores were associated with the need and unmet need for CC. Evaluating the unique needs of children who endured ACEs should be considered in the design and implementation of CC processes in the pediatric health care system.
Mannose-binding lectin serum levels and (Gly54asp) gene polymorphism in recurrent aphthous stomatitis: A case-control study
Authors: Baioumy Shereen A , Fouad Shaimaa H , Abdalgeleel Shaimaa A , Baiomy Ahmed A , Sallam Dina E , Taha Sara I
Published: December 2021

Objectives: Dysregulation of the immune response appears to play a significant role in recurrent aphthous stomatitis (RAS) development. The main objective of this case–control study is to investigate the blood levels of mannose-binding lectin (MBL) and the frequency of the MBL2 gene (gly54asp) polymorphism in RAS patients, including 40 RAS patients and 40 healthy controls. Methods: Serum MBL levels were determined by ELISA, while the PCR-restriction fragment length polymorphism was used in MBL2 genotyping. Results: The median serum MBL level was significantly lower in the RAS group than in the control group (975 ng/mL (545–1320) vs. 1760 ng/mL (1254–2134); p≤ 0.001). The MBL levels were significantly lower in the BB genotype, whereas they were significantly higher in the wild type AA with a median of 525 and 1340 ng/mL, respectively ( p =0.005). The B allele was expressed in significantly higher percentages of RAS patients than in controls. There was no significant association between MBL serum levels ( p=0.685) or MBL2 codon 54 genotypes ( p=0.382) with the type of ulcers. Conclusion: There was an association between low MBL serum levels and the variant allele B of the MBL2 (gly54asp) gene, and the susceptibility to RAS. As a result, potential novel therapeutic options for RAS patients with MBL deficiency should be investigated.
Overexpression of NEK2 is correlated with poor prognosis in human clear cell renal cell carcinoma
Authors: Wang Chenfeng , Huang Yan , Ma Xin , Wang Baojun , Zhang Xu
Published: December 2021

Objectives: Never in mitosis gene A-related kinase 2 (NEK2) has been implicated in tumorigenesis in various tissues, but its function in clear cell renal cell carcinoma (ccRCC) tumorigenesis is unclear. We evaluated the correlation between NEK2 expression and ccRCC. Methods: Immunohistochemistry analysis of NEK2 protein was done on high-density multi-organ Human Cancer tissue microarray derived from the patient samples from clear cell renal cell carcinoma. We used multiple clinical cohorts to analyze the NEK2 immunohistochemical staining expression across human cancers. The cancer genome atlas (TCGA) data analysis of NEK2 was done through UALCAN web servers. Association of NEK2 and Kaplan–Meier survival analysis was done on both of our clinical database and available TCGA datasets. Results: Using the UALCAN cancer transcriptional data analysis website, we found that NEK2 is overexpressed in ccRCC, and its expression was associated with overall survival. According to the analyses of our own clinical database and immunohistochemical staining, protein levels of NEK2 were elevated in renal carcinoma compared to adjacent normal tissues. Kaplan–Meier survival analysis of both UALCAN and our database showed that high expression of NEK2 was associated with a poor prognosis. Multivariate and univariate analyses showed that NEK2 expression was closely related to a poor prognosis. The findings suggest that NEK2 is associated with ccRCC. Conclusion: These studies show that NEK2 is over-expressed in clear cell renal cell carcinoma and plays an essential role in cancer cell survival, as such NEK2 could serve as a novel potential target for therapeutic intervention in ccRCC.
Titanium implants modified by laser microtexturing enhance the bioactivity of gastric epithelial cells and fibroblast cells
Authors: Zhang Zhaoxiong , Li Yuanchun , Zhang Ting , Yang Xiaoyang , Fan Kaihu , Wang Daohan , Li Shuliang , Hu Yahui , Fu Weihua
Published: December 2021

The clinical application of anastomotic instruments improves the efficiency of the digestive tract surgery. However, the stapler with titanium nails implanted is still controversial in terms of anastomotic complications, and further improvement and optimization are needed. The purpose of this study was to explore the optimal microtextured parameters that could enhance the bioactivity of titanium implants in vitro. Laser microtexturing technology was used to construct the groove-type microstructural surfaces with different parameters, and human gastric mucosal epithelial cells (GES-1 cells) and mouse fibroblasts (3T3 cells) were cultured on the surface of the titanium plates in vitro. The data of cell adhesion, cell proliferation and cell activity were obtained and statistically analyzed. The textured titanium plates meet the expected design. GES-1 and 3T3 cell adhesion were better in the surface of titanium plates in microstructural group than that in the polished group. GES-1 and 3T3 cells also showed higher proliferative activity in the microstructural group compared with the polished group. The laser textured titanium plates have good groove-type microstructure, which increase the surface roughness, change the surface wettability, promote the adhesion, proliferating and orderly growth of GES-1 and 3T3 cells, and show good biological properties.
“It just fits my needs better”: Autistic students and parents’ experiences of learning from home during the early phase of the COVID-19 pandemic
Authors: Heyworth Melanie , Brett Simon , Houting Jacquiline den , Magiati Iliana , Steward Robyn , Urbanowicz Anna , Stears Marc , Pellicano Elizabeth
Published: December 2021

Background and aims

The COVID-19 pandemic has caused unprecedented disruption to people's lives, especially for families, whose children have been taken out of schools during lockdown restrictions and required to learn from home. Little is known, however, about the perceived impact of the lockdown restrictions on the educational experiences of autistic children and young people – a group whose conventional schooling experiences are already often challenging. In this study, we sought to (1) understand these experiences from the perspectives of autistic young people and their parents, and (2) identify the underlying sources of positive experiences at this challenging time, in order to inform the ways in which autistic children might flourish at school in more normal times.

Methods

Ninety-one Australian participants, including 16 autistic young people aged 12–18 years, 32 autistic parents and 43 non-autistic parents of autistic young people aged 3–18 years, took part in semi-structured interviews about their experiences of life during the initial phase of the COVID-19 pandemic. The interviews were subjected to reflexive, thematic analysis to identify themes and subthemes for each research question.

Results

Overall, our participants initially found the transition to learning from home extremely challenging, with parents reporting that the support received from schools was far from adequate. After that initial period of transition, however, many autistic children reported flourishing at home both educationally and personally. For these children and families, we identified three key ingredients essential to this flourishing, including: (i) the importance of connected, trusting relationships (‘people’); (ii) the sensory and social safety of home (‘place’); and (iii) the flexibility to pace and structure learning to suit the individual child (‘time’).

Conclusions

While the initial COVID-19 lockdown presented many challenges to children learning at home, there were aspects of this otherwise-unsettling situation that enabled children to thrive and from which we can learn for the future.

Implications

These findings have important implications for understanding how and when autistic children might thrive in institutional educational settings once the pandemic subsides, focusing on the relationships between teachers and students, the nature of the physical learning environment and the need for greater flexibility in planning the school day.
Asthma and COVID-19: an update
Authors: Adir Yochai , Saliba Walid , Beurnier Antoine , Humbert Marc
Published: December 2021

As the world faces the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, concerns have been raised that asthma patients could be at increased risk of SARS-CoV-2 infection and disease severity. However, it appears that asthma is not an independent risk factor for both. Furthermore, asthma is not over-represented in hospitalised patients with severe pneumonia due to SARS-CoV-2 infection and there was no increased risk of asthma exacerbations triggered by SARS-CoV-2. There is accumulating evidence that asthma phenotypes and comorbidities are important factors in evaluating the risk for SARS-CoV-2 infection and disease severity, as findings suggest that Th2-high inflammation may reduce the risk of SARS-Cov-2 infection and disease severity in contrast to increased risk in patients with Th2-low asthma. The use of inhaled corticosteroids (ICS) is safe in asthma patients with SARS-CoV-2 infection. Furthermore, it has been proposed that ICS may confer some degree of protection against SARS-CoV-2 infection and the development of severe disease by reducing the expression of angiotensin converting enzyme-2 and transmembrane protease serine in the lung. In contrast, chronic or recurrent use of systemic corticosteroids before SARS-CoV-2 infection is a major risk factor of poor outcomes and worst survival in asthma patients. Conversely, biological therapy for severe allergic and eosinophilic asthma does not increase the risk of being infected with SARS-CoV-2 or having worse COVID-19 severity. In the present review we will summarise the current literature regarding asthma and COVID-19.
Recovering from a pandemic: pulmonary fibrosis after SARS-CoV-2 infection
Authors: Mylvaganam Ruben J. , Bailey Joseph I. , Sznajder Jacob I. , Sala Marc A.
Published: December 2021

Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10–30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage–T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis.
Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?
Authors: Haronikova Lucia , Bonczek Ondrej , Zatloukalova Pavlina , Kokas-Zavadil Filip , Kucerikova Martina , Coates Philip J. , Fahraeus Robin , Vojtesek Borivoj
Published: December 2021

Since the discovery of the first MDM2 inhibitors, we have gained deeper insights into the cellular roles of MDM2 and p53. In this review, we focus on MDM2 inhibitors that bind to the p53-binding domain of MDM2 and aim to disrupt the binding of MDM2 to p53. We describe the basic mechanism of action of these MDM2 inhibitors, such as nutlin-3a, summarise the determinants of sensitivity to MDM2 inhibition from p53-dependent and p53-independent points of view and discuss the problems with innate and acquired resistance to MDM2 inhibition. Despite progress in MDM2 inhibitor design and ongoing clinical trials, their broad use in cancer treatment is not fulfilling expectations in heterogenous human cancers. We assess the MDM2 inhibitor types in clinical trials and provide an overview of possible sources of resistance to MDM2 inhibition, underlining the need for patient stratification based on these aspects to gain better clinical responses, including the use of combination therapies for personalised medicine.
Primal-dual for classification with rejection (PD-CR): a novel method for classification and feature selection—an application in metabolomics studies
Authors: Chardin David , Humbert Olivier , Bailleux Caroline , Burel-Vandenbos Fanny , Rigau Valerie , Pourcher Thierry , Barlaud Michel
Published: December 2021

Background

Supervised classification methods have been used for many years for feature selection in metabolomics and other omics studies. We developed a novel primal-dual based classification method (PD-CR) that can perform classification with rejection and feature selection on high dimensional datasets. PD-CR projects data onto a low dimension space and performs classification by minimizing an appropriate quadratic cost. It simultaneously optimizes the selected features and the prediction accuracy with a new tailored, constrained primal-dual method. The primal-dual framework is general enough to encompass various robust losses and to allow for convergence analysis. Here, we compare PD-CR to three commonly used methods: partial least squares discriminant analysis (PLS-DA), random forests and support vector machines (SVM). We analyzed two metabolomics datasets: one urinary metabolomics dataset concerning lung cancer patients and healthy controls; and a metabolomics dataset obtained from frozen glial tumor samples with mutated isocitrate dehydrogenase (IDH) or wild-type IDH.

Results

PD-CR was more accurate than PLS-DA, Random Forests and SVM for classification using the 2 metabolomics datasets. It also selected biologically relevant metabolites. PD-CR has the advantage of providing a confidence score for each prediction, which can be used to perform classification with rejection. This substantially reduces the False Discovery Rate.

Conclusion

PD-CR is an accurate method for classification of metabolomics datasets which can outperform PLS-DA, Random Forests and SVM while selecting biologically relevant features. Furthermore the confidence score provided with PD-CR can be used to perform classification with rejection and reduce the false discovery rate.
AttCRISPR: a spacetime interpretable model for prediction of sgRNA on-target activity
Authors: Xiao Li-Ming , Wan Yun-Qi , Jiang Zhen-Ran
Published: December 2021

Background

More and more Cas9 variants with higher specificity are developed to avoid the off-target effect, which brings a significant volume of experimental data. Conventional machine learning performs poorly on these datasets, while the methods based on deep learning often lack interpretability, which makes researchers have to trade-off accuracy and interpretability. It is necessary to develop a method that can not only match deep learning-based methods in performance but also with good interpretability that can be comparable to conventional machine learning methods.

Results

To overcome these problems, we propose an intrinsically interpretable method called AttCRISPR based on deep learning to predict the on-target activity. The advantage of AttCRISPR lies in using the ensemble learning strategy to stack available encoding-based methods and embedding-based methods with strong interpretability. Comparison with the state-of-the-art methods using WT-SpCas9, eSpCas9(1.1), SpCas9-HF1 datasets, AttCRISPR can achieve an average Spearman value of 0.872, 0.867, 0.867, respectively on several public datasets, which is superior to these methods. Furthermore, benefits from two attention modules—one spatial and one temporal, AttCRISPR has good interpretability. Through these modules, we can understand the decisions made by AttCRISPR at both global and local levels without other post hoc explanations techniques.

Conclusion

With the trained models, we reveal the preference for each position-dependent nucleotide on the sgRNA (short guide RNA) sequence in each dataset at a global level. And at a local level, we prove that the interpretability of AttCRISPR can be used to guide the researchers to design sgRNA with higher activity.
The physiological and psychological effects of cognitive behavior therapy on patients with inflammatory bowel disease before COVID-19: a systematic review
Authors: Chen Jie , Chen Xuejie , Sun Yuhao , Xie Ying , Wang Xiaoyan , Li Ran , Hesketh Therese
Published: December 2021

Objective

Cognitive behavioral therapy (CBT) is now included in the treatment of patients with inflammatory bowel disease (IBD) in many settings. However, different clinical trials report different outcomes without consensus. This study aims to evaluate the impact of CBT on the mental state, quality of life and disease activity of patients with IBD.

Design

Systematic review.

Methods

This systematic review searched eligible studies from 1946 to December 8, 2019, in MEDLINE, EMBASE, CINAHL, Cochrane library, ClinicalTrials.gov, PsycINFO, Web of Science for eligible randomized controlled trials (RCT).

Results

Among the initial identified 1807 references, 11 studies met inclusion criteria. CBT was shown to improve patient's quality of life and reduce the level of depression and anxiety post-intervention but was not sustained. Evidence is not enough for the effect of CBT on disease activity, or C-reactive protein level.

Conclusions

CBT has shown short-term positive psychological effects on IBD patients, but there is insufficient evidence for sustained physical and psychological improvements of IBD patients.

PROSPERO registration: CRD42019152330.
Long-term effects of alcohol consumption on cognitive function in seniors: a cohort study in China
Authors: Han Lizhen , Jia Jinzhu
Published: December 2021

Background

In the context of increasing global aging, the long-term effects of alcohol consumption on cognitive function in older adults were analyzed in order to provide rationalized health recommendations to the elderly population.

Methods

The study used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, from which 5354 Chinese seniors aged 65–112 years were selected as the subjects, spanning the years 1998–2018. Data on alcohol, diet, activity, and cognition were collected by questionnaire and cognitive levels were judged by the Mini-Mental State Examination scale (also referenced to the Functional Assessment Staging Test). Data cleaning and preprocessing was implemented by R software. The dynamic Cox model was applied for model construction and data analysis.

Results

The results of the dynamic Cox model suggested that seniors who drank alcohol were at higher risk of cognitive decline compared to those who never drank (HR = 1.291, 95%CI: 1.175–1.419). The risk was similarly exacerbated by perennial drinking habits (i.e., longer drinking years, HR = 1.008, 95%CI: 1.004–1.013). Compared to non-alcoholic beverages, liquor (≥ 38°), liquor (< 38°), wine and rice wine all showed negative effects. Whereas, the risk of cognitive decline was relatively lower in seniors who consumed liquors (< 38°) and rice wine compared to the high-level liquor (HR: 0.672 (0.508, 0.887) and 0.732 (0.559, 0.957), respectively).

Conclusions

Alcohol consumption has a negative and long-term effects on cognitive function in seniors. For the elderly, we suggested that alcohol intake should be avoided as much as possible.
Changes in the use of diabetes drugs among community-dwelling people with Alzheimer’s disease
Authors: López-Rubio Carlos , Koponen Marjaana , Lampela Pasi , Taipale Heidi , Tanskanen Antti , Bell J. Simon , Tolppanen Anna-Maija , Hartikainen Sirpa
Published: December 2021

Background

Type 2 diabetes is common in persons with Alzheimer’s disease (AD). Management of diabetes in persons with AD is challenging due to changing goals of care and susceptibility to adverse drug events including hypoglycemia. The aim of this study was to investigate the prevalence of diabetes drug use from 5 years before to 5 years after the time of AD diagnosis among persons with and without AD.

Methods

This was a nationwide register-based study of persons with and without AD and diabetes in Finland. We analyzed data from the Medication Use and Alzheimer’s disease (MEDALZ) study that included 70,718 community-dwelling people diagnosed with AD from 2005 to 2011. The study population included 8418 persons with AD and 6666 matched persons without AD who were diagnosed with diabetes 5 years before AD diagnosis (index date). We defined the prevalence of diabetes drug use in three-month evaluation periods from 5 years before until 5 years after the index date.

Results

Nearly all people with diabetes (94% in both cohorts) used one or more diabetes drugs on the index date. The most prevalent drug metformin was used by 60.9% of people with AD and 59.1% of people without AD. The next most prevalent drugs were sulfonylureas and insulin. The prevalence of diabetes drug use was similar in people with and without AD but began to decline 1 year after AD diagnosis in the AD cohort compared to non-AD cohort.

Conclusions

The decline in diabetes drug use after AD diagnosis may be attributed to clinicians and patients seeking to avoid serious adverse drug events including hypoglycemia. In addition, the findings may reflect personalized glycemic control and unintentional weight loss in persons with AD reducing the need for diabetes drugs.
Evolution and prediction of mismatch between observed and perceived upper limb function after stroke: a prospective, longitudinal, observational cohort study
Authors: Essers Bea , Van Gils Annick , Lafosse Christophe , Michielsen Marc , Beyens Hilde , Schillebeeckx Fabienne , Veerbeek Janne M. , Luft Andreas R. , Kos Daphne , Verheyden Geert
Published: December 2021

Background

A previously shown ‘mismatch’ group of patients with good observed upper limb (UL) motor function but low perceived UL activity at six months post stroke tends to use the affected UL less in daily life than would be expected based on clinical tests, and this mismatch may also be present at 12 months. We aimed to confirm this group in another cohort, to investigate the evolution of this group from six to 12 months, and to determine factors on admission to inpatient rehabilitation and at 6 months that can discriminate between mismatch and good match groups at 12 months.

Methods

Persons after stroke were recruited on rehabilitation admission and re-assessed at six and 12 months. Observed UL function was measured with the upper extremity subscale of the Fugl-Meyer Assessment (FMA-UE) and perceived UL activity by the hand subscale of the Stroke Impact Scale 3.0 (SIS-Hand). We defined mismatch as good observed UL function (FMA-UE > 50/66) but low perceived activity (SIS-Hand≤75/100). Potential discriminators at admission and 6 months (demographic characteristics, stroke characteristics, UL somatosensory function, cognitive deficits, mental function and activity) were statistically compared for match and mismatch groups at 12 months.

Results

We included 60 participants (female: 42%) with mean (SD) age of 65 (12) years. We confirmed a mismatch group of 11 (18%) patients at 6 months, which increased to 14 (23%) patients at 12 months. In the mismatch group compared to the good match group at 12 months, patients had a higher stroke severity and more somatosensory impairments on admission and at 6 months.

Conclusions

We confirmed a group of patients with good observed UL function but low perceived activity both at six and at 12 months post stroke. Assessment of stroke severity and somatosensory impairments on admission into rehabilitation could determine mismatch at 12 months and might warrant intervention. However, large differences in clinical outcomes between patients in the mismatch group indicate the importance of tailoring training to the individual needs.
The ideal approach for treatment of cT1N+ and cT2Nany esophageal cancer.: a NCDB analysis
Authors: Huang Binhao , Chan Ernest G. , Pennathur Arjun , Luketich James D. , Zhang Jie
Published: December 2021

Background

Neoadjuvant therapy followed by surgery is recommended for locally advanced esophageal cancer. With the inaccuracies of clinical staging particularly for cT1N+ and cT2Nany tumors, some have proposed consideration of surgery followed by adjuvant treatment. Our objective is to evaluate the efficacy of neoadjuvant therapy vs surgery followed by adjuvant therapy, and to identify the ideal sequence of treatment in patients with cT1N+ and cT2Nany tumors.

Methods

We performed an analysis utilizing the National Cancer Database (2006-2015) identifying all patients with cT1N+ and cT2Nany esophageal cancer undergoing esophagectomy. The treatment was stratified as: neoadjuvant therapy (NT), adjuvant therapy (AT) and combination therapy of neoadjuvant and adjuvant (CT) groups and outcomes were analyzed.

Results

We identified 2795 patients with 81.9% (n=2289) receiving NT, 10.2% (n=285) AT, and 7.9% (n=221) CT. There were no significant differences noted in survival among AT, NT, and CT group in cT1N+(P=0.376), cT2N-(P=0.436), cT2N+(P=0.261) esophageal cancer by multivariate analysis using Cox regression model. This relationship held true in both squamous cell carcinoma and adenocarcinoma.

Conclusion

In clinical T1N+, T2Nany patients, there was no evident superiority of NT over AT. Surgery followed by adjuvant therapy can be considered to be an alternative option in these patients. Further prospective studies are needed to validate these findings.
Evaluation of depth perception and association of severity in Glaucoma patients and suspects
Authors: Adhikari Pragati Gautam , Thapa Madhu , Dahal Manisha
Published: December 2021

Background

To evaluate depth perception in Primary open angle glaucoma (POAG), glaucoma suspects compared to controls and to determine the association between depth perception and severity of glaucoma.

Methods

This was a hospital based, comparative, cross-sectional study. The ethical clearance was taken from institutional review committee of Institute of Medicine [Reference no.399 (6–11) E2 077-078]. Agematched, equal number of participants in each group (N=20) were evaluated with both Titmus and Frisby stereoacuity tests to measure depth perception as stereopsis threshold in seconds of arc. The participants were selected using the purposive sampling technique.

Results

There was no differences in age, sex, or best corrected visual acuity, intraocular pressure, central corneal thickness (CCT), found among the three groups (POAG, Glaucoma Suspects and Control) respectively. However, there was significant difference in cup disc ratio (CDR) between the groups. Equal number of male and female were there in each group, while in POAG group male to female ratio was 3:2. The mean stereoacuity threshold in control group was 53.5±23.23 seconds of arc with Titmus test and 38.75±18.83 seconds of arc with Frisby stereoacuity test. The difference in threshold was significant between control and glaucoma suspect with Titmus (t=1.991, p=0.05) and with Frisby (t=2.114, p=0.04). The difference was also significant in POAG group by Titmus (t=3.135, p=0.0033) and by Frisby (t=3.014, p=0.004). More so, with increasing severity of glaucoma, the mean threshold of stereopsis increased as seen with both Titmus and Frisby Tests (ANOVA, p < 0.001)

Conclusion

Primary open angle glaucoma patients and glaucoma suspects, showed significant reduction in depth perception. Decreased stereoacuity was associated with greater glaucomatous visual field loss.