bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the wood processing method of helium-assisted laser process
Authors: Yang Chunmei , Tian Xinchi , Xue Bo , Liu Qingwei , Zhang Jiawei , Liu Jiuqing , Yu Wenji
Published: August 2022

In order to promote the development of environmental protection, and the usage rate of green energy utilization, a progressive, innovative laser process method employing helium assisted is proposed, which optimizes the joint cutting process under the same energy consumption. This method provides a new idea for the wood process industry. The uniqueness of this paper establishes a mathematical model to address the diffusion of helium injection and the heat transfer of the laser beam on the processed surface. From the results, it can be exhibited that the oxygen concentration reduces when the helium is injected on the processed surface. The helium could destroy the combustion-supporting conditions and decrease the combustion zone of the processed joint cutting. Thus, the carbonized area of the processed surface is reduced, which could effectively enhance the processing quality of joint cutting. Notably, the helium with injection speed forms a sweeping effect on the processed surface, which could remove parts of the carbonized particles and residues on the processed surface, as well as improve the processing quality. Comparing the traditional laser process and helium-assisted laser process, the gas-assisted laser process owns higher process quality than that of traditional laser processing and cutting. In detail, it features the advantages of smaller joint cutting width, lower surface roughness and smoother surface. Eventually, a mathematical model based on the response surface method with the evaluation criteria of the kerf width, kerf depth, and surface roughness is established to analyze the interaction of laser power, cutting speed and inert gas pressure on the response factors. Comparing the error between the predicted and experimental measurement value, and the optimized process parameters could be acquired. In this paper, the helium-assisted laser process method proposed is meaningful and encouraging, which not only obtains better processing quality, but also provides a guide for developing green industry.
EEG resting-state functional connectivity: evidence for an imbalance of external/internal information integration in autism
Authors: Wantzen Prany , Clochon Patrice , Doidy Franck , Wallois Fabrice , Mahmoudzadeh Mahdi , Desaunay Pierre , Christian Mille , Guilé Jean-Marc , Guénolé Fabian , Eustache Francis , Baleyte Jean-Marc , Guillery-Girard Bérengère
Published: August 2022

Background

Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD.

Methods

Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched).

Results

We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band.

Conclusion

These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts.
Association between short-term exposure to air pollution and COVID-19 mortality in all German districts: the importance of confounders
Authors: Miller Gregor , Menzel Annette , Ankerst Donna P.
Published: August 2022

Background

The focus of many studies is to estimate the effect of risk factors on outcomes, yet results may be dependent on the choice of other risk factors or potential confounders to include in a statistical model. For complex and unexplored systems, such as the COVID-19 spreading process, where a priori knowledge of potential confounders is lacking, data-driven empirical variable selection methods may be primarily utilized. Published studies often lack a sensitivity analysis as to how results depend on the choice of confounders in the model. This study showed variability in associations of short-term air pollution with COVID-19 mortality in Germany under multiple approaches accounting for confounders in statistical models.

Methods

Associations between air pollution variables PM2.5, PM10, CO, NO, NO2, and O3 and cumulative COVID-19 deaths in 400 German districts were assessed via negative binomial models for two time periods, March 2020–February 2021 and March 2021–February 2022. Prevalent methods for adjustment of confounders were identified after a literature search, including change-in-estimate and information criteria approaches. The methods were compared to assess the impact on the association estimates of air pollution and COVID-19 mortality considering 37 potential confounders.

Results

Univariate analyses showed significant negative associations with COVID-19 mortality for CO, NO, and NO2, and positive associations, at least for the first time period, for O3 and PM2.5. However, these associations became non-significant when other risk factors were accounted for in the model, in particular after adjustment for mobility, political orientation, and age. Model estimates from most selection methods were similar to models including all risk factors.

Conclusion

Results highlight the importance of adequately accounting for high-impact confounders when analyzing associations of air pollution with COVID-19 and show that it can be of help to compare multiple selection approaches. This study showed how model selection processes can be performed using different methods in the context of high-dimensional and correlated covariates, when important confounders are not known a priori. Apparent associations between air pollution and COVID-19 mortality failed to reach significance when leading selection methods were used.
Development and validation of a predictive model for adverse left ventricular remodeling in NSTEMI patients after primary percutaneous coronary intervention
Authors: Wang Lili , Liu Tao , Wang Chaofan , Xuan Haochen , Xu Xianzhi , Yin Jie , Li Xiaoqun , Chen Junhong , Li Dongye , Xu Tongda
Published: August 2022

Introduction

To develop and validate clinical evaluators that predict adverse left ventricular remodeling (ALVR) in non-ST-elevation myocardial infarction (NSTEMI) patients after primary percutaneous coronary intervention (PCI).

Methods

The retrospective study analyzed the clinical data of 507 NSTEMI patients who were treated with primary PCI from the Affiliated Hospital of Xuzhou Medical University and the Second Affiliated Hospital of Xuzhou Medical University, between January 1, 2019 and September 31, 2021. The training cohort consisted of patients admitted before June 2020 (n = 287), and the remaining patients (n = 220) were assigned to an external validation cohort. The endpoint event was the occurrence of ALVR, which was described as an increase ≥ 20% in left ventricular end-diastolic volume (LVEDV) at 3–4 months follow-up CMR compared with baseline measurements. The occurrence probability of ALVR stemmed from the final model, which embodied independent predictors recommended by logistic regression analysis. The area under the receiver operating characteristic curve (AUC), Calibration plot, Hosmer–Lemeshow method, and decision curve analysis (DCA) were applied to quantify the performance.

Results

Independent predictors for ALVR included age (odds ratio (OR): 1.040; 95% confidence interval (CI): 1.009–1.073), the level of neutrophil to lymphocyte ratio (OR: 4.492; 95% CI: 1.906–10.582), the cardiac microvascular obstruction (OR: 3.416; 95% CI: 1.170–9.970), peak global longitudinal strain (OR: 1.131; 95% CI: 1.026–1.246), infarct size (OR: 1.082; 95% CI: 1.042–1.125) and left ventricular ejection fraction (OR: 0.925; 95% CI: 0.872–0.980), which were screened by regression analysis then merged into the nomogram model. Both internal validation (AUC: 0.805) and external validation (AUC: 0.867) revealed that the prediction model was capable of good discrimination. Calibration plot and Hosmer–Lemeshow method showed high consistency between the probabilities predicted by the nomogram (P = 0.514) and the validation set (P = 0.762) and the probabilities of actual occurrence. DCA corroborated the clinical utility of the nomogram.

Conclusions

In this study, the proposed nomogram model enabled individualized prediction of ALVR in NSTEMI patients after reperfusion and conduced to guide clinical therapeutic schedules.
The impact of clinical experience on working tasks and job-related stress: a survey among 1032 Norwegian GPs
Authors: Johnsen Tor Magne , Norberg Børge Lønnebakke , Krogh Frode Helgetun , Vonen Hanne Dahl , Getz Linn Okkenhaug , Austad Bjarne
Published: August 2022

Background

General practice is a generalist discipline fraught with complexity. For inexperienced physicians, it may be demanding to get to grips with the clinical challenges. The purpose of this article is to describe possible differences in the range of tasks between inexperienced and experienced general practitioners (GPs), and the extent to which clinical experience affects the way in which GPs perceive their daily work.

Methods

An online questionnaire was sent to all regular GPs in Norway (N = 4784) in 2018. The study sought to document the tasks performed during a typical working day and how the GPs perceived their working situation. In this study, we compare the tasks, working situation and occurrence of potentially conflictual consultations among ‘less experienced physicians’ (≤ 5 years of experience in general practice) versus ‘more experienced physicians’ (> 5 years of experience). The findings are discussed in light of theories on development of expertise.

Results

We received responses from 1032 GPs; 296 (29%) were less experienced and 735 (71%) more experienced. The two groups reported virtually the same number of consultations (19.2 vs. 20.5) and clinical problems handled (40.4 vs. 44.2) during the study day. The less experienced physicians reported a higher proportion of challenging and/or conflictual consultations, involving prescriptions for potentially addictive medication (5.7% vs. 3.1%), sickness certification (4.1% vs. 2.4%) and referral for medical investigations on weak clinical indication (8.1% vs. 5.6%). For other clinical issues there were minor or no differences. Both GP groups reported high levels of work-related stress with negative effect on self-perceived health (61.6% vs 64.6%). GPs who felt that high job demands harmed their health tended to handle a slightly higher number of medical issues per consultation and more consultations with elements of conflict.

Conclusions and implications

Inexperienced GPs in Norway handle a workload comparable to that of experienced GPs, but they perceive more conflictual consultations. These findings have relevance for training and guidance of future GP specialists. Irrespective of experience, the GPs report such high levels of negative work-related stress as to indicate an acute need for organisational changes that imply a reduced workload.
Development of a core outcome set for the evaluation of interventions to prevent COVID-19 in care homes (COS-COVID-PCARE Study)
Authors: Shepherd Victoria , Islam Ishrat , Wood Fiona , Williamson Paula R. , Goodman Claire , Bath Philip M. , Thompson Carl , Knapp Martin , Gordon Adam L. , Hood Kerenza
Published: August 2022

Background

People living in care homes have experienced devastating impact from COVID-19. As interventions to prevent the transmission of COVID-19 are developed and evaluated, there is an urgent need for researchers to agree on the outcomes used when evaluating their effectiveness. Having an agreed set of outcomes that are used in all relevant trials can ensure that study results can be compared.

Objective

The aim of the study was to develop a core outcome set (COS) for trials assessing the effectiveness of pharmacological and non-pharmacological interventions for preventing COVID-19 infection and transmission in care homes.

Methods

The study used established COS methodology. A list of candidate outcomes was identified by reviewing registered trials to evaluate interventions to prevent COVID-19 in care homes. Seventy key stakeholders participated in a Delphi survey, rating the candidate outcomes on a nine-point scale over two rounds, with the opportunity to propose additional outcomes. Stakeholders included care home representatives (n = 19), healthcare professionals (n = 20), people with personal experience of care homes (n = 7), researchers (n = 15) and others (n = 9). Outcomes were eligible for inclusion if they met an a priori threshold. A consensus meeting with stakeholders resulted in agreement of the final outcome set.

Results

Following the Delphi and consensus meeting, twenty-four outcomes were recommended for inclusion. These are grouped across four domains of infection, severity of illness, mortality, and ‘other’ (intervention specific or life impact). Due to the considerable heterogeneity between care homes, residents, and interventions, the relevance and importance of outcomes may differ between trial contexts. Intervention-specific outcomes would be included only where relevant to a given trial, thus reducing the measurement burden.

Conclusion

Using a rapid response approach, a COS for COVID-19 prevention interventions in care homes has been developed. Future work should focus on identifying instruments for measuring these outcomes, and the interpretation and application of the COS across different trial contexts. Beyond COVID-19, the outcomes identified in this COS may have relevance to other infectious diseases in care homes, and the rapid response approach may be useful as preparation for future pandemics.
An evaluation of a community-based vision care programme for the elderly
Authors: Yang She Chiu , Law Tsz Kin , Leung Yan Lok Lucas , Tam Yim Ying , Sum Rita , Lian Jinxiao , Yap Maurice
Published: August 2022

Background

This study evaluated the real-world effectiveness and potential cost-effectiveness of a community-based vision care programme for the elderly population aged 60 years or above.

Methods

Data from a total of 8899 subjects participating in a community-based comprehensive vision care programme from 2015 to 2019 were analysed to evaluate the effectiveness of the programme in terms of the prevalence of distance visual impairment (VI), the change in the prevalence of distance VI after refractive error correction, and the types of ocular disorders suspected. Distance VI was defined as a) visual acuity (VA) worse than 6/18 in any eye (worse eye) and b) VA worse than 6/18 in the better eye. The cost-effectiveness from the funder’s perspective was also estimated in terms of cost per distance VI avoided.

Results

Based on the presenting vision of the worse eye, the prevalence of distance VI was 39.1% (3482/8899, 95% CI: 38.1%-40.1%) and reduced to 13.8% (1227/8899, 95% CI: 13.1%-14.5%) based on best-corrected VA. Referenced to the presenting vision of the better eye, the prevalence of distance VI was 17.3% (1539/8899, 95% CI: 16.5%-18.1%) and decreased to 4.2% (373/8899, 95% CI: 3.8%-4.6%) with best optical correction. Uncorrected refractive error was the major cause of presenting distance VI. From the funder’s perspective, the cost per distance VI case prevented was HK$1921 based on VA in the worse eye and HK$3715 based on the better eye.

Conclusion

This community-based programme identified distance VI in the best eye of 17 out of every 100 subjects. With appropriate new or updated distance optical corrections, distance VI was reduced to about 4 in 100 subjects. Visual impairment in the elderly is common even in a relatively affluent city. A model of care which could minimise avoidable distance VI would bring benefits at individual and societal levels.
Exosome-derived lnc-HOXB8-1:2 induces tumor-associated macrophage infiltration to promote neuroendocrine differentiated colorectal cancer progression by sponging hsa-miR-6825-5p
Authors: Li Xiaojun , Lan Qiusheng , Lai Wei , Wu Heng , Xu Heyang , Fang Kai , Chu Zhonghua , Zeng Yujie
Published: August 2022

Introduction

Neuroendocrine differentiation (NED) in colorectal cancer (CRC) cells has been known for decades, and our previous meta-analysis indicated that CRC patients with neuroendocrine differentiation have a lower 5-year survival rate. In recent years, an increasing number of studies have found that exosome-derived long non-coding RNAs (lncRNAs) play important roles in cancer progression and metastasis. However, the functions and mechanism of exosome-derived lncRNAs in CRC with neuroendocrine differentiation are not yet fully clear.

Materials and methods

The clinical significance of NED was assessed in a retrospective study of 105 patients. Next-generation sequencing and bioinformatics analysis were conducted to select lnc-HOXB8-1:2 for further study. Using immunohistochemistry, qRT–PCR, western blot, transwell assay, immunofluorescence assay, fluorescence in situ hybridization assay and dual-luciferase reporter assay, the oncogenic role of exosome-derived lnc-HOXB8-1:2 was determined in CRC with NED. The mechanism underlying the lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was also explored.

Results

NED was a risk factor for the progression and mortality of CRC. lnc-HOXB8-1:2, derived from exosomes secreted by neuroendocrine differentiated colon cancer cells, was identified in our study. The proportion of M2 macrophages and the migration and invasion capacities of tumor-associated macrophages (TAMs) markedly increased after the addition of neuroendocrine differentiated CRC cell-derived exosomes. More excitingly, the expression of lnc-HOXB8-1:2 and the protein level of CXCR3 were also upregulated in TAMs. The lnc-HOXB8-1:2/hsa-miR-6825-5p/CXCR3 axis was predicted via miRanda software and confirmed by the dual-luciferase reporter assay. Furthermore, the increased expression of lnc-HOXB8-1:2 was accompanied by downregulation of hsa-miR-6825-5p expression and upregulation of CXCR3 protein levels. Overexpression of hsa-miR-6825-5p also reduced CXCR3 expression.

Conclusion

lnc-HOXB8-1:2 in exosomes derived from neuroendocrine differentiated CRC cells acted as a ceRNA competitively binding hsa-miR-6825-5p to upregulate CXCR3 expression and leading to TAM infiltration and M2 polarization, which promotes neuroendocrine differentiated CRC progression.
Healthcare vulnerability disparities in pancreatic cancer treatment and mortality using the Korean National Sample Cohort: a retrospective cohort study
Authors: Jeong Sung Hoon , Lee Hyeon Ji , Yun Choa , Yun Il , Jung Yun Hwa , Kim Soo Young , Lee Hee Seung , Jang Sung-In
Published: August 2022

Background

The gap in treatment and health outcomes after diagnosis of pancreatic cancer is a major public health concern. We aimed to investigate the differences in the health outcomes and treatment of pancreatic cancer patients in healthcare vulnerable and non-vulnerable areas.

Methods

This retrospective cohort study evaluated data from the Korea National Health Insurance Corporation-National Sample Cohort from 2002 to 2019. The position value for relative comparison index was used to define healthcare vulnerable areas. Cox proportional hazard regression was used to estimate the risk of mortality in pancreatic cancer patients according to healthcare vulnerable areas, and multiple logistic regression was used to estimate the difference in treatment.

Results

Among 1,975 patients, 279 (14.1%) and 1,696 (85.9%) lived in the healthcare vulnerable and non-vulnerable areas, respectively. Compared with the non-vulnerable area, pancreatic cancer patients in the vulnerable area had a higher risk of death at 3 months (hazard ratio [HR]: 1.33, 95% confidence interval [CI] = 1.06–1.67) and 6 months (HR: 1.23, 95% CI = 1.03–1.48). In addition, patients with pancreatic cancer in the vulnerable area were less likely to receive treatment than patients in the non-vulnerable area (odds ratio [OR]: 0.70, 95% CI = 0.52–0.94). This trend was further emphasized for chemotherapy (OR: 0.68, 95% CI = 0.48–0.95).

Conclusion

Patients with pancreatic cancer belonging to medically disadvantaged areas receive less treatment and have a higher risk of death. This may be a result of the late diagnosis of pancreatic cancer among these patients.
Theoretical attributable risk analysis and Disability Adjusted Life Years (DALYs) based on increased dairy consumption
Authors: Cohen Sarah S. , Bylsma Lauren C. , Movva Naimisha , Alexander Dominik D.
Published: August 2022

Background

Identification of modifiable risk factors that may impact chronic disease risk is critical to public health. Our study objective was to conduct a theoretical population attributable risk analysis to estimate the burden of disease from low dairy intake and to estimate the impact of increased dairy intake on United States (US)-based disability adjusted life years (DALYs).

Methods

We conducted a comprehensive literature review to identify statistically significant summary relative risk estimates (SRREs) from recent meta-analyses of dairy consumption and key chronic disease outcomes. The SRREs were applied to preventive fractions using a range of categories (low to high) for population consumption of dairy products. The preventive fraction estimates were then applied to the number of DALYs for each health outcome in the US based on 2019 WHO estimates. The population attributable risk proportion estimates were calculated using the inverse of the SRRE from each meta-analysis using the same range of categories of consumption. These values were subsequently applied to the DALYs estimates to estimate the theoretical burden of disease attributable to low dairy intake.

Results

Statistically significant SRREs were identified in recent meta-analyses of total dairy consumption in relation to breast cancer, colorectal cancer, cardiovascular disease (CVD), type 2 diabetes (T2D), stroke, and hypertension. In this theoretical analysis, nearly 850,000 DALYs (or 5.0% of estimated years of healthy life lost) due to CVD and 200,000 DALYs (4.5%) due to T2D may be prevented by increased dairy consumption. Approximately 100,000 DALYs due to breast cancer (7.5%) and approximately 120,000 DALYs (8.5%) due to colorectal cancer may be prevented by high dairy intake. The numbers of DALYs for stroke and hypertension that may be prevented by increased dairy consumption were approximately 210,000 (6.0%) and 74,000 (5.5%), respectively.

Conclusions

Consumption of dairy products has been associated with decreased risk of multiple chronic diseases of significant public health importance. The burden of disease that may potentially be prevented by increasing dairy consumption is substantial, and population-wide improvement in meeting recommended daily dairy intake goals could have a notable public health impact. However, this analysis is theoretical, and thus additional studies providing empirical evidence are needed to further clarify potential relationships between dairy intake and various health outcomes.
Efficacy and safety of surgery in renal carcinoma patients 75 years and older: a retrospective analysis
Authors: Bai Hongsong , Jiang Weixing , Wang Dong , Shou Jianzhong , Li Changling , Xing Nianzeng
Published: August 2022

Objective

To investigate the efficacy and complications of surgical treatment in patients with renal cell carcinoma aged ≥ 75 years.

Methods

From January 2009 to May 2019, we assessed 166 patients aged 75 years and older, who either had radical nephrectomy (RN) or partial nephrectomy (PN) as treatments for diagnosed renal cell carcinoma. Patients were divided into one group of patients aged 75–79 years and the second group of patients ≥ 80 years. The complications and survival were compared between the two groups.

Results

All 166 patients were successfully operated on. Differences between the two groups were statistically significant in intraoperative and postoperative complications and Clavien–Dindo score of ≥ 1 (P = 0.02, P < 0.001, P = 0.001). Univariate analysis revealed no significant correlation between a Clavien–Dindo score ≥ 1 versus gender, body mass index (BMI), lack of symptoms, KPS, baseline GFR, postoperative GFR, tumor size, tumor location, surgical method, and transfusion or no transfusion (ALL P > 0.05). Multifactor analysis showed that age ≥ 80 years, partial nephrectomy, and operation time were independent predictors of a Clavien–Dindo score ≥ 1. No significant difference was found in OS between the two groups, (P < 0.0001), and no significant difference in CSS (P = 0.056). There was no significant difference in OS and CSS between the RN and PN groups (P = 0.143, P = 0.281, respectively).

Conclusions

According to our findings, the overall safety of surgical therapy for elderly patients with renal cell carcinoma is adequate. PN should be carefully examined, especially over the age of 80. To select suitable patients based on an assessment of the tumor's complexity and patients' physical condition, such as age, underlying diseases and other conditions, technical feasibility, balance of benefits and a case-by-case.
Study of female pelvic floor muscle in overactive bladder based on MRI 3D reconstruction
Authors: Wang Yangyun , Yao Jie , Chen Na , Liu Jingjing , Shi Guowei , Wu Yi
Published: August 2022

Background

This study examined the three-dimensional (3D) morphological changes of the urination and urinary continence anatomical structures in overactive bladder (OAB) patients, to offer a morphological data for OAB diagnosis and treatment.

Methods

Eleven OAB patients, 9 healthy females and 22 pelvic organ prolapse (POP) patients were enrolled and underwent MRI scans. The anatomical components of urination (bladder detrusor) and the urinary continence (main part of the urethral sphincter, compressor urethrae, and levator ani muscle (LAM) were 3D reconstructed and measured with Amira software. We also analyze the relativity between pelvic floor muscle’s morphological parameters among the volunteers, OAB and POP group.

Results

Through 3D reconstruction, increased thickness and volume of the bladder detrusor were found in the OAB patients compared with volunteers (3.1 ± 0.7 mm vs. 1.9 ± 0.3 mm; P = 0.000 and 50,632.0 ± 19,724.7 mm3 vs. 23,386.6 ± 7826.3 mm3; P = 0.001). The volume of LAM showed no significant difference between the OAB patients and volunteers (27,089.4 ± 5015.0 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.924); whereas, LAM’s volume of the POP patients was significantly larger than that of the volunteers (34,130.6 ± 7968.3 mm3 vs. 27,294.4 ± 4461.4 mm3; P = 0.023). The thickness and volume of the main part of urethral sphincter were significantly lower in the OAB patients compared with volunteers (2.2 ± 0.5 mm vs. 2.7 ± 0.3 mm; P = 0.018 and 2558.6 ± 703.2 mm3 vs. 23,267.3 ± 681.9 mm3; P = 0.035). The volume of the compressor urethrae was significantly lower in the OAB patients than that in the volunteers (630.3 ± 301.2 mm3 vs. 866.1 ± 514.2 mm3; P = 0.247).

Conclusions

In OAB patients, the bladder detrusor has long-term tension and contraction, which thickened muscle and increased volume, and aggravate urination. The compressor urethral and main part of urethral sphincter are weaker and the anterior part of LAM hiatus is relaxed, easily resulting in leakage of urine and ultimately incontinence. The MRI 3D reconstruction and measurement can help to evaluate pelvic floor urination and continence function, and accurately diagnose.
A study to translate and validate the Thai version of the Victoria Respiratory Congestion Scale
Authors: Tantiwatniyom Tuangporn , Nagaviroj Kittiphon
Published: August 2022

Purpose

Few clinical tools are available to objectively evaluate death rattles in palliative care. The Victoria Respiratory Congestion Scale (VRCS) was adapted from the Back's scale, which has been widely utilized in research and clinical practice. The VRCS will be translated into Thai and research will be conducted to determine its validity and reliability in assessing death rattles in palliative care.

Methods

Two qualified language specialists converted the original tool into Thai and then back to English. Between September 2021 and January 2022, a cross-sectional study was undertaken at a palliative care unit at Ramathibodi Hospital to determine the Thai VRCS's validity and reliability. Two evaluators independently assessed the volume of secretion noises using the Thai VRCS. The criterion-related validity of VRCS was determined by calculating the correlation between the sound level obtained with a standard sound meter and the VRSC scores using Spearman's correlation coefficient method. To assess inter-rater reliability and agreement measurement on ratings, we utilized a two-way random-effects model with Cohen's weighted kappa agreement.

Results

Forty patients enrolled in this study with a mean age of 75.3 years. Fifty-five percent had a cancer diagnosis. Spearman's rho correlation coefficient was found to be 0.8822, p < 0.05, indicating a highly significant link. The interrater reliability analysis revealed that the interrater agreement was 95% and the Cohen's weighted kappa agreement was 0.92, indicating near-perfect agreement.

Conclusions

Thai VRCS demonstrated excellent criteria-related validity and interrater reliability. Using the Thai VRCS to assess adult palliative care patients' death rattles was recommended.
Comparing outcomes of ILD patients managed in specialised versus non-specialised centres
Authors: Marijic Pavo , Schwarzkopf Larissa , Maier Werner , Trudzinski Franziska , Kreuter Michael , Schwettmann Lars
Published: August 2022

Background

Early appropriate diagnosis and treatment of interstitial lung diseases (ILD) is crucial to slow disease progression and improve survival. Yet it is unknown whether initial management in an expert centre is associated with improved outcomes. Therefore, we assessed mortality, hospitalisations and health care costs of ILD patients initially diagnosed and managed in specialised ILD centres versus non-specialised centres and explored differences in pharmaceutical treatment patterns.

Methods

An epidemiological claims data analysis was performed, including patients with different ILD subtypes in Germany between 2013 and 2018. Classification of specialised centres was based on the number of ILD patients managed and procedures performed, as defined by the European Network on Rare Lung Diseases. Inverse probability of treatment weighting was used to adjust for covariates. Mortality and hospitalisations were examined via weighted Cox models, cost differences by weighted gamma regression models and differences in treatment patterns with weighted logistic regressions.

Results

We compared 2022 patients managed in seven specialised ILD centres with 28,771 patients managed in 1156 non-specialised centres. Specialised ILD centre management was associated with lower mortality (HR: 0.87, 95% CI 0.78; 0.96), lower all-cause hospitalisation (HR: 0.93, 95% CI 0.87; 0.98) and higher respiratory-related costs (€669, 95% CI €219; €1156). Although risk of respiratory-related hospitalisations (HR: 1.00, 95% CI 0.92; 1.10) and overall costs (€− 872, 95% CI €− 75; €1817) did not differ significantly, differences in treatment patterns were observed.

Conclusion

Initial management in specialised ILD centres is associated with improved mortality and lower all-cause hospitalisations, potentially due to more differentiated diagnostic approaches linked with more appropriate ILD subtype-adjusted therapy.
MLKL-mediated necroptosis is a target for cardiac protection in mouse models of type-1 diabetes
Authors: Cao Ting , Ni Rui , Ding Weimin , Ji Xiaoyun , Li Lan , Liao Guangneng , Lu Yanrong , Fan Guo-Chang , Zhang Zhuxu , Peng Tianqing
Published: August 2022

Background

Cardiomyocyte death contributes to cardiac pathology of diabetes. Studies have shown that the RIPK3/MLKL necroptosis signaling is activated in diabetic hearts. Deletion of RIPK3 was reported to attenuate myocardial injury and heart dysfunction in streptozocin (STZ)-induced diabetic mice, suggesting a potential role of necroptosis in diabetic cardiomyopathy. This study characterized cardiomyocyte necroptosis in diabetic hearts and investigated whether MLKL-mediated necroptosis is a target for cardiac protection in diabetes.

Methods

Type 1 diabetes was induced in RIPK3 knockout, MLKL knockout and wild-type mice. Akita Type-1 diabetic mice were injected with shRNA for MLKL. Myocardial function was assessed by echocardiography. Immuno-histological analyses determined cardiomyocyte death and fibrosis in the heart. Cultured adult mouse cardiomyocytes were incubated with high glucose in the presence of various drugs. Cell death and phosphorylation of RIPK3 and MLKL were analysed.

Results

We showed that the levels of phosphorylated RIPK3 and MLKL were higher in high glucose-stimulated cardiomyocytes and hearts of STZ-induced type-1 diabetic mice, akita mice and type-1 diabetic monkeys when compared to non-diabetic controls. Inhibition of RIPK3 by its pharmacological inhibitor or gene deletion, or MLKL deletion prevented high glucose-induced MLKL phosphorylation and attenuated necroptosis in cardiomyocytes. In STZ-induced type-1 diabetic mice, cardiomyocyte necroptosis was present along with elevated cardiac troponin I in serum and MLKL oligomerization, and co-localized with phosphorylated MLKL. Deletion of RIPK3 or MLKL prevented MLKL phosphorylation and cardiac necroptosis, attenuated serum cardiac troponin I levels, reduced myocardial collagen deposition and improved myocardial function in STZ-injected mice. Additionally, shRNA-mediated down-regulation of MLKL reduced cardiomyocyte necroptosis in akita mice. Interestingly, incubation with anti-diabetic drugs (empagliflozin and metformin) prevented phosphorylation of RIPK3 and MLKL, and reduced cell death in high glucose-induced cardiomyocytes.

Conclusions

We have provided evidence that cardiomyocyte necroptosis is present in diabetic hearts and that MLKL-mediated cardiomyocyte necroptosis contributes to diabetic cardiomyopathy. These findings highlight MLKL-mediated necroptosis as a target for cardiac protection in diabetes.
Development and validation of a model to predict cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease
Authors: Stevens Susanna R. , Segar Matthew W. , Pandey Ambarish , Lokhnygina Yuliya , Green Jennifer B. , McGuire Darren K. , Standl Eberhard , Peterson Eric D. , Holman Rury R.
Published: August 2022

Background

Among individuals with atherosclerotic cardiovascular disease (ASCVD), type 2 diabetes mellitus (T2DM) is common and confers increased risk for morbidity and mortality. Differentiating risk is key to optimize efficiency of treatment selection. Our objective was to develop and validate a model to predict risk of major adverse cardiovascular events (MACE) comprising the first event of cardiovascular death, myocardial infarction (MI), or stroke for individuals with both T2DM and ASCVD.

Methods

Using data from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), we used Cox proportional hazards models to predict MACE among participants with T2DM and ASCVD. All baseline covariates collected in the trial were considered for inclusion, although some were excluded immediately because of large missingness or collinearity. A full model was developed using stepwise selection in each of 25 imputed datasets, and comprised candidate variables selected in 20 of the 25 datasets. A parsimonious model with a maximum of 10 degrees of freedom was created using Cox models with least absolute shrinkage and selection operator (LASSO), where the adjusted R-square was used as criterion for selection. The model was then externally validated among a cohort of participants with similar criteria in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. Discrimination of both models was assessed using Harrell’s C-index and model calibration by the Greenwood-Nam-D’Agostino statistic based on 4-year event rates.

Results

Overall, 1491 (10.2%) of 14,671 participants in TECOS and 130 (9.3%) in the ACCORD validation cohort (n = 1404) had MACE over 3 years’ median follow-up. The final model included 9 characteristics (prior stroke, age, chronic kidney disease, prior MI, sex, heart failure, insulin use, atrial fibrillation, and microvascular complications). The model had moderate discrimination in both the internal and external validation samples (C-index = 0.65 and 0.61, respectively). The model was well calibrated across the risk spectrum—from a cumulative MACE rate of 6% at 4 years in the lowest risk quintile to 26% in the highest risk quintile.

Conclusion

Among patients with T2DM and prevalent ASCVD, this 9-factor risk model can quantify the risk of future ASCVD complications and inform decision making for treatments and intensity.
Medicinal waterbirds in the traditional healthcare system: an assessment of biodiversity–cultural linkages in Eastern Khyber Pakhtunkhwa, Pakistan
Authors: Rahman Qaisar , Nadeem Muhammad Sajid , Umair Muhammad , Altaf Muhammad , Ni Jian , Abbasi Arshad Mahmood , Jameel Muhammad Azhar , Pieroni Andrea , Hamed Muhammad Haroon , Ashraf Sana , Sadaf Tasnim
Published: August 2022

Background

Eastern Khyber Pakhtunkhwa is home to a vast range of medicinal and edible waterbird species due to its diverse geographical environment. Waterbird species have been used for various ailments and cultural practices since ancient times, while ethno-pharmacological applications and cultural uses of waterbird species in this area have seldom been documented. This study is the first ethnomedicinal and cultural assessment of waterbird species, and the first compilation and listing of all known data on these species in Eastern Khyber Pakhtunkhwa, Pakistan.

Methods

Interviews and questionnaires were used to collect data from native respondents (N = 100). To analyze the data, principal component analysis (PCA), relative frequency of citation (RFC), fidelity level (FL%), relative popularity level (RPL), rank order priority, and similarity index were used.

Results

In total, 64 waterbird species were utilized in cultural practices, of which 40 species are used to cure different infectious and chronic diseases such as cold, cough, flu, fever, respiratory disorders, asthma, TB, gastric ulcers, kidney stones, male impotency, obesity, paralysis, piles, cancer, arthritis, body pain, and weakness. PCA showed significant differences in the use of waterbird species among the local inhabitants of the study area, separated along the axis-2 (p < 0.05). The FL% of waterbird species varied from 12 to 100%. 100% FL was analyzed for four waterbird species, i.e., Charadrius mongolus (cold), Gallicrex cinerea (asthma), Anas platyrhynchos (cancer), and Esacus recurvirostris (body weakness). In this study, Mallard (Anas platyrhynchos) was the most popular species used in the healthcare system of Eastern Khyber Pakhtunkhwa, with high RFC (4.06), FL% (100), and RPL (1.0) values.

Conclusion

We concluded that waterbird species are more used for medicine and food purposes in the study area. However, in vitro/in vivo assessment of biochemical activities of waterbird species with a maximum FL% might be significant to produce novel drugs. Recent research shows important ethno-ornithological information about native people and their links with waterbird species, which might be helpful for the sustainable use of waterbird diversity in the research area.
Hepatitis B and C virus infections and the risk of biliary tract cancers: a meta-analysis of observational studies
Authors: Wang Yizhou , Yuan Ye , Gu Dongqing
Published: August 2022

Background

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for hepatocellular carcinoma. However, their effect on other hepatobiliary cancers, such as biliary tract cancers (BTCs), is not well established. We aimed to investigate associations between HBV or HCV infection and BTCs risk by conducting a systematic review and meta-analysis.

Methods

We searched PubMed to identify all relevant articles published before June 9, 2021. Meta-analysis was performed to calculate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The meta-analysis was evaluated by heterogeneity testing, sensitivity analyses, and publication bias assessment.

Results

In total, 48 articles involving 69,723 cases and 4,047,574 controls were obtained to calculate the associations between HBV or HCV infection and the risk of BTCs. We found that both HBV and HCV infections were associated with the risk of BTCs, with pooled ORs of 2.16 (95% CI 1.73–2.69) and 2.12 (95% CI 1.62–2.77), respectively. Subgroup analyses by ethnicity suggested that HBV infection could increase the risk of BTCs in both Asian (OR = 2.29, 95% CI 1.76–2.97) and Caucasian (OR = 1.80, 95% CI 1.18–2.75) populations. In addition, HCV infection resulted in a higher increased risk of BTCs in Caucasian populations than in Asian populations (OR = 3.93 vs. 1.51, P = 0.014). In particular, significantly increased risks of intrahepatic cholangiocarcinoma (ICC) were identified in individuals with HBV (OR = 3.96, 95% CI 3.05–5.15) or HCV infection (OR = 2.90, 95% CI 2.07–4.08).

Conclusions

This study suggests that both HBV and HCV infections are risk factors for BTCs, particularly ICC, highlighting the necessity of cancer screening for BTCs in patients with either HBV or HCV infection.
Connecting telomere maintenance and regulation to the developmental origin and differentiation states of neuroblastoma tumor cells
Authors: Yu Eun Young , Cheung Nai-Kong V. , Lue Neal F.
Published: August 2022

A cardinal feature that distinguishes clinically high-risk neuroblastoma from low-risk tumors is telomere maintenance. Specifically, neuroblastoma tumors with either active telomerase or alternative lengthening of telomeres exhibit aggressive growth characteristics that lead to poor outcomes, whereas tumors without telomere maintenance can be managed with observation or minimal treatment. Even though the need for cancer cells to maintain telomere DNA—in order to sustain cell proliferation—is well established, recent studies suggest that the neural crest origin of neuroblastoma may enforce unique relationships between telomeres and tumor malignancy. Specifically in neuroblastoma, telomere structure and telomerase activity are correlated with the adrenergic/mesenchymal differentiation states, and manipulating telomerase activity can trigger tumor cell differentiation. Both findings may reflect features of normal neural crest development. This review summarizes recent advances in the characterization of telomere structure and telomere maintenance mechanisms in neuroblastoma and discusses the findings in the context of relevant literature on telomeres during embryonic and neural development. Understanding the canonical and non-canonical roles of telomere maintenance in neuroblastoma could reveal vulnerabilities for telomere-directed therapies with potential applications to other pediatric malignancies.
Posttranslational control of lipogenesis in the tumor microenvironment
Authors: Zhu Yahui , Lin Xingrong , Zhou Xiaojun , Prochownik Edward V. , Wang Fubing , Li Youjun
Published: August 2022

Metabolic reprogramming of cancer cells within the tumor microenvironment typically occurs in response to increased nutritional, translation and proliferative demands. Altered lipid metabolism is a marker of tumor progression that is frequently observed in aggressive tumors with poor prognosis. Underlying these abnormal metabolic behaviors are posttranslational modifications (PTMs) of lipid metabolism-related enzymes and other factors that can impact their activity and/or subcellular localization. This review focuses on the roles of these PTMs and specifically on how they permit the re-wiring of cancer lipid metabolism, particularly within the context of the tumor microenvironment.
Inhibition of monogalactosyldiacylglycerol synthesis by down-regulation of MGD1 leads to membrane lipid remodeling and enhanced triacylglycerol biosynthesis in Chlamydomonas reinhardtii
Authors: Lee Jun-Woo , Lee Min-Woo , Jin Chun-Zhi , Oh Hee-Mock , Jin EonSeon , Lee Hyung-Gwan
Published: August 2022

Background

Membrane lipid remodeling involves regulating the physiochemical modification of cellular membranes against abiotic stress or senescence, and it could be a trigger to increase neutral lipid content. In algae and higher plants, monogalactosyldiacylglycerol (MGDG) constitutes the highest proportion of total membrane lipids and is highly reduced as part of the membrane lipid remodeling response under several abiotic stresses. However, genetic regulation of MGDG synthesis and its influence on lipid synthesis has not been studied in microalgae. For development of an industrial microalgae strain showing high accumulation of triacylglycerol (TAG) by promoting membrane lipid remodeling, MGDG synthase 1 (MGD1) down-regulated mutant of Chlamydomonas reinhardtii (Cr-mgd1) was generated and evaluated for its suitability for biodiesel feedstock.

Results

The Cr-mgd1 showed a 65% decrease in CrMGD1 gene expression level, 22% reduction in MGDG content, and 1.39 and 5.40 times increase in diacylglyceryltrimethylhomoserines (DGTS) and TAG, respectively. The expression levels of most genes related to the decomposition of MGDG (plastid galactoglycerolipid degradation1) and TAG metabolism (diacylglycerol O-acyltransferase1, phospholipid:diacylglycerol acyltransferase, and major lipid droplet protein) were increased. The imbalance of DGDG/MGDG ratio in Cr-mgd1 caused reduced photosynthetic electron transport, resulting in less light energy utilization and increased reactive oxygen species levels. In addition, endoplasmic reticulum stress was induced by increased DGTS levels. Thus, accelerated TAG accumulation in Cr-mgd1 was stimulated by increased cellular stress as well as lipid remodeling. Under high light (HL) intensity (400 µmol photons/m2/s), TAG productivity in Cr-mgd1–HL (1.99 mg/L/d) was 2.71 times higher than that in wild type (WT–HL). Moreover, under both nitrogen starvation and high light intensity, the lipid (124.55 mg/L/d), TAG (20.03 mg/L/d), and maximum neutral lipid (56.13 mg/L/d) productivity were the highest.

Conclusions

By inducing lipid remodeling through the mgd1 gene expression regulation, the mutant not only showed high neutral lipid content but also reached the maximum neutral lipid productivity through cultivation under high light and nitrogen starvation conditions, thereby possessing improved biomass properties that are the most suitable for high quality biodiesel production. Thus, this mutant may help understand the role of MGD1 in lipid synthesis in Chlamydomonas and may be used to produce high amounts of TAG.