bluuebunny/crossref_metadata_2025 huggingface dataset:
Girl child marriage and the social context of displacement: a qualitative comparative exploration of Syrian refugees in Jordan and Rohingya refugees in Bangladesh
Authors: Gausman Jewel , Huda Fauzia Akhter , Othman Areej , Al Atoom Maysoon , Shaheen Abeer , Hamad Iqbal , Dabobe Maysoon , Mahmood Hassan Rushekh , Ibnat Rifah , Langer Ana
Published: December 2022

Background

There is growing global evidence that girl child marriage (CM) increases during humanitarian crises. Norms, attitudes, and policies that sustain CM are deeply entrenched within families and communities, and may be further exacerbated by conflict and displacement. The purpose of this study is to understand how the social and normative environment influences attitudes and practices related to CM in two diverse humanitarian settings.

Methods

We held a total of eight focus group discussions, four in each country, with Syrian refugees in Jordan and Rohingya Refugees in Bangladesh. FGDs were conducted with fathers, mothers, and adolescent boys and girls.

Results

Similar themes emerged from both settings. Participants discussed a desire to hold onto tradition in displacement and how norms are reinforced across generations. Social influence emerged in positive and negative ways, including peer pressure and conformity and the positive influence of host communities. In both settings, girls themselves described having little agency. Participants described resistance to change, which was exacerbated by conflict and displacement, though they discussed how social influence could be an effective way to challenge existing norms that drive the practice of girl child marriage.

Conclusions

Our findings represent a more robust understanding of how norms operate within the social ecological system, and how they are reinforced across social relationships, offering an opportunity to more effectively challenge norms that sustain the practice of girl child marriage.
Risk factors associated with under-five stunting, wasting, and underweight in four provinces of the Democratic Republic of Congo: analysis of the ASSP project baseline data
Authors: Luzingu Joy Kinko , Stroupe Nancy , Alaofe Halimatou , Jacobs Elizabeth , Ernst Kacey
Published: December 2022

Background

Determining the magnitude and risk factors of undernutrition in a country that has one of the highest prevalence of undernutrition in the world is paramount for developing contextual interventions.

Methods

This study used baseline data from the ASSP project to estimate prevalence of stunting, wasting, and underweight in four provinces of DRC. It involved 3911 children aged 0–59 months old and mother pairs. Height-for-age Z scores, Weight-for-height Z scores, and Weight-for-age Z scores were calculated and used to classify child stunting, wasting and underweight respectively, based on the 2006 World Health Organization (WHO) growth reference. Hierarchical logistic regressions were used to identify risk factors associated with stunting, wasting and underweight. All analyses were conducted using STATA 15.1, and statistical significance was set atp < 0.05.

Results

The prevalence of stunting, underweight and wasting was 42.7%, 21.9% and 8.2% respectively. Increasing child’s age was a risk factor associated with stunting and underweight, while sex was not associated with the 3 indicators of undernutrition. Low levels of mother’s education, mothers working in the last 12 months prior to the survey, children living in the province of Kasai occidental, children born at a health facility, children perceived by their mothers to be born very small were associated with higher risks of stunting. Factors associated with underweight were children from the province of Kasai occidental, mothers who worked in the last 12 months prior to the survey, and children perceived to be born very small or small by their mothers. Children born to mothers aged 35–49 years and children breastfed in combination with drinking water were at higher risk of wasting.

Conclusion

Prevalence of undernutrition in DRC is high. This study has identified certain modifiable risk factors associated with stunting, wasting and underweight. To reduce the burden of undernutrition in DRC, authorities should target factors at individual and community levels by improving women’s education, child feeding practices and promoting agriculture.
Bioinformatics-based analysis of potential candidates chromatin regulators for immune infiltration in osteoarthritis
Authors: Wang Weiwei , Ou Zhixue , Peng Jianlan , Wang Ning , Zhou Yi
Published: December 2022

Background

Through the bioinformatics analysis to screen out the potential chromatin regulators (CRs) under the immune infiltration of osteoarthritis (OA), thus providing some theoretical support for future studies of epigenetic mechanisms under OA immune infiltration.

Methods

By integrating CRs and the OA gene expression matrix, we performed weighted gene co-expression network analysis (WGCNA), differential analysis, and further screened Hub genes by protein-protein interaction (PPI) analysis. Using the OA gene expression matrix, immune infiltration extraction and quantification were performed to analyze the correlations and differences between immune infiltrating cells and their functions. By virtue of these Hub genes, Hub gene association analysis was completed and their upstream miRNAs were predicted by the FunRich software. Moreover, a risk model was established to analyze the risk probability of associated CRs in OA, and the confidence of the results was validated by the validation dataset.

Results

This research acquired a total of 32 overlapping genes, and 10 Hub genes were further identified. The strongest positive correlation between dendritic cells and mast cells and the strongest negative correlation between parainflammation and Type I IFN reponse. In the OA group DCs, iDCs, macrophages, MCs, APC co-inhibition, and CCR were significantly increased, whereas B cells, NK cells, Th2 cells, TIL, and T cell co-stimulation were significantly decreased. The risk model results revealed that BRD1 might be an independent risk factor for OA, and the validation dataset results are consistent with it. 60 upstream miRNAs of OA-related CRs were predicted by the FunRich software.

Conclusion

This study identified certain potential CRs and miRNAs that could regulate OA immunity, thus providing certain theoretical supports for future epigenetic mechanism studies on the immune infiltration of OA.
The COVID-19 vaccination hesitancy among Chinese individuals with diabetes and the impact on glycemic control of vaccination: a questionnaire study
Authors: Lu Difei , Gao Ying , Qi Xiaojing , Li Ang , Zhang Junqing
Published: December 2022

Objective

The study aimed to investigate the attitudes of people with diabetes mellitus (DM) on COVID-19 vaccination and its influence on the glycemic control.

Methods

Data were collected from a consecutive series of adults (age > 18 years) with type 2 diabetes under regular follow-ups in the Integrated Care Diabetes Outpatient Clinic of Peking University First Hospital from December 1st to December 31st 2021. An online interview questionnaire was conducted, and demographic data including age, sex category, history of drug allergy, history of hypertension, the duration of diabetes, reasons for vaccine hesitancy (VH) and adverse reactions after each injection of vaccines was collected. Glucose levels were collected from medical records.

Results

Thirty-nine (22.9%) subjects experienced VH and 131 (77.1%) people living with diabetes received inactivated vaccine against COVID-19. Hesitant individuals had a higher proportion of female gender (vaccinated group vs. VH group, 62/131 vs. 26/39, p = 0.044), higher baseline glycosylated hemoglobin A1c (HbA1c) (vaccinated group vs. VH group, 6.56 ± 0.95% vs. 7.54 ± 2.01%, p < 0.001) and elevated baseline postprandial blood glucose (PBG) (vaccinated group vs. VH group, 8.32 ± 1.97 mmol/L vs. 9.44 ± 2.94 mmol/L, p = 0.015). Subjects of male gender (p = 0.025) and history of hypertension (p = 0.021) were likely to get vaccinated, while higher HbA1c was negatively associated with an elevated propensity to receive anti-COVID-19 vaccine (p = 0.003). Most common reasons for hesitating to receive COVID-19 vaccination were worrying about the possibility of leading to other diseases (30.8%), followed by fearing of glucose variation (17.9%). Systemic adverse reactions were reported in 30.5% individuals after the first injection of inactivated vaccines, and resolved within 3 days in medium. Fasting blood glucose (FBG) decreased significantly after the third injection compared with FBG after the second dose (second vs. third, 6.78 ± 1.24 mmol/L vs. 6.41 ± 1.30 mmol/L, p = 0.027). HbA1c reduced significantly from 6.56% before vaccination to 6.35% after the second injection (p = 0.012).

Conclusions

Our study demonstrated that vaccine hesitancy was lower among male subjects and people with hypertension, while vaccine confidence was reduced in people with poor glycemic control. HbA1c level was lower along with vaccination.
Trends in dental caries of deciduous teeth in Iran: a systematic analysis of the national and sub-national data from 1990 to 2017
Authors: Shoaee Shervan , Saeedi Moghaddam Sahar , Masinaei Masoud , Sofi-Mahmudi Ahmad , Hessari Hossein , Heydari Mohammad-Hossein , Shamsoddin Erfan , Parsaeian Mahboubeh , Ghasemian Anooshe , Larijani Bagher , Fakhrzadeh Hossein , Farzadfar Farshad
Published: December 2022

Background

Dental caries is the most prevalent child affliction in the world and can be reduced through effective preventive interventions. To plan cost-effective interventions, clear and integrated data are needed. This study has been designed to overcome the lack of national trend in deciduous dental caries in Iran.

Objective

To estimate the dental caries trend in deciduous teeth in the Iranian population at different ages from 1990 to 2017.

Methods

From 1990 to 2017 a literature search about dmf and its components (decayed, missed, and filled tooth, abbreviated as dt, mt, and ft) as well as dental caries was done in the Iranian population in three English (PubMed, Web of Science, and Scopus) and three national databases (in Persian). All eligible national oral health surveys in these 28 years were included. National dmft data were categorised based on age (1–4, 5–9, and 10–14), sex, province and year. The final trends were estimated using an age-spatio-temporal hierarchical model. We used the bootstrap method in multilevel models to predict the uncertainty interval (UI) of the modelled results. Finally, the estimations of dmft, dt, mt, and ft with a 95% UI were reported from 1990 to 2017.

Results

Almost 22% of the Iranian deciduous teeth were involved with dental caries in 1990 [dmft = 4.37; (95% UI 2.23, 6.62)] which more than 83% of it was dt [3.64 (1.53, 5.88)] and less than 7% was ft [0.30 (0.06, 0.65)]. During 1990–2017, dmft increased by more than 15% [in 2017, dmft = 5.03 (2.82, 7.29)]. The highest increase was seen in dt which was more than 17% [in 2017, dt = 4.27 (1.96, 6.57)].

Conclusion

Increasing dental caries among Iranian children over 28 years shows that oral health policies in Iran need critical evaluation. We need cost-effective nationwide interventions (e.g., supervised tooth brushing and improving dietary habits) and training well-experienced intermediate manpower (e.g., dental hygienists) to reduce dental caries.
Australian dental students’ knowledge on antibiotics prophylaxis for dental procedures
Authors: Thanissorn Charn , Park Joon Soo , Wang Kate N. , Tennant Marc , Page Amy T. , Kruger Estie
Published: December 2022

Background

Prescribing medicine is integral to clinical dentistry. Infective endocarditis may be rare but fatal if left untreated. As a result, judicious prescribing of antibiotics should be implemented due to potential. To our knowledge, no Australian study has examined dental students' knowledge and perceptions about antibiotic prophylaxis for dental procedures.

Methods

Australian dental students were invited to undertake the survey comprising case vignettes to investigate their medication knowledge. A total of 117 responses were received. The questions were 12 clinically relevant questions and three perception-based questions. Results were analysed using descriptive statistics as well as the chi-squared test.

Results

The 117 respondents had a mean correct response of 7.34 ± 2.64 (range 3–12 out of 12). Out of 117 students, 89 (76%) answered more than half of the questions correctly. Only three students (3%) answered all the questions correctly. Nearly two-thirds felt that they knew about antibiotic prophylaxis used for dental procedures.

Conclusion

Most respondents answered more than half, but not all, of the clinical questions correctly. It is crucial to highlight that dental student may never receive any more training on antimicrobial stewardship (AMS) at any point in their future careers. It may be ideal that this issue is addressed at the dental school. One way to target this is to potentially nationalised teaching delivery of dental AMS across Australia.
Associations between hair trace mineral concentrations and the occurrence of treponeme-associated hoof disease in elk (Cervus canadensis)
Authors: Winter Steven N. , Fernandez Maria del Pilar , Taylor Kyle R. , Wild Margaret A.
Published: December 2022

Background

Trace minerals are important for animal health. Mineral deficiency or excess can negatively affect immune function, wound healing, and hoof health in domestic livestock, but normal concentrations and health impairment associated with mineral imbalances in wild animals are poorly understood. Treponeme-associated hoof disease (TAHD) is an emerging disease of free-ranging elk (Cervus canadensis) in the U.S. Pacific Northwest. Selenium and copper levels identified in a small number of elk from areas where TAHD is established (i.e., southwestern Washington) suggested a mineral deficiency may have increased susceptibility to TAHD. Our objectives were to determine trace mineral concentrations using hair from elk originating in TAHD affected areas of Washington, California, Idaho, and Oregon and assess their associations with the occurrence of the disease.

Results

We identified limited associations between TAHD occurrence and severity with hair mineral concentrations in 72 free-ranging elk, using Firth’s logistic regression and multinomial regression models. We found consistent support for a priori hypotheses that selenium concentration, an important mineral for hoof health, is inversely associated with the occurrence of TAHD. Less consistent support was observed for effects of other minerals previously associated with hoof health (e.g., copper or zinc) or increased disease risk from potential toxicants.

Conclusion

Trace mineral analysis of hair is a non-invasive sampling technique that offers feasibility in storage and collection from live animals and carcasses. For some minerals, levels in hair correlate with visceral organs that are challenging to obtain. Our study using hair collected opportunistically from elk feet submitted for diagnostic investigations provides a modest reference of hair mineral levels in elk from the U.S. Pacific Northwest that may be useful in future determination of reference ranges. Although our results revealed high variability in mineral concentrations between elk, consistent relationship of possibly low selenium levels and TAHD suggest that further investigations are warranted.
Evolutionary and reverse engineering in Saccharomyces cerevisiae reveals a Pdr1p mutation-dependent mechanism for 2-phenylethanol tolerance
Authors: Xia Huili , Kang Yue , Ma Zilin , Hu Cuiyu , Yang Qiao , Zhang Xiaoling , Yang Shihui , Dai Jun , Chen Xiong
Published: December 2022

Background

2-Phenylethanol (2-PE), a higher alcohol with a rose-like odor, inhibits growth of the producer strains. However, the limited knowledge regarding 2-PE tolerance mechanisms renders our current knowledge base insufficient to inform rational design.

Results

To improve the growth phenotype of Saccharomyces cerevisiae under a high 2-PE concentration, adaptive laboratory evolution (ALE) was used to generate an evolved 19–2 strain. Under 2-PE stress, its OD600 and growth rate increased by 86% and 22% than that of the parental strain, respectively. Through whole genome sequencing and reverse engineering, transcription factor Pdr1p mutation (C862R) was revealed as one of the main causes for increased 2-PE tolerance. Under 2-PE stress condition, Pdr1p mutation increased unsaturated fatty acid/saturated fatty acid ratio by 42%, and decreased cell membrane damage by 81%. Using STRING website, we identified Pdr1p interacted with some proteins, which were associated with intracellular ergosterol content, reactive oxygen species (ROS), and the ATP-binding cassette transporter. Also, the results of transcriptional analysis of genes encoded these proteins confirmed that Pdr1p mutation induced the expression of these genes. Compared with those of the reference strain, the ergosterol content of the PDR1_862 strain increased by 72%–101%, and the intracellular ROS concentration decreased by 38% under 2-PE stress. Furthermore, the Pdr1p mutation also increased the production of 2-PE (11% higher).

Conclusions

In the present work, we have demonstrated the use of ALE as a powerful tool to improve yeast tolerance to 2-PE. Based on the reverse engineering, transcriptional and physiological analysis, we concluded that Pdr1p mutation significantly enhanced the 2-PE tolerance of yeast by regulating the fatty acid proportion, intracellular ergosterol and ROS. It provides new insights on Pdr1p mediated 2-PE tolerance, which could help in the design of more robust yeasts for natural 2-PE synthesis.
The impact of age on health utility values for older women with early-stage breast cancer: a systematic review and meta-regression
Authors: Wang Yubo , Gavan Sean P. , Steinke Douglas , Cheung Kwok-Leung , Chen Li-Chia
Published: December 2022

Introduction

An increasing number of postmenopausal women are diagnosed with breast cancer at an older age (≥ 70 years). There is a lack of synthesised health utility data to support decision-making for managing breast cancer in this older population. This study aimed to identify the availability of, and the subsequent impact of age on, health state utility values (HSUVs) measured by the EQ-5D for older women with early-stage breast cancer.

Method

This systematic review identified EQ-5D (3L or 5L version) HSUVs for postmenopausal women with early-stage breast cancer. Studies were identified from a previous systematic review (inception to 2009) and an electronic database search (Medline and Embase; 2009 to September 2021). Mean HSUVs were summarised by health state. Quality appraisal was performed on studies reporting HSUVs for older ages (≥ 70 years). Multivariable meta-regression assessed the association between HSUVs and age, health state, treatments received, and time of measuring the utility values (greater or less than one year post-treatment).

Results

Fifty EQ-5D HSUVs were identified from 13 studies. Mean HSUVs decreased as health state worsened: from the stable (mean=0.83) to progression (mean=0.79) and advanced (mean=0.68) states. Two studies reported six HSUVs estimated from the sample of women with a mean age ≥ 70. Meta-regression model fit improved by including age as an independent variable and attenuated the estimated utility decrements associated with worse health states. Utility decrements for the progression and advanced states were -0.052 (95%CI: -0.097, -0.007) and -0.143 (95%CI: -0.264, -0.022) respectively. The breast cancer-specific utility decrement associated with a one-year increase in age was -0.001 (95%CI: -0.004, 0.002).

Conclusion

Relevant and accurate HSUVs are essential to help support decision-making about the most effective and cost-effective ways to manage early-stage breast cancer in older women. Age has a vital role in determining health utility values in this population. This study provides analysts and decision-makers with HSUVs and utility decrements that reflect the disease process in this older population.
Estimating a social value set for EQ-5D-5L in Sweden
Authors: Sun Sun , Chuang Ling-Hsiang , Sahlén Klas-Göran , Lindholm Lars , Norström Fredrik
Published: December 2022

Background

The study aims to elicit a value set based on the EQ-VT for the EQ-5D-5L that can be used to support decision-making in Sweden.

Methods

Participants were recruited from the general population based on age, sex and urban/rural area quota sampling from five regions across Sweden. In total, 785 interviews were conducted from February 2020 to April 2021 using the EQVT 2.1 protocol, and both composite time trade-off (c-TTO) and discrete choice experiments (DCE) were used to elicit health preferences. A variety of models have been tested for the c-TTO data (generalized least square, Tobit, heteroskedastic models) and DCE data (conditional logit model), as well as the combined c-TTO and DCE data (hybrid modelling). Model selection was based on theoretical considerations, logical consistency of the parameter estimates, and significance of the parameters (p = 0.05). Model goodness-of-fit was assessed by AIC and BIC, and prediction accuracy was assessed in terms of mean absolute error. The predictions for the EQ-5D-5L health states between models were compared using scatterplots.

Results

The preferred model for generating the value set was the heteroskedastic model based on the c-TTO data, with the health utilities ranging from -0.31 for the worst (55,555) to 1 for the best (11111) EQ-5D-5L states.

Conclusion

This is the first c-TTO-based social value set for the EQ-5D-5L in Sweden. It can be used to support the health utility estimation in economic evaluations for reimbursement decision making in Sweden.
Intercondylar notch volume in patients with posterior cruciate ligament tears and tibial avulsion injuries: a study applying computed tomography
Authors: Huang Wen-Tao , Kang Kai , Yang Jin-Yu , Sun Hui , Li Tong , Wang Han , Gao Shi-Jun
Published: December 2022

Background

Two relatively common forms of injury exist in the posterior cruciate ligament (PCL) after the onset of trauma: PCL tear and tibial avulsion fracture. The mechanism for the occurrence of these different forms of injury is not known. Herein, we aimed to investigate this mechanism by comparing the intercondylar notch parameters between patients with PCL tears and those with PCL avulsion fractures of the tibial insertion.

Methods

Fifty-three patients with PCL tears (37 male, 16 female: median age of 37 years: range 18–54 years) and 46 patients with avulsion fractures of tibial insertion (33 male, 13 female: median age of 33 years: range 18–55 years) were included in this study. Three-dimensional computed tomography (CT) was applied to measure the intercondylar notch width index and intercondylar notch volume. The intercondylar notch volume was simulated as the truncated-pyramid shape. Measurements of the top and bottom areas of this model were conducted on the slice containing the most proximal (S1) and most distal (S2) levels of Blumensaat’s line. Femoral condyle height (h) was defined as the vertical distance between two parallel planes, and the volume was calculated as h(S1 + S2 + √(S1S2))/3. The values of S1, S2, h, notch volume, the body mass index (BMI), intercondylar notch width (NW), femoral condylar width (FW) and notch width index (NWI) were compared among the PCL tear and avulsion-fracture groups.

Results

The results show a significant difference in the S2 and normalized intercondylar notch volumes among patients with PCL tears and tibial avulsion injuries. Patients with PCL tears have smaller S2 and intercondylar notch volumes than those with tibial avulsion. There were no significant differences between the two groups in S1 or the 2D notch measurement parameters, such as the NW, FW and NWI. In addition, logistic regression analysis revealed notch volume and body mass index (BMI) as two significant independent predictors for PCL tears.

Conclusion

Decreased intercondylar notch volume and increased BMI are associated with an increased incidence of PCL tears. The occurrence of PCL tears and tibial avulsion injuries is influenced by the femoral intercondylar notch volume, and the measurement of the notch volume could be useful for identifying patients at risk for PCL tears.
Genetic structure of Spirometra mansoni (Cestoda: Diphyllobothriidae) populations in China revealed by a Target SSR-seq method
Authors: Xu Fang Fang , Chen Wen Qing , Liu Wei , Liu Sha Sha , Wang Yi Xing , Chen Jing , Cui Jing , Zhang Xi
Published: December 2022

Background

In China, the plerocercoid of the cestode Spirometra mansoni is the main causative agent of human and animal sparganosis. However, the population genetic structure of this parasite remains unclear. In this study, we genotyped S. mansoni isolates with the aim to improve current knowledge on the evolution and population diversity of this cestode.

Methods

We first screened 34 perfect simple sequence repeats (SSRs) using all available omic data and then constructed target sequencing technology (Target SSR-seq) based on the Illumina NovaSeq platform. Next, a series of STRUCTURE. clustering, principal component, analysis of molecular variance and TreeMix analyses were performed on 362 worm samples isolated from 12 different hosts in 16 geographical populations of China to identify the genetic structure.

Results

A total of 170 alleles were detected. The whole population could be organized and was found to be derived from the admixture of two ancestral clusters. TreeMix analysis hinted that possible gene flow occurred from Guizhou (GZ) to Sichuan (SC), SC to Jaingxi (JX), SC to Hubei (HB), GZ to Yunnan (YN) and GZ to Jiangsu (JS). Both neighbor-joining clustering and principal coordinate analysis showed that isolates from intermediate hosts tend to cluster together, while parasites from definitive hosts revealed greater genetic differences. Generally, a S. mansoni population was observed to harbor high genetic diversity, moderate genetic differentiation and a little genetic exchange among geographical populations.

Conclusions

A Target SSR-seq genotyping method was successfully developed, and an in-depth view of genetic diversity and genetic relationship will have important implications for the prevention and control of sparganosis.

Graphical Abstract
Metabarcoding of bacteria and parasites in the gut of Apodemus agrarius
Authors: Kim Soo Lim , Choi Jun Ho , Yi Myung-hee , Lee Seogwon , Kim Myungjun , Oh Singeun , Lee In-Yong , Jeon Bo-Young , Yong Tai-Soon , Kim Ju Yeong
Published: December 2022

Background

The striped field mouse Apodemus agrarius is a wild rodent commonly found in fields in Korea. It is a known carrier of various pathogens. Amplicon-based next-generation sequencing (NGS) targeting the 16S ribosomal RNA (rRNA) gene is the most common technique used to analyze the bacterial microbiome. Although many bacterial microbiome analyses have been attempted using feces of wild animals, only a few studies have used NGS to screen for parasites. This study aimed to rapidly detect bacterial, fungal and parasitic pathogens in the guts of A. agrarius using NGS-based metabarcoding analysis.

Methods

We conducted 18S/16S rDNA-targeted high-throughput sequencing on cecal samples collected from A. agrarius (n = 48) trapped in May and October 2017. Taxa of protozoa, fungi, helminths and bacteria in the cecal content were then identified.

Results

Among the protozoa identified, the most prevalent was Tritrichomonas sp., found in all of the cecal samples, followed by Monocercomonas sp. (95.8% prevalence; in 46/48 samples) and Giardia sp. (75% prevalence; in 36/48 samples). For helminths, Heligmosomoides sp. was the most common, found in 85.4% (41/48) of samples, followed by Hymenolepis sp. (10.4%; 5/48) and Syphacia sp. (25%; 12/48). The 16S rRNA gene analysis showed that the microbial composition of the cecal samples changed by season (P = 0.005), with the linear discriminant analysis effect size showing that in the spring Escherichia coli and Lactobacillus murinus were more abundant and Helicobacter rodentium was less abundant. Helicobacter japonicus was more abundant and Prevotella_uc was less abundant in males. The microbial composition changed based on the Heligmosomoides sp. infection status (P = 0.019); specifically, Lactobacillus gasseri and Lactobacillus intestinalis were more abundant in the Heligmosomoides sp.-positive group than in the Heligmosomoides sp.-negative group.

Conclusions

This study demonstrated that bacterial abundance changed based on the season and specific parasitic infection status of the trapped mice. These results highlight the advantages of NGS technology in monitoring zoonotic disease reservoirs.

Graphical Abstract
Levels of extracellular matrix metabolites are associated with changes in Ankylosing Spondylitis Disease Activity Score and MRI inflammation scores in patients with axial spondyloarthritis during TNF inhibitor therapy
Authors: Holm Nielsen Signe , Sun Shu , Bay-Jensen Anne C. , Karsdal Morten , Sørensen Inge Juul , Weber Ulrich , Loft Anne Gitte , Kollerup Gina , Thamsborg Gorm , Madsen Ole Rintek , Møller Jakob , Østergaard Mikkel , Pedersen Susanne Juhl
Published: December 2022

Background/purpose

In axial spondyloarthritis (axSpA) inflammation of the sacroiliac joints and spine is associated with local extracellular matrix (ECM) remodeling of affected tissues. We aimed to investigate the association of ECM metabolites with treatment response in axSpA patients treated with TNF-α inhibitory therapy for 46 weeks.

Methods

In a prospective clinical study of axSpA patients (n=55) initiating a TNF inhibitor (infliximab, etanercept, or adalimumab), serum concentrations of formation of type I (PRO-C1), type III (PRO-C3), and type VI (PRO-C6) collagen; turnover of type IV collagen (PRO-C4), and matrix-metalloproteinase (MMP)-degraded type III (C3M) collagen, MMP-degraded type IV (C4M), type VI (C6M), and type VII (C7M) collagen, and cathepsin-degraded type X collagen (C10C), MMP-mediated metabolite of C-reactive protein (CRPM), citrullinated vimentin (VICM), and neutrophil elastase-degraded elastin (EL-NE) were measured at baseline, week 2, week 22, and week 46.

Results

Patients were mostly males (82%), HLA-B27 positive (84%), with a median age of 40 years (IQR: 32–48), disease duration of 5.5 years (IQR: 2–10), and a baseline Ankylosing Spondylitis Disease Activity Score (ASDAS) of 3.9 (IQR: 3.0–4.5).

Compared to baseline, PRO-C1 levels were significantly increased after two weeks of treatment, C6M levels were significantly decreased after two and 22 weeks (repeated measures ANOVA, p=0.0014 and p=0.0015, respectively), EL-NE levels were significantly decreased after 2 weeks (p=0.0008), VICM levels were significantly decreased after two and 22 weeks (p=0.0163 and p=0.0374, respectively), and CRP were significantly decreased after two and 22 weeks (both p=0.0001). Baseline levels of PRO-C1, PRO-C3, C6M, VICM, and CRP were all associated with ASDAS clinically important and major improvement after 22 weeks (ΔASDAS ≥1.1) (Mann–Whitney test, p=0.006, p=0.008, p<0.001, <0.001, <0.001, respectively), while C6M, VICM and CRP levels were associated with ASDAS clinically important and major improvement after 46 weeks (ΔASDAS ≥2.0) (p=0.002, p=0.044, and p<0.001, respectively). PRO-C1 and C6M levels were associated with a Bath AS Disease Activity Score (BASDAI) response to TNF-inhibitory therapy after 22 weeks (Mann–Whitney test, p=0.020 and p=0.049, respectively). Baseline levels of PRO-C4 and C6M were correlated with the total SPARCC MRI Spine and Sacroiliac Joint Inflammation score (Spearman’s Rho ρ=0.279, p=0.043 and ρ=0.496, p=0.0002, respectively).

Conclusions

Extracellular matrix metabolites were associated with ASDAS response, MRI inflammation, and clinical treatment response during TNF-inhibitory treatment in patients with axSpA.
Neuronal CRMP2 phosphorylation inhibition by the flavonoid, naringenin, contributes to the reversal of spinal sensitization and arthritic pain improvement
Authors: Jiang Yue-Peng , Wang Song , Lai Wei-Dong , Wu Xue-Qing , Jin Yan , Xu Zheng-Hao , Moutal Aubin , Khanna Rajesh , Park Ki Duk , Shan Zhi-Ming , Wen Cheng-Ping , Yu Jie
Published: December 2022

Background

Rheumatoid arthritis patients usually suffer from arthritic chronic pain. However, due to an incomplete understanding of the mechanisms underlying autoimmune disorders, the management of arthritic pain is unsatisfactory. Here, we investigated the analgesic effect and underlying mechanism of the natural flavonoid naringenin (NAR) in collagen-induced arthritis (CIA) pain.

Methods

NAR was injected (i.p.) once per day for 42 days after initial immunization, and rats were sacrificed on the 28th (the 21st day after final immunization, PID 21) and 42nd days (PID 35). The inflammatory factors, central sensitization indicators, and CRMP2 phosphorylation, as well as the anti-rheumatoid activity and analgesic effect of NAR, were further investigated.

Results

We found that NAR decreased the arthritis score and paw swelling, as well as the mechanical and thermal pain. The immunofluorescence results also showed a dose dependent effect of NAR on reducing the expressions of spinal cFos, IBA-1, and GFAP on the 28th (PID 21) and 42nd day (PID 35). NAR decreased the phosphorylation of CRMP2 S522 and the expression of the kinase CDK5 in the spinal dorsal horn, but pCRMP2 Y479 was unchanged. In addition, CRMP2 was co-localized with NEUN, but not IBA-1 or GFAP, indicating the involvement of neural CRMP2 phosphorylation in CIA-related pain. Finally, CRMP2 S522 phosphorylation selective inhibitor (S)-lacosamide also alleviated arthritic pain.

Conclusions

Taken together, our results demonstrate that NAR alleviates inflammation and chronic pain in CIA model, which might be related to its inhibition of neuronal CRMP2 S522 phosphorylation, potentially mitigating the central sensitization. Our study provide evidence for the potential use of NAR as non-opioid-dependent analgesia in arthritic pain.
Multiparametric autoantibody analysis: a new paradigm for the diagnosis of connective tissue diseases
Authors: Bizzaro Nicola , Villalta Danilo , Bini Vittorio , Migliorini Paola , Franceschini Franco , Piantoni Silvia , Garrafa Emirena , Riccieri Valeria , Fioravanti Antonella , Bellisai Francesca , Tampoia Marilina , Fornaro Marco , Iannone Florenzo , Ghirardello Anna , Zen Margherita , Palterer Boaz , Parronchi Paola , Infantino Maria , Benucci Maurizio , Rigon Amelia , Arcarese Luisa , Del Rosso Stefania , Canti Valentina , Bartoloni Elena , Gerli Roberto ,   FIRMA Collaborators, Bistoni Onelia , Cafaro Giacomo , Perricone Carlo , Topini Fabiana , Cavazzana Ilaria , Fredi Micaela , Masneri Stefania , Cheleschi Sara , Bacarelli Maria-Romana , Cammelli Daniele , Manfredi Mariangela , Giacomelli Roberto , Querini Patrizia Rovere
Published: December 2022

Background

In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls.

Methods

Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren’s syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies.

Results

Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies.

Conclusions

This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.
Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions
Authors: Khoo Thomas , Sidhu Navkiran , Marine Franca , Lester Susan , Quinlivan Alannah , Rowett Debra , Buchbinder Rachelle , Hill Catherine L.
Published: December 2022

Background

Biologic and targeted synthetic disease modifying agents (b/tsDMARDs) have broadened the treatment landscape for autoimmune diseases particularly in patients refractory to conventional DMARDs. More recently, the introduction of biosimilars has reduced the price of bDMARDs, potentially improving accessibility. Though efficacy and safety have been described, patient attitudes to b/tsDMARDs are not well-understood. We aim to investigate patients’ beliefs about biologic and biosimilar therapy, and the factors influencing their perceptions.

Methods

Patient consumer groups (Arthritis Australia, Crohn’s and Colitis Australia) assisted in advertising an online questionnaire for people with a self-reported diagnosis of inflammatory arthritis (IA) or inflammatory bowel disease (IBD). The questionnaire incorporated the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS). Sources and favourability of biologic/biosimilar information were analysed, using the chi-square and a non-parametric trend test for unordered and ordered categorical variables respectively, comparing respondents with IA and IBD.

Results

Eight hundred and thirty eight people (686–IA, 144–IBD, 8 both) responded. 658 (79%) used b/tsDMARDs. The BMQ demonstrated high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics. 95% of respondents obtained medication information from specialists though most used multiple sources (median 4). The most positive resources were specialists and specialist nurses. 73/141 (52%) respondents with IBD obtained information from specialist nurses compared with 202/685 (29%) with IA (p = 0.012). Respondents with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Younger respondents and those with higher BMQ concern scores more frequently consulted less reliable sources (e.g. social media). 502 respondents (60%) answered the biosimilar questions. Only 23 (4.6%) reported currently using a biosimilar and 336 (66.9%) were unsure if biosimilars were available in Australia. Specialist recommendation was the most frequent factor that would influence a patient to change from originator to biosimilar (352/495, 71.1%).

Conclusions

There is a high level of trust in specialists’ recommendations about b/tsDMARDs, although most people also utilise additional information sources. Contextual factors influencing resource selection include age, reading ability and degree of concern about medicines. People with IA and IBD have similar attitudes though those with IBD more frequently access specialist nurse advice.
Promising biological agents represented in Bacillus velezensis 33RB and Aspergillus niger 46SF endophytic isolates for controlling Populus tomentosa wilt and anthracnose diseases
Authors: Dawwam Ghada E. , Sehim Amira E.
Published: December 2022

Background

Poplar fungal infections are difficult to control and result in severe economic loss. As a viable alternative to chemical pesticides, biocontrol is an effective safe method for disease control.

Results

Inhibitory activity of Bacillus velezensis 33RB and Aspergillus niger 46SF was evaluated against numerous phytopathogens. The bacterial strain displayed the highest inhibitory activity toward Colletotrichum gloeosporioides BJ02 and Fusarium oxysporum 20RF (61.2 and 49.4%, respectively). Also, the maximum inhibitory activity of A. niger 46SF was exhibited (75.51 and 70.83%) against C. gloeosporioides BJ02 and F. oxysporum 20RF, respectively. The minimum volume (6.25 ml) of sterilized cultural filtrate of bacterial and fungal strains significantly inhibited the growth of C. gloeosporioides BJ02 by 73.3 and 83.3%, respectively, and F. oxysporum 20RF reached 40.4 and 78.8%, respectively. B. velezensis 33RB and A. niger 46SF displayed the highest inhibition toward C. gloeosporioides BJ02 and F. oxysporum 20RF at neutral pH and pH 5, respectively. Moreover, the highest inhibitory activity of B. velezensis 33RB and A. niger 46SF was achieved at 37 °C and 28 °C, respectively. Pathogenicity tests on sterilized detached leaves indicated that these isolates could potentially affect anthracnose and fusarium wilt diseases. Several secondary bioactive metabolites that assured the biocontrol efficacy of tested microbes were detected by liquid chromatography–mass spectrometry (LC–MS). The most detectable compounds included organic acids such as fumaric, DL-malic, citric, isobutyric, and glutamic acids. Also, numerous fatty acids such as lauric, linoleic, oleic, stearic, and myristic acids with diverse biological functions, including antimicrobial properties, were determined.

Conclusions

Bacillus velezensis 33RB and A. niger 46SF were potential alternatives to chemical pesticides as biological control agents for the phytopathogens C. gloeosporioides BJ02 and F. oxysporum with environmentally friendly and sustainable properties.
Neurophysiologic evaluation of patients with cervical spondylotic myelopathy
Authors: Jawad Zahraa Y. , Hamdan Farqad B. , Nema Ihssan S.
Published: December 2022

Background

Cervical spondylotic myelopathy (CSM) is a neurodegenerative disease caused by repetitive spinal cord damage that has resulted in significant clinical morbidity. The clinical evaluation of signs and symptoms, as well as neuroimaging and several neurophysiological tests, are used to make the diagnosis.

Objectives

To investigate changes in the cutaneous silent period (CuSP), cortical silent period (CoSP), and H-reflex in CSM patients, and to correlate these tests with the Japanese Orthopedic Association (JOA) score and Nurick’s grading, as well as to determine the diagnostic value of each of them.

Methods

Twenty patients (14 males and 6 females) with CSM were clinically diagnosed and documented by magnetic resonance imaging (MRI), and they were paired with another 20 healthy volunteers (13 males and 7 females) as a control group. CuSP, CoSP, and H-reflex tests were performed on both groups.

Results

In CSM patients, CuSP latency and duration are substantially longer and shorter in CSM patients, respectively. The degree of changes in CuSP latency is well correlated with the severity of the disease. Further, CoSP duration is significantly shortened. The H-reflex parameters did not differ significantly between the patient and control groups.

Conclusion

The shortened CoSP’s duration and the prolonged CuSP's latency suggest malfunction of the inhibitory and excitatory circuits in the spinal cord. The CuSP is more sensitive and specific than the CoSP in the diagnosis of a patient with CSM.
Diagnostic accuracy of hysterosalpingo-lidocaine-foam sonography combined with power Doppler (HyLiFoSy-PD) compared to laparoscopy and dye testing in tubal patency assessment in cases of infertility
Authors: Sharaf Marwa F. , Fawzy Ibrahim , Elkhateb Islam T. , Elmahgoub Yassin , Idris Omaima , Aboulghar Mona
Published: December 2022

Background

Tubal patency testing is an essential part of female subfertility evaluation. Hysterosalpingogram is less invasive and less expensive compared to laparoscopy and dye testing (LDT), i.e., laparoscopic chromopertubation. Hysterosalpingo-foam sonography (HyFoSy) uses commercial echogenic gel foam that is easily visible on ultrasound to assess the tubes. It offers a safer and less painful alternative to HSG, with no radiation exposure. Hysterosalpingo-lidocaine-foam sonography with power Doppler (HyLiFoSy-PD) uses lidocaine-made gel foam as a contrast medium. It was postulated to as to be less painful and easier to detect on ultrasound, compared with hysterosalpingo-foam sonography using other contrast media and that it can also be used whenever the commercial gel used with HyFoSy is not available or is relatively expensive.

Methodology

This prospective diagnostic accuracy study was carried out between February 2018 and 2020 at the Cairo Fetal Medicine Unit, Department of Obstetrics and Gynecology, Cairo University. One hundred twenty-two infertile patients, who were already scheduled for LDT as a part of their infertility work-up, were consecutively recruited for this study. The HyLiFoSy-PD (index test) was performed 1 week before the scheduled LDT for these patients. Using an intrauterine pediatric Folley’s balloon catheter, 20 ml of lidocaine-made gel foam was slowly infused intrauterine, while observing their flow in both fallopian tubes using a grayscale and power Doppler transvaginal two-dimensional ultrasound system. All patients then underwent LDT (reference test). The results of HyLiFoSy-PD were compared with those of LDT to determine the accuracy of HyLiFoSy-PD in tubal patency assessment. We also assessed the procedure duration, associated pain, and other complications.

Results

Comparing HyLiFoSy-PD with LDT in the 115 patients who completed the procedure, results showed 98.1% sensitivity, 90% specificity, 99% positive predictive value, 81.8% negative predictive value, 9.81 positive likelihood ratio, 0.02 negative likelihood ration, and 97.4% overall accuracy in the assessment of tubal patency (odds ratio = 463.5 with confidence interval = 79.39–2706; P-value: 0.687). The median procedure duration was 11 min. All patients experienced some degree of pain during the procedure with 91 patients (79%) reported mild pain and 24 patients (21%) reported moderate pain.

Conclusion

HyLiFoSy-PD was found to be an accurate tool in tubal patency assessment. It was also found to be safe and well-tolerated.
Hereditary Endocrine Tumor Registries
Authors: Moore Edwina C , Ioannou Liane , Ruseckaite Rasa , Serpell Jonathan , Ahern Susannah
Published: December 2022

Context

Endocrine neoplasia syndromes are phenotypically complex, and there is a misconception that they are universally rare. Genetic alterations are increasingly recognized; however, true prevalence is unknown. The purpose of a clinical registry is to monitor the quality of health care delivered to a specified group of patients through the collection, analysis, and reporting of relevant health-related information. This leads to improved clinical practice, decision-making, patient satisfaction, and outcome.

Objective

This review aims to identify, compare, and contrast active registries worldwide that capture data relevant to hereditary endocrine tumors (HETs).

Methods

Clinical registries were identified using a systematic approach from publications (Ovid MEDLINE, EMBASE) peer consultation, clinical trials, and web searches. Inclusion criteria were hereditary endocrine tumors, clinical registries, and English language. Exclusion criteria were institutional audits, absence of clinical data, or inactivity. Details surrounding general characteristics, funding, data fields, collection periods, and entry methods were collated.

Results

Fifteen registries specific for HET were shortlisted with 136 affiliated peer-reviewed manuscripts.

Conclusion

There are few clinical registries specific to HET. Most of these are European, and the data collected are highly variable. Further research into their effectiveness is warranted. We note the absence of an Australian registry for all HET, which would provide potential health and economic gains. This review presents a unique opportunity to harmonize registry data for HET locally and further afield.