bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal application of stereotactic body radiotherapy and radiofrequency ablation treatment for different multifocal hepatocellular carcinoma lesions in patients with Barcelona Clinic Liver Cancer stage A4–B1: a pilot study
Authors: Wang Feiqian , Numata Kazushi , Takeda Atsuya , Ogushi Katsuaki , Fukuda Hiroyuki , Nihonmatsu Hiromi , Hara Koji , Chuma Makoto , Tsurugai Yuichirou , Maeda Shin
Published: October 2021

Background

In clinical practice, many hepatocellular carcinoma (HCC) patients in Barcelona Clinical Liver Cancer (BCLC) stage A4–B1 cannot receive the curative treatments of liver transplantation, resection, and radiofrequency ablation (RFA), which are the recommended options according to liver cancer guidelines. Our aim is to study the feasibility of RFA and stereotactic body radiotherapy (SBRT) as a curative treatment for different multifocal HCCs in BCLC stage A4–B1 patients.

Methods

From September 2014 to August 2019, 39 multifocal HCC lesions (median diameter: 16.6 mm) from 15 patients (median age: 73 years) were retrospectively selected. Among them, 23 were treated by RFA and the other 16 by SBRT because of predictable insufficiency and/or risk related to RFA performance. The indicators for evaluating this novel therapy were the tumor response, prognosis (recurrence and survival), and adverse effects (deterioration of laboratory test values and severe complications).

Results

The median follow-up duration was 31.3 months (range: 15.1–71.9 months). The total patients with a one-year complete response, stable disease, or disease progression were 11, 1, and 3, respectively. In total, 8 and 2 patients had confronted intrahepatic or local recurrence, respectively. The one-year progression-free survival rate and local control rate were 80% (12/15 patients) and 97.4% (38/39 lesions), respectively. The median time to progression was 20.1 (2.8–45.1) months. The one- and two-year survival rates were 100 and 88.9%, respectively. In up to five months’ observation, no patient showed severe complications. Seven, four, and two patients had slight changes in their white blood cells, platelet count, or albumin–bilirubin grade, respectively.

Conclusions

For patients with BCLC stage A4–B1, RFA and SBRT treatment for different multifocal HCCs may be a potential option because of the favorable prognosis and safety. However, before its application in clinical practice, prospective, controlled, large-scale studies are needed to further confirm our conclusions.
Predicting response to immunotherapy plus chemotherapy in patients with esophageal squamous cell carcinoma using non-invasive Radiomic biomarkers
Authors: Zhu Ying , Yao Wang , Xu Bing-Chen , Lei Yi-Yan , Guo Qi-Kun , Liu Li-Zhi , Li Hao-Jiang , Xu Min , Yan Jing , Chang Dan-Dan , Feng Shi-Ting , Zhu Zhi-Hua
Published: October 2021

Objectives

To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC).

Methods

A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation.

Results

Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility.

Conclusions

The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.
Concentrations of oligosaccharides in human milk and child growth
Authors: Menzel Philipp , Vogel Mandy , Austin Sean , Sprenger Norbert , Grafe Nico , Hilbert Cornelia , Jurkutat Anne , Kiess Wieland , Binia Aristea
Published: October 2021

Background

The relationship between human milk oligosaccharides (HMO) and child growth has been investigated only insufficiently with ambiguous results. Therefore, this study examines potential influencing factors of HMO concentrations and how HMO are associated with child growth parameters.

Methods

Milk samples from the German LIFE Child cohort of healthy children were analyzed for 9 HMO. Putative associations with maternal and child cofactors and child height, head circumference and BMI between 3 months and 7 years of age were examined. Secretor status, defined as the presence of 2′-fucosyllactose, was investigated for associations with infant outcomes.

Results

Our population consisted of 21 (14.7%) non-secretor and 122 (85.3%) secretor mothers. Maternal age was significantly associated with higher 3′SL concentrations; gestational age was associated with LNT, 6′SL and LNFP-I. Pre-pregnancy BMI was negatively associated with LNnT only in non-secretors. The growth velocity of non-secretors’ children was inversely associated with LNnT at 3 months to 1 year (R = 0.95 [0.90, 0.99],p = 0.014), 1 to 2 years (R = 0.80 [0.72, 0.88],p < 0.001) and 5 to 6 years (R = 0.71 [0.57, 0.87],p = 0.002). 2’FL was negatively associated with BMI consistently, reaching statistical significance at 3 months and 4 and 5 years. Children of non-secretors showed higher BMI at 3 months, 6 months, and 3, 6, and 7 years of age.

Conclusion

We found that some associations between HMO and infant growth may extend beyond the infancy and breastfeeding periods. They highlight the importance of both maternal and infant parameters in the understanding of the underlying associations.

Trial registration

The study is registered with ClinicalTrial.gov:NCT02550236.
Efficacy and cost-effectiveness of a Transdiagnostic group-based exercise intervention: study protocol for a pragmatic multi-site randomized controlled trial
Authors: Wolf Sebastian , Seiffer Britta , Zeibig Johanna-Marie , Welkerling Jana , Bauer Leonie Louisa , Frei Anna Katharina , Studnitz Thomas , Rosenstiel Stephanie , Fiedler David Victor , Helmhold Florian , Ray Andreas , Herzog Eva , Takano Keisuke , Nakagawa Tristan , Kropp Saskia , Franke Sebastian , Peters Stefan , El-Kurd Nadja , Zwanzleitner Lena , Sundmacher Leonie , Ramos-Murguialday Ander , Hautzinger Martin , Sudeck Gorden , Ehring Thomas
Published: October 2021

Background

Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD).

Methods

This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention “ImPuls”, among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios.

Discussion

Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings.

Trial registration

The study was registered in the German Clinical Trials Register (ID: DRKS00024152, 05/02/2021).
Modeling the change trajectory of sleep duration and its associated factors: based on an 11-year longitudinal survey in China
Authors: Fang Junyan , Wen Zhonglin , Ouyang Jinying , Wang Huihui
Published: October 2021

Background

Sleep duration is a vital public health topic, yet most existing studies have been limited to cross-sectional surveys or inconsistent classifications of sleep duration categories, and few characterized its continuous development process. The current study aimed to depict its change trajectory in the general population and identify associated factors from a dynamic perspective.

Methods

A total of 3788 subjects (45.4% male, mean age 46.72 ± 14.89 years) from the China Health and Nutrition Survey were recruited, and their daily sleep duration for five consecutive measurements from 2004 to 2015 was recorded. We adopted latent growth modelling to establish systematic relations between sleep duration and time. Participants’ sociodemographic characteristics, lifestyle, and health factors were taken as covariates.

Results

The change in sleep duration could be depicted by a linear decreasing trajectory with the mean yearly decrease at 2.5 min/day. The trajectory did not differ by residence, BMI category, chronic disease situation, smoking status, or drinking status. Moreover, there were sex and age differences in the trajectory, and females and those under 30 were prone to larger decrease rates.

Conclusion

The quantified yearly change in sleep duration provided insights for the prediction and early warning of insufficient sleep. Public health interventions focusing on slowing down the decrease rates among females and young individuals are warranted.
Sexual health concerns in women with intellectual disabilities: a systematic review in qualitative studies
Authors: Matin Behzad Karami , Ballan Michelle , Darabi Fatemeh , Karyani Ali Kazemi , Soofi Moslem , Soltani Shahin
Published: October 2021

Background

Studies indicate that women with intellectual disabilities (ID) face various personal and socio-environmental barriers in their sexual lives. This study aimed to identify the concerns and sexual health needs experienced by women with ID.

Method

A systematic review of relevant qualitative articles was conducted in PubMed, Web of Science Scopus and PsycINFO databases from June 2018 to August 2018. We designed our search strategy according to two main foci: (1) sexuality; and (2) women with ID. In the study, searches were limited to articles published from January 2000 to December 2017. In this review, studies on women ages 16 and over were included.

Results

Within the four databases, the search found 274 unique articles. After three steps of screening (title, abstract and full text), 22 studies were included in the final review. The articles mentioned difficulties with lack of sexual experience, negative experiences with sexuality, negative attitudes towards sexuality by nondisabled individuals, limited cognitive capacities to understand sexual identity, difficulty with finding the right partner, lack of access to sexual health information, lack of school-based sexuality education, violence and sexual abuse, lack of support from families and caregivers about sexuality, fear of sexual acts and unwanted pregnancy, shyness in expressing sexual desires, and limited knowledge of sexual behaviors.

Conclusion

Our findings indicate that women with ID need to be provided with school-based sexuality education tailored to the level of understanding needed to attain the requisite knowledge to form relationships, understand sexual and romantic relationships, and practice safe sex when they choose this option. Families along with education and healthcare systems should provide opportunities for women with ID to talk about their sexual needs and make their own choices.
Mediating effect of the parent-child relationship on the association between parenting stress and children’s eating behaviors
Authors: Jang Myoungock , Brown Roger , Park Moonkyoung
Published: October 2021

Background

Emerging evidence suggests that parenting stress plays a significant role in children’s eating behavior. However, the nature of the relationship between parenting stress and children’s health behaviors is still not well understood, possibly because there is limited understanding of the mediating factors. The purpose of this study was to examine the mediating effect of the parent–child relationship on the association between parenting stress and children’s eating behaviors in families with young children.

Methods

Using a cross-sectional study design, we recruited mothers of families with children aged four to six years in the United States. We asked the mothers select one child if she has more than one eligible child. Mothers answered well-validated questionnaires regarding parenting stress, the parent–child relationship, and children’s eating behaviors. We utilized a structural equation model to analyze the mediating factors.

Results

A total of 172 mothers of children participated in this study. The children’s mean age was 4.92 (SD 0.89) years; 50% of children were female and 71.2% were non-Hispanic Whites. Parenting stress was associated with subcategories of the parent–child relationship (satisfaction with parenting [b* = − 0.69,p < .01], communication [b* = 0.45,p < 0.01], and limit setting [b* = − 0.82,p < .01]). The subcategories of communication and limit setting were negatively associated with food responsiveness in children (b* = − 0.24,p < .01; b* = − 0.46,p < .01, respectively). Limit setting was negatively associated with emotional overeating in children (b* = − 0.49,p < .01). Communication mediated the association between parenting stress and food responsiveness in children (b* = − 0.11,p < .01). The mediating role of limit setting was established in the association between parenting stress and food responsiveness as well as in the association between parenting stress and emotional overeating (b* = 0.38,p < .01; b* = 0.40,p < .01, respectively).

Conclusions

The parent–child relationship is an important component in improving children’s eating behaviors in families that have parents with higher parenting stress levels.
Influence of perceived barriers and facilitators for physical activity on physical activity levels in patients with rheumatoid arthritis or spondyloarthritis: a cross-sectional study of 150 patients
Authors: Davergne Thomas , Tekaya Rawdha , Sellam Jérémie , Tournadre Anne , Mitrovic Stéphane , Ruyssen-Witrand Adeline , Hudry Christophe , Dadoun Sabrina , Avouac Jérôme , Fautrel Bruno , Gossec Laure
Published: October 2021

Background

Barriers and facilitators to physical activity in inflammatory arthritis can be assessed through the Inflammatory arthritis FAcilitators and Barriers (IFAB) questionnaire. The objective was to measure the correlation between IFAB and self-reported physical activity levels.

Methods

This was an international, multicentric, cross-sectional study in 2019–20. Consecutive spondyloarthritis (axSpA), rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients completed the 10-item IFAB, which ranges from − 70 to 70 with lower scores indicating more barriers. Physical activity was measured by the IPAQ-S questionnaire, steps per day collected by smartphone, and psychological readiness to change by stages of behaviour change. Spearman correlations and multivariable linear regression were calculated.

Results

Of 245 patients included, 150 were analysed: 69 (46%) axSpA, 63 (42%) RA, 18 (12%) PsA. Mean age was 48.6 years (standard deviation, SD 17.1), mean disease duration 11.7 (10.1) years and 60% were women. Barriers to physical activity were moderate: mean IFAB, 6 (SD 19.2); 39 (26%) patients scored less than − 5, corresponding to significant barriers. The mean physical activity was 2837 (SD 2668, median 1784) MET-minutes per week. The IPAQ-S questionnaire was correlated with the IFAB (rho 0.28, p < 0.001), as well as the stage of behaviour change (rho 0.35, p < 0.001) though not with steps per day. Multivariable analyses were confirmatory.

Conclusion

Perceived barriers and facilitators to physical activity were correlated with physical activity, indicating that targeting patients with high barriers and low facilitators to physical activity could be an effective option to improve physical activity levels.

Trial registration

ClinicalTrial NCT04426747. Registered 11 June 2020 - Retrospectively registered.
Application of concentrated growth factor to autotransplantation with inflammation in recipient area
Authors: Keranmu Dilinuer , Ainiwaer Ailimaierdan , Nuermuhanmode Nijiati , Ling Wang
Published: October 2021

Objective

The purpose of this study was to apply concentrated growth factor (CGF) to the transplanted area with inflammation, to observe the clinical effects of CGF on the inflammation area assisted by 3D printing technology.

Methods

A total of 52 compromised mandibular first or second molar with chronic periapical lesions were transplanted with mature third molars. The patients were divided into CGF group (n = 26) and control group (n = 26) and transplanted into fresh extraction sockets with or without CGF. All the patients underwent clinical and radiographic examinations during the follow-up.

Results

Average surgery and extra-oral time were 39 min (± 7.8) and 42 s (± 10.2). The success rates of CGF group and control group were 100% and 92.3% respectively. Most of the periapical lesions in CGF group healed completely within 3 months, which was significantly faster than control group. The initial stability of CGF group was better than control group immediately after operation, and the degree of pain in CGF group was lower than control group on the 1st and 3rd day after operation.

Conclusions

The application of CGF in recipient site with chronic periapical lesions can accelerate the regeneration of alveolar bone and the healing of inflammation, greatly shorten the healing period. Meanwhile, CGF help to reduce postoperative pain and reaction at the early stage of healing and increase the success rate of autogenous tooth transplantation (ATT). Additionally, the use of 3D printing model can greatly reduce the extra-oral time of donor teeth.
Quantitative ultrasound assessment of the effect of parity on bone mineral density in females
Authors: Akil Shahnaz , Al-Mohammed Huda , Al-Batati Norah , Tirsen Maissa , Al-Otaibi Ahad , AlZahrani Aram , Bakhder Deena , AlSubaie Ruba , AbuAlsaud Samar
Published: October 2021

Background

The effect of pregnancy and breastfeeding on a female’s bone mineral density (BMD) is controversial. This prospective study aims to investigate the effect of parity on BMD among pre-menopausal multiparous females using quantitative ultrasound as a screening method and females with no pregnancies (nulliparous) as a control group.

Methods

A portable ultrasound-based bone densitometer (DMS PEGASUS SMART, Mauguio, France) was used to indirectly assess the BMD in 51 multiparous (29–45 years) and 51 nulliparous Arabic females (18–35 years) by quantifying the broadband ultrasound attenuation (BUA) from their right calcaneus bone. BUA > 70 db/mhz = normal, BUA 65–69.9 db/mhz = below average, BUA 55–64.9 db/mhz = osteopenia and BUA < 55 db/mhz = osteoporosis.

Results

There was a significant difference in mean BUA between multiparous and nulliparous females (74.1 db/mhz vs. 69.3 db/mhz, p = 0.006). The prevalence of normal BMD was significantly higher in the nulliparous group than in the multiparous group (70.6% vs. 47.1%, p = 0.02). Osteoporosis was found in the multiparous group only (3/51). Among the multiparous females who breastfed (43/51), a total of 51.2% (22/43) had normal BMD, 25.6% (11/43) had BMD below average, 18.6% (8/43) had osteopenia and 4.7% (2/43) had osteoporosis. No significant differences in mean BUA (p = 0.2) were found between the group of females who breastfed for one year (13/43; BUA: 70.5 ± 9.4), the group of females who breastfed for 6–11 months (8/43; BUA: 70.6 ± 10.0) and those who breastfed for less than six months (22/43; BUA: 71.6 ± 9.4). A binary logistic regression model built for predicting BMD normality showed significance for the variable parity (p = 0.03), while the effect of the possible confounding variables BMI and age on BMD normality was found to be non- significant (p = 0.1 and p = 0.6, respectively).

Conclusion

Parity affects the BMD, as assessed by a portable ultrasound-based bone densitometer, of young and middle-aged females as compared to the BMD of nulliparous females.
The innovation and practice of “Hand as Foot teaching method” in the teaching of motion system injury course
Authors: He Bin , Li Qiang , Zhao Jianmin , Liu Rui , Li Yizhou , Xu Yafei
Published: October 2021

Background

In view of the teaching characteristics of the motion system injury course and the actual clinical teaching. The orthopedic teaching team of the Affiliated Hospital of Inner Mongolia Medical University took the lead in proposing the "Hand as Foot teaching method" and applied it in clinical teaching. Through this teaching method, students’ understanding and memorization of key and difficult issues in motion system injuries are strengthened, teacher-student interaction is increased, and teaching effect is improved. 

Methods

The "Hand as Foot teaching method" was used to teach the key and difficult problems to the clinical undergraduate medical students of Inner Mongolia Medical University, and the teaching process was complemented by PPT + model teaching aids.

Results

The "Hand as Foot teaching method" is generally welcomed by medical students and has achieved good teacher-student interaction, and is effective in understanding and remembering difficult knowledge points.

Conclusion

The "Hand as Foot teaching method" is a novel teaching method that can be applied in clinical teaching. This image teaching method improves the teaching effect, enlivens the classroom atmosphere, and enhances the interaction between teachers and students, which makes students’ learning process from abstract to intuitive, from simple rote memorization to comprehension and memory, and achieves satisfactory results. It can complement each other with the traditional teaching method of pure PPT + teaching aids model, and to some extent it is worth promoting in the motion system injury courses.
Identifying competencies for integrated knowledge translation: a Delphi study
Authors: Yeung Euson , Scodras Stephanie , Salbach Nancy M. , Kothari Anita , Graham Ian D.
Published: October 2021

Background

Considerable progress has been made to advance the field of knowledge translation to address the knowledge-to-action gap in health care; however, there remains a growing concern that misalignments persist between research being conducted and the issues faced by knowledge users, such as clinicians and health policy makers, who make decisions in the health care context. Integrated knowledge translation (IKT) is a collaborative research model that has shown promise in addressing these concerns. It takes advantage of the unique and shared competencies amongst researchers and knowledge users to ensure relevance of the research process and its outcomes. To date, core competencies have already been identified to facilitate training in knowledge translation more generally but they have yet to be prioritized for IKT more specifically. The primary aim of this study was to recruit a group of researchers and knowledge users to identify and prioritize core competencies for researchers and knowledge users to engage with IKT.

Methods

We recruited health care knowledge users (KUs) and researchers with experience and knowledge of IKT for a quantitative, cross-sectional study. We employed a modified Delphi approach consisting of three e-survey rounds to establish consensus on competencies important to IKT for KUs and researchers based on mean rating of importance and agreement between participants.

Results

Nineteen (73%) of the initial 26 participants were researchers (response rate = 41% in the first round; retention in subsequent rounds > 80%). Participants identified a total of 46 competencies important for IKT (18 competencies for KUs, 28 competencies for researchers) under 3 broad domains. Technical research skills were deemed extremely important for researchers, while both groups require teamwork and knowledge translation skills.

Conclusions

This study provides important insight into distinct and overlapping IKT competencies for KUs and researchers. Future work could focus on how these can be further negotiated and contextualized for a wide range of IKT contexts, projects and teams. Greater attention could also be paid to establishing competencies of the entire team to support the research co-production process.
Incidence of Brucella infection in various livestock species raised under the pastoral production system in Isiolo County, Kenya
Authors: Njeru Josiah , Nthiwa Daniel , Akoko James , Oyas Harry , Bett Bernard
Published: October 2021

Background

We implemented a longitudinal study to determine the incidence of Brucella infection in cattle, camels, sheep and goats that were being raised in a pastoral area in Isiolo County, Kenya. An initial cross-sectional survey was implemented to identify unexposed animals for follow up; that survey used 141 camels, 216 cattle, 208 sheep and 161 goats. Sera from these animals were screened for Brucella spp. using the Rose Bengal Plate test (RBPT), a modified RBPT, and an indirect multispecies Enzyme Linked Immunosorbent Assay (iELISA). Results of RBPT and iELISA were interpreted in parallel to determine seroprevalence. A total of 30 camels, 31 cattle, 22 sheep and 32 goats that were seronegative by all the above tests were recruited in a subsequent longitudinal study for follow up. These animals were followed for 12 months and tested for anti-Brucella antibodies using iELISA. Seroconversion among these animals was defined by a positive iELISA test following a negative iELISA result in the previous sampling period. All seropositive samples were further tested using real-time PCR-based assays to identify Brucella species. These analyses targeted the alkB and BMEI1162 genes for B. abortus, and B. melitensis, respectively. Data from the longitudinal study were analysed using Cox proportional hazards model that accounted for within-herds clustering of Brucella infections.

Results

The overall incidence rate of Brucella infection was 0.024 (95% confidence interval [CI]: 0.014–0.037) cases per animal-months at risk. Brucella infection incidence in camels, cattle, goats and sheep were 0.053 (0.022–0.104), 0.028 (0.010–0.061), 0.013 (0.003–0.036) and 0.006 (0.0002–0.034) cases per animal-months at risk, respectively. The incidence rate of Brucella infection among females and males were 0.020 (0.009–0.036) and 0.016 (0.004–0.091), respectively. Real-time PCR analyses showed that B. abortus was more prevalent than B. melitensis in the area. Results of multivariable Cox regression analysis identified species (camels and cattle) as an important predictor of Brucella spp. exposure in animals.

Conclusions

This study estimated an overall brucellosis incidence of 0.024 cases per animal-months at risk with camels and cattle having higher incidence than sheep and goats. These results will inform surveillance studies in the area.
CTNNA3 genetic polymorphism may be a new genetic signal of type 2 diabetes in the Chinese Han population: a case control study
Authors: Zhang Yunjun , Zhou Xiaoman , Dai Wanjuan , Sun Juan , Lin Mei , Zhang Yutian , Ding Yipeng
Published: October 2021

Background

Type 2 Diabetes (T2D) is the result of a combination of genes and environment. The identified genetic loci can only explain part of T2D risk. Our study is aimed to explore the association between CTNNA3 single nucleotide polymorphisms (SNPs) and T2D risk.

Methods

We conducted a 'case–control' study among 1002 Chinese Han participants. Four candidate SNPs of CTNNA3 were selected (rs10822745 C/T, rs7920624 A/T, rs2441727 A/G, rs7914287 A/G), and logistic regression analysis was used to evaluate the association between candidate SNPs and T2D risk. We used single factor analysis of variance to analyze the differences of clinical characteristics among different genotypes. In this study, haplotype analysis was conducted by plink1.07 and Haploview software and linkage disequilibrium (LD) was calculated. The interaction of candidate SNPs in T2D risk was evaluated by multi-factor dimensionality reduction (MDR). Finally, we conducted a false-positive report probability (FPRP) analysis to detect whether the significant findings were just chance or noteworthy observations.

Results

The results showed that CTNNA3-rs7914287 was a risk factor for T2D (‘T’: OR = 1.33, p = 0.003; ‘TT’: OR = 2.21, p = 0.001; ‘TT’ (recessive): OR = 2.09, p = 0.001; Log-additive: OR = 1.34, p = 0.003). The results of subgroup analysis showed that rs7914287 was significantly associated with the increased risk of T2D among participants who were older than 60 years, males, smoking, drinking, or BMI > 24. We also found that rs2441727 was associated with reducing the T2D risk among participants who were older than 60 years, smoking, or drinking. In addition, rs7914287 was associated with T2D patients with no retinal degeneration; rs10822745 and rs7920624 were associated with the course of T2D patients. High density lipoprotein levels had significant differences under different genotypes of rs10822745. Under the different genotypes of rs7914287, the levels of aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase were also significantly different.

Conclusion

We found that CTNNA3 genetic polymorphisms can be used as a new genetic signal of T2D risk in Chinese Han population. Especially, CTNNA3-rs7914287 showed an outstanding and significant association with T2D risk in both overall analysis and subgroup analysis.
Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression
Authors: Chien Chu-Yen , Chen Ying-Chen , Lee Chien‑Hsing , Wu Jia-Rong , Huang Tsai-Wang , Huang Ren-Yeong , Cheng Wan-Chien , Hsieh Alexander Cheng-Ting , Shieh Yi-Shing
Published: October 2021

Background

Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy.

Methods

The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay.

Results

Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3′untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3′UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC.

Conclusions

These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.
Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation
Authors: Alavi Matin , Farkhondeh Tahereh , Aschner Michael , Samarghandian Saeed
Published: October 2021

Aim and background

Cancer represents a major health problem with an exceedingly high toll on the patients, their families, and the economy. Cancers are also associated with high mortality rates. Existing therapies for cancer are generally ineffective with many side effects.

Method

A search was conducted on Pubmed, Google Scholar, Scopus, and web of science databases, and articles related to anticancer effects of resveratrol were collected.

Results

Resveratrol is a natural compound that can activate the Nrf2 transcription factor. Nfr2 translocates to the nucleus and induces antioxidant gene expression. In different cell lines, resveratrol can increase apoptosis and inhibit the proliferation of cancer cells.

Conclusion

We found that resveratrol shows efficacy for the treatment of cancer, but due to high controversy on the Nrf2 signaling pathway and mechanisms of resveratrol action, additional studies should be conducted to better characterize its mode-of-action in cancer.

Graphical Abstract
Quantitative phosphoproteomic analysis reveals chemoresistance-related proteins and signaling pathways induced by rhIL-6 in human osteosarcoma cells
Authors: Zhang Rui , Wang Huan , Li Erliang , Wu Yonghong , Wen Yanhua , Li Chenyu , Liao Bo , Ma Qiong
Published: October 2021

Background

IL-6 plays a pivotal role in resistance to chemotherapeutics, including lobaplatin. However, the underlying mechanisms are still unclear. This study was to investigate the changes in phosphoproteins and their related signaling pathways in the process of IL-6-induced chemoresistance to lobaplain in osteosarcoma cells.

Methods

We performed a quantitative phosphoproteomic analysis of the response of SaOS-2 osteosarcoma cells to recombinant human IL-6 (rhIL-6) intervention prior to lobaplatin treatment. The cells were divided into the control group (Con), the lobaplatin group (Lob), and the rhIL-6-and-lobaplatin group (IL-6). Three biological replicates of each group were included. The differentially expressed phosphoproteins were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Netphos 3.1 was used for the prediction of kinases, and STRING was used for the visualization of protein–protein interactions. The conserved motifs surrounding the phosphorylated residues were analyzed using the motif-x algorithm. Western blot analysis was performed to verify the differential expression of p-FLNC, its predicted kinase and the related signaling pathway. The results of the bioinformatic analysis were validated by immunohistochemical staining of clinical specimens.

Results

In total, 3373 proteins and 12,183 peptides, including 3232 phosphorylated proteins and 11,358 phosphorylated peptides, were identified and quantified. Twenty-three significantly differentially expressed phosphoproteins were identified in the comparison between the IL-6 and Lob groups, and p-FLNC ranked second among these phosphoproteins. GO and KEGG analyses revealed the pivotal role of mitogen-activated protein kinase signaling in drug resistance induced by rhIL-6. Four motifs, namely, -SPxxK-, -RxxSP-, -SP-, and -SPK-, demonstrated higher expression in the IL-6 group than in the Lob group. The western blot analysis results verified the higher expression of p-FLNC, AKT1, and p-ERK and the lower expression of p-JNK in the IL-6 group than in the Con and Lob groups. The immunohistochemical staining results showed that p-FLNC, AKT1 and p-ERK1/2 were highly expressed in platinum-resistant clinical specimens but weakly expressed in platinum-sensitive specimens, and platinum-resistant osteosarcoma specimens demonstrated weak expression of p-JNK.

Conclusions

This phosphoproteomic study is the first to reveal the signature associated with rhIL-6 intervention before lobaplatin treatment in human osteosarcoma cells. p-FLNC, AKT1, and MAPK signaling contributes to resistance to lobaplatin in osteosarcoma SaOS-2 cells and may represent molecular targets to overcome osteosarcoma chemoresistance.
Clinical M2 macrophages-related genes to aid therapy in pancreatic ductal adenocarcinoma
Authors: Xu Qianhui , Chen Shaohuai , Hu Yuanbo , Huang Wen
Published: October 2021

Background

Increasing evidence supports that infiltration M2 Macrophages act as pivotal player in tumor progression of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, comprehensive analysis of M2 Macrophage infiltration and biological roles of hub genes (FAM53B) in clinical outcome and immunotherapy was lack.

Method

The multiomic data of PDAC samples were downloaded from distinct datasets. CIBERSORT algorithm was performed to uncover the landscape of TIME. Weighted gene co-expression network analysis (WGCNA) was performed to identify candidate module and significant genes associated with M2 Macrophages. Kaplan-Meier curve and receiver operating characteristic (ROC) curves were applied for prognosis value validation. Mutation data was analyzed by using “maftools” R package. Gene set variation analysis (GSVA) was employed to assign pathway activity estimates to individual sample. Immunophenoscore (IPS) was implemented to estimate immunotherapeutic significance of risk score. The half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs was predicted by using the pRRophetic algorithm. Finally, quantitative real-time polymerase chain reaction was used to determine FAM53B mRNA expression and TIMER database was utilized to uncover its possible role in immune infiltration of PDAC.

Results

Herein, 17,932 genes in 234 samples (214 tumor and 20 normal) were extracted from three platforms. Taking advantage of WGCNA, significant module (royalblue) and 135 candidate genes were considered as M2 Macrophages-related genes. Subsequently, risk signature including 5 hub genes was developed by multiple analysis, which exhibited excellent prognostic performance. Besides, comprehensive prognostic nomogram was constructed to quantitatively estimate risk. Then, intrinsic link between risk score with tumor mutation burden (TMB) was explored. Additionally, risk score significantly correlated with diversity of tumor immune microenvironment (TIME). PDAC samples within different risk presented diverse signaling pathways activity and experienced significantly distinct sensitivity to administering chemotherapeutic or immunotherapeutic agents. Finally, the biological roles of FAM53B were revealed in PDAC.

Conclusions

Taken together, comprehensive analyses of M2 Macrophages profiling will facilitate prognostic prediction, delineating complexity of TIME, and contribute insight into precision therapy for PDAC.
Long noncoding RNA SNHG4: a novel target in human diseases
Authors: Chu Qingfei , Gu Xinyu , Zheng Qiuxian , Guo Zixuan , Shan Dandan , Wang Jing , Zhu Haihong
Published: October 2021

Recently, long noncoding RNAs (lncRNAs) have attracted great attention from researchers. LncRNAs are non-protein-coding RNAs of more than 200 nucleotides in length. Multiple studies have been published on the relationship between lncRNA expression and the progression of human diseases. LncRNA small nucleolar RNA host gene 4 (SNHG4), a member of the lncRNA SNHG family, is abnormally expressed in a variety of human diseases, including gastric cancer, renal cell carcinoma, glioblastoma, neuroblastoma, prostate cancer, colorectal cancer, osteosarcoma, cervical cancer, liver cancer, lung cancer, non-small-cell lung cancer, neonatal pneumonia, diabetic retinopathy, neuropathic pain, acute cerebral infarction, acute myeloid leukaemia, and endometriosis. In this paper, the structure of SNHG4 is first introduced, and then studies in humans, animal models and cells are summarized to highlight the expression and function of SNHG4 in the above diseases. In addition, the specific mechanism of SNHG4 as a competing endogenous RNA (ceRNA) is discussed. The findings indicate that SNHG4 can be used as a biomarker for disease prognosis evaluation and as a potential target for disease diagnosis and treatment.
Rethinking the economic costs of hospitalization for malaria: accounting for the comorbidities of malaria patients in western Kenya
Authors: Watts Caroline , Atieli Harrysone , Alacapa Jason , Lee Ming-Chieh , Zhou Guofa , Githeko Andrew , Yan Guiyun , Wiseman Virginia
Published: October 2021

Background

Malaria causes significant mortality and morbidity in sub-Saharan Africa, especially among children under five years of age and places a huge economic burden on individuals and health systems. While this burden has been assessed previously, few studies have explored how malaria comorbidities affect inpatient costs. This study in a malaria endemic area in Western Kenya, assessed the total treatment costs per malaria episode including comorbidities in children and adults.

Methods

Total economic costs of malaria hospitalizations were calculated from a health system and societal perspective. Patient-level data were collected from patients admitted with a malaria diagnosis to a county-level hospital between June 2016 and May 2017. All treatment documented in medical records were included as health system costs. Patient and household costs included direct medical and non-medical expenses, and indirect costs due to productivity losses.

Results

Of the 746 patients admitted with a malaria diagnosis, 64% were female and 36% were male. The mean age was 14 years (median 7 years). The mean length of stay was three days. The mean health system cost per patient was Kenyan Shilling (KSh) 4288 (USD 42.0) (95% confidence interval (CI) 95% CI KSh 4046–4531). The total household cost per patient was KSh 1676 (USD 16.4) (95% CI KSh 1488–1864) and consisted of: KSh 161 (USD1.6) medical costs; KSh 728 (USD 7.1) non-medical costs; and KSh 787 (USD 7.7) indirect costs. The total societal cost (health system and household costs) per patient was KSh 5964 (USD 58.4) (95% CI KSh 5534–6394). Almost a quarter of patients (24%) had a reported comorbidity. The most common malaria comorbidities were chest infections, diarrhoea, and anaemia. The inclusion of comorbidities compared to patients with-out comorbidities led to a 46% increase in societal costs (health system costs increased by 43% and patient and household costs increased by 54%).

Conclusions

The economic burden of malaria is increased by comorbidities which are associated with longer hospital stays and higher medical costs to patients and the health system. Understanding the full economic burden of malaria is critical if future malaria control interventions are to protect access to care, especially by the poor.
Opening the policy blackbox: unravelling the process for changing national diagnostic and treatment guidelines for vivax malaria in seven countries
Authors: Ruwanpura Varunika , Neukom Josselyn , Grietens Koen Peeters , Price Ric N. , Thriemer Kamala , Lynch Caroline A.
Published: October 2021

Background

The changing global health landscape has highlighted the need for more proactive, efficient and transparent health policy-making. After more than 60 years of limited development, novel tools for vivax malaria are finally available, but need to be integrated into national policies. This paper maps the malaria policy-making processes in seven endemic countries, to identify areas where it can be improved to align with best practices and optimal efficiency.

Methods

Data were collected during a workshop, convened by the Asia Pacific Malaria Elimination Network’s Vivax Working Group in 2019, and subsequent interviews with key stakeholders from Cambodia, Ethiopia, Indonesia, Pakistan, Papua New Guinea (PNG), Sri Lanka and Vietnam. Documentation of policy processes provided by respondents was reviewed. Data analysis was guided by an analytic framework focused on three a priori defined domains: “context,” “actors” and “processes”.

Results

The context of policy-making varied with available funding for malaria, population size, socio-economic status, and governance systems. There was limited documentation of the process itself or terms of reference for involved actors. In all countries, the NMP plays a critical role in initiating and informing policy change, but the involvement of other actors varied considerably. Available evidence was described as a key influencer of policy change; however, the importance of local evidence and the World Health Organization’s endorsement of new treatments and diagnostics varied. The policy process itself and its complexity varied but was mostly semi-siloed from other disease specific policy processes in the wider Ministry of Health. Time taken to change and introduce a new policy guideline previously varied from 3 months to 3 years.

Conclusions

In the medium to long term, a better alignment of anti-malarial policy-making processes with the overall health policy-making would strengthen health governance. In the immediate term, shortening the timelines for policy change will be pivotal to meet proposed malaria elimination milestones.
Limited Plasmodium sporozoite gliding motility in the absence of TRAP family adhesins
Authors: Beyer Konrad , Kracht Simon , Kehrer Jessica , Singer Mirko , Klug Dennis , Frischknecht Friedrich
Published: October 2021

Background

Plasmodium sporozoites are the highly motile forms of malaria-causing parasites that are transmitted by the mosquito to the vertebrate host. Sporozoites need to enter and cross several cellular and tissue barriers for which they employ a set of surface proteins. Three of these proteins are members of the thrombospondin related anonymous protein (TRAP) family. Here, potential additive, synergistic or antagonistic roles of these adhesion proteins were investigated.

Methods

Four transgenic Plasmodium berghei parasite lines that lacked two or all three of the TRAP family adhesins TRAP, TLP and TREP were generated using positive–negative selection. The parasite lines were investigated for their capacity to attach to and move on glass, their ability to egress from oocysts and their capacity to enter mosquito salivary glands. One strain was in addition interrogated for its capacity to infect mice.

Results

The major phenotype of the TRAP single gene deletion dominates additional gene deletion phenotypes. All parasite lines including the one lacking all three proteins were able to conduct some form of active, if unproductive movement.

Conclusions

The individual TRAP-family adhesins appear to play functionally distinct roles during motility and infection. Other proteins must contribute to substrate adhesion and gliding motility.

Graphical Abstract