bluuebunny/crossref_metadata_2025 huggingface dataset:
Corporate Environmental Performance and Financial Performance: Evidence from the Most Polluting Companies in India
Authors: Ezhilarasi G.
Published: April 2023

This article primarily investigates the association between corporate environmental performance (CEP) and financial performance (FP) of a firm and it also examines the effects of good, mixed, and poor environmental performers on FP. To achieve the objective, annual reports of 145 most polluting companies in India have been used from 2009–2010 to 2018–2019. On the basis of Global Reporting Initiative framework, the CEP scores have been measured in terms of quantitative (binary coding system) and qualitative (three-point scale) aspects using the content analysis technique. Subsequently, the scores are used to analyse the linkage between CEP disclosure and firms’ FP. Employing static and dynamic panel data analyses, the study observes quantitative as well as qualitative CEP performs significant part in expanding the firms’ market value and also notices innovation oriented investment boost the FP. On the contrary, the study finds out the expenditure on research and development and CEP together negatively influence firms’ FP. Further, it also reveals good performers make better CEP disclosure in their annual reports compared with mixed and poor performers on all aspects of environmental performance indicators of GRI guidelines and also observes a positive linkage between good performers and firm’s FP.
Public Health Spending in the Philippines: A Cointegration and Causality Analysis Using Autoregressive Distributed Lag Approach
Authors: Espinosa Jaycar P. , Cabauatan Ronaldo R. , Tatlonghari Virgilio M.
Published: April 2023

For several decades now, the budget allocated by the Philippine government health spending (public health expenditure; PHE) has steadily risen, but the desired health outcomes for Filipinos leave much to be desired if viewed historically. This study explains how per capita PHE in the Philippines is conditioned by a set of factors based on time series data from 1960 to 2019. To achieve this, an autoregressive distributed lag model with an error correction model component was designed to estimate long-run and short-run dynamics. Based on the results, income, youth population, industrialisation, and selected health outcomes significantly influence PHE. Since most of the factors exert significant effects, coupled with the finding of a long-run cointegrating relationship and fairly stable parameters, reliable PHE estimates can be made by Philippine health and fiscal authorities and enable policymakers to design and implement the needed level of intervention in the country’s public health sector.
Role of p53/circRNA0085439/Ku70 axis in DNA damage response in lung cells exposed to ZnO nanoparticles: Involvement of epigenetic regulation
Authors: Zhou Meiling , Xiao Liang , Jin Jing , Wang Yin , Guo Peiyu , Luo Jinhua , Skonieczna Magdalena , Huang Ruixue
Published: April 2023

Background

Nano-Zinc oxide (Nano-ZnO) has been increasingly applied in agriculture, industry and biomedicine. However, the genotoxic effects of Nano-ZnO and the underlying mechanisms remain incompletely clear.

Methods

Human bronchial epithelial cell line (HBE) was used to observe the effects of Nano-ZnO on DNA damage repair-related proteins and epithelial mesenchymal transition (EMT) by Western blotting. Then, CRISPR/cas9-based technique was used to create p53 knockout (p53-KO) cell line. RNA-seq analysis was performed to uncover the circular RNA (circRNA) profile after Nano-ZnO treatment in p53-KO cells compared with p53 wild-type (p53-wt) cells. LC–MS/MS was used to discover the potential binding proteins of circRNA_0085439 in the p53 deficiency background after Nano-ZnO treatment. Nano-ZnO-induced DNA damage and EMT were also investigated in vivo by instillation of Nano-ZnO (50 µg/mouse).

Results

Nano-ZnO exposure caused DNA damage and EMT at both in vitro and in vivo background, which was reflected by increased DNA damage associated proteins such as ATM and ATR and γ H2AX. p53 expression increased at the early stage post Nano-ZnO treatment decreased later. RNA-seq assay showed a highest increase of circRNA_0085439 expression in p53-KO cells compared with the p53-wt cells after Nano-ZnO exposure. Silencing of p53 expression promoted its translocation of circRNA_0085439 from cytoplasm to nucleus leading to the formation of circRNA_0085439/Ku70 complex resulting in the decreased expression of Ku70 protein. In addition, increased EMT markers, N-cadherin and Vimentin, was observed in lung epithelial cells and in mouse lungs at day 7 after Nano-ZnO exposure.

Conclusions

This study unraveled the epigenetic mechanisms underlying Nano-ZnO-induced DNA damage and EMT. The effect of Nano-ZnO-induced DNA damage through p53/circRNA_0085439/Ku70 pathway likely contribute to Nano-ZnO-induced cell cytotoxicity and apoptosis. Our findings will provide information to further elucidate the molecular mechanisms of Nano-ZnO-induced cytotoxicity and genotoxicity.
Two birds with one stone: triple negative breast cancer therapy by PtCo bimetallic nanozyme coated with gemcitabine-hyaluronic acid-polyethylene glycol
Authors: Sharifi Majid , Kheradmandi Rasoul , Alizadeh Morteza
Published: April 2023

For the treatment of triple-negative breast cancer (TNBC), without expression of estrogen, progesterone and HER2 receptors, specific treatment guideline is still under criticism, especially in tumor hypoxia. But assuming the molecular similarity of TNBC with breast cancer gene-1-related cancers, gemcitabine may be used in TNBC treatment on the nanozyme platform combined with photodynamic therapy (PDT). After designing the nanozyme with four components, platinum–cobalt: with catalase/peroxidase capabilities, hyaluronic acid: nanozyme targeting by interacting with CD44 receptor, poly[ethylene glycol]: water-soluble macromolecule for immune escape, and Gem: antitumor drug, its physicochemical properties was investigated by thermogravimetric, X-ray diffraction and energy dispersive X-ray, and therapeutic effects in in vitro and in vivo. The results show that platinum–cobalt@gemcitabine-hyaluronic acid-polyethylene glycol (PtCo@Gem-HA-PEG) especially synergized with PDT has high toxicity on 4T1 cells and tumor by enhancing the catalase-/peroxidase-like activities to produce O2, O2•− and •OH, and increase the intracellular free radicals. PtCo@Gem-HA-PEG inhibits tumor development by increasing drug accumulation in the tumor and enhancing apoptotic mechanisms through synergistic activity with PDT. Nevertheless, the major organ damage confirmed by the histological method in the long-term application of PtCo@Gem-HA-PEG, makes their application challenging due to permanent catalytic activity. However, results of improved drug permeability based on reduced hypoxia, higher drug retention, and enzyme-like activity that could be synergized with other therapeutic approaches like a PDT, have made their use attractive. Hence, this study provides a promising path in the TNBC treatment by nanozymes, which requires further toxicological investigations.

Graphic Abstract
Fast all versus all genotype comparison using DNA/RNA sequencing data: method and workflow
Authors: Eschrich Steven A. , Yu Xiaoqing , Teer Jamie K.
Published: April 2023

Background

Massively parallel sequencing includes many liquid handling steps which introduce the possibility of sample swaps, mixing, and duplication. The unique profile of inherited variants in human genomes allows for comparison of sample identity using sequence data. A comparison of all samples vs. each other (all vs. all) provides both identification of mismatched samples and the possibility of resolving swapped samples. However, all vs. all comparison complexity grows as the square of the number of samples, so efficiency becomes essential.

Results

We have developed a tool for fast all vs. all genotype comparison using low level bitwise operations built into the Perl programming language. Importantly, we have also developed a complete workflow allowing users to start with either raw FASTQ sequence files, aligned BAM files, or genotype VCF files and automatically generate comparison metrics and summary plots. The tool is freely available at https://github.com/teerjk/TimeAttackGenComp/.

Conclusions

A fast and easy to use method for genotype comparison as described here is an important tool to ensure high quality and robust results in sequencing studies.
Genomic and functional characterization of carbapenem-resistant Klebsiella pneumoniae from hospital wastewater
Authors: Xie Zhiqiang , Huang Jiangqing , zhang Shengcen , Xu BinBin , Zhang Qianwen , Li Bin
Published: April 2023

Background

The emergence of carbapenem-resistantKlebsiella pneumoniae(CRKP) attracted extensive attention. Information on CRKP from hospital wastewater (HWW) is limited. The aims of this study were to investigate the genomic characteristics and to evaluate the survivability characteristics of 11 CRKP from HWW in a Chinese teaching hospital in Fujian province.

Results

A total of 11 CRKP from HWW were recovered in this study. All CRKP from HWW were resistant to most antibiotics. Comparative genetic analysis demonstrated that all CRKP isolates were clustered into the three distinct phylogenetic clades and clade 2 and clade 3 were mixtures of samples collected from both HWW and clinical settings. Varieties of resistance genes, virulence genes and plasmid replicon types were detected in CRKP from HWW. In vitro transfer ofblaKPC-2was successful for 3blaKPC-2-positive CRKP from HWW with high conjugation frequency. Our study demonstrated that the genetic environments ofblaKPC−2shared core structure with ISKpn27-blaKPC−2-ISKpn6. Group analysis showed that CRKP from HWW had a lower survivability in serum compared to clinical CRKP (p < 005); and CRKP from HWW had no significant difference in survivability in HWW compared to clinical CRKP (p > 005).

Conclusions

We analyzed the genomic and survivability characteristics of CRKP from HWW in a Chinese teaching hospital. These genomes represent a significant addition of genomic data from the genus and could serve as a valuable resource for future genomic studies about CRKP from HWW.
The Preventiometer - reliability of a cardiovascular multi-device measurement platform and its measurement agreement with a cohort study
Authors: Junge Martin , Krüger Markus , Wahner-Roedler Dietlind L. , Bauer Brent A. , Dörr Marcus , Bahls Martin , Chenot Jean-François , Biffar Reiner , Schmidt Carsten O.
Published: April 2023

Background

Multimedia multi-device measurement platforms may make the assessment of prevention-related medical variables with a focus on cardiovascular outcomes more attractive and time-efficient. The aim of the studies was to evaluate the reliability (Study 1) and the measurement agreement with a cohort study (Study 2) of selected measures of such a device, the Preventiometer.

Methods

In Study 1 (N = 75), we conducted repeated measurements in two Preventiometers for four examinations (blood pressure measurement, pulse oximetry, body fat measurement, and spirometry) to analyze their agreement and derive (retest-)reliability estimates. In Study 2 (N = 150), we compared somatometry, blood pressure, pulse oximetry, body fat, and spirometry measurements in the Preventiometer with corresponding measurements used in the population-based Study of Health in Pomerania (SHIP) to evaluate measurement agreement.

Results

Intraclass correlations coefficients (ICCs) ranged from .84 to .99 for all examinations in Study 1. Whereas bias was not an issue for most examinations in Study 2, limits of agreement for most examinations were very large compared to results of similar method comparison studies.

Conclusion

We observed a high retest-reliability of the assessed clinical examinations in the Preventiometer. Some disagreements between Preventiometer and SHIP examinations can be attributed to procedural differences in the examinations. Methodological and technical improvements are recommended before using the Preventiometer in population-based research.
Comparison of correctly and incorrectly classified patients for in-hospital mortality prediction in the intensive care unit
Authors: Stenwig Eline , Salvi Giampiero , Salvo Rossi Pierluigi , Skjærvold Nils Kristian
Published: April 2023

Background

The use of machine learning is becoming increasingly popular in many disciplines, but there is still an implementation gap of machine learning models in clinical settings. Lack of trust in models is one of the issues that need to be addressed in an effort to close this gap. No models are perfect, and it is crucial to know in which use cases we can trust a model and for which cases it is less reliable.

Methods

Four different algorithms are trained on the eICU Collaborative Research Database using similar features as the APACHE IV severity-of-disease scoring system to predict hospital mortality in the ICU. The training and testing procedure is repeated 100 times on the same dataset to investigate whether predictions for single patients change with small changes in the models. Features are then analysed separately to investigate potential differences between patients consistently classified correctly and incorrectly.

Results

A total of 34 056 patients (58.4%) are classified as true negative, 6 527 patients (11.3%) as false positive, 3 984 patients (6.8%) as true positive, and 546 patients (0.9%) as false negatives. The remaining 13 108 patients (22.5%) are inconsistently classified across models and rounds. Histograms and distributions of feature values are compared visually to investigate differences between groups.

Conclusions

It is impossible to distinguish the groups using single features alone. Considering a combination of features, the difference between the groups is clearer. Incorrectly classified patients have features more similar to patients with the same prediction rather than the same outcome.
Ischemia prediction score (IsPS) in patients with strangulated small bowel obstruction: a retrospective cohort study
Authors: Murao Shuhei , Fujino Shiki , Danno Katsuki , Takeda Takashi , Yamamoto Kei , Higashiguchi Masaya , Noguchi Kozo , Hirao Takafumi , Oka Yoshio
Published: April 2023

Backgrounds

Intestinal ischemia of strangulated small bowel obstruction (SSBO) requires prompt identification and early intervention. This study aimed to evaluate the risk factors and develop a prediction model of intestinal ischemia requiring bowel resection in SSBO.

Methods

This was a single-center, retrospective cohort study of consecutive patients underwent emergency surgery for SSBO from April 2007 to December 2021. Univariate analysis was performed to identify the risk factors for bowel resection in these patients. Two clinical scores (with contrasted computed tomography [CT] and without contrasted CT) were developed to predict intestinal ischemia. The scores were validated in an independent cohort.

Results

A total of 127 patients were included, 100 in the development cohort (DC) and 27 in the validation cohort (VC). Univariate analysis showed that high white blood cell count (WBC), low base excess (BE), ascites and reduced bowel enhancement were significantly associated with bowel resection. The ischemia prediction score (IsPS) comprised 1 point each for WBC ≥ 10,000/L, BE ≤ -1.0 mmol/L, ascites, and 2 points for reduced bowel enhancement. The simple IsPS (s-IsPS, without contrasted CT) of 2 or more had a sensitivity of 69.4%, specificity of 65.4%. The modified IsPS (m-IsPS, with contrasted CT) of 3 or more had a sensitivity of 86.7%, specificity of 76.0%. AUC of s-IsPS was 0.716 in DC and 0.812 in VC, and AUC of m-IsPS was 0.838 and 0.814.

Conclusion

IsPS predicted possibility of ischemic intestinal resection with high accuracy and can help in the early identification of intestinal ischemia in SSBO.
Rapidly progressive IgA nephropathy with membranoproliferative glomerulonephritis-like lesions in an elderly man following the third dose of an mRNA COVID-19 vaccine: a case report
Authors: Morimoto Nobuhisa , Mori Takayasu , Shioji Shingo , Taguchi Towako , Watanabe Hatsumi , Sakai Keigo , Mori Katsuo , Yamamura Ayumi , Hanioka Asami , Akagi Yuichiro , Fujiki Tamami , Mandai Shintaro , Mori Yutaro , Ando Fumiaki , Susa Koichiro , Iimori Soichiro , Naito Shotaro , Sohara Eisei , Ohashi Kenichi , Uchida Shinichi
Published: April 2023

Background

As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist.

Case presentation

We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy.

Conclusions

Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted.
Longitudinal prospective cohort study to assess peripheral motor function with extensive electrophysiological techniques in patients with Spinal Muscular Atrophy (SMA): the SMA Motor Map protocol
Authors: Ros Leandra A. A. , Goedee H. Stephan , Franssen Hessel , Asselman Fay-Lynn , Bartels Bart , Cuppen Inge , van Eijk Ruben P. A. , Sleutjes Boudewijn T. H. M. , van der Pol W. Ludo , Wadman Renske I.
Published: April 2023

Background

Hereditary spinal muscular atrophy (SMA) is a motor neuron disorder with a wide range in severity in children and adults. Two therapies that alter splicing of the Survival Motor Neuron 2 (SMN2) gene, i.e. nusinersen and risdiplam, improve motor function in SMA, but treatment effects vary. Experimental studies indicate that motor unit dysfunction encompasses multiple features, including abnormal function of the motor neuron, axon, neuromuscular junction and muscle fibres. The relative contributions of dysfunction of different parts of the motor unit to the clinical phenotype are unknown. Predictive biomarkers for clinical efficacy are currently lacking. The goals of this project are to study the association of electrophysiological abnormalities of the peripheral motor system in relation to 1) SMA clinical phenotypes and 2) treatment response in patients treated with SMN2-splicing modifiers (nusinersen or risdiplam).

Methods

We designed an investigator-initiated, monocentre, longitudinal cohort study using electrophysiological techniques (‘the SMA Motor Map’) in Dutch children (≥ 12 years) and adults with SMA types 1–4. The protocol includes the compound muscle action potential scan, nerve excitability testing and repetitive nerve stimulation test, executed unilaterally at the median nerve. Part one cross-sectionally assesses the association of electrophysiological abnormalities in relation to SMA clinical phenotypes in treatment-naïve patients. Part two investigates the predictive value of electrophysiological changes at two-months treatment for a positive clinical motor response after one-year treatment with SMN2-splicing modifiers. We will include 100 patients in each part of the study.

Discussion

This study will provide important information on the pathophysiology of the peripheral motor system of treatment-naïve patients with SMA through electrophysiological techniques. More importantly, the longitudinal analysis in patients on SMN2-splicing modifying therapies (i.e. nusinersen and risdiplam) intents to develop non-invasive electrophysiological biomarkers for treatment response in order to improve (individualized) treatment decisions.

Trial registration

NL72562.041.20 (registered at https://www.toetsingonline.nl. 26–03-2020).
Virtual Reality Experience during Labour (VIREL); a qualitative study
Authors: Musters A. , Vandevenne A. S. , Franx A. , Wassen M. M. L. H.
Published: April 2023

Background

There is increasing evidence that virtual reality (VR) is effective in the reduction of labour pain. The implementation of alternative methods like VR to reduce labour pain can contribute to reduce patient request for pharmacological pain management methods and associated side effects. The aim of this study is to examine women’s experiences, preferences and satisfaction in regard to the use of VR during labour.

Methods

A qualitative interview study was conducted in a non-university teaching hospital in The Netherlands. Two VR applications, respectively a guided meditation and an interactive game were tested in eligible women with a singleton pregnancy, scheduled for induction of labour. For the primary outcome, patients’ VR experience and application preference (meditation vs. game) were examined using a post-intervention questionnaire and a semi-structured interview. Three categories (with sub-categories) were used to guide interviews: “The VR experience”, “Pain reduction”, and “Usability of the VR application”. Labour pain before and directly after VR was evaluated using the NRS score.

Results

Twenty-four women, of whom 14 were nulliparous and ten multiparous, were included and 12 of these women participated in semi-structured interviews. Using within-subject paired t-test comparisons, compared to pain pre-VR, patients reported a highly significant 26% decrease in mean NRS scores during VR meditation (pain pre-VR = 6.71 + − 1.65 vs. pain after VR = 4.96 + − 2.01) [p < 0.001]. Compared to pain before VR game, patients also reported a highly significant 19% decrease in mean NRS scores during VR game (pain before VR game = 6.89 + − 1.88 vs. pain after VR game = 5.61 + − 2.23) [p = 0.001].

Conclusion

All women were highly satisfied with VR use during labour. Patients reported a highly significant reduction in pain during the interactive VR game and during meditation, patients preferred guided meditation. These results can contribute to the development of a potential promising new non-pharmacological tool to reduce labour pain.

Trial registration

ClinicalTrials.gov Identifier: NCT04858984, date of registration: 26/04/2021 (retrospectively registered).
The role of serum metrics in anti- VEGF treatment for macular edema induced by retinal vein occlusion
Authors: Wang Yun-Chang , Zhou Chuan-Qi , Li Rong-Rong , Cai Yi , Wang Meng-Meng , Yuan Li-Fei , He Yi-Qing
Published: April 2023

Aim

To evaluate association between pretreatment serum metrics and best corrected visual acuity ( BCVA) of patients with macular edema secondary to retinal vein occlusion and its subtypes after intravitreal ranibizumab or conbercept implant.

Methods

This prospective research included 201 patients(201 eyes) who were diagnosed with macular edema secondary to retinal vein occlusion at Heibei Eye Hospital between January 2020 and January 2021, who all received intravitreal anti- vascular endothelial growth factor treatment. Serum metrics were measured before the first treatment, and correlations between BCVA and each of four parameters— platelets, neutrophil- to- lymphocyte ratio(NLR), platelet- to- lymphocyte ratio(PLR) and monocyte- to- lymphocyte ratio(MLR)— were analyzed to identify predictors of effective intravitreal injection treatment outcomes.

Results

The mean platelets was significantly different in the effective and ineffective group for RVO-ME (273.02 ± 41.49 × 109/L,214.54 ± 44.08 × 109/L P < 0.01),BRVO-ME (269.43 ± 49.52 × 109/L,214.72 ± 40.42 × 109/L P < 0.01), and CRVO-ME (262.32 ± 32.41 × 109/L,209.27 ± 42 0.91 × 109/L P < 0.01). The cutoff value of the platelets was 266.500, the area under the curve was 0.857,and the sensitivity and specificity were 59.8% and 93.6%, respectively. The mean PLR was significantly different in the effective and ineffective group for RVO-ME (154.66 ± 49.60, 122.77± 44.63 P < 0.01),BRVO-ME (152.24 ± 54.99, 124.72 ± 41.46 P = 0.003), and CRVO-ME (152.06±44.23, 118.67 ± 41.80 P = 0.001). The cutoff value of the platelets was 126.734, the area under the curve was 0.699, and the sensitivity and specificity were 70.7% and 63.3%, respectively. There were no statistical differencies between the effective and ineffective group(RVO- ME and its subtypes) in NLR and MLR.

Conclusion

Higher pretreatment platelets and PLR were associated with BCVA in patients with RVO- ME and its subtypes who were treated with anti- VEGF drugs. The platelets and PLR may be used as predictive and prognostic tools for effective intravitreal injection treatment outcomes.
Multi-drug resistant Klebsiella-induced corneal ulcer following pterygium surgery: a case report
Authors: Calisir Kenan , Mohamed Hassan Muhumed , Yussuf Aisha Abdirahman
Published: April 2023

Background

Management of pterygium is dependent on the grading of pterygium and its clinical presentation (inflamed or quiescent), and surgical excision is the final choice of treatment for the pterygium extending beyond the limbus. Infectious keratitis is one of the most commonly reported complications in recent years. To the best of our knowledge, Klebsiella keratitis after pterygium surgery has not been described in the current literature. Here, we report a patient with corneal ulcer formation following pterygium surgical excision.

Case presentation

A 62-year-old woman presented with complaints of pain, blurred vision, photophobia and redness in her left eye for a month. She had a history of pterygium surgical excision two months ago. Slit-lamp examination showed conjunctival congestion, a central whitish corneal ulcer with a central epithelial defect, and hypopyon. Corneal scraped sample revealed multidrug resistant (MDR) Klebsiella pneumonia and the strain was found to be sensitive to cefoxitin and ciprofloxacin. Intracameral cefuroxime (1 mg/0.1 mL) injection, fortified cefuroxime ophthalmic suspension (50 mg/mL) and moxifloxacin ophthalmic suspension (0.5%) were successfully administered to control the infection. Since residual central stromal opacification remained persistent, final visual acuity did not improve beyond finger counting at two meters.

Conclusions

Klebsiella keratitis is a rare and sight-threatening complication following pterygium excision. This report emphasizes the importance of close follow-up examination following pterygium surgeries.
Dose–response relationship between active smoking and lung cancer mortality/prevalence in the Chinese population: a meta-analysis
Authors: Ai Feiling , Zhao Jian , Yang Wenyi , Wan Xia
Published: April 2023

Background

The dose‒response relationship-based relative risk (RR) of smoking exposure could better predict the risk of lung cancer than the dichotomous RR. To date, there is a lack of large-scale representative studies illustrating the dose‒response relationship between smoking exposure and lung cancer deaths, and no study has systematically pooled the current evidence in the Chinese population.

Objectives

To elucidate the dose‒response relationship of smoking and the risk of lung cancer mortality in the Chinese population.

Methods

Data were derived from studies on dose‒response relationships of smoking exposure and the risk of lung cancer among Chinese adults published before June 30th, 2021. Based on smoking exposure indicators and RR of lung cancer mortality, a series of dose‒response relationship models were developed. For smokers, 10 models were built to fit the dose‒response relationships between pack-years and RR of lung cancer deaths. For quitters, quit-years and corresponding RRs were used, and the pooled dichotomous RR value was used as the starting point to avoid overestimation. Finally, the results were compared with the estimates from 2019 Global Burden of Disease (GBD) study.

Results

A total of 12 studies were included. Among 10 dose‒response relationship models of pack-years with the RR of lung cancer mortality, the integrated-exposure–response (IER) model achieved the best fit. In all models, less than 60 pack-years presented RRs below 10. For former smokers, the RR decreased to 1 when quit-years reached up to 7 years. Both smokers and quitters had much lower RRs than that of the global level estimated by GBD.

Conclusion

The risk of lung cancer mortality rose with pack-years and decreased with quit-years among Chinese adults, and both values were far below global level. The results suggested that the dose–response RR of lung cancer deaths associated with smoking in China should be estimated separately.
Geographical evolutionary pathway of global tuberculosis incidence trends
Authors: Lei Yanhui , Wang Jinfeng , Wang Yang , Xu Chengdong
Published: April 2023

Backgrounds

Tuberculosis (TB) remains a serious public health and human development problem, especially in developing countries. Despite the effectiveness of directly observed therapy, short course programs in reducing transmission and progression of TB, poverty reduction and socioeconomic development remain crucial factors in decreasing TB incidence. However, the geographical pathway on the planet is not yet clear.

Objectives

This study was to reconstruct the geographical evolutionary process of TB in 173 countries and territories from 2010 to 2019 to analyze the socioeconomic determinants that impact the global TB epidemic. In addition, the TB incidence in 2030 was predicted.

Methods

This study analyses TB incidence data from 173 countries and territories between 2010 and 2019. The Geotree model would be used to reconstruct the geographical evolutionary process of TB, which provides a simplified schema for geo-visualizing the trajectories of TB incidence and their socioeconomic drivers. Additionally, to estimate the future TB incidence in 2030, a multilevel model was utilized in conjunction with the hierarchical nature of the Geotree based on a stratified heterogeneity analysis.

Results

Global TB incidence was found to be associated with the country type and development stages. Between 2010 and 2019, the average TB incidence rate in 173 countries and territories was -27.48%, with marked spatially stratified heterogeneity by country type and development stage. Low-income and lower-middle-income countries were most vulnerable to TB. Upper-middle-income countries experienced a faster decline in TB incidence than high-income countries, and TB incidence generally decreased as the development stage increased, except for the lower-middle development stage in 2019.The highest average rate of decline in TB incidence was observed in the upper-middle development stage of high-income countries, with a reduction of 45.24%. Meanwhile, 37 high-income countries in the high development stage demonstrated an average rate of change of -13.93%. Socioeconomic determinants, including gross domestic product per capita, urbanization rate, and sociodemographic index, were found to inhibit TB incidence. Based on current trends, the predicted average global TB incidence in 2030 is 91.581 per 100,000 population.

Conclusions

The trajectories of the global TB incidence have been reconstructed to formulate targeted public health responses. To eliminate TB, countries at similar development stage can draw on the experiences of countries at higher development stages that are tailored to their unique characteristics. By learning from successful TB control strategies, countries can take strategic steps toward eradicating TB and improving public health outcomes.
Dissemination of public health research to prevent non-communicable diseases: a scoping review
Authors: Turon Heidi , Wolfenden Luke , Finch Meghan , McCrabb Sam , Naughton Shaan , O’Connor Sean R , Renda Ana , Webb Emily , Doherty Emma , Howse Eloise , Harrison Cheryce L , Love Penelope , Smith Natasha , Sutherland Rachel , Yoong Sze Lin
Published: April 2023

Background

Dissemination is a critical element of the knowledge translation pathway, and a necessary step to ensure research evidence is adopted and implemented by key end users in order to improve health outcomes. However, evidence-based guidance to inform dissemination activities in research is limited. This scoping review aimed to identify and describe the scientific literature examining strategies to disseminate public health evidence related to the prevention of non-communicable diseases.

Methods

Medline, PsycInfo and EBSCO Search Ultimate were searched in May 2021 for studies published between January 2000 and the search date that reported on the dissemination of evidence to end users of public health evidence, within the context of the prevention of non-communicable diseases. Studies were synthesised according to the four components of Brownson and colleagues’ Model for Dissemination of Research (source, message, channel and audience), as well as by study design.

Results

Of the 107 included studies, only 14% (n = 15) directly tested dissemination strategies using experimental designs. The remainder primarily reported on dissemination preferences of different populations, or outcomes such as awareness, knowledge and intentions to adopt following evidence dissemination. Evidence related to diet, physical activity and/or obesity prevention was the most disseminated topic. Researchers were the source of disseminated evidence in over half the studies, and study findings/knowledge summaries were more frequently disseminated as the message compared to guidelines or an evidence-based program/intervention. A broad range of dissemination channels were utilised, although peer-reviewed publications/conferences and presentations/workshops predominated. Practitioners were the most commonly reported target audience.

Conclusions

There is a significant gap in the peer reviewed literature, with few experimental studies published that analyse and evaluate the effect of different sources, messages and target audiences on the determinants of uptake of public health evidence for prevention. Such studies are important as they can help inform and improve the effectiveness of current and future dissemination practices in public health contexts.
Recurrent metastatic retroperitoneal dedifferentiated liposarcoma: a case report and literature review
Authors: Liao Tuming , Du Wei , Li Xiongcai , He Shen , Guan Gangqiang , Zhu Herong , Wu Jiaqiao
Published: April 2023

Background

Retroperitoneal liposarcoma (RPLPS), a rare tumor, is often treated using surgical procedures as the first choice for treatment. However, there is no consensus on the scope of surgical resection. In addition, the treatment outcomes of conventional radiotherapy and chemotherapy have not been satisfactory, particularly for specific types of LPS, such as dedifferentiated LPS. In this case study, we present a brief review of other cases of RPLPS, highlighting the selection of surgical scope for RPLPS and related adjuvant treatment for advanced RPLPS.

Case presentation

A case study is reported regarding an extremely rare recurrent and metastatic retroperitoneal dedifferentiated LPS. The primary RPLPS tumor, with a diameter of 20 cm and a weight of 2.5 kg, occupied the whole left abdomen and adhered to the left kidney. A surgical tumor resection combined with a left nephrectomy is performed. During the 6th -month postoperative follow-up examination, we observed the local recurrence of the tumor in the operation area, in addition to multiple metastatic tumors in both lungs. Further, the prescribed 3-month targeted treatment with anlotinib significantly reduced the size of the metastatic pulmonary tumors. However, the recurrent retroperitoneal tumors showed no significant change in size. Eventually, we observed no substantial evidence of tumor progression, with the patient’s condition under control.

Conclusion

The case demonstrated that the postoperative recurrence of widespread RPLPS required R0 resection to cure the disease, considering targeted therapy for advanced RPLPS control.
Emergency medicine doctoral education in Africa: a scoping review of the published literature
Authors: Craig Wesley , Rambharose Sanjeev , Khan Waseela , Stassen Willem
Published: April 2023

Background

While Africa accounts for a significant proportion of world population, and disease and injury burden, it produces less than 1% of the total research output within emergency care. Emergency care research capacity in Africa may be expanded through the development of doctoral programmes that aim to upskill the PhD student into an independent scholar, through dedicated support and structured learning. This study therefore aims to identify the nature of the problem of doctoral education in Africa, thereby informing a general needs assessment within the context of academic emergency medicine.

Methods

A scoping review, utilising an a priori, piloted search strategy was conducted (Medline via PubMed and Scopus) to identify literature published between 2011 and 2021 related to African emergency medicine doctoral education. Failing that, an expanded search was planned that focused on doctoral education within health sciences more broadly. Titles, abstracts, and full texts were screened for inclusion in duplicate, and extracted by the principal author. The search was rerun in September 2022.

Results

No articles that focused on emergency medicine/care were found. Following the expanded search, a total of 235 articles were identified, and 27 articles were included. Major domains identified in the literature included specific barriers to PhD success, supervision practices, transformation, collaborative learning, and research capacity improvement.

Conclusions

African doctoral students are hindered by internal academic factors such as limited supervision and external factors such as poor infrastructure e.g. internet connectivity. While not always feasible, institutions should offer environments that are conducive to meaningful learning. In addition, doctoral programmes should adopt and enforce gender policies to help alleviate the gender differences noted in PhD completion rates and research publication outputs. Interdisciplinary collaborations are potential mechanisms to develop well-rounded and independent graduates. Post-graduate and doctoral supervision experience should be a recognised promotion criterion to assist with clinician researcher career opportunities and motivation. There may be little value in attempting to replicate the programmatic and supervision practices of high-income countries. African doctoral programmes should rather focus on creating contextual and sustainable ways of delivering excellent doctoral education.
Prevalence, causes and impact of TP53-loss phenocopying events in human tumors
Authors: Fito-Lopez Bruno , Salvadores Marina , Alvarez Miguel-Martin , Supek Fran
Published: April 2023

Background

TP53 is a master tumor suppressor gene, mutated in approximately half of all human cancers. Given the many regulatory roles of the corresponding p53 protein, it is possible to infer loss of p53 activity – which may occur due to alterations in trans – from gene expression patterns. Several such alterations that phenocopy p53 loss are known, however additional ones may exist, but their identity and prevalence among human tumors are not well characterized.

Results

We perform a large-scale statistical analysis on transcriptomes of ~ 7,000 tumors and ~ 1,000 cell lines, estimating that 12% and 8% of tumors and cancer cell lines, respectively, phenocopy TP53 loss: they are likely deficient in the activity of the p53 pathway, while not bearing obvious TP53 inactivating mutations. While some of these cases are explained by amplifications in the known phenocopying genes MDM2, MDM4 and PPM1D, many are not. An association analysis of cancer genomic scores jointly with CRISPR/RNAi genetic screening data identified an additional common TP53-loss phenocopying gene, USP28. Deletions in USP28 are associated with a TP53 functional impairment in 2.9–7.6% of breast, bladder, lung, liver and stomach tumors, and have comparable effect size to MDM4 amplifications. Additionally, in the known copy number alteration (CNA) segment harboring MDM2, we identify an additional co-amplified gene (CNOT2) that may cooperatively boost the TP53 functional inactivation effect of MDM2. An analysis of cancer cell line drug screens using phenocopy scores suggests that TP53 (in)activity commonly modulates associations between anticancer drug effects and various genetic markers, such as PIK3CA and PTEN mutations, and should thus be considered as a drug activity modifying factor in precision medicine. As a resource, we provide the drug-genetic marker associations that differ depending on TP53 functional status.

Conclusions

Human tumors that do not bear obvious TP53 genetic alterations but that phenocopy p53 activity loss are common, and the USP28 gene deletions are one likely cause.
A novel protein encoded by circRsrc1 regulates mitochondrial ribosome assembly and translation during spermatogenesis
Authors: Zhang Shu , Wang Chang , Wang Yue , Zhang Hao , Xu Chen , Cheng Yiwei , Yuan Yan , Sha Jiahao , Guo Xuejiang , Cui Yiqiang
Published: April 2023

Background

Circular RNAs (circRNAs) are a large class of mammalian RNAs. Several protein products translated by circRNAs have been reported to be involved in the development of various tissues and systems; however, their physiological functions in male reproduction have yet not been explored.

Results

Here, we report an endogenous circRNA (circRsrc1) that encodes a novel 161-amino-acid protein which we named Rsrc1-161aa through circRNA sequencing coupled with mass spectrometry analysis on mouse testicular tissues. Deletion of Rsrc1-161aa in mice impaired male fertility with a significant decrease in sperm count and motility due to dysfunctions of mitochondrial energy metabolism. A series of in vitro rescue experiments revealed that circRsrc1 regulates mitochondrial functions via its encoded protein Rsrc1-161aa. Mechanistically, Rsrc1-161aa directly interacts with mitochondrial protein C1qbp and enhances its binding activity to mitochondrial mRNAs, thereby regulating the assembly of mitochondrial ribosomes and affecting the translation of oxidative phosphorylation (OXPHOS) proteins and mitochondrial energy metabolism.

Conclusions

Our studies reveal that Rsrc1-161aa protein encoded by circRsrc1 regulates mitochondrial ribosome assembly and translation during spermatogenesis, thereby affecting male fertility.
Efficient manipulation of gene expression using Natronobacterium gregoryi Argonaute in zebrafish
Authors: Dong Zhangji , Chen Xu , Zhuo Run , Li Yuanyuan , Zhou Zhihao , Sun Ying , Liu Yan , Liu Mei
Published: April 2023

Background

Natronobacterium gregoryi Argonaute (NgAgo) was found to reduce mRNA without generating detectable DNA double-strand breaks in a couple of endogenous genes in zebrafish, suggesting its potential as a tool for gene knockdown. However, little is known about how it interacts with nucleic acid molecules to interfere with gene expression.

Results

In this study, we first confirmed that coinjection of NgAgo and gDNA downregulated target genes, generated gene-specific phenotypes and verified some factors (including 5’ phosphorylation, GC ratio, and target positions) of gDNAs affecting gene downregulation. Therein, the sense and antisense gDNAs were equally effective, suggesting that NgAgo possibly binds to DNA. NgAgo-VP64 with gDNAs targeting promoters upregulated the target genes, further providing evidence that NgAgo interacts with genomic DNA and controls gene transcription. Finally, we explain the downregulation of NgAgo/gDNA target genes by interference with the process of gene transcription, which differs from that of morpholino oligonucleotides.

Conclusions

The present study provides conclusions that NgAgo may target genomic DNA and that target positions and the gDNA GC ratio influence its regulation efficiency.
Clinical and genetic characteristics of children with COX20-associated mitochondrial disorder: case report and literature review
Authors: Chen Liqing , Liu Yan
Published: April 2023

Background

The deficiency of cytochrome c oxidase 20 is a rare autosomal recessive mitochondrial disorder characterized by ataxia, dysarthria, dystonia and sensory neuropathy.

Case presentation

In this study, we describe a patient from a non-consanguineous family exhibiting developmental delay, ataxia, hypotonia, dysarthria, strabismus, visual impairment and areflexia. An examination of nerve conduction showed a normal result at first but revealed axonal sensory neuropathy later. This situation has not been reported in any literatures. The whole-exome sequencing analysis revealed that the patient harbored compound heterozygous mutations (c.41 A > G and c.259G > T) of the COX20 gene. By literature review, 5 patients carried the same compound heterozygous mutations.

Conclusion

COX20 might be considered as a potential gene for the early-onset ataxia and the axonal sensory neuropathy. Our patient exhibited strabismus and visual impairment, which expands the clinical presentation of COX20 related mitochondrial disorders caused by the compound heterozygous variants (c.41 A > G and c.259G > T). However, a clear genotype/phenotype correlation has not yet been established. Additional researches and cases are needed to further confirm the correlation.
Novel, heterozygous, de novo pathogenic variant (c.4963delA: p.Thr1656Glnfs*42) of the NF1 gene in a Chinese family with neurofibromatosis type 1
Authors: Yang Lisha , Fu Jiewen , Cheng Jingliang , Zhou Baixu , Chen Maomei , Anuchapreeda Songyot , Fu Junjiang
Published: April 2023

Neurofibromatosis type 1 (NF1) presents an autosomal dominant, haploinsufficient, and multisystemic disorder with patches of skin café-au-lait spots, lisch nodules in the iris, even tumors in the peripheral nervous system or fibromatous skin. In this study, a Chinese young woman who suffered from NF1 disease with first-trimester spontaneous abortion was recruited. Analysis for whole exome sequencing (WES), Sanger sequencing, short tandem repeat (STR), and co-segregation was carried out. As results, a novel, heterozygous, de novo pathogenic variant (c.4963delA:p.Thr1656Glnfs*42) of the NF1 gene in the proband was identified. This pathogenic variant of the NF1 gene produced a truncated protein that lost more than one-third of the NF1 protein at the C-terminus including half of the CRAL-TRIO lipid-binding domain and nuclear localization signal (NLS), thus leading to pathogenicity (ACMG criteria: PVS1 + PM2 + PM2). Analysis for NF1 conservation in species revealed high conservation in different species. Analysis of NF1 mRNA levels in different human tissues showed low tissue specificity, which may affect multiple organs presenting other symptoms or phenotypes. Moreover, prenatal NF1 gene diagnosis showed both alleles as wild types. Thus, this NF1 novel variant probably underlays the NF1 pathogenesis in this pedigree, which would help for the diagnosis, genetic counseling, and clinical management of this disorder.