bluuebunny/crossref_metadata_2025 huggingface dataset:
Delivering vaping cessation interventions to adolescents and young adults on Instagram: protocol for a randomized controlled trial
Authors: Lyu Joanne Chen , Olson Sarah S. , Ramo Danielle E. , Ling Pamela M.
Published: December 2022

Background

Adolescent and young adult use of electronic nicotine delivery systems (“vaping”) has increased rapidly since 2018. There is a dearth of evidence-based vaping cessation interventions for this vulnerable population. Social media use is common among young people, and smoking cessation groups on social media have shown efficacy in the past. The objective of this study is to describe the protocol for a randomized controlled trial (RCT) testing the efficacy of an Instagram-based vaping cessation intervention for adolescents and young adults.

Methods

Adolescents and young adults aged 13–21 residing in California who have vaped at least once per week in the past 30 days will be recruited through social media ads, community partners, and youth serving organizations. Participants will be randomly assigned to intervention or control conditions: the intervention group takes place on Instagram, where participants receive up to 3 posts per weekday for 25 days over 5 weeks; the control group will be directed to kickitca.org, a website offering links to chatline and texting cessation services operated by the California Smokers' Helpline. The primary outcome is biochemically verified 7-day point prevalence abstinence for nicotine vaping; secondary outcomes are vaping reduction by 50% or more, vaping quit attempts, readiness to quit vaping, confidence in ability to quit, desire to quit, commitment to abstinence, and use of evidence-based cessation strategies. Both the primary outcome and secondary outcomes will be assessed immediately, 3 months, and 6 months after the treatment.

Discussion

This is the first RCT to test a vaping cessation intervention delivered through Instagram. If effective, it will be one of the first evidence-based interventions to address vaping among adolescents and young adults and add to the evidence base for social media interventions for this population.

Trial registration

ClinicalTrials.gov: NCT04707911, registered on January 13, 2021.
Mixed methods assessment of personal heat exposure, sleep, physical activity, and heat adaptation strategies among urban residents in the Boston area, MA
Authors: Milando Chad W. , Black-Ingersoll Flannery , Heidari Leila , López-Hernández Ibrahim , de Lange Julie , Negassa Abgel , McIntyre Alina M. , Martinez M. Pilar Botana , Bongiovanni Roseann , Levy Jonathan I. , Kinney Patrick L. , Scammell Madeleine K. , Fabian M. Patricia
Published: December 2022

The growing frequency, intensity, and duration of extreme heat events necessitates interventions to reduce heat exposures. Local opportunities for heat adaptation may be optimally identified through collection of both quantitative exposure metrics and qualitative data on perceptions of heat. In this study, we used mixed methods to characterize heat exposure among urban residents in the area of Boston, Massachusetts, US, in summer 2020. Repeated interviews ofN = 24 study participants ascertained heat vulnerability and adaptation strategies. Participants also used low-cost sensors to collect temperature, location, sleep, and physical activity data. We saw significant differences across temperature metrics: median personal temperature exposures were 3.9 °C higher than median ambient weather station temperatures. Existing air conditioning (AC) units did not adequately control indoor temperatures to desired thermostat levels: even with AC use, indoor maximum temperatures increased by 0.24 °C per °C of maximum outdoor temperature. Sleep duration was not associated with indoor or outdoor temperature. On warmer days, we observed a range of changes in time-at-home, expected given our small study size. Interview results further indicated opportunities for heat adaptation interventions including AC upgrades, hydration education campaigns, and amelioration of energy costs during high heat periods. Our mixed methods design informs heat adaptation interventions tailored to the challenges faced by residents in the study area. The strength of our community-academic partnership was a large part of the success of the mixed methods approach.
A novel autophagy-related long non-coding RNAs prognostic risk score for clear cell renal cell carcinoma
Authors: Tang Fucai , Tang Zhicheng , Lu Zechao , Cai Yueqiao , Lai Yongchang , Mai Yuexue , Li Zhibiao , Lu Zeguang , Zhang Jiahao , Li Ze , He Zhaohui
Published: December 2022

Background

As the main histological subtype of renal cell carcinoma, clear cell renal cell carcinoma (ccRCC) places a heavy burden on health worldwide. Autophagy-related long non-coding RNAs (ARlncRs) have shown tremendous potential as prognostic signatures in several studies, but the relationship between them and ccRCC still has to be demonstrated.

Methods

The RNA-sequencing and clinical characteristics of 483 ccRCC patients were downloaded download from the Cancer Genome Atlas and International Cancer Genome Consortium. ARlncRs were determined by Pearson correlation analysis. Univariate and multivariate Cox regression analyses were applied to establish a risk score model. A nomogram was constructed considering independent prognostic factors. The Harrell concordance index calibration curve and the receiver operating characteristic analysis were utilized to evaluate the nomogram. Furthermore, functional enrichment analysis was used for differentially expressed genes between the two groups of high- and low-risk scores.

Results

A total of 9 SARlncRs were established as a risk score model. The Kaplan–Meier survival curve, principal component analysis, and subgroup analysis showed that low overall survival of patients was associated with high-risk scores. Age, M stage, and risk score were identified as independent prognostic factors to establish a nomogram, whose concordance index in the training cohort, internal validation, and external ICGC cohort was 0.793, 0.671, and 0.668 respectively. The area under the curve for 5-year OS prediction in the training cohort, internal validation, and external ICGC cohort was 0.840, 0.706, and 0.708, respectively. GO analysis and KEGG analysis of DEGs demonstrated that immune- and inflammatory-related pathways are likely to be critically involved in the progress of ccRCC.

Conclusions

We established and validated a novel ARlncRs prognostic risk model which is valuable as a potential therapeutic target and prognosis indicator for ccRCC. A nomogram including the risk model is a promising clinical tool for outcomes prediction of ccRCC patients and further formulation of individualized strategy.
Effect of CTP-mediated PTEN on 5637 bladder cancer cells and the underlying molecular mechanism
Authors: Yu Bei , Huang Yuan , Yang Yue , Hu Haifeng , Yang Jin
Published: December 2022

Objective

The aim of the present study was to explore the effect of cytoplasmic transduction peptide (CTP)-phosphatase and tensin homolog (PTEN) on the proliferation, cell cycle, apoptosis, migration and invasion of bladder cancer cells and the underlying molecular mechanism.

Methods

A eukaryotic expression vector, pTT5-CTP-PTEN, was constructed. The constructed vector was transfected into HEK 293-6E cells to express a fusion protein, CTP-PTEN. The fusion protein was purified. 5637 bladder cancer cells were cocultured with purified CTP-PTEN fusion protein. Target gene expression, protein expression, cell proliferation, cell cycle, apoptosis, cell invasion and cell migration were examined by reverse transcription polymerase chain reaction (RT-PCR), western blot, MTT assay, flow cytometry, Transwell assay, and cell scratch assay, respectively.

Results

Both PTEN and CTP-PTEN fusion protein inhibited the proliferation, cell cycle, invasion and migration of bladder cancer cells and promoted the apoptosis of bladder cancer cells. The effect of CTP-PTEN was more significant.

Conclusions

The fused expression of CTP and PTEN significantly increased the penetrability of the tumor suppressor gene PTEN into cancer cells. The CTP-PTEN fusion protein exhibited a significant carcinostatic effect on 5637 bladder cancer cells.
Characterization of immunologically detectable T-cell sensitization, Immunohistochemical detection of pro-inflammatory cytokines, and clinical parameters of patients after allogeneic intraoral bone grafting procedures: a prospective randomized controlled clinical trial in humans
Authors: Solakoglu Önder , Götz Werner , von Baehr Volker , Heydecke Guido , Pantel Klaus , Schwarzenbach Heidi
Published: December 2022

Background

The null hypotheses were tested that intraoral bone augmentation using two different allogeneic materials has no impact on the patient’s blood levels of material-specific lymphocytes and on the immunohistochemical detection of pro-inflammatory cytokines IL-1α, IL1ß and TNF-α and T-cell markers CD4, CD8 in biopsies of the test groups.

Methods

In this prospective RCT, 60 systemically healthy participants were randomly assigned to two allogeneic test groups (1: Maxgraft®, freeze-dried, multiple donors, and 2: Puros®, solvent-dehydrated, single donor) and an autologous control group (10 patients). Plasma samples were collected pre-(T1) and postoperatively (2 weeks (T2) and 4 months (T3)). The Lymphocyte Transformation Test (LTT) was used for analyzing levels of transformed lymphocytes for type IV immune reactions by 3H-thymidine activity. Bone biopsies were harvested at T3 and immunohistochemically analyzed for IL-1α, IL1ß, TNF-α, CD4, CD8 and correlated with the immunological and clinical findings.

Results

A statistically significant difference between the tested materials was observed for LTT measurements at T3 (p = 0.033). Furthermore, three groups were identified: Group A (LTT negative T1-T3, n = 48), group B (LTT positive T1-T3, n = 7), group C (developing positive LTT at T2, n = 5). A highly significant elevation of IL-1α, IL1ß, TNF-α in patients of group C (p = 0.0001) and a significant elevation of CD4+ cells in patients of group B (p = 0.005) was shown.

Conclusion

Our data show that following allogeneic bone grafting, local and systemic immunological reactions can be detected in some patients. These findings were statistically significant for the timepoint T3 between the tested materials as well as for the groups B and C correlated with group A for both tested materials. Therefore, the null hypotheses were rejected. A preoperative compatibility test for allogeneic materials in order to improve patient safety and the predictability of these materials would be desirable.

Trial registration

Ethical commission of the Ärztekammer Hamburg, Germany (PV5211) as well as by the German Registry of Clinical Studies (DRKS00013010) on 30/07/2018 (http://apps.who.int/trialsearch/).
Three-dimensional quantitative analysis of dental and skeletal characteristics of skeletal Class I unilateral posterior crossbite in adults
Authors: Wu Jingwen , Bek Joanna Ser Yun , Luo Mengqi , Xu Hao , Wang Yanmin , Han Xianglong
Published: December 2022

Background

To study the dentoskeletal characteristics and the degree of compensations in skeletal Class I adults with unilateral posterior crossbite (UPCB).

Methods

A sample of 40 adults was chosen for this cross-sectional study. 20 skeletal Class I adults with UPCB (mean age: 22.20 ± 2.88 years), were compared to 20 skeletal Class I adults with normal occlusion (mean age: 27.56 ± 5.76 years). The respective dentoskeletal measurements were made on cross-sectional images from cone-beam computed tomography scans.

Results

Skeletally, both groups showed significant differences (P < 0.05) in mandibular corpus length and menton deviation with the UPCB group showing the greatest displacement. Maxillomandibular vertical asymmetry and condylar positional asymmetry were not significant in both groups (P > 0.05). For dental variables on the second premolar and first molar, the UPCB group showed greater linear and angular differences when compared to the control group (P < 0.05). On the crossbite side, maxillary posterior teeth were more buccally inclined, and mandibular posterior teeth were more lingually inclined. However, on the non-crossbite side, both maxillary and mandibular posterior teeth were lingually inclined.

Conclusion

Adults with UPCB showed distinct transverse dentoskeletal asymmetry. No asymmetry was found in the condylar position and the mandibular height in UPCB adults.
CBCT analysis of crestal soft tissue thickness before implant placement and its relationship with cortical bone thickness
Authors: Cui Xiaoxi , Reason Tyler , Pardi Vanessa , Wu Qiang , Martinez Luna Acela A.
Published: December 2022

Background

The importance of crestal soft tissue thickness and its influence in peri-implant tissue health has been evaluated in few clinical studies. Cone beam computed tomography imaging offers a unique opportunity to investigate variations in crestal soft tissue thickness. The aim of this retrospective study was to evaluate the possible correlation between crestal soft tissue thickness and hard tissue measurements on CBCT images, and to compare crestal soft tissue thickness among different patients and edentulous site groups.

Methods

CBCT images of partially edentulous adult patients treated at ECU School of Dental Medicine were evaluated. 267 patients with 321 edentulous sites were included. Demographic data were collected from electronic health records. Cross-sectional CBCT images at the center of each edentulous site were used to measure soft tissue and hard tissue parameters. Linear mixed models were used to compare crestal soft tissue thickness and hard tissue measurements by gender, age groups, and edentulous sites. Pearson correlation was applied to evaluate the correlation between crestal soft tissue thickness and different hard tissue measurements. Association between crestal soft tissue thickness and independent variables (gender, age groups, edentulous sites) was evaluated using repeated measure logistic regression, while the crestal soft tissue thickness was dichotomized by a threshold of 2 mm.

Results

Mean age of patients included was 60 (range 21–85 years). Female to male ratio was 1.07. Mean crestal soft tissue thickness of all non-grafted native bone sites was 2.17 mm. Mean thickness of cortical bone at alveolar crest was 0.94 mm. Thickness of buccal and lingual cortical plates 5 mm apical to alveolar crest were 1.17 mm and 1.58 mm, respectively. Pearson’s correlation showed moderate positive correlation among hard tissue measurements, but weak correlation between soft tissue thickness and hard tissue measurements. Anterior sites [OR = 3.429 (1.100–10.69)] and maxillary posterior sites [OR = 1.937 (1.077–3.482)] had higher odds of presenting with more than 2 mm of soft tissue at the alveolar crest.

Conclusion

More than half of the patients had crestal soft tissues at edentulous sites thicker than 2 mm. Thickness of crestal soft tissue was not significantly associated with hard tissue measurements. Edentulous anterior sites and maxillary posterior sites presented with thicker crestal soft tissue at alveolar crest as compared to mandibular posterior sites.
Using Delphi method to develop Chinese women’s cervical cancer screening intention scale based on planned behavior theory
Authors: Xin Tingting , Ding Xian , Gao Han , Li Chunting , Jiang Yuting , Chen Xiao
Published: December 2022

Background

Cervical cancer is the most common malignant tumor in women with a high mortality rate. However, the awareness and participation of women in cervical cancer screening were not high, and rare attention was paid to cervical cancer screening. The extensive promotion and execution of cervical cancer screening in China are still facing difficulties. In order to fully comprehend and evaluate the barriers and promote factors of cervical cancer screening in women, the objective of this study was to develop a scientifically sound and clinically useful Chinese cervical cancer screening intention scale. This study would allow for the development of targeted interventions which may contribute to the increase of individual participation in cervical cancer screening going forward.

Methods

This study used the Delphi method to construct a Chinese cervical cancer screening intention scale based on the theory of planned behavior (TPB) and evaluate its validity. The study was based on the overview of the TPB questionnaire proposed by Ajzen, and was conducted through the literature search and two rounds of the Delphi expert consultation. According to the literature search published from 2012 to 2022, the scale item pool was established and a questionnaire was designed. A survey of 16 experts from 6 different provinces, cities and regions in China was conducted, and the Delphi technique was used to collect and analyze expert opinions data.

Results

The final scale consisted of 4 dimensions and 23 items. The response rates in two rounds of expert consultation were 80% and 93.75%, respectively, with authority coefficients of 0.928 and 0.930. Variation coefficients varied from 0.07 to 0.21. Dimensions included “attitude towards behavior”, “subjective norm”, “perceived behavioral control” and “behavioral intention”.

Conclusions

Women’s cervical cancer screening intentions could be assessed with the scale, since it had high validity and reliability, as well as high authority and coordination, meanwhile affording explanations and improving the efficiency of interventions.
Retraction Note: Calycosin-7-O-β-D-glucoside promotes oxidative stress-induced cytoskeleton reorganization through integrin-linked kinase signaling pathway in vascular endothelial cells
Authors: Jiang Yue-Hua , Sun Wei , Li Wei , Hu Hong-Zhen , Zhou Le , Jiang Hui-Hui , Xu Jing-Xin
Published: December 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-015-0839-5.
The impact of a mindfulness bracelet on emotional affect in medical students: a prospective cohort study
Authors: LoBasso Michael , Jones Ian A. , Shapiro Johanna , Saadat Soheil , Wray Alisa
Published: December 2022

Background

There is concern that negative changes in emotional outlook among medical students may impair the behavior of students, diminish learning, and ultimately affect patient care. Although most medical students begin their professional education with idealism, enthusiasm, and attention to humanity, they often have difficulty balancing their happiness with social and professional responsibilities. The following study aimed to determine if a simple mindfulness reminder (in the form of a bracelet) will impact emotional affect in first-year medical students. The second aim is to better understand the changes in emotional affect as students start medical school.

Methods

First year medical students were invited to participate at the start of the academic year. Baseline survey data and demographic data were obtained prior to participants being given the mindfulness bracelet and a standardized presentation explaining its purpose. Follow-up surveys were obtained at one- and two-month intervals. Statistical analysis was based on sum score of the survey. Change of sum score over time was tested by using repeated measurement analysis.

Results

Data collection included 104 students at the initial distribution of the survey. Follow-up surveys were obtained from 78 and 69 students at the first- and second-month mark, respectively. No significant associations were detected between frequency of mindfulness bracelet usage and emotional affect. However, there was a significant decrease in positive affect over the first month of medical school (p < 0.01), followed by a significant recovery in positive affect in the second month of medical school (p < 0.01). Demographic data did not reveal statistically significant differences among demographic groups and progression of emotional affect.

Conclusions

Although the mindfulness bracelet intervention did not yield significant improvement in emotional affect, our results are consistent with other studies demonstrating that the first year of medical school negatively impacts the emotional outlook of students. Future studies are needed to explore practical interventions and to better understand and address the negative effect that early medical school education has on student’s emotional state.
Is there a civic duty to support medical AI development by sharing electronic health records?
Authors: Müller Sebastian
Published: December 2022

Medical artificial intelligence (AI) is considered to be one of the most important assets for the future of innovative individual and public health care. To develop innovative medical AI, it is necessary to repurpose data that are primarily generated in and for the health care context. Usually, health data can only be put to a secondary use if data subjects provide their informed consent (IC). This regulation, however, is believed to slow down or even prevent vital medical research, including AI development. For this reason, a number of scholars advocate a moral civic duty to share electronic health records (EHRs) that overrides IC requirements in certain contexts. In the medical AI context, the common arguments for such a duty have not been subjected to a comprehensive challenge. This article sheds light on the correlation between two normative discourses concerning informed consent for secondary health record use and the development and use of medical AI. There are three main arguments in favour of a civic duty to support certain developments in medical AI by sharing EHRs: the ‘rule to rescue argument’, the ‘low risks, high benefits argument’, and the ‘property rights argument’. This article critiques all three arguments because they either derive a civic duty from premises that do not apply to the medical AI context, or they rely on inappropriate analogies, or they ignore significant risks entailed by the EHR sharing process and the use of medical AI. Given this result, the article proposes an alternative civic responsibility approach that can attribute different responsibilities to different social groups and individuals and that can contextualise those responsibilities for the purpose of medical AI development.
The mediating effects of coping style and resilience on the relationship between parenting style and academic procrastination among Chinese undergraduate nursing students: a cross-sectional study
Authors: Huang Haitao , Ding Yueming , Liang Yipei , Zhang Yiming , Peng Qianwen , Wan Xiao , Chen Chaoran
Published: December 2022

Background

How to kindle the learning enthusiasm of nursing students and reduce the incidence of academic procrastination is an important factor in reducing student attrition and improving the quality of nursing education.

Objectives

To investigate the mediating role of coping style and resilience on the association between parenting styles and academic procrastination among nursing undergraduates.

Methods

A cross-sectional study of 683 nursing undergraduates was conducted in China from March to May 2022. Parenting styles, coping style, resilience, and academic procrastination were measured using questionnaires. Descriptive analysis, Pearson’s correlation analysis and Hayes' PROCESS Macro in SPSS 25.0 were used to test the model.

Results

Positive parenting style had a significantly direct effect on academic procrastination and through three significantly indirect pathways: (1) through positive coping style (B =  − 0.048, 95% CI: − 0.074 to − 0.025), accounting for 14.71% of the total effect; (2) through negative coping style (B =  − 0.044, 95% CI: − 0.071 to − 0.021), accounting for 13.64% of the total effect; and (3) through resilience (B =  − 0.074, 95% CI: − 0.107 to − 0.044), accounting for 22.82% of the total effect. Moreover, negative parenting style had a significantly direct effect on academic procrastination and through two significantly indirect pathways: (1) through negative coping style (B = 0.056, 95% CI: 0.032 to 0.086), accounting for 21.73% of the total effect, and (2) through resilience (B = 0.028, 95% CI: 0.004 to 0.055), accounting for 10.93% of the total effect.

Conclusions

Intervention measures to reduce the academic procrastination of nursing undergraduates should include the evaluations of coping styles and resilience of nursing students and cultivation strategies to promote their positive coping styles and resilience.
Universal health coverage of five essential health services in mothers before and after the Haiti 2010 earthquake: a retrospective cohort study using difference-in-difference
Authors: Hirose Naoki , Chen Sanmei , Shiba Koichiro , Patil Crystal L. , Rahman Md Moshiur , Shimpuku Yoko
Published: December 2022

Background

In January 2010, Haiti was hit by a 7.0-magnitude earthquake. The impact of the earthquake on Universal Health Coverage in mothers remains unclear. This study explores the association between the 2010 Haiti earthquake and access to the five quality essential health services among women who gave birth in the two years before and after the earthquake.

Methods

From the Sixth Demographic and Health Survey in Haiti, we extracted data for women aged 15–49 who had reported a live birth in the two years before and after the 2010 Haiti earthquake. We used difference-in-difference analyses for antenatal care, delivery care, and vaccination, and multivariate logistic regression analyses for family planning and malaria prevention, to assess the impact of the acute damage (household-level damage, such as housing damage and/or loss of a family member, or region-level damage, such as living in a region where 50% or more of the houses were damaged) of the earthquake on these mothers’ access to quality essential health services.

Results

Mothers who had not suffered acute earthquake damage were more likely to live in rural areas and had less education and household wealth. The difference-in-difference and multivariate logistic regression analyses did not show strong evidence of any significant association between acute earthquake damage and access to quality health services. However, after the earthquake, access to quality health services deteriorated for both mothers with and without acute earthquake damage (-5.6% and -6.2% for antenatal care, -6.5% and 0% for delivery care, and -9.5% and -13.1% for vaccination, respectively).

Conclusions

The earthquake adversely affected mothers’ access to quality essential health services regardless of their exposure to acute earthquake damage. Mothers in rural areas who avoided such damage might also have experienced long-term negative effects from the earthquake, which was likely exacerbated by other structural factors such as lower education and economic status.
Gut microbiota modulates bleomycin-induced acute lung injury response in mice
Authors: Yoon Young me , Hrusch Cara L. , Fei Na , Barrón Gabriel M. , Mills Kathleen A. M. , Hollinger Maile K. , Velez Tania E. , Leone Vanessa A. , Chang Eugene B. , Sperling Anne I.
Published: December 2022

Background

Airway instillation of bleomycin (BLM) in mice is a widely used, yet challenging, model for acute lung injury (ALI) with high variability in treatment scheme and animal outcomes among investigators. Whether the gut microbiota plays any role in the outcome of BLM-induced lung injury is currently unknown.

Methods

Intratracheal instillation of BLM into C57BL/6 mice was performed. Fecal microbiomes were analyzed by 16s rRNA amplicon and metagenomic sequencing. Germ-free mice conventionalization and fecal microbiota transfer between SPF mice were performed to determine dominant commensal species that are associated with more severe BLM response. Further, lungs and gut draining lymph nodes of the mice were analyzed by flow cytometry to define immunophenotypes associated with the BLM-sensitive microbiome.

Results

Mice from two SPF barrier facilities at the University of Chicago exhibited significantly different mortality and weight loss during BLM-induced lung injury. Conventionalizing germ-free mice with SPF microbiota from two different housing facilities recapitulated the respective donors’ response to BLM. Fecal microbiota transfer from the facility where the mice had worse mortality into the mice in the facility with more survival rendered recipient mice more susceptible to BLM-induced weight loss in a dominant negative manner. BLM-sensitive phenotype was associated with the presence ofHelicobacterandDesulfovibrioin the gut, decreased Th17-neutrophil axis during steady state, and augmented lung neutrophil accumulation during the acute phase of the injury response.

Conclusion

The composition of gut microbiota has significant impact on BLM-induced wasting and death suggesting a role of the lung-gut axis in lung injury.
Gender disparities in time-to-initiation of cardioprotective glucose-lowering drugs in patients with type 2 diabetes and cardiovascular disease: a Danish nationwide cohort study
Authors: Funck Kristian Løkke , Bjerg Lasse , Isaksen Anders Aasted , Sandbæk Annelli , Grove Erik Lerkevang
Published: December 2022

Background

We aimed to examine the impact of gender and specific type of cardiovascular disease (CVD) diagnosis (ischemic heart disease [IHD], heart failure, peripheral artery disease [PAD] or stroke) on time-to-initiation of either a sodium glucose cotransporter 2 inhibitor or glucagon-like peptide 1 analogue (collectively termed cardioprotective GLD) after a dual diagnosis of type 2 diabetes (T2DM) and CVD.

Methods

In a nationwide cohort study, we identified patients with a new dual diagnosis of T2DM and CVD (January 1, 2012 and December 31, 2018). Cumulative user proportion (CUP) were assessed. Poisson models were used to estimate the initiation rate of cardioprotective GLDs. The final analyses were adjusted for potential confounders.

Results

In total, we included 70,538 patients with new-onset T2DM and CVD (38% female, mean age 70 ± 12 years at inclusion). During 183,256 person-years, 6,276 patients redeemed a prescription of a cardioprotective GLD. One-year CUPs of cardioprotective GLDs were lower in women than men. Initiation rates of GLDs were lower in women (female-to-male initiation-rate-ratio crude: 0.76, 95% CI 0.72–0.81); adjusted 0.92, 95% CI 0.87–0.97). In CVD-stratified analysis, the adjusted initiation rate ratio was lower in female patients with IHD and heart failure (IHD: 0.91 [95% CI 0.85–0.98], heart failure: 0.85 [95% CI 0.73–1.00], PAD: 0.92 [95% CI 0.78–1.09], and stroke: 1.06 [95% CI 0.93–1.20]).

Conclusions

Among patients with a new dual diagnosis of T2DM and CVD, female gender is associated with lower initiation rates of cardioprotective GLDs, especially if the patient has IHD or heart failure.
Lyve-1 deficiency enhances the hepatic immune microenvironment entailing altered susceptibility to melanoma liver metastasis
Authors: Jauch Anna Sophia , Wohlfeil Sebastian A. , Weller Céline , Dietsch Bianca , Häfele Verena , Stojanovic Ana , Kittel Maximilian , Nolte Hendrik , Cerwenka Adelheid , Neumaier Michael , Schledzewski Kai , Sticht Carsten , Reiners-Koch Philipp-Sebastian , Goerdt Sergij , Géraud Cyrill
Published: December 2022

Background

Hyaluronan receptor LYVE-1 is expressed by liver sinusoidal endothelial cells (LSEC), lymphatic endothelial cells and specialized macrophages. Besides binding to hyaluronan, LYVE-1 can mediate adhesion of leukocytes and cancer cells to endothelial cells. Here, we assessed the impact of LYVE-1 on physiological liver functions and metastasis.

Methods

Mice with deficiency of Lyve-1 (Lyve-1-KO) were analyzed using histology, immunofluorescence, microarray analysis, plasma proteomics and flow cytometry. Liver metastasis was studied by intrasplenic/intravenous injection of melanoma (B16F10 luc2, WT31) or colorectal carcinoma (MC38).

Results

Hepatic architecture, liver size, endothelial differentiation and angiocrine functions were unaltered in Lyve-1-KO. Hyaluronan plasma levels were significantly increased in Lyve-1-KO. Besides, plasma proteomics revealed increased carbonic anhydrase-2 and decreased FXIIIA. Furthermore, gene expression analysis of LSEC indicated regulation of immunological pathways. Therefore, liver metastasis of highly and weakly immunogenic tumors, i.e. melanoma and colorectal carcinoma (CRC), was analyzed. Hepatic metastasis of B16F10 luc2 and WT31 melanoma cells, but not MC38 CRC cells, was significantly reduced in Lyve-1-KO mice. In vivo retention assays with B16F10 luc2 cells were unaltered between Lyve-1-KO and control mice. However, in tumor-free Lyve-1-KO livers numbers of hepatic CD4+, CD8+ and regulatory T cells were increased. In addition, iron deposition was found in F4/80+ liver macrophages known to exert pro-inflammatory effects.

Conclusion

Lyve-1 deficiency controlled hepatic metastasis in a tumor cell-specific manner leading to reduced growth of hepatic metastases of melanoma, but not CRC. Anti-tumorigenic effects are likely due to enhancement of the premetastatic hepatic immune microenvironment influencing early liver metastasis formation.
Ursolic acid: a natural modulator of signaling networks in different cancers
Authors: Zafar Sameen , Khan Khushbukhat , Hafeez Amna , Irfan Muhammad , Armaghan Muhammad , Rahman Anees ur , Gürer Eda Sönmez , Sharifi-Rad Javad , Butnariu Monica , Bagiu Iulia-Cristina , Bagiu Radu Vasile
Published: December 2022

Incidence rate of cancer is estimated to increase by 40% in 2030. Furthermore, the development of resistance against currently available treatment strategies has contributed to the cancer-associated mortality. Scientists are now looking for the solutions that could help prevent the disease occurrence and could provide a pain-free treatment alternative for cancers. Therefore, efforts are now put to find a potent natural compound that could sever this purpose. Ursolic acid (UA), a triterpene acid, has potential to inhibit the tumor progression and induce sensitization to conventional treatment drugs has been documented. Though, UA is a hydrophobic compound therefore it is usually chemically modified to increase its bioavailability prior to administration. However, a thorough literature indicating its mechanism of action and limitations for its use at clinical level was not reviewed. Therefore, the current study was designed to highlight the potential mechanism of UA, its anti-cancer properties, and potential applications as therapeutic compound. This endeavour is a valuable contribution in understanding the hurdles preventing the translation of its potential at clinical level and provides foundations to design new studies that could help enhance its bioavailability and anti-cancer potential for various cancers.
Modelling longitudinal binary outcomes with outcome dependent observation times: an application to a malaria cohort study
Authors: Martins Adelino , Herzog Sereina A. , Mugenyi Levicatus , Faes Christel , Hens Niel , Abrams Steven
Published: December 2022

Background 

In spite of the global reduction of 21% in malaria incidence between 2010 and 2015, the disease still threatens many lives of children and pregnant mothers in African countries. A correct assessment and evaluation of the impact of malaria control strategies still remains quintessential in order to eliminate the disease and its burden. Malaria follow-up studies typically involve routine visits at pre-scheduled time points and/or clinical visits whenever individuals experience malaria-like symptoms. In the latter case, infection triggers outcome assessment, thereby leading to outcome-dependent sampling (ODS). Commonly used methods to analyze such longitudinal data ignore ODS and potentially lead to biased estimates of malaria-specific transmission parameters, hence, inducing an incorrect assessment and evaluation of malaria control strategies.

Methods 

In this paper, a new method is proposed to handle ODS by use of a joint model for the longitudinal binary outcome measured at routine visits and the clinical event times. The methodology is applied to malaria parasitaemia data from a cohort of $$n = 988$$

n
=
988

Ugandan children aged 0.5–10 years from 3 regions (Walukuba—300 children, Kihihi—355 children and Nagongera—333 children) with varying transmission intensities (entomological inoculation rate equal to 2.8, 32 and 310 infectious bites per unit year, respectively) collected between 2011–2014.

Results 

The results indicate that malaria parasite prevalence and force of infection (FOI) increase with age in the region of high malaria intensity with highest FOI in age group 5–10 years. For the region of medium intensity, the prevalence slightly increases with age and the FOI for the routine process is highest in age group 5–10 years, yet for the clinical infections, the FOI gradually decreases with increasing age. For the region with low intensity, both the prevalence and FOI peak at the age of 1 year after which the former remains constant with age yet the latter suddenly decreases with age for the clinically observed infections.

Conclusion 

Malaria parasite prevalence and FOI increase with age in the region of high malaria intensity. In all study sites, both the prevalence and FOI are highest among previously asymptomatic children and lowest among their symptomatic counterparts. Using a simulation study inspired by the malaria data at hand, the proposed methodology shows to have the smallest bias, especially when consecutive positive malaria parasitaemia presence results within a time period of 35 days were considered to be due to the same infection.
Estimation of bed net coverage indicators in Tanzania using mobile phone surveys: a comparison of sampling approaches
Authors: Worges Matt , Kamala Benjamin , Yukich Joshua , Chacky Frank , Lazaro Samwel , Dismas Charles , Aroun Sijenun , Ibrahim Raya , Khamis Mwinyi , Gitanya Mponeja P. , Mwingizi Deodatus , Metcalfe Hannah , Bantanuka Willhard , Deku Sena , Dadi David , Serbantez Naomi , Loll Dana , Koenker Hannah
Published: December 2022

Background

Threats to maintaining high population access with effective bed nets persist due to errors in quantification, bed net wear and tear, and inefficiencies in distribution activities. Monitoring bed net coverage is therefore critical, but usually occurs every 2–3 years through expensive, large-scale household surveys. Mobile phone-based survey methodologies are emerging as an alternative to household surveys and can provide rapid estimates of coverage, however, little research on varied sampling approaches has been conducted in sub-Saharan Africa.

Methods

A nationally and regionally representative cross-sectional mobile phone survey was conducted in early 2021 in Tanzania with focus on bed net ownership and access. Half the target sample was contacted through a random digit dial methodology (n = 3500) and the remaining half was reached through a voluntary opt-in respondent pool (n = 3500). Both sampling approaches used an interactive voice response survey. Standard RBM-MERG bed net indicators and AAPOR call metrics were calculated. In addition, the results of the two sampling approaches were compared.

Results

Population access (i.e., the percent of the population that could sleep under a bed net, assuming one bed net per two people) varied from a regionally adjusted low of 48.1% (Katavi) to a high of 65.5% (Dodoma). The adjusted percent of households that had a least one bed net ranged from 54.8% (Pemba) to 75.5% (Dodoma); the adjusted percent of households with at least one bed net per 2 de facto household population ranged from 35.9% (Manyara) to 55.7% (Dodoma). The estimates produced by both sampling approaches were generally similar, differing by only a few percentage points. An analysis of differences between estimates generated from the two sampling approaches showed minimal bias when considering variation across the indicator for households with at least one bed net per two de facto household population.

Conclusion

The results generated by this survey show that overall bed net access in the country appears to be lower than target thresholds. The results suggest that bed net distribution is needed in large sections of the country to ensure that coverage levels remain high enough to sustain protection against malaria for the population.
Influence of age on the association between the triglyceride-glucose index and all-cause mortality in patients with cardiovascular diseases
Authors: Wang Lu , Wang Yang , Liu Rui , Xu Lin , Zhong Wen , Li Lijuan , Wang Changyi , He Chengqi , Fu Chenying , Wei Quan
Published: December 2022

Background

In patients with cardiovascular diseases, it is reported that the triglyceride-glucose index (TGI) potentially indicates prognosis. However, the results are controversial. Moreover, whether age has an impact on the predictive value of TGI remains unclear.

Methods

Participants with cardiovascular diseases were enrolled using the China Health and Retirement Longitudinal Study (CHARLS) registry. TGI was calculated as ln (triglyceride×glucose/2). The survival status was recorded every 2 years in the follow-up waves. Multivariate regression analysis was carried out to determine the relationship between TGI levels and long-term all-cause mortality in patients grouped by different age. Patients younger than 65 years old were regarded as middle-aged group. Otherwise, they were classified as old group.

Results

In total, 2923 patients with cardiovascular diseases and baseline blood test results were included. After 7 years of follow-up, 242 (8.91%) patients died. Cox regression analysis revealed that higher TGI levels were associated with a higher risk of long-term all-cause mortality in middle-aged participants (hazard ratio [HR], 3.64; 95% confidence interval [CI] 1.44–9.22, P = 0.006) but not in old participants (HR 1.20, 95% CI 0.62–2.32, P = 0.594, P for interaction = 0.017), after adjusting physical activity and other factors. Kaplan–Meier estimate analysis and restricted cubic spline curves showed similar results.

Conclusion

TGI was a promising marker for predicting all-cause mortality in middle-aged patients after cardiovascular diseases. Patients younger than 65 years old who have a higher level of TGI may develop a higher risk of all-cause mortality, and they are encouraged to control vascular risk factors and take more physical activity to improve their prognosis. Additionally, whether intervention in regulating TGI levels is beneficial for the prognosis of these patients needs further investigation.
Black phosphorous-based biomaterials for bone defect regeneration: a systematic review and meta-analysis
Authors: Huang Jinfeng , Santos Ana Cláudia , Tan Quanchang , Bai Hao , Hu Xiaofan , Mamidi Narsimha , Wu Zixiang
Published: December 2022

Critical-sized bone defects are always difficult to treat, and they are associated with a significant burden of disease in clinical practice. In recent decades, due to the fast development of biomaterials and tissue engineering, many bioinspired materials have been developed to treat large bone defects. Due to the excellent osteoblastic ability of black phosphorous (BP), many BP-based biomaterials have been developed to treat bone defects. Therefore, there are abundant studies as well as a tremendous amount of research data. It is urgent to conduct evidence-based research to translate these research data and results into validated scientific evidence. Therefore, in our present study, a qualitative systematic review and a quantitative meta-analysis were performed. Eighteen studies were included in a systematic review, while twelve studies were included in the meta-analysis. Our results showed that the overall quality of experimental methods and reports of biomaterials studies was still low, which needs to be improved in future studies. Besides, we also proved the excellent osteoblastic ability of BP-based biomaterials. But we did not find a significant effect of near-infrared (NIR) laser in BP-based biomaterials for treating bone defects. However, the quality of the evidence presented by included studies was very low. Therefore, to accelerate the clinical translation of BP-based biomaterials, it is urgent to improve the quality of the study method and reporting in future animal studies. More evidence-based studies should be conducted to enhance the quality and clinical translation of BP-based biomaterials.
Development of novel monoclonal antibodies against nsp12 of SARS-CoV-2
Authors: Machitani Mitsuhiro , Takei Junko , Kaneko Mika K. , Ueki Saori , Ohashi Hirofumi , Watashi Koichi , Kato Yukinari , Masutomi Kenkichi
Published: December 2022

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global pandemic of coronavirus disease 19. Coronaviruses, including SARS-CoV-2, use RNA-dependent RNA polymerase (RdRP) for viral replication and transcription. Since RdRP is a promising therapeutic target for infection of SARS-CoV-2, it would be beneficial to develop new experimental tools for analysis of the RdRP reaction of SARS-CoV-2. Here, we succeeded to develop novel mouse monoclonal antibodies (mAbs) that recognize SARS-CoV-2 nsp12, catalytic subunit of the RdRP. These anti-nsp12 mAbs, RdMab-2, -13, and -20, specifically recognize SARS-CoV-2 nsp12 by western blotting analysis, while they exhibit less or no cross-reactivity to SARS-CoV nsp12. In addition, SARS-CoV-2 nsp12 was successfully immunoprecipitated using RdMab-2 from lysates of cells overexpressing SARS-CoV-2 nsp12. RdMab-2 was able to detect SARS-CoV-2 nsp12 transiently expressed in established culture cells such as HEK293T cells by indirect immunofluorescence technique. These novel mAbs against SARS-CoV-2 nsp12 are useful to elucidate the RdRP reaction of SARS-CoV-2 and biological cell response against it.
Biomechanical evaluation of aortic regurgitation from cusp prolapse using an ex vivo 3D-printed commissure geometric alignment device
Authors: Zhu Yuanjia , Park Matthew H. , Imbrie-Moore Annabel , Wilkerson Robert , Madira Sarah , Woo Y. Joseph
Published: December 2022

Background

Aortic regurgitation (AR) is one of the most common cardiac valvular diseases, and it is frequently caused by cusp prolapse. However, the precise relationship of commissure position and aortic cusp prolapse with AR is not fully understood. In this study, we developed a 3D-printed commissure geometric alignment device to investigate the effect of commissure height and inter-commissure angle on AR and aortic cusp prolapse.

Methods

Three porcine aortic valves were explanted from hearts obtained from a meat abattoir and were mounted in the commissure geometric alignment device. Nine commissure configurations were tested for each specimen, exploring independent and concurrent effects of commissure height and inter-commissure angle change on AR and aortic cusp prolapse. Each commissure configuration was tested in our 3D printed ex vivo left heart simulator. Hemodynamics data, echocardiography, and high-speed videography were obtained.

Results

AR due to aortic cusp prolapse was successfully generated using our commissure geometric alignment device. Mean aortic regurgitation fraction measured for the baseline, high commissure, low commissure, high commissure and wide inter-commissure angle, high commissure and narrow inter-commissure angle, low commissure and wide inter-commissure angle, low commissure and narrow inter-commissure angle, wide commissure, and narrow commissure configurations from all samples were 4.6 ± 1.4%, 9.7 ± 3.7%, 4.2 ± 0.5%, 11.7 ± 5.8%, 13.0 ± 8.5%, 4.8 ± 0.9%, 7.3 ± 1.7%, 5.1 ± 1.2%, and 7.1 ± 3.1%, respectively.

Conclusions

AR was most prominent when commissure heights were changed from their native levels with concomitant reduced inter-commissure angle. Findings from this study provide important evidence demonstrating the relationship between commissure position and aortic cusp prolapse and may have a significant impact on patient outcomes after surgical repair of aortic valves.