bluuebunny/crossref_metadata_2025 huggingface dataset:
GRNDaD: big data and sickle cell disease
Authors: Lanzkron Sophie , Manwani Deepa , Desai Payal , Kanter Julie , Little Jane
Published: February 2022

Big data are used in the pursuit of precision medicine in the general population. Applying these tools to patients with sickle cell disease (SCD) is essential for ensuring that they receive the most appropriate customized therapy for their disease. For these tools to be applied, there must be a large number of willing, fully phenotyped participants in collaborative registries. Working collaboratively to respond to unmet clinical needs and the lack of a large multisite registry, SCD providers at multiple sites developed The Globin Regional Data and Discovery (GRNDaD) registry. The specific goals of GRNDaD are to (1) prospectively obtain high-quality curated data on the evolving population affected by SCD; (2) improve adherence to guideline-based care; (3) provide a platform for ongoing quality improvement across sites; (4) allow for real-time investigation of therapies, and collaborate broadly to address research questions using GRNDaD as a shared platform. GRNDaD’s current strength lies in the generous participation of people living with SCD, collaborative investigators, and the opportunity to conduct quality improvement activities across a large number of sites. GRNDaD will serve as the data collection tool for the Health Resources and Services Administration Sickle Cell Treatment Demonstration Program and for the newly established National Alliance for Sickle Cell Centers (https://www.sicklecellcenters.org/). GRNDaD is a robust collaborative registry that providers and researchers will use to identify genetic markers that will help predict outcomes and lead to a better understanding of the natural history of SCD in the modern era of novel therapies.
Genetic analysis of disease resilience of wean-to-finish pigs under a natural disease challenge model using reaction norms
Authors: Cheng Jian , Lim KyuSang , Putz Austin M. , Wolc Anna , Harding John C. S. , Dyck Michael K. , Fortin Frederic , Plastow Graham S. ,   PigGen Canada, Dekkers Jack C. M.
Published: February 2022

Background

Disease resilience is the ability to maintain performance across environments with different disease challenge loads (CL). A reaction norm describes the phenotypes that a genotype can produce across a range of environments and can be implemented using random regression models. The objectives of this study were to: (1) develop measures of CL using growth rate and clinical disease data recorded under a natural polymicrobial disease challenge model; and (2) quantify genetic variation in disease resilience using reaction norm models.

Methods

Different CL were derived from contemporary group effect estimates for average daily gain (ADG) and clinical disease phenotypes, including medical treatment rate (TRT), mortality rate, and subjective health scores. Resulting CL were then used as environmental covariates in reaction norm analyses of ADG and TRT in the challenge nursery and finisher, and compared using model loglikelihoods and estimates of genetic variance associated with CL. Linear and cubic spline reaction norm models were compared based on goodness-of-fit and with multi-variate analyses, for which phenotypes were separated into three traits based on low, medium, or high CL.

Results

Based on model likelihoods and estimates of genetic variance explained by the reaction norm, the best CL for ADG in the nursery was based on early ADG in the finisher, while the CL derived from clinical disease traits across the nursery and finisher was best for ADG in the finisher and for TRT in the nursery and across the nursery and finisher. With increasing CL, estimates of heritability for nursery and finisher ADG initially decreased, then increased, while estimates for TRT generally increased with CL. Genetic correlations for ADG and TRT were low between high versus low CL, but high for close CL. Linear reaction norm models fitted the data significantly better than the standard genetic model without genetic slopes, while the cubic spline model fitted the data significantly better than the linear reaction norm model for most traits. Reaction norm models also fitted the data better than multi-variate models.

Conclusions

Reaction norm models identified genotype-by-environment interactions related to disease CL. Results can be used to select more resilient animals across different levels of CL, high-performance animals at a given CL, or a combination of these.
Comparison of linkage disequilibrium estimated from genotypes versus haplotypes for crossbred populations
Authors: Alemu Setegn Worku , Bijma Piter , Calus Mario P. L. , Liu Huiming , Fernando Rohan L. , Dekkers Jack C. M.
Published: February 2022

Background

Linkage disequilibrium (LD) is commonly measured based on the squared coefficient of correlation $$\left({r}^{2}\right)$$

r

2

between the alleles at two loci that are carried by haplotypes. LD can also be estimated as the $${r}^{2}$$

r

2

between unphased genotype dosage at two loci when the allele frequencies and inbreeding coefficients at both loci are identical for the parental lines. Here, we investigated whether $${r}^{2}$$

r

2

for a crossbred population (F1) can be estimated using genotype data. The parental lines of the crossbred (F1) can be purebred or crossbred.

Methods

We approached this by first showing that inbreeding coefficients for an F1 crossbred population are negative, and typically differ in size between loci. Then, we proved that the expected $${r}^{2}$$

r

2

computed from unphased genotype data is expected to be identical to the $${r}^{2}$$

r

2

computed from haplotype data for an F1 crossbred population, regardless of the inbreeding coefficients at the two loci. Finally, we investigated the bias and precision of the $${r}^{2}$$

r

2

estimated using unphased genotype versus haplotype data in stochastic simulation.

Results

Our findings show that estimates of $${r}^{2}$$

r

2

based on haplotype and unphased genotype data are both unbiased for different combinations of allele frequencies, sample sizes (900, 1800, and 2700), and levels of LD. In general, for any allele frequency combination and $${r}^{2}$$

r

2

value scenarios considered, and for both methods to estimate $${r}^{2}$$

r

2

, the precision of the estimates increased, and the bias of the estimates decreased as sample size increased, indicating that both estimators are consistent. For a given scenario, the $${r}^{2}$$

r

2

estimates using haplotype data were more precise and less biased using haplotype data than using unphased genotype data. As sample size increased, the difference in precision and biasedness between the $${r}^{2}$$

r

2

estimates using haplotype data and unphased genotype data decreased.

Conclusions

Our theoretical derivations showed that estimates of LD between loci based on unphased genotypes and haplotypes in F1 crossbreds have identical expectations. Based on our simulation results, we conclude that the LD for an F1 crossbred population can be accurately estimated from unphased genotype data. The results also apply for other crosses (F2, F3, Fn, BC1, BC2, and BCn), as long as (selected) individuals from the two parental lines mate randomly.
Sudanese emergency departments: a study to identify the barriers to a well-functioning triage
Authors: Ibrahim Bayan E.
Published: February 2022

Background

Triage system is a sorting system that categorizes patients on the basis of the severity of their condition and the availability of the resources in the emergency department. There has been little attention in the public literature to triage systems in Sudan. The aim of this study was to explore the triage system and identify the barriers in its application in hospitals in Sudan.

Methods

A cross-sectional hospital based study was conducted at eight hospitals in Khartoum during December 2020. A multi-stage cluster sampling was applied. Data were obtained by interviewing emergency department staff using a structured questionnaire. The data were analyzed using statistical package for social sciences to find the association between various variables by chi-square test.

Results

Most of the respondents stated that the triage system was deficient. Most of the participants of this study agreed that the role played by the administration in taking legislative decisions is crucial in improving the triage system. Among the factors found to be significant to a well-functioning triage system were, the need for substantial capital expenditure, p-value: 0.026, prudent legislative decisions, p-value: 0.026, adequate training of staff on means of performing efficient triaging, p-value: 0.007 and raising the awareness of the staff on the correct application of triage guidelines, p-value: 0.017.

Conclusion

Currently there is no formal triage system in the State of Khartoum and has yet to be established. Policy making by administrators will play an important role in its implementation. It is suggested that prompt executive orders on improving the current triage system in Khartoum, should be carried out sooner than later, as the ripple effects of a well-functioning triage will decrease the average length of stay, mortality and morbidity rates and will eventually increase the patient’s satisfaction.
Determinants of suboptimal immune recovery among a Chinese Yi ethnicity population with sustained HIV suppression
Authors: Chen Liyu , Liu Chang-Hai , Kang Shuang , Du Lingyao , Ma Fanghua , Li Changmin , Bai Lang , Li Hong , Tang Hong
Published: February 2022

Objectives

Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence.

Methods

This retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/μL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery.

Results

There were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/μL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/μL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients.

Conclusions

Our study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART.

Trial registration None
Sources of information used by women during pregnancy and the perceived quality
Authors: Vogels-Broeke Maaike , Daemers Darie , Budé Luc , de Vries Raymond , Nieuwenhuijze Marianne
Published: February 2022

Background

Access to reliable information is critical to women’s experience and wellbeing during pregnancy and childbirth. In our information-rich society, women are exposed to a wide range of information sources. The primary objective of this study was to explore women’s use of information sources during pregnancy and to examine the perceived usefulness and trustworthiness of these sources.

Method

A quantitative cross-sectional study of Dutch women's experiences with various information sources during pregnancy, including professional (e.g. healthcare system), and informal sources, divided into conventional (e.g. family or peers) and digital sources (e.g. websites or apps). Exploratory backward stepwise multiple regression was performed to identify associations between the perceived quality of information sources and personal characteristics.

Results

A total of 1922 pregnant women were included in this study. The most commonly used information sources were midwives (91.5%), family or friends (79.3%), websites (77.9%), and apps (61%). More than 80% of women found professional information sources trustworthy and useful, while digital sources were perceived as less trustworthy and useful. Personal factors explain only a small part of the variation in the perceived quality of information sources.

Conclusion

Even though digital sources are perceived as less trustworthy and useful than professional and conventional sources, they are among the most commonly used sources of information for pregnant women. To meet the information needs of the contemporary generation of pregnant women it is essential that professionals help in the development of digital information sources.
Positive H. pylori status predicts better prognosis of non-cardiac gastric cancer patients: results from cohort study and meta-analysis
Authors: Jia Zhifang , Zheng Min , Jiang Jing , Cao Donghui , Wu Yanhua , Zhang Yuzheng , Fu Yingli , Cao Xueyuan
Published: February 2022

Background

Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis.

Methods

Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith’s plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results.

Results

A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74–1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72–0.90) and disease-free survival (HR 0.83, 95%CI: 0.67–0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract.

Conclusions

In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.
A health economics study of long-acting injectable once-monthly paliperidone palmitate in schizophrenia: a one-year mirror-image study in China
Authors: Liu Jie , Wang Qian , Su Lei , Yang Limin , Zou Lianyong , Bai Ludong
Published: February 2022

Schizophrenia is ranked among the top 25 leading causes of disability worldwide in 2013 which resulting in social and economic burden. By observing patients with schizophrenia one year before and after switching from oral antipsychotics (OAPs) to once-monthly paliperidone palmitate (PP1M), we can better understand the change of total costs in schizophrenic patients, including direct costs and indirect costs, after switching treatment patterns.

A total of 100 schizophrenic (ICD-10) patients from Shandong Mental Health Center were collected from December 2016 to June 2019. Treatment modalities, health care resource utilization and costs were compared before and after switching directly from oral antipsychotics to PP1M.

Of the 82 patients included in the main analyses, treatment with PP1M resulted in an increase in direct costs of 31.92% (P < 0.01), an increase in medicine costs of approximately 142% (P < 0.01), and a reduction in hospital costs of 68.15% (P > 0.05). There was no significant increase in total costs (P = 0.25), while 31.92% increase in direct costs (P < 0.01), and 35.62% decrease in indirect costs (P < 0.01) after conversion to PP1M. Compared with before administration of PP1M, patients with ≥ 1 inpatient stay in 1 year Pre-PP1M treatment with OAPs (n = 32) had a 20.16% decrease in direct costs (P < 0.01), a 144% increase in medicine costs (P < 0.01), and a significant 72.02% decrease in hospital costs (P < 0.01). The observed reduction in the number of hospitalizations (t = 2.56, P ≤ 0.01) and inpatient stays (t = 1.73, P < 0.05) and after transition to PP1M resulted in a reduction in hospitalization costs (P < 0.01).

Switching from OAPs to PP1M decreased the household workforce burden without increasing clinical healthcare costs. Direct costs were significantly reduced in patients with ≥ 1 inpatient stay in 1 year pre-PP1M treatment with OAPs after the switch, which decreased by improving adherence to therapy and reducing the number and length of hospital stays, suggesting that those patients may benefit after switching to PP1M.
Exploring treatment adherence in long-term sick-listed workers and the impact of coping strategies, illness perceptions and perceived health
Authors: Hoekstra Tialda , Wilming Loes , Sjobbema Christiaan , Brouwer Sandra
Published: February 2022

Background

Treatment adherence is important to improve return to work in sick-listed workers. Especially in long-term sick-listed workers who apply for a disability benefit and therefore have not (fully) returned to work, it is of great value to gain insight in the adherence to advice of physicians. Non-adherence could be one of the main reasons why they have not returned to work and are sick-listed for a long-term. The aim of the study is to explore treatment adherence and possible associated factors to advice from medical and occupational health physicians in long-term sick-listed workers.

Methods

The study is a cross-sectional survey study among 561 long-term (partly) sick-listed workers applying for a disability benefit. Associations of sociodemographic characteristics, disease related factors, coping strategies (Utrecht Coping List, UCL), illness perception (Illness Cognition Questionnaire, ICQ) and perceived health (Short-Form 12, SF12) with treatment adherence (measured with the Medical Outcomes Study Measures of Patient Adherence, MOS-MPA) were analysed separately for adherence to medical advice (n = 348, mean age 51.3 ± 9.1 years, 55.9% female) and adherence to occupational advice (n = 229, mean age 50.4 ± 9.5 years, 54.1% female).

Results

Among participants, 63.3% to 76.4% reported they were able to do what the physician told them to do. However, about half of the participants found it easy to follow-up and implement the suggestions of the physician (54.3% for medical advice and 50.2% for occupational advice). Having a mental health disorder was negatively associated with adherence to medical advice. An active coping strategy, acceptance of the disease, and perceiving positive long-term consequences of the disease were associated with a higher adherence, whereas focusing on the negative consequences was associated with a lower adherence, both for medical and occupational advice.

Conclusions

The tendency to adhere to medical and occupational advice in long-term sick-listed workers is relatively low. In order to increase return to work in this population, medical and occupational health physicians should especially be aware of the adherence of sick-listed workers with mental health disorders, but also on those who focus on the negative consequences of their (physical or mental health) disorder.
The effects of involvement in training and volunteering with families of people with dementia on the knowledge and attitudes of volunteers towards dementia
Authors: Cheung Daphne Sze Ki , Ho Lily Yuen Wah , Kwok Robin Ka Ho , Lai Daniel Lok Lam , Lai Claudia Kam Yuk
Published: February 2022

Background

Volunteers have been a valuable resource in supporting people with dementia and their caregivers in the community. However, factors such as misconceptions, negative attitudes towards dementia, and a lack of motivation might impact the quality of volunteer care. The present paper aims to examine the effect of training and service provision on the knowledge and attitudes of volunteers towards dementia and the association between knowledge and attitudes with the levels of motivation to volunteer.

Methods

The present study is part of an effectiveness-implementation cluster randomized clinical hybrid trial using a music-with-movement intervention to promote the well-being of people with dementia and their informal caregivers. Volunteers were recruited to receive training to support the delivery of the intervention. Training and enrichment workshops were offered to volunteers during the one-year project. Before and after their training and service, the recruited volunteers were asked to complete the following assessments: Dementia Attitudes Scale, and the Alzheimer’s Disease Knowledge Scale. The levels of motivation to volunteer was measured with Volunteer Functions Inventory at baseline. Wilcoxon signed-rank test and multiple regression test were applied for statistical analyses.

Results

A total of 107 volunteers were recruited, and 81 of them completed a mean period of 47.32 weeks of training and service. Significant improvements in their total score on the Alzheimer’s Disease Knowledge Scale (p = .009) and Dementia Attitudes Scale (p < .001) were found. Dementia attitude (β = .57, p < .001) and knowledge (β = -.18, p = .038) were found to have the most significant association with the levels of motivation to be a volunteer at baseline.

Conclusions

The present study illustrated the importance of quality volunteer training and voluntary service in improving the dementia knowledge and attitudes of volunteers. It also shed light on the association between knowledge and attitudes with the levels of motivation to volunteer. Accordingly, future research and public health policymakers should address more efforts to amplify the advantage of volunteers as a vital asset in dementia care.

Trial registration

NCT03575026 (ClinicalTrials.gov), First registration on 02/07/2018.
Acceptability and feasibility of video-based coaching to enhance clinicians’ communication skills with patients
Authors: Freytag Jennifer , Chu Jinna , Hysong Sylvia J. , Street Richard L. , Markham Christine M. , Giordano Thomas P. , Westbrook Robert A. , Njue-Marendes Sarah , Johnson Syundai R. , Dang Bich N.
Published: February 2022

Background

Despite a growing call to train clinicians in interpersonal communication skills, communication training is either not offered or is minimally effective, if at all. A critical need exists to develop new ways of teaching communication skills that are effective and mindful of clinician time pressures. We propose a program that includes real-time observation and video-based coaching to teach clinician communication skills. In this study, we assess acceptability and feasibility of the program using clinician interviews and surveys.

Methods

The video-based coaching intervention targets five patient-centered communication behaviors. It uses trained communication coaches and live feed technology to provide coaching that is brief (less than 15 min), timely (same day) and theory-informed. Two coaches were trained to set up webcams and observe live video feeds of clinician visits in rooms nearby. As coaches watched and recorded the visit, they time stamped illustrative clips in real time. Video clips were a critical element of the program. During feedback sessions, coaches used video clips to promote discussion and self-reflection. They also used role play and guided practice techniques to enforce new tips. Clinicians included residents (n = 15), fellows (n = 4), attending physicians (n = 3), and a nurse practitioner (n = 1) at two primary care clinics in Houston, Texas. We administered surveys to clinicians participating in the program. The survey included questions on quality and delivery of feedback, and credibility of the coaches. We also interviewed clinicians following the intervention. We used rapid analysis to identify themes within the interviews.

Results

Survey measures showed high feasibility and acceptability ratings from clinicians, with mean item scores ranging from 6.4 to 6.8 out of 7 points. Qualitative analysis revealed that clinicians found that 1) coaches were credible and supportive, 2) feedback was useful, 3) video-clips allowed for self-reflection, 4) getting feedback on the same day was useful, and 5) use of real patients preferred over standardized patients.

Conclusions

Video-based coaching can help clinicians learn new communication skills in a way that is clinician-centered, brief and timely. Our study demonstrates that real-time coaching using live feed and video technology is an acceptable and feasible way of teaching communication skills.
The role of urgent care centers in headache management: a quality improvement project
Authors: Minen Mia T. , Khanns Dennique , Guiracocha Jenny , Ehrlich Annika , Khan Fawad A. , Ali Ashhar S. , Birlea Marius , Singh Niranjan N. , Peretz Addie , Larry Charleston I. V.
Published: February 2022

Background

Patients with headache often seek urgent medical care to treat pain and associated symptoms that do not respond to therapeutic options at home. Urgent Cares (UCs) may be suitable for the evaluation and treatment of such patients but there is little data on how headache is evaluated in UC settings and what types of treatments are available. We conducted a study to evaluate the types of care available for patients with headache presenting to UCs.

Design

Cross-Sectional.

Methods

Headache specialists across the United States contacted UCs to collect data on a questionnaire. Questions asked about UC staffing (e.g. number and backgrounds of staff, hours of operation), average length of UC visits for headache, treatments and tests available for patients presenting with headache, and disposition including to the ED.

Results

Data from 10 UC programs comprised of 61 individual UC sites revealed: The vast majority (8/10; 80%) had diagnostic testing onsite for headache evaluation. A small majority (6/10; 60%) had the American Headache Society recommended intravenous medications for acute migraine available. Half (5/10) had a headache protocol in place. The majority (6/10; 60%) had no follow up policy after UC discharge.

Conclusions

UCs have the potential to provide expedited care for patients presenting for evaluation and treatment of headache. However, considerable variability exists amongst UCs in their abilities to manage headaches. This study reveals many opportunities for future research including the development of protocols and professional partnerships to help guide the evaluation, triage, and treatment of patients with headache in UC settings.
Upregulation of NOD1 and NOD2 contribute to cancer progression through the positive regulation of tumorigenicity and metastasis in human squamous cervical cancer
Authors: Zhang Yuanyuan , Li Ning , Yuan Guangwen , Yao Hongwen , Zhang Die , Li Nan , Zhang Gongyi , Sun Yangchun , Wang Wenpeng , Zeng Jia , Xu Ningzhi , Liu Mei , Wu Lingying
Published: February 2022

Background

Metastatic cervical squamous cell carcinoma (CSCC) has poor prognosis and is recalcitrant to the current treatment strategies, which warrants the necessity to identify novel prognostic markers and therapeutic targets. Given that CSCC is a virus-induced malignancy, we hypothesized that the pattern recognition receptors (PRRs) involved in the innate immune response likely play a critical role in tumor development.

Methods

A bioinformatics analysis, qPCR, IHC, immunofluorescence, and WB were performed to determine the expression of NOD1/NOD2. The biological characteristics of overexpression NOD1 or NOD2 CSCC cells were compared to parental cells: proliferation, migration/invasion and cytokines secretion were examined in vitro through CCK8/colony formation/cell cycle profiling/cell counting, wound healing/transwell, and ELISA assays, respectively. The proliferative and metastatic capacity of overexpression NOD1 or NOD2 CSCC cells were also evaluated in vivo. FCM, mRNA and protein arrays, ELISA, and WB were used to identify the mechanisms involved, while novel pharmacological treatment were evaluated in vitro and in vivo. Quantitative variables between two groups were compared by Student’s t test (normal distribution) or Mann-Whitney U test (non-normal distribution), and one-way or two-way ANOVA was used for comparing multiple groups. Pearson χ2 test or Fisher’s exact test was used to compare qualitative variables. Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. P values of < 0.05 were considered statistically significant.

Results

NOD1 was highly expressed in CSCC with lymph-vascular space invasion (LVSI, P < 0.01) and lymph node metastasis (LM, P < 0.01) and related to worse overall survival (OS, P = 0.016). In vitro and in vivo functional assays revealed that the upregulation of NOD1 or NOD2 in CSCC cells promoted proliferation, invasion, and migration. Mechanistically, NOD1 and NOD2 exerted their oncogenic effects by activating NF-κb and ERK signaling pathways and enhancing IL-8 secretion. Inhibition of the IL-8 receptor partially abrogated the effects of NOD1/2 on CSCC cells.

Conclusions

NOD1/2-NF-κb/ERK and IL-8 axis may be involved in the progression of CSCC; the NOD1 significantly enhanced the progression of proliferation and metastasis, which leads to a poor prognosis. Anti-IL-8 was identified as a potential therapeutic target for patients with NOD1high tumor.
As a prognostic biomarker of clear cell renal cell carcinoma RUFY4 predicts immunotherapy responsiveness in a PDL1-related manner
Authors: Miao Daojia , Shi Jian , Xiong Zhiyong , Xiao Wen , Meng Xiangui , Lv Qingyang , Xie Kairu , Yang Hongmei , Zhang Xiaoping
Published: February 2022

Background

Clear cell renal cell carcinoma (ccRCC) is one of the most lethal malignancies in the urinary system and the existing immunotherapy has not achieved satisfactory outcomes. Therefore, this study aims at establishing a novel gene signature for immune infiltration and clinical outcome (overall survival and immunotherapy responsiveness) in ccRCC patients.

Methods

Based on RNA sequencing data and clinical information in The Cancer Genome Atlas (TCGA) database, we calculated proportions of immune cells in 611 samples using an online tool CIBERSORTx. Multivariate survival analysis was conducted to determine crucial survival-associated immune cells and immune-infiltration-related genes (IIRGs). Next, the clinical specimens and common renal cancer cell lines were applied to confirm IIRGs expression at protein and RNA levels. Finally, functional enrichment analyses and siRNA technology targeted toRUFY4were implemented to verify its function of predicting immunotherapy response.

Results

Follicular helper T cells (TFHs) and Regulatory T cells (Tregs) were highly infiltrated in the tumor microenvironment (TME) and their relative proportions were independent prognostic factors for patients. Among IIRGs of TFHs and TREGs,RUFY4was found to be highly activated in tumor microenvironment and its co-expression network was enriched inPDL1/PD1checkpoint pathway in cancer. Additionally, knockdown ofRUFY4led to the decline ofPDL1and proliferation ability in ccRCC cell lines.

Conclusion

TFHs and Tregs were considered as prognostic biomarkers andRUFY4was an immunotherapeutic predictor of ccRCC patients in aPDL1-Related manner.
Cross-sectional study of asymptomatic malaria and seroepidemiological surveillance of seven districts in Gia Lai province, Vietnam
Authors: San Nguyen Ngoc , Kien Nguyen Xuan , Manh Nguyen Duc , Van Thanh Nguyen , Chavchich Marina , Binh Nguyen Thi Huong , Long Tran Khanh , Edgel Kimberly A. , Rovira-Vallbona Eduard , Edstein Michael D. , Martin Nicholas J.
Published: February 2022

Background

Malaria elimination by 2030 is an aim of many countries in the Greater Mekong Sub-region, including Vietnam. However, to achieve this goal and accelerate towards malaria elimination, countries need to determine the extent and prevalence of asymptomatic malaria as a potential reservoir for malaria transmission and the intensity of malaria transmission. The purpose of this study was to determine the prevalence of asymptomatic malaria and seropositivity rate in several districts of Gia Lai province in the Central Highlands of Vietnam.

Methods

A cross-sectional survey of asymptomatic malaria and serological testing was conducted in 3283 people living at 14 communes across seven districts in Gia Lai province in December 2016 to January 2017. Finger prick capillary blood samples were tested for malaria using rapid diagnostic testing and polymerase chain reaction (PCR), as well as detecting antibodies against 3 Plasmodium falciparum and 4 Plasmodium vivax antigens by indirect enzyme-linked immunosorbent assay (ELISA). Age-seroprevalence curves were fitted using reverse catalytic models with maximum likelihood.

Results

The study population was predominantly male (65.9%, 2165/3283), adults (88.7%, 2911/3283) and of a minority ethnicity (72.2%, 2371/3283), with most participants being farmers and outdoor government workers (90.2%, 2960/3283). Using a small volume of blood (≈ 10 µL) the PCR assay revealed that 1.74% (57/3283) of the participants had asymptomatic malaria (P. falciparum 1.07%, P. vivax 0.40%, Plasmodium malariae 0.15% and mixed infections 0.12%). In contrast, the annual malaria prevalence rates for clinical malaria in the communities where the participants lived were 0.12% (108/90,395) in 2016 and 0.22% (201/93,184) in 2017. Seropositivity for at least one P. falciparum or one P. vivax antigen was 38.5% (1257/3262) and 31.1% (1022/3282), respectively. Age-dependent trends in the proportion of seropositive individuals in five of the districts discriminated the three districts with sustained low malaria prevalence from the two districts with higher transmission.

Conclusions

Asymptomatic Plasmodium carriers were found to be substantially more prevalent than clinical cases in seven districts of Gia Lai province, and a third of the population had serological evidence of previous malaria exposure. The findings add knowledge on the extent of asymptomatic malaria and transmission for developing malaria elimination strategies for Vietnam.
Glioma targeted therapy: insight into future of molecular approaches
Authors: Yang Keyang , Wu Zhijing , Zhang Hao , Zhang Nan , Wu Wantao , Wang Zeyu , Dai Ziyu , Zhang Xun , Zhang Liyang , Peng Yun , Ye Weijie , Zeng Wenjing , Liu Zhixiong , Cheng Quan
Published: February 2022

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males are more susceptible than females. According to the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), standard of care and prognosis of gliomas can be dramatically different. Generally, circumscribed gliomas are usually benign and recommended to early complete resection, with chemotherapy if necessary. Diffuse gliomas and other high-grade gliomas according to their molecule subtype are slightly intractable, with necessity of chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide chemotherapy define the current standard of care. Here, we discuss novel feasible or potential targets for treatment of gliomas, especially IDH-wild type glioblastoma. Classic targets such as the p53 and retinoblastoma (RB) pathway and epidermal growth factor receptor (EGFR) gene alteration have met failure due to complex regulatory network. There is ever-increasing interest in immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), tumor microenvironment, and combination of several efficacious methods. With many targeted therapy options emerging, biomarkers guiding the prescription of a particular targeted therapy are also attractive. More pre-clinical and clinical trials are urgently needed to explore and evaluate the feasibility of targeted therapy with the corresponding biomarkers for effective personalized treatment options.
Describing implementation outcomes for a virtual community of practice: The ECHO Ontario Mental Health experience
Authors: Serhal Eva , Pereira Cheryl , Armata Rosaria , Hardy Jenny , Sockalingam Sanjeev , Crawford Allison
Published: February 2022

Background

Project ECHO is a virtual education model aimed at building capacity among healthcare providers to support optimal management for a range of health conditions. The expansion of the ECHO model, further amplified by the pandemic, has demonstrated an increased need to evaluate implementation success to ensure that interventions are implemented as planned. This study describes how Proctor et al.’s implementation outcomes (acceptability, adoption, appropriateness, costs, feasibility, fidelity, penetration, and sustainability) were adapted and used to assess the implementation of ECHO Ontario Mental Health (ECHO-ONMH), a mental health-focused capacity-building programme.

Methods

Using Proctor et al.’s implementation outcomes, the authors developed an implementation outcomes framework for ECHO-ONMH more generally. Using this, outcome measures and success thresholds were identified for each outcome for the ECHO-ONMH context, and then applied to evaluate the implementation of ECHO-ONMH using data from the first 4 years of the programme.

Results

An ECHO-ONMH implementation outcomes framework was developed using Proctor’s implementation outcomes. ECHO-ONMH adapted implementation outcomes suggest that ECHO-ONMH was implemented successfully in all domains except for penetration, which only had participation from 13/14 regions. Acceptability, appropriateness and adoption success thresholds were surpassed for all 4 years, showing strong signs of sustainability. The programme was deemed feasible all 4 years and was found to be more cost-effective. ECHO-ONMH also showed high rates of fidelity to the ECHO model, and high rates of penetration.

Conclusions

This is the first study to use Proctor et al.’s implementation outcomes to describe implementation success for a virtual capacity-building model. The proposed ECHO implementation outcomes framework provides a base for similar interventions to evaluate implementation success, which is an important precursor to understanding learning, service or health outcomes related to the model. Additionally, these findings can act as a benchmark for other international ECHOs and educational programmes.
The role of teamwork and non-technical skills for improving emergency surgical outcomes: an international perspective
Authors: Stahel Philip F. , Cobianchi Lorenzo , Dal Mas Francesca , Paterson-Brown Simon , Sakakushev Boris E. , Nguyen Christine , Fraga Gustavo P. , Yule Steven , Damaskos Dimitrios , Healey Andrew J. , Biffl Walter , Ansaloni Luca , Catena Fausto
Published: February 2022

The assurance of patient safety in emergency general surgery remains challenging due to the patients’ high-risk underlying conditions and the wide variability in emergency surgical care provided around the globe. The authors of this article convened as an expert panel on patient safety in surgery at the 8thInternational Conference of the World Society of Emergency Surgery (WSES) in Edinburgh, Scotland, on September 7–10, 2021. This review article represents the proceedings from the expert panel discussions at the WSES congress and was designed to provide an international perspective on optimizing teamwork and non-technical skills in emergency general surgery.
Cardiac dysfunction in Multisystem Inflammatory Syndrome in Children: An Italian single-center study
Authors: Mannarino Savina , Raso Irene , Garbin Massimo , Ghidoni Elena , Corti Carla , Goletto Sara , Nespoli Luisa , Santacesaria Sara , Zoia Elena , Camporesi Anna , Izzo Francesca , Dilillo Dario , Fiori Laura , D’Auria Enza , Silvestri Annalisa De , Dolci Alberto , Calcaterra Valeria , Zuccotti Gianvincenzo
Published: February 2022

Background

Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients.

Methods

A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children’s Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%). Pre-existing, clinical, and laboratory factors were assessed for evaluating outcomes at discharge.

Results

Thirty-two patients were considered. Cardiac manifestations of MIS-C were reported in 26 patients (81%). Group A included 10 patients (9 M/1F, aged 13 years [IQR 5–15]), and group B included 22 patients (15 M/7 M, aged 9 years [IQR 7–13]). Significant differences were noted among clinical presentations (shock, diarrhea, intensive care unit admission), laboratory markers (leucocytes, neutrophils, and protein C-reactive), and cardiac markers (troponin T and N-terminal pro B-type Natriuretic Peptide) between the groups, with higher compromission in Group A. We found electrocardiogram anomalies in 14 patients (44%) and rhythm alterations in 3 patients (9%), without differences between groups. Mitral regurgitation and coronary involvement were more prevalent in group A. Total length of hospital stay and cardiac recovery time were not statistically different between groups. A recovery of cardiac functioning was reached in all patients.

Conclusion

Despite significant differences in clinical presentations and need for intensive care, all of the MIS-C patients with significant cardiac involvement in this study completely recovered. This suggests that the heart is an involved organ and did not influence prognosis if properly treated and supported in the acute phase.
Benchmarking clustering algorithms on estimating the number of cell types from single-cell RNA-sequencing data
Authors: Yu Lijia , Cao Yue , Yang Jean Y. H. , Yang Pengyi
Published: February 2022

Background

A key task in single-cell RNA-seq (scRNA-seq) data analysis is to accurately detect the number of cell types in the sample, which can be critical for downstream analyses such as cell type identification. Various scRNA-seq data clustering algorithms have been specifically designed to automatically estimate the number of cell types through optimising the number of clusters in a dataset. The lack of benchmark studies, however, complicates the choice of the methods.

Results

We systematically benchmark a range of popular clustering algorithms on estimating the number of cell types in a variety of settings by sampling from the Tabula Muris data to create scRNA-seq datasets with a varying number of cell types, varying number of cells in each cell type, and different cell type proportions. The large number of datasets enables us to assess the performance of the algorithms, covering four broad categories of approaches, from various aspects using a panel of criteria. We further cross-compared the performance on datasets with high cell numbers using Tabula Muris and Tabula Sapiens data.

Conclusions

We identify the strengths and weaknesses of each method on multiple criteria including the deviation of estimation from the true number of cell types, variability of estimation, clustering concordance of cells to their predefined cell types, and running time and peak memory usage. We then summarise these results into a multi-aspect recommendation to the users. The proposed stability-based approach for estimating the number of cell types is implemented in an R package and is freely available from (https://github.com/PYangLab/scCCESS).