bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell multiomics of human fetal hematopoiesis define a developmental-specific population and a fetal signature
Authors: Sommarin Mikael N. E. , Olofzon Rasmus , Palo Sara , Dhapola Parashar , Soneji Shamit , Karlsson Göran , Böiers Charlotta
Published: June 2023

Knowledge of human fetal blood development and how it differs from adult blood is highly relevant to our understanding of congenital blood and immune disorders and childhood leukemia, of which the latter can originate in utero. Blood formation occurs in waves that overlap in time and space, adding to heterogeneity, which necessitates single-cell approaches. Here, a combined single-cell immunophenotypic and transcriptional map of first trimester primitive blood development is presented. Using CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), the molecular profile of established immunophenotype-gated progenitors was analyzed in the fetal liver (FL). Classical markers for hematopoietic stem cells (HSCs), such as CD90 and CD49F, were largely preserved, whereas CD135 (FLT3) and CD123 (IL3R) had a ubiquitous expression pattern capturing heterogenous populations. Direct molecular comparison with an adult bone marrow data set revealed that the HSC state was less frequent in FL, whereas cells with a lymphomyeloid signature were more abundant. An erythromyeloid–primed multipotent progenitor cluster was identified, potentially representing a transient, fetal-specific population. Furthermore, differentially expressed genes between fetal and adult counterparts were specifically analyzed, and a fetal core signature was identified. The core gene set could separate subgroups of acute lymphoblastic leukemia by age, suggesting that a fetal program may be partially retained in specific subgroups of pediatric leukemia. Our detailed single-cell map presented herein emphasizes molecular and immunophenotypic differences between fetal and adult blood cells, which are of significance for future studies of pediatric leukemia and blood development in general.
topr: an R package for viewing and annotating genetic association results
Authors: Juliusdottir Thorhildur
Published: June 2023

Background

The successful identification of genetic loci for complex traits in genome-wide association studies (GWAS) has resulted in thousands of GWAS summary statistics becoming publicly available for hundreds of complex traits from multiple cohorts and studies. Visualisation is an important aid for interpreting, comparing, validating, and obtaining an overview of large amounts of data. However, the current software is limited in its ability and flexibility to annotate and simultaneously display multiple GWAS results which is useful when interpreting and comparing association results. Therefore, I created thetoprR package to facilitate visualisation, annotation, and comparisons of single or multiple GWAS results. It contains functions tailored for viewing and analysing GWAS results.

Results

toprprovides a fast and elegant visual display of association results, along with the annotation of association peaks with their nearest gene. Association results from multiple analyses can be viewed simultaneously over the entire genome or in a more detailed regional view along with gene information. Users can perform the essential steps of visually exploring and annotating association results and generating elegant publication-ready plots.

Conclusions

topris developed as a package for the R statistical computing environment, released under the GNU General Public License, and is freely available on the Comprehensive R Archive Network (http://cran.r-project.org/package=topr). The source code is available at GitHub (https://github.com/totajuliusd/topr).toprprovides several advantages and advances over the current alternatives, particularly in its gene annotation functionality and customisable display of single- or multiple-association results. Withtopr, I provide a flexible tool with multiple features to aid in the analysis and evaluation of GWAS association results.
PATH-SURVEYOR: pathway level survival enquiry for immuno-oncology and drug repurposing
Authors: Obermayer Alyssa N. , Chang Darwin , Nobles Gabrielle , Teng Mingxiang , Tan Aik-Choon , Wang Xuefeng , Chen Y. Ann , Eschrich Steven , Rodriguez Paulo C. , Grass G. Daniel , Meshinchi Soheil , Tarhini Ahmad , Chen Dung-tsa , Shaw Timothy I.
Published: June 2023

Pathway-level survival analysis offers the opportunity to examine molecular pathways and immune signatures that influence patient outcomes. However, available survival analysis algorithms are limited in pathway-level function and lack a streamlined analytical process. Here we present a comprehensive pathway-level survival analysis suite, PATH-SURVEYOR, which includes a Shiny user interface with extensive features for systematic exploration of pathways and covariates in a Cox proportional-hazard model. Moreover, our framework offers an integrative strategy for performing Hazard Ratio ranked Gene Set Enrichment Analysis and pathway clustering. As an example, we applied our tool in a combined cohort of melanoma patients treated with checkpoint inhibition (ICI) and identified several immune populations and biomarkers predictive of ICI efficacy. We also analyzed gene expression data of pediatric acute myeloid leukemia (AML) and performed an inverse association of drug targets with the patient’s clinical endpoint. Our analysis derived several drug targets in high-risk KMT2A-fusion-positive patients, which were then validated in AML cell lines in the Genomics of Drug Sensitivity database. Altogether, the tool offers a comprehensive suite for pathway-level survival analysis and a user interface for exploring drug targets, molecular features, and immune populations at different resolutions.
The trends in death of primary liver cancer caused by specific etiologies worldwide: results from the Global Burden of Disease Study 2019 and implications for liver cancer management
Authors: Li Yongzhi , Ou Zejin , Yu Danfeng , He Huan , Zheng Liting , Chen Jiaqi , Chen Caiyun , Xiong Hushen , Chen Qing
Published: June 2023

Background

Over past decades, epidemiological patterns of liver cancer (LC) have changed dramatically. The Global Burden of Disease (GBD) study provides an opportunity for tracking the progress in cancer control with its annual updated reports at national, regional and global level, which can facilitate the health decision-making and the allocation of health resources. Therefore, we aim to estimate the global, regional and national trends of death caused by liver cancer due to specific etiologies and attributable risks from 1990 to 2019.

Materials and methods

Data was collected from the GBD study 2019. Estimated annual percentage changes (EAPC) were used to quantify the trends of age-standardized death rate (ASDR). We applied a linear regression for the calculation of estimated annual percentage change in ASDR.

Results

From 1990 to 2019, the ASDR of liver cancer decreased globally (EAPC =  − 2.23, 95% confidence interval [CI]: − 2.61 to − 1.84). Meanwhile, declining trends were observed in both sexes, socio-demographic index (SDI) areas, and geographies, particularly East Asia (EAPC =  − 4.98, 95% CI: − 5.73 to − 4.22). The ASDR for each of the four major etiologies fell globally, while liver cancer caused by hepatitis B had the largest drop (EPAC =  − 3.46, 95% CI: − 4.01 to − 2.89). China has had dramatic decreases in death rates on a national scale, particularly when it comes to the hepatitis B etiology (EAPC =  − 5.17, 95% CI: − 5.96 to − 4.37). However, certain nations, such as Armenia and Uzbekistan, saw a rise in liver cancer mortality. Controlling smoking, alcohol, and drug use contributed to a drop in LC-related mortality in the majority of socio-demographic index areas. Nevertheless, the excessive body mass index (BMI) was portrayed as the underlying cause for LC fatalities.

Conclusion

From 1990 to 2019, there was a worldwide decrease in deaths caused by liver cancer and its underlying causes. However, rising tendencies have been observed in low-resource regions and countries. The trends in drug use- and high BMI-related death from liver cancer and its underlying etiologies were concerning. The findings indicated that efforts should be increased to prevent liver cancer deaths through improved etiology control and risk management.
Prognostic value of pre-therapeutic nutritional risk factors in elderly patients with locally advanced esophageal squamous cell carcinoma receiving definitive chemoradiotherapy or radiotherapy
Authors: Qiu Jianjian , Yang Jun , Yu Yilin , Wang Zhiping , Lin Hancui , Ke Dongmei , Zheng Hongying , Li Jiancheng , Yao Qiwei
Published: June 2023

Background

The nutritional status of cancer patients is a crucial factor in determining their prognosis. The objective of this study was to investigate and compare the prognostic value of pretreatment nutrition-related indicators in elderly esophageal squamous cell carcinoma (ESCC). Risk stratification was performed according to independent risk factors and a new nutritional prognostic index was constructed.

Methods

We retrospectively reviewed 460 older locally advanced ESCC patients receiving definitive chemoradiotherapy (dCRT) or radiotherapy (dRT). This study included five pre- therapeutic nutrition-related indicators. The optimal cut-off values for these indices were calculated from the Receiver Operating Curve (ROC). Univariate and multivariate COX analyses were employed to determine the association between each indicator and clinical outcomes. The predictive ability of each independently nutrition-related prognostic indicator was assessed using the time-dependent ROC (time-ROC) and C-index.

Results

Multivariate analyses indicated that the geriatric nutrition risk index (GNRI), body mass index (BMI), the controlling nutritional status (CONUT) score, and platelet-albumin ratio (PAR) could independently predict overall survival (OS) and progression-free survival (PFS) in elderly patients with ESCC (all p < 0.05), except for prognostic nutritional index (PNI). Based on four independently nutrition-related prognostic indicators, we developed pre-therapeutic nutritional prognostic score (PTNPS) and new nutritional prognostic index (NNPI). No-risk (PTNPS = 0–1 point), moderate-risk (PTNPS = 2 points), and high-risk (PTNPS = 3–4 points) groups had 5-year OS rates of 42.3%, 22.9%, and 8.8%, respectively (p < 0.001), and 5-year PFS rates of 44.4%, 26.5%, and 11.3%, respectively (p < 0.001). The Kaplan–Meier curves showed that the mortality of elderly ESCC patients in the high-risk group was higher than that in the low-risk group according to the NNPI.

Analysis of time-AUC and C-index revealed that the NNPI (C-index: 0.663) had the greatest predictive power on the prognosis in older ESCC patients.

Conclusions

In elderly ESCC patients, the GNRI, BMI, CONUT score, and PAR can be used as objective assessment measures for the risk of nutrition-related death. Compared to the other four indexes, the NNPI has the greatest prognostic value for prognosis, and elderly patients with a higher nutritional risk have a poor prognosis, which is helpful in guiding early clinical nutrition intervention.
Trends and influencing factors of HIV health education receive rate among 0.57 million migrants in China from 2009 to 2017: a national population-based study
Authors: Che Yue , Wang Jun , Song Chao , Wang Xueyao , Bai Yang , Liu Jue
Published: June 2023

Introduction

China has implemented Basic Public Health Service (BPHS) in 2009, aiming to improve the health status of the people, and the content of service includes implying health education for residents. As an important group of people, the migrants can easily become main reason for major infectious diseases such as HIV between different provinces, but the effect of receiving health education is still unknown for migrants. Therefore, the health education of China’s migrant population has received widespread attention.

Methods

This study used the data of the China Migrants Dynamic Survey (CMDS) from 2009 to 2017, and evaluated the trend of HIV health education acceptance rate of different migrant groups across the country (n = 570,614). Logistic regression model was used to test the influencing factors of HIV health education rate. Results: The study found that the overall HIV health education rate of Chinese migrants decreased from 2009 to 2017, and different types of migrants showed different trends. The proportion of migrants aged 20–35 who receive education fluctuates, and ethnic minorities, western regions, and migrants with high education were more likely to receive HIV health education. Conclusion: These findings identify when implementing health education for migrants, we can carry out more education for specific groups to promote the health equity of the migrant population.
Vaccination in the childhood and awareness of basic public health services program among internal migrants: a nationwide cross-sectional study
Authors: Wang Jun , Bai Yang , Zhu Jingmin , Wang Xueyao , Liu Jue
Published: June 2023

Background

Vaccination is proved to be one of the most effective and efficient way to prevent illness and reduce health inequality. Studies about association between vaccination inequalities in the childhood and awareness of basic public health services program among internal migrants in China are lacking. In this study, we aimed to explore the association between migrants’ vaccination status between 0 and 6 years old and their awareness of the National Basic Public Health Services (BPHSs) project in China.

Methods

We included 10,013 respondents aged 15 years old or above of eight provinces from 2017 Migrant Population Dynamic Monitoring Survey in China, a nationwide cross-sectional study. Univariate and multivariable logistic regressions were used to assess vaccination inequalities and the awareness of public health information.

Results

Only 64.8% migrants were vaccinated in their childhood, which is far below the goal of national requirement of 100% vaccination. This also indicated the vaccination inequalities among migrants. Female, the middle-aged, married or having a relationship, the highly educated and the healthy population had higher awareness of this project than others. Both univariate and multivariate logistic regressions showed greatly significant association between vaccination status and some vaccines. Specifically, after adding convariates, the results showed that there were significant associations between the vaccination rates of eight recommended vaccines in the childhood and their awareness of BPHSs project (all p values < 0.001), including HepB vaccine (OR: 1.28; 95%CI: 1.19, 1.37), HepA vaccine (OR: 1.27; 95%CI: 1.15, 1.41), FIn vaccine (OR: 1.28; 95%CI: 1.16, 1.45), JE vaccine (OR: 1.14; 95%CI: 1.04, 1.27), TIG vaccine (OR: 1.27; 95%CI: 1.05, 1.47), DTaP vaccine (OR: 1.30; 95%CI: 1.11–1.53), MPSV vaccine (OR: 1.26; 95%CI: 1.07–1.49), HF vaccine (OR: 1.32; 95%CI: 1.11, 1.53), except for RaB vaccine (OR: 1.07; 95%CI: 0.89, 1.53).

Conclusions

The vaccination inequalities exist among migrants. There is a strong relationship between the vaccination status in the childhood and the awareness rate of BPHSs project among migrants. From our findings we could know that the promotion of vaccination rates of the disadvantaged population such as the internal migrants or other minority population can help them increase the awareness of free public health services, which was proved to be beneficial for health equity and effectiveness and could promote public health in the future.
L-shaped association of serum 25-hydroxyvitamin D with all-cause and cardiovascular mortality in older people with chronic kidney disease: results from the NHANES database prospective cohort study
Authors: Li Rugang , Li Yang , Fan Zhongcheng , Liu Zhaoqi , Lin Juhua , He Min
Published: June 2023

Background

This study was conducted to assess the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cardiovascular disease (CVD) mortality in older people with chronic kidney disease (CKD) in the United States.

Methods

We identified 3230 CKD participants aged ≥ 60 years from the National Health and Nutrition Examination Survey (2001–2018). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. Mortality outcomes were determined by linkage to National Death Index (NDI) records through December 31, 2019. Restricted cubic spline based on Cox regression models were utilized to elucidate the nonlinear relationship between serum 25(OH)D concentrations and mortality in patients with CKD.

Results

During median 74 months of follow-up, 1615 all-cause death and 580 CVD death were recorded. We found an L-shaped association between serum 25(OH)D concentrations and all-cause and CVD mortality, reaching a plateau at 90 nmol/L. Accordingly, per one-unit increment in natural log-transformed 25(OH)D was associated with a 32% and 33% reduced risk of all-cause mortality (hazard ratio [HR] 0.68; 95%CI, 0.56 to 0.83) and CV mortality (HR 0.69; 95%CI, 0.49 to 0.97) in participants with serum 25(OH)D < 90 nmol/L, but no considerable difference was observed in participants with serum 25(OH)D ≥ 90 nmol/L. Compared with those in the deficiency group (< 50 nmol/L), insufficient (50 to < 75 nmol/L) and sufficient group (≥ 75 nmol/L) were significantly associated with lower all-cause mortality (HR,0.83; 95%CI, 0.71 to 0.97 and HR, 0.75; 95%CI, 0.64 to 0.89) and CV mortality (HR,0.87; 95%CI, 0.68 to 1.10 and HR, 0.77; 95%CI, 0.59 to < 1.0), respectively.

Conclusion

An L-shaped relationship between serum 25(OH)D levels with all-cause and CVD mortality was observed in elderly CKD patients in the United States. A 25(OH)D concentration of 90 nmol/L may be the target to reduce the risk of premature death.
Association between AXIN1 gene polymorphism (rs9921222) of WNT signaling pathway and susceptibility to osteoporosis in Egyptian patients: a case-control study
Authors: Nassar Eman Saad , Elnemr Rehab , Shaaban Ahmed , Elhameed Asmaa Abd , Taleb Raghda Saad Zaghloul
Published: June 2023

Background

Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility.

Methods

A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk.

Results

We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03–136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23–31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7–110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6–36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001).

Conclusion

AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP.
A qualitative descriptive study exploring clinicians’ perspectives of the management of older trauma care in rural Australia
Authors: Ferrah Noha , Parker Catriona , Ibrahim Joseph , Gabbe Belinda , Cameron Peter
Published: June 2023

Background

For older trauma patients who sustain trauma in rural areas, the risk of adverse outcomes associated with advancing age, is compounded by the challenges encountered in rural healthcare such as geographic isolation, lack of resources, and accessibility. Little is known of the experience and challenges faced by rural clinicians who manage trauma in older adults. An understanding of stakeholders’ views is paramount to the effective development and implementation of a trauma system inclusive of rural communities. The aim of this descriptive qualitative study was to explore the perspectives of clinicians who provide care to older trauma patients in rural settings.

Method

We conducted semi-structured interviews of health professionals (medical doctors, nurses, paramedics, and allied health professionals) who provide care to older trauma patients in rural Queensland, Australia. A thematic analysis consisting of both inductive and deductive coding approaches, was used to identify and develop themes from interviews.

Results

Fifteen participants took part in the interviews. Three key themes were identified: enablers of trauma care, barriers, and changes to improve trauma care of older people. The resilience of rural residents, and breadth of experience of rural clinicians were strengths identified by participants. The perceived systemic lack of resources, both material and in the workforce, and fragmentation of the health system across the state were barriers to the provision of trauma care to older rural patients. Some changes proposed by participants included tailored education programs that would be taught in rural centres, a dedicated case coordinator for older trauma patients from rural areas, and a centralised system designed to streamline the management of older trauma patients coming from rural regions.

Conclusions

Rural clinicians are important stakeholders who should be included in discussions on adapting trauma guidelines to the rural setting. In this study, participants formulated pertinent and concrete recommendations that should be weighed against the current evidence, and tested in rural centres.
Bivalent mRNA vaccine effectiveness against SARS-CoV-2 variants of concern
Authors: Kumari Monika , Su Shih-Chieh , Liang Kang-Hao , Lin Hsiu-Ting , Lu Yu-Feng , Chen Kai-Chi , Chen Wan-Yu , Wu Han-Chung
Published: June 2023

Background

Sequential infections with SARS-CoV-2 variants such as Alpha, Delta, Omicron and its sublineages may cause high morbidity, so it is necessary to develop vaccines that can protect against both wild-type (WT) virus and its variants. Mutations in SARS-CoV-2’s spike protein can easily alter viral transmission and vaccination effectiveness.

Methods

In this study, we designed full-length spike mRNAs for WT, Alpha, Delta, and BA.5 variants and integrated each into monovalent or bivalent mRNA-lipid nanoparticle vaccines. A pseudovirus neutralization assay was conducted on immunized mouse sera in order to examine the neutralizing potential of each vaccine.

Results

Monovalent mRNA vaccines were only effective against the same type of virus. Interestingly, monovalent BA.5 vaccination could neutralize BF.7 and BQ.1.1. Moreover, WT, Alpha, Delta, BA.5, and BF.7 pseudoviruses were broadly neutralized by bivalent mRNA vaccinations, such as BA.5 + WT, BA.5 + Alpha, and BA.5 + Delta. In particular, BA.5 + WT exhibited high neutralization against most variants of concern (VOCs) in a pseudovirus neutralization assay.

Conclusions

Our results show that combining two mRNA sequences may be an effective way to develop a broadly protective SARS-CoV-2 vaccine against a wide range of variant types. Importantly, we provide the optimal combination regimen and propose a strategy that may prove useful in combating future VOCs.
Scenarios of maternal mortality reduction by 2030 in the Americas: insights from its tempo
Authors: Sanhueza Antonio , Mujica Oscar J. , Soliz Patricia N. , Cox Adrienne L. , de Mucio Bremen
Published: June 2023

Background

The enduring threat of maternal mortality to health worldwide and in the Americas has been recognized in the global and regional agendas and their targets to 2030. To inform the direction and amount of effort needed to meet those targets, a set of equity-sensitive regional scenarios of maternal mortality ratio (MMR) reduction based on its tempo or speed of change from baseline year 2015 was developed.

Methods

Regional scenarios by 2030 were defined according to: i) the MMR average annual rate of reduction (AARR) needed to meet the global (70 per 100,000) or regional (30 per 100,000) targets and, ii) the horizontal (proportional) or vertical (progressive) equity criterion applied to the cross-country AARR distribution (i.e., same speed to all countries or faster for those with higher baseline MMR). MMR average and inequality gaps –absolute (AIG), and relative (RIG)– were scenario outcomes.

Results

At baseline, MMR was 59.2 per 100,000; AIG was 313.4 per 100,000 and RIG was 19.0 between countries with baseline MMR over twice the global target and those below the regional target. The AARR needed to meet the global and regional targets were -7.60% and -4.54%, respectively; baseline AARR was -1.55%. In the regional MMR target attainment scenario, applying horizontal equity would decrease AIG to 158.7 per 100,000 and RIG will remain invariant; applying vertical equity would decrease AIG to 130.9 per 100,000 and RIG would decrease to 13.5 by 2030.

Conclusion

The dual challenge of reducing maternal mortality and abating its inequalities will demand hefty efforts from countries of the Americas. This remains true to their collective 2030 MMR target while leaving no one behind. These efforts should be mainly directed towards significantly speeding up the tempo of the MMR reduction and applying sensible progressivity, targeting on groups and territories with higher MMR and greater social vulnerabilities, especially in a post-pandemic regional context.
Currently recommended skin scores correlate highly in the assessment of patients with Juvenile Dermatomyositis (JDM)
Authors: Gebreamlak Alexander , Sawicka Katherine M. , Garrett Rose , Goh Y. Ingrid , Baker Kayla M. , Feldman Brian M.
Published: June 2023

Background

Juvenile Dermatomyositis (JDM) is a rare, chronic, and life-threatening childhood autoimmune disease. Currently, there are recommended, reliable and validated measurement tools for assessment of skin disease activity in JDM including the Disease Activity Score (skinDAS), Cutaneous Assessment Tool (CAT), and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). The Physician’s global assessment skin visual analog scale (Skin VAS) is also widely used for skin activity in JDM. For the purpose of comparative international studies, we wanted to compare these tools to the Physician’s skin VAS (as a standard) to identify which performs better.

Objectives

We sought to compare the correlations of these scoring tools, and separately assess the responsiveness each tool demonstrates following patient treatment, in order to see if one tool may be preferred. This was determined by assessing how well these tools correlate with each other, and the Physician’s skin VAS over time, as well as the responsiveness of each tool after patient treatment.

Methods

Skin scores were recorded at a baseline (first visit after June 1st, 2018) and all follow-up office visits at the Juvenile Dermatomyositis Clinic. Following baseline visits, patients were followed up as clinically indicated. A subset of newly diagnosed patients (inception cohort) was identified. Correlations were assessed at the baseline visit and over time for the whole cohort. The correlations over time were derived using Generalized Estimating Equations (GEEs). Standardized response means with 95% confidence intervals were calculated to test score responsiveness for the nested inception cohort.

Results

The skinDAS, CAT and CDASI all correlated highly with each other and with the Physician’s skin VAS. The three scoring tools accurately reflected Physician’s skin VAS scores over time. In addition, all tools showed moderate to high responsiveness following treatment.

Conclusion

All studied skin score tools performed well in our study and appear to be useful. Since no tool far outperforms the others, arbitrary consensus will be needed to select a single standard measurement tool for the purposes of efficiency and global comparability.
Boost modalities in cervical cancer: dosimetric comparison between intracavitary BT vs. intracavitary + interstitial BT vs. SBRT.
Authors: Benkhaled Sofian , Diakité Kadiatou , Jullian Nicolas , Poeta Sara , Vandekerkhove Christophe , Van Houtte Paul , Van Gestel Dirk , De Caluwé Alex
Published: June 2023

Purpose / objective

This study compares the dosimetric plans of three distinct boost modalities in cervical cancer (CC): intracavitary (IC) with tandem/ovoids brachytherapy (BT), IC + interstitial (IS) BT, and Stereotactic-Body-Radiotherapy (SBRT). The aim is to determine the dosimetric impact in terms of target coverage and organ at risk (OAR) doses.

Materials and methods

24 consecutive IC + IS BT boost treatment plans were retrospectively identified. For each plan included, two additional plans were created: IC-BT and SBRT. Importantly, no planning target volume (PTV) or planning (organ at) risk volume (PRV) margins were generated, therefore all structures were identical for any boost modality. Two different normalizations were performed: (1) Normalization to the target: prescription of 7.1 Gy to the D90% (defined as the minimum dose covering 90%) of the high-risk clinical target volume (HR-CTV); (2) Normalization to the OARs. HR-CTV coverage and OARs sparing were compared. The equivalent doses in 2 Gy fractions (EQD2) of EBRT and BT for CTV-HR and OARs were calculated using the linear-quadratic model with α/β of 10 (EQD210) and 3 (EQD23), respectively

Results

A total of 72 plans were investigated. In the first normalization, the mean EQD23−D2cc (defined as the minimal dose of the 2 cc) of OAR was significantly higher in the IC-BT plans, and the bladder D2cc hard constraint could not be reached. IC + IS BT leads to a 1 Gy mean absolute decrease of bladder EQD23-D2cc (relative dose: -19%), allowing to reach the hard constraint. SBRT (without PTV) delivers the lowest EQD23-D2cc to the OAR. In the second normalization, IC-BT provides a significantly lower dose to the EQD210-D90% (6.62 Gy) and cannot achieve the coverage goal. SBRT (without PTV) yields the highest dose to the D90% of HR-CTV and a significantly lower EQD210-D50% and D30%.

Conclusion

The key dosimetric benefit of BT over SBRT without PTV is a significantly higher D50% and D30% in the HR-CTV, which increases the local and conformal dose to the target. IC + IS BT vs. IC-BT provides significantly better target coverage and a lower dose to the OARs, making it the preferred boost modality in CC.
Yangqing Chenfei formula alleviates silica-induced pulmonary inflammation in rats by inhibiting macrophage M1 polarization
Authors: Tian Xinrong , Wei Yu , Hou Runsu , Liu Xinguang , Tian Yange , Zhao Peng , Li Jiansheng
Published: June 2023

Background

Yangqing Chenfei formula (YCF) is a traditional Chinese medicine formula for early-stage silicosis. However, the therapeutic mechanism is unclear. The purpose of this study was to determine the mechanism for the effects of YCF on early-stage experimental silicosis.

Methods

The anti-inflammatory and anti-fibrotic effects of YCF were determined in a silicosis rat model, which was established by intratracheal instillation of silica. The anti-inflammatory efficacy and molecular mechanisms of YCF were examined in a lipopolysaccharide (LPS)/interferon (IFN)-γ-induced macrophage inflammation model. Network pharmacology and transcriptomics were integrated to analyze the active components, corresponding targets, and anti-inflammatory mechanisms of YCF, and these mechanisms were validated in vitro.

Results

Oral administration of YCF attenuated the pathological changes, reduced inflammatory cell infiltration, inhibited collagen deposition, decreased the levels of inflammatory factors, and reduced the number of M1 macrophages in the lung tissue of rats with silicosis. YCF5, the effective fraction of YCF, significantly attenuated the inflammatory factors induced by LPS and IFN-γ in M1 macrophages. Network pharmacology analysis showed that YCF contained 185 active components and 988 protein targets, which were mainly associated with inflammation-related signaling pathways. Transcriptomic analysis showed that YCF regulated 117 reversal genes mainly associated with the inflammatory response. Integrative analysis of network pharmacology and transcriptomics indicated that YCF suppressed M1 macrophage-mediated inflammation by regulating signaling networks, including the mTOR, mitogen-activated protein kinases (MAPK), PI3K-Akt, NF-κB, and JAK-STAT signaling pathways. In vitro studies confirmed that the active components of YCF significantly decreased the levels of p-mTORC1, p-P38, and p-P65 by suppressing the activation of related-pathways.

Conclusion

YCF significantly attenuated the inflammatory response in rats with silicosis via the suppression of macrophage M1 polarization by inhibiting a “multicomponent-multitarget-multipathway” network.
On some inequalities for uniformly convex mapping with estimations to normal distributions
Authors: Butt Saad Ihsan , Sayyari Yamin , Agarwal Praveen , Nieto Juan J. , Umar Muhammad
Published: June 2023

In this paper, we introduce notable Jensen–Mercer inequality for a general class of convex functions, namely uniformly convex functions. We explore some interesting properties of such a class of functions along with some examples. As a result, we establish Hermite–Jensen–Mercer inequalities pertaining uniformly convex functions by considering the class of fractional integral operators. Moreover, we establish Mercer–Ostrowski inequalities for conformable integral operator via differentiable uniformly convex functions. Finally, we apply our inequalities to get estimations for normal probability distributions (Gaussian distributions).
Construction of Cupriavidus necator displayed with superoxide dismutases for enhanced growth in bioelectrochemical systems
Authors: Chen Ke , Ma Chunling , Cheng Xiaolei , Wang Yuhua , Guo Kun , Wu Ranran , Zhu Zhiguang
Published: June 2023

It is of great significance to utilize CO2 as feedstock to synthesize biobased products, particularly single cell protein (SCP) as the alternative food and feed. Bioelectrochemical system (BES) driven by clean electric energy has been regarded as a promising way for Cupriavidus necator to produce SCP from CO2 directly. At present, the key problem of culturing C. necator in BES is that reactive oxygen species (ROS) generated in cathode chamber are harmful to bacterial growth. Therefore, it is necessary to find a solution to mitigate the negative effect of ROS. In this study, we constructed a number of C. necator strains displayed with superoxide dismutase (SOD), which allowed the decomposition of superoxide anion radical. The effects of promoters and signal peptides on the cell surface displayed SOD were analyzed. The proteins displayed on the surface were further verified by the fluorescence experiment. Finally, the growth of C. necator CMS incorporating a pBAD-SOD-E-tag-IgAβ plasmid could achieve 4.9 ± 1.0 of OD600 by 7 days, equivalent to 1.7 ± 0.3 g/L dry cell weight (DCW), and the production rate was 0.24 ± 0.04 g/L/d DCW, around 2.7-fold increase than the original C. necator CMS (1.8 ± 0.3 of OD600). This study can provide an effective and novel strategy of cultivating strains for the production of CO2-derived SCP or other chemicals in BES.

Graphical Abstract
Promoting dairy consumption behavior in the school setting: an experiment based on the transtheoretical model
Authors: Rouhani-Tonekaboni Nooshin , Sabrkonandeh Sara , Ashouri Asieh , Kasmaei Parisa , Mirzaei-Alavijeh Mehdi
Published: June 2023

Background

Nutrition education is a key component of health promotion programs which leads to the improvement of students’ nutritional behaviors. The transtheoretical model (TTM) is one of the models extensively used in changing people’s behaviors. This study aimed to change the dairy consumption behavior based on the TTM in female students.

Methods

A controlled trial was conducted with 159 female students (intervention group: 56; control group: 103) in the 10-11th grades from two public schools in Soumesara city located in the west of Gilan Province, Iran. Demographic characteristics, knowledge, TTM constructs and stage of change of dairy consumption were collected using a valid and reliable researcher-made questionnaire. Data were gathered before and one month after the educational intervention. Chi-square test, t-test and ANCOVA were used to analyze the data and a p-value < 0.05 was considered statistically significant.

Results

Fifty-two students from the intervention and 93 from the control group completed the study. Only 15% of the students were in the action or maintenance stages of dairy consumption. After the intervention, mean scores of behavioral processes of change, cognitive processes of change, decisional balance, and self-efficacy improved in the intervention group (P < 0.05 for all). Also, 37% and 16% of the participants in the intervention and control groups, respectively, were in the action or maintenance phase (P < 0.001).

Conclusions

This study showed that implementing an intervention based on the TTM would positively affect students’ dairy consumption behaviors. Also, it is suggested that the TTM be assessed in terms of other daily nutritional needs in students to promote their nutritional behaviors.

Trial Registration

The study was registered in the Iranian Registry of Clinical Trials (IRCT) (available online at https://en.irct.ir/trial/50003) on April 11, 2020 with the number IRCT20200718048132N1 and was approved by research ethics committee of Guilan University of Medical Sciences, Iran.
Diet and bowel function in children with Hirschsprung’s disease: development and content validation of a patient-reported questionnaire
Authors: Telborn Lovisa , Kumlien Christine , Granéli Christina , Axelsson Irene , Stenström Pernilla
Published: June 2023

Background

Although dietary adjustments are recommended frequently for bowel symptoms, evidence of diet’s impact on bowel function is lacking. The aim was to develop a patient-reported outcome instrument, for children with and without Hirschsprung’s disease (HD), to explore experiences of dietary effects on bowel function.

Methods

Children with and without HD and their parents participated. Questionnaire items regarding the impact of diet on bowel function originated from focus group discussions. Specific food items, reported in the literature or in focus groups to cause bowel functional effects, were listed requesting each item’s effect size and effect type. Content validity was tested within two separate semistructured interviews. A pilot test was performed. Assessing comprehension, relevance and wording clarity structurally, revisions were made accordingly. Children’s bowel function was assessed through the validated Rintala Bowel Function Score.

Results

A total of 13 children with and without HD, median age 7 (range 2–15) years, and 18 parents participated in the validation. Each question’s relevance had been ranked highly early in the validation process but most questions needed refining for improving clarity and comprehension. Wordings regarding bowel symptoms and emotions connected to food in particular were perceived to be sensitive and complex. Specifically wording regarding some bowel symptoms (gases, pain) and parental stress emotions (guilt, ambivalence) were, consistent with participants’ opinions, subjected to multiple step revisions. Following the validation process, which included two semistructure interviews with different participants and then a pilot test with a third cohort, a full track overview of changes and rewording made in all steps of the validation process was presented. The final questionnaire then comprised 13 questions assessing foods’ significance for bowel function, emotions, social impact and 90 specific food items’ possible effects and effect sizes on bowel function.

Conclusions

The Diet and Bowel Function questionnaire, enabling answering by children, was developed and the content validated qualitatively. This report presents insights into the whole validation process, declaring reasons for the selected question- and answering options, and their wordings. The Diet and Bowel Function questionnaire can be used as a survey questionnaire to enhance understanding of dietary effects on bowel function in children, and its results can be supportive in improving dietary-treatment programs.
Combined and comparative analytical studies with stability studies and validation for estimation of prenoxdiazine HCl in pharmaceutical dosage form
Authors: Shah Ronak , Nagar Akhil , Bardiya Ruchita , Shirkhedkar Atul , Purohit Drashti , Bendale Atul
Published: June 2023

Background

A precise, accurate, economical and reproducible UV, RP-HPLC and UPLC method has been developed for the estimation of Prenoxdiazine hydrochloride in pharmaceutical and bulk dosage form. Each of the developed method has been validated for the analysis of Prenoxdiazine hydrochloride.

Result

The validation of the analytical methods was carried out based on various parameters like precision, linearity, accuracy, specificity, LOD, and LOQ for all the three methods. The parameters were found statistically significant for the analysis of Prenoxdiazine hydrochloride. The method was found sensitive in the presence of analytical impurities. The retention time of the Prenoxdiazine HCl was found to be 2.5 and 2.9 min, using common solvents acetonitrile and methanol, in UPLC and HPLC, respectively.

Conclusion

The method may be useful in the wide range of analysis for the estimation of Prenoxdiazine hydrochloride. It is found to be robust upon the change in solvent flow rate, column temperatures. Further, the study has investigated the stability of the sample under stressed condition like thermal, oxidative, and photolytic. Here, we tried to develop and compare cost-effective methods for Prenoxdiazine HCl using most common industrial methods which are never studied.
Exploring the probiotic potentiality and antibacterial activity of idli batter isolates of lactic acid bacteria from West Bengal, India
Authors: Sircar Bijayanta , Mandal Shyamapada
Published: June 2023

Background

The lactic acid bacteria (LAB), from diverse sources, are of great importance as probiotics, and several authors from around the globe have reported LAB, isolated from various fermented foods, as potential antimicrobial agents. The current study explored the antibacterial activity and probiotic property of idli batter isolates of LAB, for the first time from Malda (West Bengal, India).

Results

The LAB procured from fresh and fermented idli batter samples had antibacterial activity against pathogenic as well as food-borne bacteria with zone diameter of inhibition of 16, 18 and 23 mm with concentrations 25, 50 and 75 μl/well, respectively, as determined by agar-well diffusion method. The identification of isolated LAB was executed through biochemical tests, 16S rRNA gene sequencing and phylogenetic analysis. The LAB isolates from fresh idli batter: LMEM1001 and LMEM1002, showed maximum (96.81% and 95.20%, respectively) similarities withLactiplantibacillus pentosusandLactiplantibacillus plantarum,respectively, whereas the fermented idli batter isolates, LMEM1006 and LMEM1008, showed maximum (96.11% and 98.40%, respectively) similarities withLactiplantibacillus plantarumandLimosilactobacillus fermentum,respectively. Safety profiling of isolated LAB was executed using antibiogram, DNase and gelatinase tests.

Conclusions

The idli batter-derived lactobacilli have been demonstrated as good probiotics, which displayed excellent antibacterial activity against clinical and food-borne bacteria. Overall, the idli batter isolates of LAB might be useful as probiotics for human consumption and as biotherapeutics in combating bacterial antibiotic resistance.
Case report of spontaneous sino-cutaneous fistula in chronic rhinosinusitis
Authors: Wong Song Yeu , Lim Li Yun , Ramli Ramiza Ramza , Tang Ing Ping
Published: June 2023

Background

Chronic rhinosinusitis (CRS) is a common disease characterized by inflammation of the paranasal sinuses, with symptoms such as nasal blockage, facial pain, hyposmia, and headache. While these symptoms are often treated as a common cold, the disease can lead to serious complications if left untreated. We present an unusual case of CRS in which the patient presented to the ophthalmology department with persistent pus discharge from the left upper eyelid for 6 months, despite being treated with multiple courses of antibiotics and undergoing incision and drainage procedures.

Case presentation

A 69-year-old male patient presented with a 6-month history of persistent pus discharge from the left upper eyelid, despite being treated with multiple courses of oral antibiotics and three incision and drainage procedures. He also complained of yellowish nasal discharge and bilateral nasal blockage for the past year but did not seek medical attention for these symptoms. Physical examination revealed pus discharge from the left upper eyelid and widening of the nasomaxillary groove. Nasoendoscopic examination showed bilateral grade 3 nasal polyps with mucopus secretion. CT scan of the paranasal sinuses revealed that the odd presentation was due to the chronic inflammatory process in the paranasal sinuses, which had led to osteitis and hyperostosis. This patient underwent endoscopic sinus surgery (ESS) with left frontal trephination and fat obliteration of the left frontal sinus. The postoperative histopathological report confirmed the diagnosis of benign inflammatory nasal polyp with acute on chronic inflammation. The patient was asymptomatic at 3-month follow-up post-operation.

Conclusion

Our case report highlights the importance of considering CRS as a possible underlying cause of such unusual presentations, even when the symptoms may appear unrelated. Early diagnosis and treatment of CRS can prevent serious complications and improve patient outcomes. The inflammatory process of CRS leading to osteitis and hyperostosis of the paranasal sinuses complicates the clinical presentation, distorts the usual anatomical structures, and may complicate the operation. CT scan of the paranasal sinus is highly recommended before any sinus surgery. At times, ESS may not be sufficient to eradicate frontal sinus disease. In these cases, an external approach is necessary with or without obliteration of the sinus cavity.