bluuebunny/crossref_metadata_2025 huggingface dataset:
Mismatch between actual and preferred extent of telework: cross-sectional and prospective associations with well-being and burnout
Authors: Heiden Marina , Hallman David M. , Svensson Malin , Mathiassen Svend Erik , Svensson Sven , Bergström Gunnar
Published: September 2023

Background

This study aimed to determine whether telework mismatch, i.e., lack of fit between actual and preferred extent of telework, is cross-sectionally and prospectively associated with well-being and burnout.

Methods

A questionnaire was sent to employees in a Swedish manufacturing company in November 2020 (baseline) and September 2021 (follow-up). It contained questions about well-being (WHO-5 Well-Being Index) and burnout (Copenhagen Psychosocial Questionnaire III), as well as the preferred extent of telework and extent of telework performed. Telework mismatch was calculated as the difference between the actual and preferred extent of telework. Change in mismatch over time was categorized as 1) less mismatch at follow-up than at baseline, 2) more mismatch at follow-up, and 3) identical levels of mismatch at baseline and follow-up. Multivariate and univariate analyses of variance were used to determine the effects of mismatch and change in mismatch over time on baseline ratings and changes in ratings of well-being and burnout. All analyses were performed with and without adjustment for age, sex, marital status, children, type of employment, commuting time and extent of telework performed.

Results

The response rate was 39% at baseline (n = 928, 67% men, mean(SD) age: 45(11) years) and 60% at follow-up (n = 556, 64% men, mean(SD) age: 46(11) years). A cross-sectional association was found between telework mismatch and well-being, showing that employees who teleworked more than they would like reported worse well-being than those who teleworked less than they would like. No statistically significant association was found between telework mismatch and burnout. The ability of telework mismatch at baseline to predict changes in well-being or burnout over 10 months was small and non-significant. No association was found between change in telework mismatch over the 10-month period and corresponding changes in well-being or burnout.

Conclusion

Our results suggest that telework should be thoughtfully practiced in companies/organizations to avoid negative consequences for employees who already telework more than they prefer. Studies are needed to determine how long-term changes in match between preferred and actual extent of telework is associated with employee well-being, including how the association is modified by the nature of the job and the work environment.
Bilateral inguinal hernia repair by laparoscopic totally extraperitoneal (TEP) vs. laparoscopic transabdominal preperitoneal (TAPP)
Authors: Hidalgo Nils Jimmy , Guillaumes Salvador , Bachero Irene , Butori Eugenia , Espert Juan José , Ginestà César , Vidal Óscar , Momblán Dulce
Published: September 2023

Background

The guidelines recommend laparoscopic repair for bilateral inguinal hernia. However, few studies compare the totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) techniques in bilateral inguinal hernias. This study aimed to compare the outcomes of TEP and TAPP in bilateral inguinal hernia.

Methods

We conducted a retrospective cohort study of patients operated on for bilateral inguinal hernia by TEP and TAPP repair from 2016 to 2020. Intraoperative complications, operative time, acute postoperative pain, hospital stay, postoperative complications, chronic inguinal pain, and recurrence were compared.

Results

A total of 155 patients were included in the study. TEP was performed in 71 patients (46%) and TAPP in 84 patients (54%). The mean operative time was longer in the TAPP group than in the TEP group (107 min vs. 82 min, p < 0.001). The conversion rate to open surgery was higher in the TEP group than in the TAPP group (8.5% vs. 0%, p = 0.008). The mean hospital stay was longer in the TAPP group than in the TEP group (p < 0.001). We did not observe significant differences in the proportion of postoperative complications (p = 0.672), postoperative pain at 24 h (p = 0.851), chronic groin pain (p = 0.593), and recurrence (p = 0.471). We did not observe an association between the choice of surgical technique (TEP vs. TAPP) with conversion rate, operative time, hospital stay, postoperative complications, chronic inguinal pain, or hernia recurrence when performing a multivariable analysis adjusted for the male sex, age, BMI, ASA, recurrent hernia repair, surgeon, and hernia size > 3cm.

Conclusions

Bilateral inguinal hernia repair by TEP and TAP presented similar outcomes in our study.
The global prevalence of oral leukoplakia: a systematic review and meta-analysis from 1996 to 2022
Authors: Zhang Chang , Li Bingjie , Zeng Xiamei , Hu XiaoSheng , Hua Hong
Published: September 2023

Background

Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence.

Methods

The search terms ("Oral leukoplakia" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0.

Results

We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not.

Conclusion

Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia.
Transformation to a patient-centred medical home led and delivered by an urban Aboriginal and Torres Strait Islander community, and association with engagement and quality-of-care: quantitative findings from a pilot study
Authors: Mathew Saira , Barzi Federica , Clifford-Motopi Anton , Brown Renee , Ward James , Mills Richard , Turner Lyle , White Antoinette , Eaton Martie , Butler Danielle
Published: September 2023

Background

The patient-centred medical home (PCMH) is a model of team-based primary care that is patient-centred, coordinated, accessible, and focused on quality and safety. In response to substantial population growth and increasing demand on existing primary care services, the Institute for Urban Indigenous Health (IUIH) developed the IUIH System of Care-2 (ISoC2), based on an international Indigenous-led PCMH. ISoC2 was piloted at an urban Aboriginal and Torres Strait Islander Community-Controlled Health Service in South-East Queensland between 2019–2020, with further adaptations made to ensure its cultural and clinical relevance to local Aboriginal and Torres Strait Islander people. Little is known on the implementation and impact of PCMH in the Australian Indigenous primary care setting. Changes in implementation process measures and outcomes relating to engagement and quality-of-care are described here.

Methods

De-identified routinely collected data extracted from electronic health records for clients regularly attending the service were examined to assess pre-post implementation changes relevant to the study. Process measures included enrolment in PCMH team-based care, and outcome measures included engagement with the health service, continuity-of-care and clinical outcomes.

Results

The number of regular clients within the health service increased from 1,186 pre implementation to 1,606 post implementation; representing a small decrease as a proportion of the services’ catchment population (38.5 to 37.6%). In clients assigned to a care team (60% by end 2020), care was more evenly distributed between providers, with an increased proportion of services provided by the Aboriginal and Torres Strait Islander Health Worker (16–17% versus 10–11%). Post-implementation, 41% of clients had continuity-of-care with their assigned care team, while total, preventive and chronic disease services were comparable pre- and post-implementation. Screening for absolute cardiovascular disease risk improved, although there were no changes in clinical outcomes.

Conclusions

The increase in the number of regular clients assigned to a team and their even distribution of care among care team members provides empirical evidence that the service is transforming to a PCMH. Despite a complex transformation process compounded by the COVID-19 pandemic, levels of service delivery and quality remained relatively stable, with some improvements in risk factor screening.
What are barriers and facilitators in sustaining lean management in healthcare? A qualitative literature review
Authors: Kunnen Y. S. , Roemeling O. P. , Smailhodzic E.
Published: September 2023

Background

Lean management (LM) is a continuous improvement methodology originating from manufacturing and is widely adopted in healthcare to improve processes. LM shows promising results in healthcare and research on the topic is increasing. However, it can be difficult to sustain LM over time, and an overview of facilitators or barriers that influence the sustainment of LM in a healthcare context is unavailable.

Methods

Prior to search, five inclusion and exclusion criteria were defined to establish suitability of identified articles for our research question. This study was based on 24 selected peer-reviewed studies that reported on the sustainment of LM in healthcare organisations, published in the last five years. Following the Preferred Reporting Items for Systemtic Reviews and Meta-Analyses (PRISMA) guidelines, all articles were scanned, retrieved for full-text and analysed thematically.

Results

Following thematic analysis, we identified four overarching themes: Mobilising Employees, Guiding Change Efforts, Methods, and Local Context. Key facilitators for supporting LM are fostering an improvement culture and learning culture, providing professional development opportunities, assigning more responsibilities to employees in decision making processes and appointing change agents to act as local LM leaders. Key barriers for sustaining LM include overburdening employees with responsibilities, omitting staff involvement during LM implementation, lack of patient engagement, lack of resources to engage with LM, a lack of leadership commitment and follow-up on projects, and a lack of knowledge of LM among leaders.

Conclusion

Overall, studies emphasise the importance of actively involving and engaging the workforce to embed LM into organisational culture. Reflecting on the origins of LM, healthcare organisations can find inspiration in the virtue of respecting people in their journey to sustain and cultivate an improvement culture. LM provides potential to change healthcare for the better and could help healthcare organisations to cope with increasing external pressures.
A novel natural killer-related signature to effectively predict prognosis in hepatocellular carcinoma
Authors: Xi Deyang , Wang Jialu , Yang Yinshuang , Ji Fang , Li Chunyang , Yan Xuebing
Published: September 2023

Background

Hepatocellular carcinoma (HCC) is a prevalent tumor that poses a significant threat to human health, with 80% of cases being primary HCC. At present, Early diagnosis and predict prognosis of HCC is challenging and the it is characterized by a high degree of invasiveness, both of which negatively impact patient prognosis. Natural killer cells (NK) play an important role in the development, diagnosis and prognosis of malignant tumors. The potential of NK cell-related genes for evaluating the prognosis of patients with hepatocellular carcinoma remains unexplored. This study aims to address this gap by investigating the association between NK cell-related genes and the prognosis of HCC patients, with the goal of developing a reliable model that can provide novel insights into evaluating the immunotherapy response and prognosis of these patients. This work has the potential to significantly advance our understanding of the complex interplay between immune cells and tumors, and may ultimately lead to improved clinical outcomes for HCC patients.

Methods

For this study, we employed transcriptome expression data from the hepatocellular carcinoma cancer genome map (TCGA-LIHC) to develop a model consisting of NK cell-related genes. To construct the NK cell-related signature (NKRLSig), we utilized a combination of univariate COX regression, Area Under Curve (AUC) LASSO COX regression, and multivariate COX regression. To validate the model, we conducted external validation using the GSE14520 cohort.

Results

We developed a prognostic model based on 5-NKRLSig (IL18RAP, CHP1, VAMP2, PIC3R1, PRKCD), which divided patients into high- and low-risk groups based on their risk score. The high-risk group was associated with a poor prognosis, and the risk score had good predictive ability across all clinical subgroups. The risk score and stage were found to be independent prognostic indicators for HCC patients when clinical factors were taken into account. We further created a nomogram incorporating the 5-NKRLSig and clinicopathological characteristics, which revealed that patients in the low-risk group had a better prognosis. Moreover, our analysis of immunotherapy and chemotherapy response indicated that patients in the low-risk group were more responsive to immunotherapy.

Conclusion

The model that we developed not only sheds light on the regulatory mechanism of NK cell-related genes in HCC, but also has the potential to advance our understanding of immunotherapy for HCC. With its strong predictive capacity, our model may prove useful in evaluating the prognosis of patients and guiding clinical decision-making for HCC patients.
RTS,S/AS01E vaccine defaults in Ghana: a qualitative exploration of the perspectives of defaulters and frontline health service providers
Authors: Okyere Joshua , Bediako Vincent Bio , Ackah Josephine Akua , Acheampong Emmanuella , Owusu Bernard Afriyie , Agbemavi Wonder , Nwameme Adanna Uloaku , Kamau Edward Mberu , Asampong Emmanuel
Published: September 2023

Background

While Ghana has a good track record in the Expanded Programme on Immunization, there are substantial challenges with regards to subsequent vaccinations, particularly after the first year of life of the child. Given that the last dose of the RTS, S/AS01E vaccine against malaria is administered at 24 months, there is a high likelihood of default. Hence, it is imperative to understand the dynamics and reasons for the defaults to enable the development of effective implementation strategies. This study explored why caregivers default on the RTS, S/AS01E vaccine from the perspective of health service providers and caregivers.

Methods

This study employed an exploratory, descriptive approach. Using a purposive sampling technique, caregivers who defaulted and health service providers directly involved in the planning and delivery of the RTS, S/AS01E vaccine at the district level were recruited. A total of five health service providers and 30 mothers (six per FGD) participated in this study. Data analysis was done using NVivo-12 following Collaizi’s thematic framework for qualitative analysis. The study relies on the Standards for Reporting Qualitative Research.

Results

Reasons for defaulting included the overlap of timing of the last dose and the child starting school, disrespectful attitudes of some health service providers, concerns about adverse side effects and discomforts, travel out of the implementing district, the perception that the vaccines are too many, and lack of support from partners.

Conclusion

To reduce the occurrence of defaulting on the RTS, S/AS01E vaccine programme, stakeholders must reconsider the timing of the last dose of the vaccine. The schedule of the RTS, S/AS01E vaccine should be aligned with the established EPI schedule of Ghana. This will significantly limit the potential of defaults, particularly for the last dose. Also, the findings from this study underscore a need to encourage male partner involvement in the RTS, S/AS01E vaccine programme. Health promotion programmes could be implemented to raise caregivers’ awareness of potential adverse reactions and discomforts—this is necessary to prepare the caregiver for the vaccine process psychologically.
Barriers to accessing malaria treatment amongst school-age children in rural Malawi
Authors: Mhango Patani , Malata Monica Patricia , Chipeta Effie , Sixpence Alick , Taylor Terrie E. , Wilson Mark L. , Cohee Lauren M. , Mangani Charles , Mathanga Don P.
Published: September 2023

Background

Over the last two decades, many countries have moved from malaria control toward malaria elimination. However, some sub-Saharan African countries, like Malawi, have recently seen a reversal in malaria control progress with reported increases in confirmed malaria cases. This may be the result of inadequate access to effective malaria control interventions by key population groups that perpetuate transmission. This study aimed to assess the barriers to accessing malaria treatment among school-aged children (SAC) in Malawi.

Methods

A qualitative study was conducted between September and October 2020, where data were gathered in rural Malawi using free-listing interviews, key-informant interviews, semi-structured interviews and focus group discussions. Purposively sampled participants included SAC, parents of SAC, health workers and key stakeholders at community and district levels. Interviews were digitally recorded and transcribed verbatim. Data were organized using NVivo 12 software and analysed using the thematic method.

Results

The study recruited 252 participants, with 156 being SAC, equally divided between boys and girls. Health system barriers to malaria treatment included long waiting hours and queues at clinics, frequent stock-outs of medical supplies, and travel time to the facility. Provider barriers included negative attitude and limited service hours. Individual and cultural barriers included fear of malaria tests and beliefs associating witchcraft as the best treatment for malaria. In addition, COVID-19-related barriers included the inability to follow preventive measures, a shift in focus from malaria to COVID-19, and fear of contracting COVID-19 and/or being tested for COVID-19 at the facility.

Conclusions

This study shows most of the barriers to accessing malaria treatment among SAC are similar to those experienced by other population groups. Furthermore, COVID-19 adversely affected SAC’s access to treatment. Interventions that support SAC access to prompt diagnosis and treatment are urgently needed to improve the effective control of malaria.
Clinically conserved genomic subtypes of gastric adenocarcinoma
Authors: Jeong Yun Seong , Eun Young-Gyu , Lee Sung Hwan , Kang Sang-Hee , Yim Sun Young , Kim Eui Hyun , Noh Joo Kyung , Sohn Bo Hwa , Woo Seon Rang , Kong Moonkyoo , Nam Deok Hwa , Jang Hee-Jin , Lee Hyun-Sung , Song Shumei , Oh Sang Cheul , Lee Jeeyun , Ajani Jaffer A. , Lee Ju-Seog
Published: September 2023

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.
Non-spatial and spatial heterogeneity revealed a suppressive immune feature of Siglec-15 in lung adenocarcinomas
Authors: Li Baihui , Guo Yan , Yi Yeran , Huang Ziqi , Ren Yulin , Wang Hao , Yang Lili
Published: September 2023

Background

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has emerged as a novel immunotherapy candidate, which deserves a comprehensive investigation in lung adenocarcinoma (LUAD).

Methods

Multiplex fluorescence‐based immunohistochemistry was conducted to assess Siglec-15 expression and tumor-infiltrating immune cells in LUAD from Tianjin cohort, with validation cohorts Xinchao 04 and 07.

Results

This study revealed that Siglec-15 was positively correlated with CD8+ T cells and tumor-associated macrophages (TAMs) infiltration, but CD8+ T cells were mostly infiltrated in the stroma area, not in the tumor area. Spatially, fewer CD8+ T cells surrounded Siglec-15+ tumor cells in PD-L1− cells, and more TAMs surrounded Siglec-15+ tumor cells in PD-L1−/+ cells. Siglec-15+ TAMs infiltrated with more CD8+ T cells, and were closer to CD8+ T cells than Siglec-15− TAMs and Siglec-15+ tumor cells. Siglec-15+ TAMs infiltrated with more Tregs and were closer to Tregs than Siglec-15+ tumor cells. Siglec-15+ tumor cells or TAMs reversed CD8+ T cells prognosis value, and enhanced the prognosis value of Tregs and TAMs. The immunotyping based on Siglec-15 and CD8A / CD8+ T cells revealed that patients with high CD8A and Siglec-15 expression exhibited immune activation. Patients with low CD8A expression / CD8+ T cells infiltration and Siglec-15 overexpression were related to the activation of immunosuppressive signature and metabolism-related pathway, and infiltrated with more TAMs.

Conclusions

We revealed the distinct characteristics between Siglec-15+ tumor cells and TAMs in relation to CD8+ T cells, and a unique relationship between Siglec-15 and immunosuppressive TIME in LUAD, which may provide potential value for anti-Siglec-15 therapy.
Off‐loading and compression therapy strategies to treat diabetic foot ulcers complicated by lower limb oedema: a scoping review
Authors: Tansley Justine , Collings Richard , Williams Jennifer , Paton Joanne
Published: September 2023

Background

Lower limb oedema is a common co‐morbidity in those with diabetes and foot ulceration and is linked with increased amputation risk. There is no current guidance for the treatment of concurrent diabetic foot ulcers and lower limb oedema, leading to uncertainty around the safety and efficacy of combination approaches incorporating offloading and compression therapies.

To determine indications and contraindications for such strategies and identify any other supplementary treatment approaches, a scoping review was undertaken to map the evidence relating to off‐loading and compression therapy strategies to treat both diabetic foot ulcers and lower limb oedema in combination.

Methods

Following the Joanna Briggs Institute (JBI) and PRISMA – Scoping Review (ScR) guidance, this review included published and unpublished literature from inception to April 2022. Literature was sourced using electronic databases including Cochrane Library, PubMed, CINAHL, AMED; websites; professional journals and reference lists of included literature. Eligible literature discussed the management of both diabetic foot ulceration and lower limb oedema and included at least one of the treatment strategies of interest. Data extraction involved recording any suggested off‐loading, compression therapy or supplementary treatment strategies and any suggested indications, contraindications and cautions for their use.

Results

Five hundred twenty‐two publications were found relating to the management of diabetic foot ulcers with an off‐loading strategy or the management of lower limb oedema with compression therapy. 51 publications were eligible for inclusion in the review. The majority of the excluded publications did not discuss the situation where diabetic foot ulceration and lower limb oedema present concurrently.

Conclusions

Most literature, focused on oedema management with compression therapy to conclude that compression therapy should be avoided in the presence of severe peripheral arterial disease. Less literature was found regarding off‐loading strategies, but it was recommended that knee‐high devices should be used with caution when off‐loading diabetic foot ulcers in those with lower limb oedema. Treatment options to manage both conditions concurrently was identified as a research gap. Integrated working between specialist healthcare teams, was the supplementary strategy most frequently recommended. In the absence of a definitive treatment solution, clinicians are encouraged to use clinical reasoning along with support from specialist peers to establish the best, individualised treatment approach for their patients.

Trial registration

Open Science Framework (osf.io/crb78).
Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis
Authors: Fan Zhenziang , Kernan Kate F. , Qin Yidi , Canna Scott , Berg Robert A. , Wessel David , Pollack Murray M. , Meert Kathleen , Hall Mark , Newth Christopher , Lin John C. , Doctor Allan , Shanley Tom , Cornell Tim , Harrison Rick E. , Zuppa Athena F. , Sward Katherine , Dean J. Michael , Park H. J. , Carcillo Joseph A.
Published: September 2023

Background

One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network’s objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

Methods

We assessed differences in 32 cytokines, immune depression (low whole blood ex vivo TNF response to endotoxin) and thrombotic microangiopathy (low ADAMTS13 activity) biomarkers, seven viral DNAemias, and macrophage activation syndrome (MAS) defined by combined hepatobiliary dysfunction and disseminated intravascular coagulation, and mortality in 117 children with hyperferritinemic sepsis (ferritin level > 500 ng/mL) compared to 280 children with sepsis without hyperferritinemia. Causal inference analysis of these 41 variables, MAS, and mortality was performed.

Results

Mortality was increased in children with hyperferritinemic sepsis (27/117, 23% vs 16/280, 5.7%; Odds Ratio = 4.85, 95% CI [2.55–9.60]; z = 4.728; P-value < 0.0001). Hyperferritinemic sepsis had higher C-reactive protein, sCD163, IL-22, IL-18, IL-18 binding protein, MIG/CXCL9, IL-1β, IL-6, IL-8, IL-10, IL-17a, IFN-γ, IP10/CXCL10, MCP-1/CCL2, MIP-1α, MIP-1β, TNF, MCP-3, IL-2RA (sCD25), IL-16, M-CSF, and SCF levels; lower ADAMTS13 activity, sFasL, whole blood ex vivo TNF response to endotoxin, and TRAIL levels; more Adenovirus, BK virus, and multiple virus DNAemias; and more MAS (P-value < 0.05). Among these variables, only MCP-1/CCL2 (the monocyte chemoattractant protein), MAS, and ferritin levels were directly causally associated with mortality. MCP-1/CCL2 and hyperferritinemia showed direct causal association with depressed ex vivo whole blood TNF response to endotoxin. MCP-1/CCL2 was a mediator of MAS. MCP-1/CCL2 and MAS were mediators of hyperferritinemia.

Conclusions

These findings establish hyperferritinemic sepsis as a high-risk condition characterized by increased cytokinemia, viral DNAemia, thrombotic microangiopathy, immune depression, macrophage activation syndrome, and death. The causal analysis provides rationale for designing anti-inflammatory trials that reduce macrophage activation to improve survival and enhance infection clearance in pediatric hyperferritinemic sepsis.
Correcting batch effects in large-scale multiomics studies using a reference-material-based ratio method
Authors: Yu Ying , Zhang Naixin , Mai Yuanbang , Ren Luyao , Chen Qiaochu , Cao Zehui , Chen Qingwang , Liu Yaqing , Hou Wanwan , Yang Jingcheng , Hong Huixiao , Xu Joshua , Tong Weida , Dong Lianhua , Shi Leming , Fang Xiang , Zheng Yuanting
Published: September 2023

Background

Batch effects are notoriously common technical variations in multiomics data and may result in misleading outcomes if uncorrected or over-corrected. A plethora of batch-effect correction algorithms are proposed to facilitate data integration. However, their respective advantages and limitations are not adequately assessed in terms of omics types, the performance metrics, and the application scenarios.

Results

As part of the Quartet Project for quality control and data integration of multiomics profiling, we comprehensively assess the performance of seven batch effect correction algorithms based on different performance metrics of clinical relevance, i.e., the accuracy of identifying differentially expressed features, the robustness of predictive models, and the ability of accurately clustering cross-batch samples into their own donors. The ratio-based method, i.e., by scaling absolute feature values of study samples relative to those of concurrently profiled reference material(s), is found to be much more effective and broadly applicable than others, especially when batch effects are completely confounded with biological factors of study interests. We further provide practical guidelines for implementing the ratio based approach in increasingly large-scale multiomics studies.

Conclusions

Multiomics measurements are prone to batch effects, which can be effectively corrected using ratio-based scaling of the multiomics data. Our study lays the foundation for eliminating batch effects at a ratio scale.
Quartet protein reference materials and datasets for multi-platform assessment of label-free proteomics
Authors: Tian Sha , Zhan Dongdong , Yu Ying , Wang Yunzhi , Liu Mingwei , Tan Subei , Li Yan , Song Lei , Qin Zhaoyu , Li Xianju , Liu Yang , Li Yao , Ji Shuhui , Wang Shanshan ,   Proteomic Massive Analysis and Quality Control Consortium, Qin Zhaoyu , He Qingyu , Yin Xingfeng , Dai Lunzhi , Deng Haiteng , Peng Chao , Wu Ping , Tan Minjia , Jiang Jing , Zhang Yaoyang , Li Yunxia , Liu Wenqin , Chen Wei , Wang Rui , Zi Jin , Li Qidan , Bai Mingzhou , Wang Zeng , Mei Zhanlong , Cheng Zhongyi , Zhu Jun , Wu Xuemei , Yang Xing , Zhou Yue , Zheng Yuanting , He Fuchu , Qin Jun , Ding Chen
Published: September 2023

Background

Quantitative proteomics is an indispensable tool in life science research. However, there is a lack of reference materials for evaluating the reproducibility of label-free liquid chromatography-tandem mass spectrometry (LC–MS/MS)-based measurements among different instruments and laboratories.

Results

Here, we develop the Quartet standard as a proteome reference material with built-in truths, and distribute the same aliquots to 15 laboratories with nine conventional LC–MS/MS platforms across six cities in China. Relative abundance of over 12,000 proteins on 816 mass spectrometry files are obtained and compared for reproducibility among the instruments and laboratories to ultimately generate proteomics benchmark datasets. There is a wide dynamic range of proteomes spanning about 7 orders of magnitude, and the injection order has marked effects on quantitative instead of qualitative characteristics.

Conclusion

Overall, the Quartet offers valuable standard materials and data resources for improving the quality control of proteomic analyses as well as the reproducibility and reliability of research findings.
Mottling as a prognosis marker in cardiogenic shock
Authors: Merdji Hamid , Bataille Vincent , Curtiaud Anais , Bonello Laurent , Roubille François , Levy Bruno , Lim Pascal , Schneider Francis , Khachab Hadi , Dib Jean-Claude , Seronde Marie-France , Schurtz Guillaume , Harbaoui Brahim , Vanzetto Gerald , Marchand Severine , Gebhard Caroline Eva , Henry Patrick , Combaret Nicolas , Marchandot Benjamin , Lattuca Benoit , Biendel Caroline , Leurent Guillaume , Gerbaud Edouard , Puymirat Etienne , Bonnefoy Eric , Meziani Ferhat , Delmas Clément
Published: September 2023

Aims

Impact of skin mottling has been poorly studied in patients admitted for cardiogenic shock. This study aimed to address this issue and identify determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all etiologies.

Methods and results

FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October, 2016. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 660 had skin mottling assessed at admission (85.5%) with almost 39% of patients in cardiogenic shock presenting mottling. The need for invasive respiratory support was significantly higher in patients with mottling (50.2% vs. 30.1%, p < 0.001) and likewise for the need for renal replacement therapy (19.9% vs. 12.4%, p = 0.09). However, the need for mechanical circulatory support was similar in both groups. Patients with mottling at admission presented a higher length of stay (19 vs. 16 days, p = 0.033), a higher 30-day mortality rate (31% vs. 23.3%, p = 0.031), and also showed significantly higher mortality at 1-year (54% vs. 42%, p = 0.003). The subgroup of patients in whom mottling appeared during the first 24 h after admission had the worst prognosis at 30 days.

Conclusion

Skin mottling at admission in patients with cardiogenic shock was statistically associated with prolonged length of stay and poor outcomes. As a perfusion-targeted resuscitation parameter, mottling is a simple, clinical-based approach and may thus help to improve and guide immediate goal-directed therapy to improve cardiogenic shock patients’ outcomes.

Graphical Abstract
Self-determination theory interventions versus usual care in people with diabetes: a systematic review with meta-analysis and trial sequential analysis
Authors: Mathiesen Anne Sophie , Zoffmann Vibeke , Lindschou Jane , Jakobsen Janus Christian , Gluud Christian , Due-Christensen Mette , Rasmussen Bodil , Marqvorsen Emilie Haarslev Schröder , Lund-Jacobsen Trine , Skytte Tine Bruhn , Thomsen Thordis , Rothmann Mette Juel
Published: September 2023

Background

Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes.

Methods

We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE.

Results

Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95% CI −4.85, 4.86, I2 = 0%; 225 participants, 3 trials, TSA-adjusted CI −11.83, 11.83), all-cause mortality, serious adverse events, diabetes distress, depressive symptoms, adverse events, glycated hemoglobulin A1c, or motivation (controlled). The certainty of the evidence was low to very low for all outcomes. We found beneficial effect on motivation (autonomous and amotivation; low certainty evidence).

Conclusions

We found no effect of self-determination-based interventions on our primary or secondary outcomes. The evidence was of very low certainty.

Systematic review registration

PROSPERO CRD42020181144
Generation and characterization of a zebrafish knockout model of abcb4, a homolog of the human multidrug efflux transporter P-glycoprotein
Authors: Park Jinhee , Kim Hyosung , Alabdalla Leen , Mishra Smriti , Mchaourab Hassane
Published: September 2023

The ATP-binding cassette subfamily B member 1 (ABCB1), encoding a multidrug transporter referred to as P-glycoprotein (Pgp), plays a critical role in the efflux of xenobiotics in humans and is implicated in cancer resistance to chemotherapy. Therefore, developing high-throughput animal models to screen for Pgp function and bioavailability of substrates and inhibitors is paramount. Here, we generated and validated a zebrafish knockout line of abcb4, a human Pgp transporter homolog. CRISPR/Cas9 genome editing technology was deployed to generate a frameshift mutation in exon 4 of zebrafish abcb4. The zebrafish abcb4 homozygous mutant exhibited elevated accumulation of fluorescent rhodamine 123, a substrate of human Pgp, in the intestine and brain area of embryos. Moreover, abcb4 knockout embryos were sensitized toward toxic compounds such as doxorubicin and vinblastine compared to the WT zebrafish. Immunostaining for zebrafish Abcb4 colocalized in the endothelial brain cells of adult zebrafish. Transcriptome profiling using Gene Set Enrichment Analysis uncovered that the 'cell cycle process,' 'mitotic cell cycles,' and 'microtubule-based process' were significantly downregulated in the abcb4 knockout brain with age. This study establishes and validates the abcb4 knockout zebrafish as an animal model to study Pgp function in vivo. Unexpectedly it reveals a potentially novel role for zebrafish abcb4 in age-related changes in the brain. The zebrafish lines generated here will provide a platform to aid in the discovery of modulators of Pgp function as well as the characterization of human mutants thereof.
Identification of Fazael 2 (4000–3900 BCE) as first lost wax casting workshop in the Chalcolithic Southern Levant
Authors: Rose Thomas , Bar Shay , Asscher Yotam , Goren Yuval
Published: September 2023

Apart from many lost wax cast metal fragments, crucible fragments and several heated sediment nodules were found at the Chalcolithic site Fazael 2 (central Jordan Valley). Petrographic investigations on the heated sediment nodules revealed many features characteristic of the Chalcolithic Southern Levantine lost wax casting moulds. Heating temperatures were assessed using infrared spectroscopy, showing that casting did not vitrify the clay fraction in the moulds. Consequently, Fazael is the first identified Chalcolithic Southern Levant production site for lost wax cast metal items. These findings confirm the existence of a metallurgical tradition with lost wax casting in the Jordan Valley parallel to the unalloyed copper metallurgy in the Northern Negev. Moreover, crucibles and heated sediment nodules are made of local ferruginous loess, a material not mentioned in previous studies on lost wax casting mould fragments. Therefore, the existence of more than one such production site must be assumed.
Game-based learning in computer science education: a scoping literature review
Authors: Videnovik Maja , Vold Tone , Kiønig Linda , Madevska Bogdanova Ana , Trajkovik Vladimir
Published: September 2023

Using games in education has the potential to increase students’ motivation and engagement in the learning process, gathering long-lasting practical knowledge. Expanding interest in implementing a game-based approach in computer science education highlights the need for a comprehensive overview of the literature research. This scoping review aims to provide insight into current trends and identify research gaps and potential research topics concerning game-based learning in computer science. Using standard methodology for scoping review, we identified 113 articles from four digital libraries published between 2017 and 2021. Those articles were analyzed concerning the educational level, type of the game, computer science topic covered by the game, pedagogical strategies, and purpose for implementing this approach in different educational levels. The results show that the number of research articles has increased through the years, confirming the importance of implementing a game-based approach in computer science. Different kinds of games, using different technology, concerning different computer science topics are presented in the research. The obtained results indicate that there is no standardized game or standardized methodology that can be used for the creation of an educational game for computer science education. Analyzed articles mainly implement a game-based approach using learning by playing, and no significant focus is given to the effectiveness of learning by designing a game as a pedagogical strategy. Moreover, the approach is mainly implemented for developing computational thinking or programming skills, highlighting the need for its implementation in other topics beyond programming.
Unified earthquake catalogue and mapping of Gutenberg–Richter parameters for the East African Rift System
Authors: Letamo Alemayehu , Kavitha B. , Tezeswi T. P.
Published: September 2023

Background

The initial phase of earthquake hazard assessment involves the consolidation of diverse magnitude scales, thereby requiring the homogenization of various magnitudes. Moment magnitude (Mw) emerges as the preferred descriptor for a range of magnitudes, encompassing local magnitude (ML), teleseismic magnitude (e.g., mb and MS), duration magnitudes (MD), and other magnitude proxies. Unlike alternative scales, Mw does not exhibit saturation at high magnitudes, enhancing its reliability. To achieve uniformity in magnitude representation, diverse regression techniques are employed, with the General Orthogonal Regression (GOR) method being widely regarded as the most dependable, accounting for uncertainty in both independent and dependent variables.

Methods

This study utilized the International Seismological Centre (ISC) Catalogue (http://www.isc.ac.uk/) to compile an array of events related to the East Africa Rift System (EARS). Subsequently, the General Orthogonal Regression method was applied to merge and harmonize the collected data. Furthermore, the research computed Gutenberg-Richter b-values using the newly unified magnitude.

Results

Notably, the conversion relationships between magnitude proxies, including MS-mb, mb-Mw, MS-Mw, and ML-Mw, exhibited robust correlations, with coefficients of 0.86, 0.80, 0.88, and 0.94, respectively. In contrast, the relationship between ML and mb proxies revealed a notably weaker correlation, registering a coefficient of 0.54. Ultimately, the study identified a magnitude of completeness and a b-value of 3.8 and 0.71, respectively, for the EARS region, providing valuable insights for earthquake hazard assessment in this area.

Conclusion

Generally, the homogeneous catalogue is a step forward in seismicity assessment and geodynamic activities in the EARS. Hence, developing the empirical equations for the area is essential for future studies on seismic hazards and engineering applications due to the peculiarity of EARS’s geological and tectonic characteristics.
Inadvertent catheter misplacement into the subclavian artery during ultrasound-guided internal jugular venous catheterization: a case report
Authors: Kohyama Tomoki , Fujimaki Keisuke , Sasamori Hiroki , Tokumine Joho , Moriyama Kiyoshi , Yorozu Tomoko
Published: September 2023

Background

Ultrasound-guided central venous catheterization has become a standard procedure. However, mechanical complications are still reported.

Case presentation

An 85-year-old woman presented with coagulopathic bladder tamponade. Ultrasound-guided right internal jugular venous catheterization was planned because of difficult peripheral venous access. A guidewire was advanced through a needle inserted at the midpoint of the right carotid triangle. The guidewire was identified in the short axis, but not in the long-axis ultrasound view, leading to inadvertent insertion of the catheter into the right subclavian artery through the internal jugular vein. Stent graft insertion was performed for perforation closure. The patient exhibited no symptoms of cerebral ischemia following stent graft insertion.

Discussion

This case demonstrated that the needle-sticking site should not be placed close to the clavicle for ultrasound-guided internal jugular venous catheterization, as it may not confirm the position of guidewire in the long-axis ultrasound view.