bluuebunny/crossref_metadata_2025 huggingface dataset:
A composite strategy of genome-wide association study and copy number variation analysis for carcass traits in a Duroc pig population
Authors: Ding Rongrong , Zhuang Zhanwei , Qiu Yibin , Wang Xingwang , Wu Jie , Zhou Shenping , Ruan Donglin , Xu Cineng , Hong Linjun , Gu Ting , Zheng Enqin , Cai Gengyuan , Huang Wen , Wu Zhenfang , Yang Jie
Published: August 2022

Background

Carcass traits are important in pig breeding programs for improving pork production. Understanding the genetic variants underlies complex phenotypes can help explain trait variation in pigs. In this study, we integrated a weighted single-step genome-wide association study (wssGWAS) and copy number variation (CNV) analyses to map genetic variations and genes associated with loin muscle area (LMA), loin muscle depth (LMD) and lean meat percentage (LMP) in Duroc pigs.

Results

Firstly, we performed a genome-wide analysis for CNV detection using GeneSeek Porcine SNP50 Bead chip data of 3770 pigs. A total of 11,100 CNVs were detected, which were aggregated by overlapping 695 CNV regions (CNVRs). Next, we investigated CNVs of pigs from the same population by whole-genome resequencing. A genome-wide analysis of 21 pigs revealed 23,856 CNVRs that were further divided into three categories (851 gain, 22,279 loss, and 726 mixed), which covered 190.8 Mb (~ 8.42%) of the pig autosomal genome. Further, the identified CNVRs were used to determine an overall validation rate of 68.5% for the CNV detection accuracy of chip data. CNVR association analyses identified one CNVR associated with LMA, one with LMD and eight with LMP after applying stringent Bonferroni correction. The wssGWAS identified eight, six and five regions explaining more than 1% of the additive genetic variance for LMA, LMD and LMP, respectively. The CNVR analyses and wssGWAS identified five common regions, of which three regions were associated with LMA and two with LMP. Four genes (DOK7, ARAP1, ELMO2 and SLC13A3) were highlighted as promising candidates according to their function.

Conclusions

We determined an overall validation rate for the CNV detection accuracy of low-density chip data and constructed a genomic CNV map for Duroc pigs using resequencing, thereby proving a value genetic variation resource for pig genome research. Furthermore, our study utilized a composite genetic strategy for complex traits in pigs, which will contribute to the study for elucidating the genetic architecture that may be influenced and regulated by multiple forms of variations.
Mendelian randomization of circulating proteome identifies actionable targets in heart failure
Authors: Moncla Louis-Hippolyte Minvielle , Mathieu Samuel , Sylla Mame Sokhna , Bossé Yohan , Thériault Sébastien , Arsenault Benoit J. , Mathieu Patrick
Published: August 2022

Background

Heart failure (HF) is a prevalent cause of mortality and morbidity. The molecular drivers of HF are still largely unknown.

Results

We aimed to identify circulating proteins causally associated with HF by leveraging genome-wide genetic association data for HF including 47,309 cases and 930,014 controls. We performed two-sample Mendelian randomization (MR) with multiple cis instruments as well as network and enrichment analysis using data from blood protein quantitative trait loci (pQTL) (2,965 blood proteins) measured in 3,301 individuals. Nineteen blood proteins were causally associated with HF, were not subject to reverse causality and were enriched in ligand-receptor and glycosylation molecules. Network pathway analysis of the blood proteins showed enrichment in NF-kappa B, TGF beta, lipid in atherosclerosis and fluid shear stress. Cross-phenotype analysis of HF identified genetic overlap with cardiovascular drugs, myocardial infarction, parental longevity and low-density cholesterol. Multi-trait MR identified causal associations between HF-associated blood proteins and cardiovascular outcomes. Multivariable MR showed that association of BAG3, MIF and APOA5 with HF were mediated by the blood pressure and coronary artery disease. According to the directional effect and biological action, 7 blood proteins are targets of existing drugs or are tractable for the development of novel therapeutics. Among the pathways, sialyl Lewis x and the activin type II receptor are potential druggable candidates.

Conclusions

Integrative MR analyses of the blood proteins identified causally-associated proteins with HF and revealed pleiotropy of the blood proteome with cardiovascular risk factors. Some of the proteins or pathway related mechanisms could be targeted as novel treatment approach in HF.
Effects of N and P enrichment on plant photosynthetic traits in alpine steppe of the Qinghai-Tibetan Plateau
Authors: Shen Hao , Dong Shikui , Xiao Jiannan , Zhi Yangliu
Published: August 2022

Background

N (nitrogen) and P (phosphorus) play important roles in plant growth and fitness, and both are the most important limiting factors that affect grassland structure and function. However, we still know little about plant physiological responses to N and P enrichment in alpine grassland of the Qinghai-Tibetan Plateau. In our experiment, five dominant common herbaceous species were selected and their photosynthetic parameters, leaf N content, and aboveground biomass were measured.

Results

We found that species-specific responses to N and P enrichment were obvious at individual level. N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1, simultaneously) significantly promoted net photosynthetic rate of Leymus secalinus. Differential responses also existed in the same functional groups. Responses of forb species to the nutrients addition varied, Aconitum carmichaeli was more sensitive to nutrients addition including N addition (72 kg Nha−1 yr−1), P addition (36 kg Pha−1 yr−1) and NP addition (72 kg Nha−1 yr−1and 36 kg P ha−1 yr−1). Responses of plant community photosynthetic traits were not so sensitive as those of plant individuals under N and P enrichment.

Conclusions

Our findings highlighted that photosynthetic responses of alpine plants to N and P enrichment were species-specific. Grass species Leymus secalinus had a higher competitive advantage compared with other species under nutrient enrichment. Additionally, soil pH variation and nutrients imbalance induced by N and P enrichment is the main cause that affect photosynthetic traits of plant in alpine steppe of the Qinghai-Tibetan Plateau.
Cortical symptoms described in emergency calls for patients with suspected large vessel occlusion: a descriptive analysis of 157 emergency calls
Authors: Vuorinen Pauli , Kiili Joonas , Alanko Essi , Huhtala Heini , Ollikainen Jyrki , Setälä Piritta , Hoppu Sanna
Published: August 2022

Background

Emergency medical dispatchers typically use the dispatch code for suspected stroke when the caller brings up one or more symptoms from the face-arm-speech triad. Paramedics and emergency department physicians are trained to suspect large vessel occlusion stroke when the stroke patient presents with hemiparesis and cortical symptoms: neglect, aphasia, and conjugate eye deviation (CED). We hypothesized that these symptoms could be evident in the emergency call.

In this study, we aimed to describe common symptoms mentioned in the emergency calls for paramedic-suspected thrombectomy candidates. Secondly, we wanted to explore how the question about CED arises in the Finnish suspected stroke dispatch protocol. Our third aim was to find out if the symptoms brought up in suspected stroke and non-stroke dispatches differed from each other.

Methods

This was a retrospective study with a descriptive analysis of emergency calls for patients with paramedic-suspected large vessel occlusion stroke. We listened to the emergency calls for 157 patients transported to Tampere University Hospital, a Finnish comprehensive stroke centre. Two researchers listened for symptoms brought up in these calls and filled out a pre-planned case report form.

Results

Speech disturbance was the most common symptom brought up in 125 (80%) calls. This was typically described as an inability to speak any words (n = 65, 52% of calls with speech disturbance). Other common symptoms were falling down (n = 63, 40%) and facial asymmetry (n = 41, 26%). Suspicion of stroke was mentioned by 44 (28%) callers. When the caller mentioned unconsciousness the emergency dispatcher tended to use a non-stroke dispatch code. The dispatchers adhered poorly to the protocol and asked about CED in only 57% of suspected stroke dispatches. We found CED in 12 emergency calls and ten of these patients were diagnosed with large vessel occlusion.

Conclusion

In cases where paramedics suspected large vessel occlusion stroke, typical stroke symptoms were described during the emergency call. Speech disturbance was typically described as inability to say anything. It is possible to further develop suspected stroke dispatch protocols to recognize thrombectomy candidates from ischemic cortical signs such as global aphasia and CED.
Feasibility of quantification based on novel evaluation with stool DNA and fecal immunochemical test for colorectal cancer detection
Authors: Xu Hongli , Chen Huixin , Hu Junjie , Xiong Zhiguo , Li Dongqing , Wang Shun , Yu Jing
Published: August 2022

Background

Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China.

Methods

Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring.

Results

The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (< 165) at after surgery.

Discussion

The novel evaluation with sDNA test and FIT has increased sensitivity for screening of CRC and AA. The novel evaluation may have potential importance as an indicator of early CRC. Additionally, the dynamic changes of the comprehensive value after surgery were correlated with CRC treatment.
Systematic transcriptome profiling of pyroptosis related signature for predicting prognosis and immune landscape in lower grade glioma
Authors: Yu Huihan , Gong Meiting , Qi Jian , Zhao Chenggang , Niu Wanxiang , Sun Suling , Li Shuyang , Hong Bo , Qian Junchao , Wang Hongzhi , Chen Xueran , Fang Zhiyou
Published: August 2022

Background

Pyroptosis is a programmed cell death mediated by the gasdermin superfamily, accompanied by inflammatory and immune responses. Exogenously activated pyroptosis is still not well characterized in the tumor microenvironment. Furthermore, whether pyroptosis-related genes (PRGs) in lower-grade glioma (LGG) may be used as a biomarker remains unknown.

Methods

The RNA-Sequencing and clinical data of LGG patients were downloaded from publicly available databases. Bioinformatics approaches were used to analyze the relationship between PRGs and LGG patients’ prognosis, clinicopathological features, and immune status. The NMF algorithm was used to differentiate phenotypes, the LASSO regression model was used to construct prognostic signature, and GSEA was used to analyze biological functions and pathways. The expression of the signature genes was verified using qRT-PCR. In addition, the L1000FWD and CMap tools were utilized to screen potential therapeutic drugs or small molecule compounds and validate their effects in glioma cell lines using CCK-8 and colony formation assays.

Results

Based on PRGs, we defined two phenotypes with different prognoses. Stepwise regression analysis was carried out to identify the 3 signature genes to construct a pyroptosis-related signature. After that, samples from the training and test cohorts were incorporated into the signature and divided by the median RiskScore value (namely, Risk-H and Risk-L). The signature shows excellent predictive LGG prognostic power in the training and validation cohorts. The prognostic signature accurately stratifies patients according to prognostic differences and has predictive value for immune cell infiltration and immune checkpoint expression. Finally, the inhibitory effect of the small molecule inhibitor fedratinib on the viability and proliferation of various glioma cells was verified using cell biology-related experiments.

Conclusion

This study developed and validated a novel pyroptosis-related signature, which may assist instruct clinicians to predict the prognosis and immunological status of LGG patients more precisely. Fedratinib was found to be a small molecule inhibitor that significantly inhibits glioma cell viability and proliferation, which provides a new therapeutic strategy for gliomas.
Normal gastrointestinal mucosa at biopsy and subsequent cancer risk: nationwide population-based, sibling-controlled cohort study
Authors: Sun Jiangwei , Fang Fang , Olén Ola , Song Mingyang , Halfvarson Jonas , Roelstraete Bjorn , Khalili Hamed , Ludvigsson Jonas F.
Published: August 2022

Background

While individuals with normal gastrointestinal (GI) mucosa on endoscopy have a lower risk of colorectal cancer, risks of other cancers remain unexplored.

Methods

Through Sweden’s 28 pathology departments, we identified 415,092 individuals with a first GI biopsy with histologically normal mucosa during 1965–2016 and no prior cancer. These individuals were compared to 1,939,215 matched reference individuals from the general population. Follow-up began 6 months after biopsy, and incident cancer data were retrieved from the Swedish Cancer Register. Flexible parametric model was applied to estimate cumulative incidences and hazard ratios (HRs) for cancers. We also used full siblings (n = 441,534) as a secondary comparison group.

Results

During a median follow-up of 10.9 years, 40,935 individuals with normal mucosa (incidence rate: 82.74 per 10,000 person-years) and 177,350 reference individuals (incidence rate: 75.26) developed cancer. Restricting the data to individuals where follow-up revealed no cancer in the first 6 months, we still observed an increased risk of any cancer in those with a histologically normal mucosa (average HR = 1.07; 95%CI = 1.06–1.09). Although the HR for any and specific cancers decreased shortly after biopsy, we observed a long-term excess risk of any cancer, with an HR of 1.08 (95%CI = 1.05–1.12) and a cumulative incidence difference of 0.93% (95%CI = 0.61%-1.25%) at 30 years after biopsy. An elevated risk of gastric cancer, lung cancer, and hematological malignancy (including lymphoproliferative malignancy) was also observed at 20 or 30 years since biopsy. Sibling analyses confirmed the above findings.

Conclusion

Individuals with a histologically normal mucosa at biopsy and where follow-up revealed no cancer in the first 6 months, may still be at increased risk of cancer, although excess risks are small.
Psychometric property and measurement invariance of internet addiction test: the effect of socio-demographic and internet use variables
Authors: Lu Xi , Yeo Kee Jiar , Guo Fang , Zhao Zhenqing , Wu Ou
Published: August 2022

Background

According to the validation literature on items of Young’s Internet Addiction Test (IAT), this study rephrased disputable items to improve the psychometric properties of this Chinese version of IAT and identify the presence of differential item function (DIF) among demographic and Internet use factors; detect the effect of demographic and Internet use factors on IAT after adjusting for DIF.

Methods

An online questionnaire was distributed to college students in Zhe Jiang province in two stage. The 1st phase study collected 384 valid responses to examine the quality of IAT items by using Rasch Model analysis and exploring factor analysis (EFA). The online questionnaire was modified according to the 1st phase study and distributed online for the 2nd phase study which collected a total of 1131 valid responses. The 2nd phase study applied confirmatory factor analysis (CFA) and a multiple indicator multiple causes (MIMIC) model to verify the construct of IAT, potential effect of covariates on IAT latent factors, as well as the effect of differential item functioning (DIF).

Results

Rasch model analysis in the 1st phase study indicated a 5-point rating scale was performed better, no sever misfit was found on item. The overall property of Chinese version IAT with the 5-point scale was good to excellent person and item separation (2.66 and 6.86). A three-factor model was identified by EFA. In the 2nd phase study, IAT 13 were detected with DIF for gender in MIMIC model. After correcting DIF effect, the significant demographic and Internet use factors on IAT were time spent online per day, year 3, year 2, general users.

Conclusion

Item improvement was efficient that the problematic items found in literature was performed good in this study. The overall psychometric property of this Chinese version IAT was good with limited DIF effect in one item. Item improvement on IAT13 was encouraged in the future study to avoid gender bias and benefit for epidemiology on PIU.
Self-medication and ILI etiologies among individuals presenting at pharmacies with influenza-like illness: Guatemala City, 2018 influenza season
Authors: Ramay Brooke M. , Jara Jorge , Moreno Maria Purificación , Lupo Patrizia , Serrano Carlos , Alvis Juan P. , Arriola C. Sofia , Veguilla Vic , Kaydos-Daniels S. Cornelia
Published: August 2022

Objectives

We aimed to characterize the proportion of clients presenting to community pharmacies with influenza-like illness (ILI) and the severity of their illness; the proportion with detectable influenza A, influenza B, and other pathogens (i.e., parainfluenza I, II, and III, adenovirus, respiratory syncytial virus, human metapneumovirus); and to describe their self-medication practices.

Methods

A cross-sectional study was conducted in six pharmacies in Guatemala City. Study personnel collected nasopharyngeal and oropharyngeal swabs from participants who met the ILI case definition and who were self-medicating for the current episode. Participants were tested for influenza A and B and other pathogens using real-time RT-PCR. Participants’ ILI-associated self-medication practices were documented using a questionnaire.

Results

Of all patients entering the pharmacy during peak hours who responded to a screening survey (n = 18,016) 6% (n = 1029) self-reported ILI symptoms, of which 45% (n = 470/1029) met the study case definition of ILI. Thirty-one percent (148/470) met inclusion criteria, of which 87% (130/148) accepted participation and were enrolled in the study. Among 130 participants, nearly half tested positive for viral infection (n = 55, 42.3%) and belonged to groups at low risk for complications from influenza. The prevalence of influenza A was 29% (n = 35). Thirteen percent of the study population (n = 17) tested positive for a respiratory virus other than influenza. Sixty-four percent of participants (n = 83) reported interest in receiving influenza vaccination if it were to become available in the pharmacy. Medications purchased included symptom-relieving multi-ingredient cold medications (n = 43/100, 43%), nonsteroidal anti-inflammatory drugs (n = 23, 23%), and antibiotics (n = 16, 16%). Antibiotic use was essentially equal among antibiotic users regardless of viral status. The broad-spectrum antibiotics ceftriaxone and azithromycin were the most common antibiotics purchased.

Conclusions

During a typical influenza season, a relatively low proportion of all pharmacy visitors were experiencing influenza symptoms. A high proportion of clients presenting to pharmacies with ILI tested positive for a respiratory virus. Programs that guide appropriate use of antibiotics in this population are needed and become increasingly important during pandemics caused by respiratory viral pathogens.
Effectiveness of mechanical treatment with customized insole and minimalist flexible footwear for women with calcaneal spur: randomized controlled trial
Authors: Ribeiro Ana Paula , de Souza Brenda Luciano , João Silvia Maria Amado
Published: August 2022

Backround

Calcaneal spurs are described as bony outgrowths arising on medial calcaneal, where inappropriate footwear can promote disease progression.

Objective

Investigate the effectiveness of mechanical treatment with customized insole and minimalist flexible footwear during gait training program in women with calcaneal spur.

Methods

Design: A single-blinded, randomized and controlled trial. Setting: Biomechanics laboratory. Participants: Forty-three women, 29 with calcaneal spur and 14 control.

Intervention

Gait training program with use of the minimalist flexible footwear (MFGn = 15, age: 48.9 ± 9.4, height: 1.61 ± 0.1, BMI: 32.1 ± 7.0) and customized insole on footwear (COIGn = 14, age: 50.3 ± 5.8, height: 1.62 ± 0.1, BMI: 32.2 ± 4.3) and control (CGn = 14, age: 47.8 ± 8.6, height: 1.63 ± 0.1, BMI: 27.5 ± 4.5), followed of the evaluations: baseline (T0) and after three (T3) and six (T6) months. Duration of the intervention was of the six months consecutive for at least 42 h per week (six hours a day, seven days a week). Outcome primary were calcaneus pain (visual analogue scale), Foot Function Index (FFI), Foot Health Status Questionnaire (FHSQ-Br) and 6-min walk test (6MWT). Secondary was plantar pressure distribution by a pressure platform system during gait and static index foot posture (FPI). Statistical analysis: analysis of variance for repeated measure and between groups were used to detect treatment-time interactions (α = 5%). Effect size with D Cohen’s also was used between T0 and after six (T6) months of intervention.

Results

The MFG and COIG were effective at reducing pain after six months (MFG: 2.5–4.5 CI,p = 0.001; COIG: 1.5–3.5 CI,p = 0.011). The FFI and FHSQ-Br showed improvements with MFG and COIG after T6 (MFG: 13.7–15.4 CI,p = 0.010; COIG: 11.3–15.0 CI,p = 0.001). The 6MWT increased with MFG (589.3–622.7 CI) and COIG (401.3–644.7 CI) and foot pronation was decreased after T3 and T6 MFG (FPI Right: 4.2–5.4 CI; Left: 3.6–5.4 CI) COIG (FPI Right: 3.4–6.8 CI; Left: 3.3–5.7 CI). The contact area reduced on forefoot and rearfoot with MFG and GOIG and midfoot and rearfoot with MFG. Maximum force was reduced on foot with MFG after T3 and T6. The peak pressure was reduced on the forefoot with MFG and COIG and on midfoot and rearfoot with MFG.

Conclusions

The mechanical treatment with customized insole and minimalist flexible footwear during gait training program during six months in women with calcaneal spur reduced the calcaneus pain, increased function and health feet and reduced plantar load on the rearfoot, midfoot and forefoot. However, the footwear alone was more effective than when combined customized insole, given the greater efficacy on clinical and biomechanical aspects.

Trial registration

ClinicalTrials.govNCT03040557(date of first registration: 02/02/2017).
Establishing risk-based recall interval for caries management among 11-12-year-old Pakistani children
Authors: Taqi Muhammad , Razak Ishak Abdul , Ab-Murat Norintan , Zaidi Syed Jaffar Abbas
Published: August 2022

Background

This study aims to investigate the rate of caries increment among 11-12-year-old Pakistani children over 18 months using modified International Caries Detection and Assessment Systems II (ICDAS) and subsequently establish an appropriate dental recall interval for our targeted population according to their caries risk intensity.

Methods

A prospective longitudinal study was conducted in Bhakkar, Punjab, Pakistan. The 226 children from seven schools of Bhakkar with the highest student enrolment were conveniently selected. Caries risk assessment was performed using a computer-based reduced Cariogram program. Caries increment among cavitated lesions was measured by modified Beck's method or adjusted caries increment. Two ICDAS II cutoffs were created for the analysis of cavitated lesion (ICDAS code 3–6) and cavitated plus non-cavitated lesion (ICDAS code A-6).

Results

At the risk assessment stage, 39.8% of the children were classified as low risk, 30.5% as medium risk, and 29.7% as high risk. Caries increment at both cutoff points increased with caries risk at all follow-ups. The highest caries increment was recorded at the third follow-up among high-risk children at cutoff 3–6 (1.95 ± 3.18) and A-6 (4.01 ± 4.31). However, the lowest caries increment was recorded at the third follow-up among low-risk children at cutoff 3–6 (0.18 ± 1.42) and A-6 (1.11 ± 3.33).

Conclusion

Based on the study findings for Pakistani children with cavitated lesions, the recommended risk-based recall interval for caries management is 18 months for those with low and medium caries risk and six months for those with high caries risk. On the other hand, recommendations for risk-based recall intervals for caries management in non-cavitated and cavitated lesions are six months for low-risk, moderate risk and high-risk for Pakistani 11-12-year-old children.
Psychometric validation of the death literacy index and benchmarking of death literacy level in a representative uk population sample
Authors: Graham-Wisener Lisa , Toner Paul , Leonard Rosemary , Groarke Jenny M.
Published: August 2022

Background

Death literacy includes the knowledge and skills that people need to gain access to, understand, and make informed choices about end of life and death care options. The Death Literacy Index (DLI) can be used to determine levels of death literacy across multiple contexts, including at a community/national level, and to evaluate the outcome of public health interventions. As the first measure of death literacy, the DLI has potential to significantly advance public health approaches to palliative care. The current study aimed to provide the first assessment of the psychometric properties of the DLI in the UK, alongside population-level benchmarks.

Methods

A large nationally representative sample of 399 participants, stratified by age, gender and ethnicity, were prospectively recruited via an online panel. The factor structure of the 29-item DLI was investigated using confirmatory factor analysis. Internal consistency of subscales was assessed alongside interpretability. Hypothesised associations with theoretically related/unrelated constructs were examined to assess convergent and discriminant validity. Descriptive statistics were used to provide scaled mean scores on the DLI.

Results

Confirmatory factor analysis supported the original higher-order 8 factor structure, with the best fitting model including one substituted item developed specifically for UK respondents. The subscales reported high internal consistency. Good convergent and discriminant validity was evidenced in relation to objective knowledge of the death system, death competency, actions relating to death and dying in the community and loneliness. Good known-groups validity was achieved with respondents with professional/lived experience of end-of-life care reporting higher levels of death literacy. There was little socio-demographic variability in DLI scores. Scaled population-level mean scores were near the mid-point of DLI subscale/total, with comparatively high levels of experiential knowledge and the ability to talk about death and dying.

Conclusions

Psychometric evaluations suggest the DLI is a reliable and valid measure of death literacy for use in the UK, with population level benchmarks suggesting the UK population could strengthen capacity in factual knowledge and accessing help. International validation of the DLI represents a significant advancement in outcome measurement for public health approaches to palliative care.

Pre-registration

https://osf.io/fwxkh/
Digital health for emotional and self-management support of caregivers of children receiving growth hormone treatment: a feasibility study protocol
Authors: Cervera-Torres Sergio , Núñez-Benjumea Francisco José , de Arriba Muñoz Antonio , Chicchi Giglioli Irene Alice , Fernández-Luque Luis
Published: August 2022

Background

Caregivers of children undergoing growth hormone treatment often face stress and stigma. In this regard, family-centered approaches are increasingly considered, wherein caregivers’ mental wellbeing is taken into account to optimize children’s health-related outcomes and behaviors (e.g., treatment adherence). Here, mindfulness and parenting-based programs have been developed to support the mental wellbeing of caregivers and, in turn, promote richer interactions with the children. Nevertheless, this type of program can face drawbacks, such as the scheduling and availability of family members. Recent digital health (DH) solutions (e.g., mobile apps) are showing promising advantages as self-management support tools for improving wellbeing and behaviors related to the treatments. Although, further evidence is necessary in the field of Growth Hormone Treatment (GHt). Accordingly, this study aims to examine the usability of a mobile DH solution and the feasibility of a DH intervention designed to promote emotional and mental wellbeing of caregivers of children undergoing GHt.

Methods

This is a prospective mixed-methods (qualitative-quantitative) exploratory study composed of two sub-studies, including caregivers of children undergoing GHt. Sub-study one (SS1; n = 10) focuses on the usability of the DH solution (detecting potential barriers and facilitators) and an ad hoc semi-structured interview will be administered to the caregivers after using the DH solution for one month. Sub-study two (SS2; n = 55) aims to evaluate the feasibility of the DH intervention on caregivers’ perceived distress, positive affectivity, mental wellbeing, self-efficacy, together with the children’s quality of life and treatment adherence. All these parameters will be assessed via quantitative methods before and after 3-months of the DH intervention. Usability and engagement will also be assessed during and at the end of the study.

Results

It is expected that significant amounts of data will be captured with regards of the feasibility of the DH solution.

Discussion

The manuscript provides a complete protocol for a study that will include qualitative and quantitative information about, on one hand, the user-friendliness of the DH solution, and on the other, the effects on caregivers’ emotional, as well as, behavioral parameters in terms of the usability and engagement to the DH solution. The findings will contribute to the evidence planning process for the future adoption of digital health solutions for caregiver support and better health-related outcomes.

Trial registration ClinicalTrials.gov, ID: NCT04812665.
Fostering a just culture in healthcare organizations: experiences in practice
Authors: van Baarle Eva , Hartman Laura , Rooijakkers Sven , Wallenburg Iris , Weenink Jan-Willem , Bal Roland , Widdershoven Guy
Published: August 2022

Background

A just culture is regarded as vital for learning from errors and fostering patient safety. Key to a just culture after incidents is a focus on learning rather than blaming. Existing research on just culture is mostly theoretical in nature.

Aim

This study aims to explore requirements and challenges for fostering a just culture within healthcare organizations.

Methods

We examined initiatives to foster the development of a just culture in five healthcare organizations in the Netherlands. Data were collected through interviews with stakeholders and observations of project group meetings in the organizations.

Results

According to healthcare professionals, open communication is particularly important, paying attention to different perspectives on an incident. A challenge related to open communication is how to address individual responsibility and accountability. Next, room for emotions is regarded as crucial. Emotions are related to the direct consequences of incidents, but also to the response of the outside world, including the media and the health inspectorate.

Conclusions

A challenge in relation to emotions is how to combine attention for emotions with focusing on facts, both within and outside the organization. Finally, healthcare professionals attach importance to commitment and exemplary behavior of management. A challenge as a manager here is how to keep distance while also showing commitment. Another challenge is how to combine openness with privacy of the parties involved, and how to deal with less nuanced views in other layers of the organization and in the outside world. Organizing reflection on the experienced tensions may help to find the right balance.
High neutrophil to lymphocyte ratio with type 2 diabetes mellitus predicts poor prognosis in patients undergoing percutaneous coronary intervention: a large-scale cohort study
Authors: He Jining , Bian Xiaohui , Song Chenxi , Zhang Rui , Yuan Sheng , Yin Dong , Dou Kefei
Published: August 2022

Background

Inflammation plays a crucial role in the pathogenesis and progression of coronary artery disease (CAD). The neutrophil to lymphocyte ratio (NLR) is a novel inflammatory biomarker and its association with clinical outcomes in CAD patients with different glycemic metabolism after percutaneous coronary intervention (PCI) remains undetermined. Therefore, this study aimed to investigate the effect of NLR on the prognosis of patients undergoing PCI with or without type 2 diabetes mellitus (T2DM).

Methods

We consecutively enrolled 8,835 patients with CAD hospitalized for PCI at Fuwai hospital. NLR was calculated using the following formula: neutrophil (*109/L)/lymphocyte (*109/L). According to optimal cut-off value, study patients were categorized as higher level of NLR (NLR-H) and lower level of NLR (NLR-L) and were further stratified as NLR-H with T2DM and non-T2DM, and NLR-L with T2DM and non-T2DM. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), defined as all-cause mortality, myocardial infarction (MI), stroke and target vessel revascularization.

Results

A total of 674 (7.6%) MACCEs were recorded during a median follow-up of 2.4 years. The optimal cut-off value of NLR was 2.85 determined by the surv_cutpoint function. Compared to those in the NLR-H/T2DM groups, patients in the NLR-L/non-T2DM, NLR-H/non-T2DM and NLR-L/T2DM groups were at significantly lower risk of 2-year MACCEs [adjusted hazard ratio (HR): 0.67, 95% confidence interval (CI): 0.52 to 0.87, P = 0.003; adjusted HR: 0.62, 95%CI: 0.45 to 0.85, P = 0.003; adjusted HR: 0.77, 95%CI: 0.61 to 0.97, P = 0.025; respectively]. Remarkably, patients in the NLR-L/non-T2DM group also had significantly lower risk of a composite of all-cause mortality and MI than those in the NLR-H/T2DM group (adjusted HR: 0.57, 95%CI: 0.35 to 0.93, P = 0.024). Multivariable Cox proportional hazards model also indicated the highest risk of MACCEs in diabetic patients with higher level of NLR than others (P for trend = 0.009). Additionally, subgroup analysis indicated consistent impact of NLR on MACCEs across different subgroups.

Conclusions

Presence of T2DM with elevated NLR is associated with worse clinical outcomes in CAD patients undergoing PCI. Categorization of patients with elevated NLR and T2DM could provide valuable information for risk stratification of CAD patients.
The role of hexose transporter-like sensor hxs1 and transcription activator involved in carbohydrate sensing azf1 in xylose and glucose fermentation in the thermotolerant yeast Ogataea polymorpha
Authors: Semkiv Marta V. , Ruchala Justyna , Tsaruk Aksynia Y. , Zazulya Anastasiya Z. , Vasylyshyn Roksolana V. , Dmytruk Olena V. , Zuo MingXing , Kang Yingqian , Dmytruk Kostyantyn V. , Sibirny Andriy A.
Published: August 2022

Background

Fuel ethanol from lignocellulose could be important source of renewable energy. However, to make the process feasible, more efficient microbial fermentation of pentose sugars, mainly xylose, should be achieved. The native xylose-fermenting thermotolerant yeastOgataea polymorphais a promising organism for further development. Efficacy of xylose alcoholic fermentation byO. polymorphawas significantly improved by metabolic engineering. Still, genes involved in regulation of xylose fermentation are insufficiently studied.

Results

We isolated an insertional mutant ofO.polymorphawith impaired ethanol production from xylose. The insertion occurred in the geneHXS1that encodes hexose transporter-like sensor, a close homolog ofSaccharomyces cerevisiaesensors Snf3 and Rgt2. The role of this gene in xylose utilization and fermentation was not previously elucidated. We additionally analyzedO.polymorphastrains with the deletion and overexpression of the corresponding gene. Strains with deletion of theHXS1gene had slower rate of glucose and xylose consumption and produced 4 times less ethanol than the wild-type strain, whereas overexpression ofHXS1led to 10% increase of ethanol production from glucose and more than 2 times increase of ethanol production from xylose. We also constructed strains ofO.polymorphawith overexpression of the geneAZF1homologous toS. cerevisiae AZF1gene which encodes transcription activator involved in carbohydrate sensing. Such transformants produced 10% more ethanol in glucose medium and 2.4 times more ethanol in xylose medium. Besides, we deleted theAZF1gene inO. polymorpha. Ethanol accumulation in xylose and glucose media in such deletion strains dropped 1.5 and 1.8 times respectively. Overexpression of theHXS1andAZF1genes was also obtained in the advanced ethanol producer from xylose. The corresponding strains were characterized by 20–40% elevated ethanol accumulation in xylose medium. To understand underlying mechanisms of the observed phenotypes, specific enzymatic activities were evaluated in the isolated recombinant strains.

Conclusions

This paper shows the important role of hexose sensor Hxs1 and transcription factor Azf1 in xylose and glucose alcoholic fermentation in the native xylose-fermenting yeastO. polymorphaand suggests potential importance of the corresponding genes for construction of the advanced ethanol producers from the major sugars of lignocellulose.
Coupling analysis of population aging and economic growth with spatial-temporal variation: a case study in China
Authors: Wang Shaobin , Ren Zhoupeng , Xiao Zhuoyao , Wang Na , Yang Hao , Pu Haixia
Published: August 2022

Background

China now faces an increasingly aging society which may exert economic pressure in the long run. This study illustrates the spatial pattern and evolution of population aging and economic development in China. The coupling coordination degree of population aging and economic development at the national and provincial levels are calculated and demonstrated, and the spatial patterns and characteristics are investigated.

Methods

This paper presents a coupling analysis of the elderly population rate (EPR) and per capita Gross Regional Product (GRPpc) in China by using the coupling and coordination model. Further, the spatial pattern and evolution of population aging and economic development are investigated based on the standard deviational ellipse. The collected data is at the level of provincial administrative units in mainland China covering the period 2002 to 2020.

Results

The results reveal the spatial difference in the coupling and coordination degree between EPR and GRPpc across provinces. The eastern coastal areas are higher than the central and western regions of China. The orientation and directions of EPR are more than GRPpc, indicating that the polarization in population aging is more severe than economic development. Significant positive correlations between coupling coordination degree and sustainable competitiveness are detected.

Conclusions

Policymakers should fully consider regional differences and sustainable development in policy formulation of China. The western and northeastern provinces should be given priority in the regional sustainable development plan. At the same time, the coordination between population aging and economic development also requires to be examined especially.
Immunotherapy for type 1 diabetes mellitus by adjuvant-free Schistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP)
Authors: Huang Haoming , Hu Dian , Chen Zhuo , Xu Jiarong , Xu Rengui , Gong Yusheng , Fang Zhengming , Wang Ting , Chen Wei
Published: August 2022

Background

Type 1 diabetes mellitus (T1DM) is an autoimmune disease mediated by autoreactive T cells and dominated by Th1 response polarization. Insulin replacement therapy faces great challenges to this autoimmune disease, requiring highly frequent daily administration. Intriguingly, the progression of T1DM has proven to be prevented or attenuated by helminth infection or worm antigens for a relatively long term. However, the inevitable problems of low safety and poor compliance arise from infection with live worms or direct injection of antigens. Microneedles would be a promising candidate for local delivery of intact antigens, thus providing an opportunity for the clinical immunotherapy of parasitic products.

Methods

We developed aSchistosoma japonicum-egg tip-loaded asymmetric microneedle patch (STAMP) system, which serves as a new strategy to combat TIDM. In order to improve retention time and reduce contamination risk, a specific imperfection was introduced on the STAMP (asymmetric structure), which allows the tip to quickly separate from the base layer, improving reaction time and patient’s comfort. After loadingSchistosoma japonicum-egg as the immune regulator, the effects of STAMP on blood glucose control and pancreatic pathological progression improvement were evaluated in vivo. Meanwhile, the immunoregulatory mechanism and biosafety of STAMP were confirmed by histopathology, qRT-PCR, ELISA and Flow cytometric analysis.

Results

Here, the newly developed STAMP was able to significantly reduce blood glucose and attenuate the pancreatic injury in T1DM mice independent of the adjuvants. The isolatedSchistosoma japonicum-eggs micron slowly degraded in the skin and continuously released egg antigen for at least 2 weeks, ensuring localization and safety of antigen stimulation. This phenomenon should be attributed to the shift of Th2 immune response to reduce Th1 polarization.

Conclusion

Our results exhibited that STAMP could significantly regulate the blood glucose level and attenuate pancreatic pathological injury in T1DM mice by balancing the Th1/Th2 immune responses, which is independent of adjuvants. This technology opens a new window for the application of parasite products in clinical immunotherapy.
How does academia respond to the burden of infectious and parasitic disease?
Authors: Zhao Wenjing , Wang Lili , Zhang Lin
Published: August 2022

Background

Academic research is one of the main avenues through which humans can fight the threat of infectious diseases. However, there have been concerns regarding whether the academic system has provided sufficient efforts to fight infectious diseases we potentially face. Answering these questions could contribute to evidence-based recommendations for setting research priorities and third-mission policies.

Methods

With a focus on one of the most common categories of communicable diseases, infectious and parasitic diseases (IPDs), we searched Web of Science for articles and reviews relevant to IPDs published during the period 2000–2019 and retrieved WHO data on disease burden in corresponding years. The academic response patterns were explored by IPD subcategory and by human development level (an index established by the United Nations). We conduct the analysis in particular to gain insight into the dynamic relationship between disease burden and research effort on IPDs, scientific efforts contributed by countries with different development levels, and the variation trends in international joint efforts.

Results

The greatest burden of IPDs is clustered in the developing regions of Africa, but has received academic response from both developed and developing countries. Highly developed countries dominate the ranks of academic research in this area, yet there is also a clear increase in research efforts from the countries most affected, despite their low human development scale. In fact, the overall analysis reveals an improved capability for addressing local problems from African regions. In terms of international collaboration, highly developed countries such as the United States and United Kingdom have commonly collaborated with needy regions, whereas prolific but developing nations, like China, have not.

Conclusions

From a global perspective, academia has positively responded to health needs caused by IPDs. Although the relevant research output contribution is primarily from the highly developed countries, concentrated and specialized efforts from the undeveloped regions to ease their local burden can be clearly observed. Our findings also indicate a tendency to focus more on local health needs for both developed and undeveloped regions. The insights revealed in this study should benefit a more informed and systemic plan of research priorities.
Characteristics and genetic analysis of patients suspected with early-onset systemic lupus erythematosus
Authors: Lee Wan-Fang , Fan Wen-Lang , Tseng Min-Hua , Yang Huang-Yu , Huang Jing-Long , Wu Chao-Yi
Published: August 2022

Background

Systemic lupus erythematosus (SLE) is rarely diagnosed before 5-years-old. Those with disease onset at a very young age are predicted by a higher genetic risk and a more severe phenotype. We performed whole-exome sequencing to survey the genetic etiologies and clinical manifestations in patients fulfilling 2012 SLICC SLE classification criteria before the age of 5.

Case presentation

Among the 184 childhood-onset SLE patients regularly followed in a tertiary medical center in Taiwan, 7 cases (3.8%) of which onset ≦ 5 years of age were identified for characteristic review and genetic analysis. Compared to those onset at elder age, cases onset before the age of 5 are more likely to suffer from proliferative glomerulonephritis, renal thrombotic microangiopathy, neuropsychiatric disorder and failure to thrive. Causative genetic etiologies were identified in 3. In addition to the abundance of autoantibodies, patient with homozygous TREX1 (c.292_293 ins A) mutation presented with chilblain-like skin lesions, peripheral spasticity, endocrinopathy and experienced multiple invasive infections. Patient with SLC7A7 (c.625 + 1 G > A) mutation suffered from profound glomerulonephritis with full-house glomerular deposits as well as hyperammonemia, metabolic acidosis and episodic conscious disturbance. Two other cases harbored variants in lupus associating genes C1s, C2, DNASE1 and DNASE1L3 and another with CFHR4. Despite fulfilling the classification criteria for lupus, many of the patients required treatments beyond conventional therapy.

Conclusions

Genetic etiologies and lupus mimickers were found among a substantial proportion of patients suspected with early-onset SLE. Detail clinical evaluation and genetic testing are important for tailored care and personalized treatment.