bluuebunny/crossref_metadata_2025 huggingface dataset:
HOXA9 forms a repressive complex with nuclear matrix–associated protein SAFB to maintain acute myeloid leukemia
Authors: Agrawal-Singh Shuchi , Bagri Jaana , Giotopoulos George , Azazi Dhoyazan M. A. , Horton Sarah J. , Lopez Cecile K. , Anand Shubha , Bach Anne-Sophie , Stedham Frances , Antrobus Robin , Houghton Jack W. , Vassiliou George S. , Sasca Daniel , Yun Haiyang , Whetton Anthony D. , Huntly Brian J. P.
Published: December 2022

HOXA9 is commonly upregulated in acute myeloid leukemia (AML), in which it confers a poor prognosis. Characterizing the protein interactome of endogenous HOXA9 in human AML, we identified a chromatin complex of HOXA9 with the nuclear matrix attachment protein SAFB. SAFB perturbation phenocopied HOXA9 knockout to decrease AML proliferation, increase differentiation and apoptosis in vitro, and prolong survival in vivo. Integrated genomic, transcriptomic, and proteomic analyses further demonstrated that the HOXA9-SAFB (H9SB)–chromatin complex associates with nucleosome remodeling and histone deacetylase (NuRD) and HP1γ to repress the expression of factors associated with differentiation and apoptosis, including NOTCH1, CEBPδ, S100A8, and CDKN1A. Chemical or genetic perturbation of NuRD and HP1γ–associated catalytic activity also triggered differentiation, apoptosis, and the induction of these tumor-suppressive genes. Importantly, this mechanism is operative in other HOXA9-dependent AML genotypes. This mechanistic insight demonstrates the active HOXA9-dependent differentiation block as a potent mechanism of disease maintenance in AML that may be amenable to therapeutic intervention by targeting the H9SB interface and/or NuRD and HP1γ activity.
Single-cell RNA sequencing revealed the liver heterogeneity between egg-laying duck and ceased-laying duck
Authors: Du Xue , Lai Shujing , Zhao Wanqiu , Xu Xiaoqin , Xu Wenwu , Zeng Tao , Tian Yong , Lu Lizhi
Published: December 2022

Background

In the late phase of production, ducks untimely cease laying, leading to a lower feed conversion. Liver plays a vital role in the synthesis and transport of yolk materials during egg formation in birds. However, the molecular mechanism of liver in ceased-laying duck is far from clear, higher resolution and deeper analysis is needed. Sing-cell RNA-sequencing of10 × Genomicsplatform can help to map the liver single cell gene expression atlas of Shaoxing duck and provide new insights into the liver between egg-laying and ceased-laying ducks.

Results

About 20,000 single cells were profiled and 22 clusters were identified. All the clusters were identified as 6 cell types. The dominant cell type is hepatocyte, accounted for about 60% of all the cells. Of note, the heterogeneity of cells between egg-laying duck and ceased-laying duck mainly occurred in hepatocytes. Cells of cluster 3 and 12 were the unique hepatocyte states of egg-laying ducks, while cells of cluster 0 and 15 were the unique hepatocyte states of ceased-laying ducks. The expression mode of yolk precursor transporters, lipid metabolizing enzymes and fibrinogens were different in hepatocytes between egg-laying duck and ceased-laying duck.APOV1,VTG2,VTG1,APOB,RBP,VTDBandSCDmight be activated in egg-laying ducks, whileAPOA1,APOA4,APOC3,FGBandFGGmight be activated in ceased-laying ducks.

Conclusions

Our study further proofs thatAPOV1andAPOBplay key roles in egg production, rather thanAPOA1andAPOA4. It is also the first to detect a correlation between the higher expression ofAPOC3,FGB,FGGand ceased-laying in duck.
Integrated metabolomic and transcriptomic analyses of regulatory mechanisms associated with uniconazole-induced dwarfism in banana
Authors: Qin Liuyan , Li Chaosheng , Guo Chenglin , Wei Liping , Tian Dandan , Li Baoshen , Wei Di , Zhou Wei , Long Shengfeng , He Zhangfei , Huang Sumei , Wei Shaolong
Published: December 2022

Background

Uniconazole is an effective plant growth regulator that can be used in banana cultivation to promote dwarfing and enhance lodging resistance. However, the mechanisms underlying banana dwarfing induced by uniconazole are unknown. In uniconazole-treated bananas, gibberellin (GA) was downregulated compared to the control groups. An integrative analysis of transcriptomes and metabolomes was performed on dwarf bananas induced by uniconazole and control groups. The key pathways involved in uniconazole-induced dwarfism in banana were determined according to the overlap of KEGG annotation of differentially expressed genes and (DEGs) differential abundant metabolites (DAMs).

Results

Compared with the control groups, the levels of some flavonoids, tannins, and alkaloids increased, and those of most lipids, amino acids and derivatives, organic acids, nucleotides and derivatives, and terpenoids decreased in uniconazole-treated bananas. Metabolome analysis revealed the significant changes of flavonoids in uniconazole-treated bananas compared to control samples at both 15 days and 25 days post treatment. Transcriptome analysis shows that the DEGs between the treatment and control groups were related to a series of metabolic pathways, including lignin biosynthesis, phenylpropanoid metabolism, and peroxidase activity. Comprehensive analysis of the key pathways of co-enrichment of DEGs and DAMs from 15 d to 25 d after uniconazole treatment shows that flavonoid biosynthesis was upregulated.

Conclusions

In addition to the decrease in GA, the increase in tannin procyanidin B1 may contribute to dwarfing of banana plants by inhibiting the activity of GA. The increased of flavonoid biosynthesis and the change of lignin biosynthesis may lead to dwarfing phenotype of banana plants. This study expands our understanding of the mechanisms underlying uniconazole-induced banana dwarfing.
Do COVID-19 pandemic-related behavior changes affect perioperative respiratory adverse events in children undergoing cardiac interventional catheterization?
Authors: Ji Wei , Zhang Kan , Li Mengqi , Wang Siyuan , Sun Liping , Huang Yue , Bai Jie , Zhang Mazhong , Zheng Jijian
Published: December 2022

Background

The novel coronavirus disease (COVID-19) suddenly broke out in China in December 2019. Pandemic-related behavioral changes can cause perioperative respiratory adverse events in children with congenital heart disease (CHD). Here, we compared the incidence of perioperative respiratory adverse events (PRAEs) in CHD children with and without upper respiratory infection (URI) undergoing the cardiac catheterization before and during the COVID-19 pandemic.

Methods

This prospective observational single-center study was based at a tertiary care center in Shanghai, China. A total of 359 children with CHD with and without recent URI were included between January 2019 and March 2021. The overall incidence of PRAEs (laryngospasm, bronchospasm, coughing, airway secretion, airway obstruction, and oxygen desaturation) in non-URI and URI children undergoing elective cardiac catheterization was compared before and during the COVID-19 pandemic. A logistic regression model was fitted to identify the potential risk factors associated with PRAEs.

Results

Of the 564 children enrolled, 359 completed the study and were finally analyzed. The incidence of URIs decreased substantially during the COVID-19 pandemic (14% vs. 41%, P < 0.001). Meanwhile, the overall PRAEs also significantly declined regardless of whether the child had a recent URI (22.3% vs. 42.3%, P = 0.001 for non-URI and 29.2% vs. 58.7%, P = 0.012 for URI, respectively). Post-operative agitation in children without URI occurred less frequently during the pandemic than before (2.3% vs. 16.2%, P = 0.001). Behaviors before the COVID-19 pandemic (odds ratio = 2.84, 95% confidence interval [CI] 1.76–4.58) and recent URI (odds ratio = 1.79, 95% CI 1.09–2.92) were associated with PRAEs.

Conclusions

COVID-19 pandemic-related behavioral changes were associated with a reduction in PRAEs in non-URI and URI children undergoing elective therapeutic cardiac catheterization.
Estimation of average treatment effect based on a multi-index propensity score
Authors: Xu Jiaqin , Wei Kecheng , Wang Ce , Huang Chen , Xue Yaxin , Zhang Rui , Qin Guoyou , Yu Yongfu
Published: December 2022

Background

Estimating the average effect of a treatment, exposure, or intervention on health outcomes is a primary aim of many medical studies. However, unbalanced covariates between groups can lead to confounding bias when using observational data to estimate the average treatment effect (ATE). In this study, we proposed an estimator to correct confounding bias and provide multiple protection for estimation consistency.

Methods

With reference to the kernel function-based double-index propensity score (Ker.DiPS) estimator, we proposed the artificial neural network-based multi-index propensity score (ANN.MiPS) estimator. The ANN.MiPS estimator employed the artificial neural network to estimate the MiPS that combines the information from multiple candidate models for propensity score and outcome regression. A Monte Carlo simulation study was designed to evaluate the performance of the proposed ANN.MiPS estimator. Furthermore, we applied our estimator to real data to discuss its practicability.

Results

The simulation study showed the bias of the ANN.MiPS estimators is very small and the standard error is similar if any one of the candidate models is correctly specified under all evaluated sample sizes, treatment rates, and covariate types. Compared to the kernel function-based estimator, the ANN.MiPS estimator usually yields smaller standard error when the correct model is incorporated in the estimator. The empirical study indicated the point estimation for ATE and its bootstrap standard error of the ANN.MiPS estimator is stable under different model specifications.

Conclusions

The proposed estimator extended the combination of information from two models to multiple models and achieved multiply robust estimation for ATE. Extra efficiency was gained by our estimator compared to the kernel-based estimator. The proposed estimator provided a novel approach for estimating the causal effects in observational studies.
Exploring Western Australian Women’s experiences of sharing positive birth stories
Authors: Neucom Zaneta Ann , Prandl Kelly Johanna
Published: December 2022

Background

Fear can impact childbirth experiences, yet most birth stories women hear portray birth as unfavourable, and women must actively seek out positive birth stories.

Aims and objectives

We aim to explore how women feel when sharing positive birth stories and the socially constructed motivations for or against sharing. Research question: What are the experiences of women who share positive birth stories?

Methods

A qualitative descriptive approach was adopted, adhering to Standards of Reporting Qualitative Research (SRQR) guidelines, and underpinned by an interpretivist research philosophy. Participants were recruited via Facebook using a non-probability, voluntary-response, purposive sampling method. Twelve English-speaking Western Australian women aged 24–38 years identified as having had a positive vaginal birth experience within the past 5 years. Semi-structured interviews were transcribed verbatim and analysed using thematic analysis.

Findings

The theme Not Safe to Share and sub-themes The Perils of Sharing and Changing the Narrative explores how participants repeatedly felt unable to share their birth stories because society’s dominant view of childbirth was negative. It describes the experienced or anticipated reactions that contributed to feeling unsafe and how participants withheld or altered their stories to feel accepted. The theme Safe Spaces and sub-theme The Joys of Sharing, explored participants’ love of sharing their birth stories in safe spaces, allowing re-access to feelings of elation, validation of their stories, and opportunity to empower others.

Conclusions

Women often feel reluctant to share their positive birth stories. Findings may help understand the lack of availability of positive birth stories in our society. Normalising the positive birth experience may improve the experience of sharing positive birth stories, potentially improving society’s view of childbirth.
Prevalence of Listeria monocytogenes infection in women with spontaneous abortion, normal delivery, fertile and infertile
Authors: Ahmadi Amjad , Ramazanzadeh Rashid , Derakhshan Safoura , Khodabandehloo Mazaher , Farhadifar Fariba , Roshani Daem , Mousavi Atefeh , Hedayati Manouchehr Ahmadi , Taheri Mohammad
Published: December 2022

Background

Listeria monocytogenes with a vast range of natural reservoirs is more known for being a food-borne pathogen. Human infections have shown an impact on pregnancy outcomes, so, this study surveyed the frequency of L. monocytogenes infection involving different groups of women.

Methods

This study enrolled a total sample consisting of 109 women with spontaneous abortion, 109 women with normal delivery, 100 fertile women, and 99 infertile women aged 19–40 years and willing to participate in the study. The research tool in this study was a questionnaire and Polymerase chain reaction (PCR) test.

Results

According to the results, the frequency of L. monocytogenes infection was 4/109 (3.66%) observed among women with spontaneous abortion, 2/109 (1.83%) among women with normal delivery, 3/100 (3%) among fertile women, and 0/99 (0%) among infertile women.

Conclusion

There was no significant relationship between Listeria monocytogenes infection and pregnancy outcomes of spontaneous abortion and infertility.
Early postoperative decrease of skeletal muscle mass predicts recurrence and poor survival after surgical resection for perihilar cholangiocarcinoma
Authors: Yasuta Sho , Sugimoto Motokazu , Kudo Masashi , Kobayashi Shin , Takahashi Shinichiro , Konishi Masaru , Gotohda Naoto
Published: December 2022

Background

Preoperative sarcopenia is a predictor of poor survival in cancer patients. We hypothesized that sarcopenia could progress as occult metastasis arose, especially after highly invasive surgery for highly aggressive malignancy. This study aimed to evaluate the associations of postoperative changes in skeletal muscle mass volume with survival outcomes in patients who underwent surgery for perihilar cholangiocarcinoma.

Methods

Fifty-six patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma were studied. The skeletal muscle index (SMI) at the third lumbar vertebra was calculated from axial computed tomography images taken preoperatively and 3–6 months postoperatively (early postoperative period). The associations of clinicopathological variables, including changes of SMI after surgery, with overall survival and recurrence-free survival were evaluated. Moreover, the associations of decreased SMI and elevated serum carbohydrate antigen 19–9 level with early recurrence and poor survival was compared.

Results

Among 56 patients, 26 (46%) had sarcopenia preoperatively and SMI decreased in 29 (52%) in the early postoperative period. During the median follow-up of 57.9 months, 35 patients (63%) developed recurrence and 29 (50%) died. Decreased SMI in the early postoperative period was independently associated with a shorter overall survival (hazard ratio, 2.39; 95% confidence interval, 1.00–6.18; P = 0.049) and a shorter recurrence-free survival (hazard ratio, 2.14; 95% confidence interval, 1.04–4.57; P = 0.039), whereas elevated carbohydrate antigen 19–9 level was not.

Conclusions

Decreased SMI in the early postoperative period may be used as a predictor for recurrence and poor survival in patients undergoing surgery for perihilar cholangiocarcinoma.
A health promoting-lifestyle prediction model for dementia prevention among chinese adults: based on the health belief model
Authors: Li Hua , Zhang Jinying , Wang Li , Yang Tiantian , Yang Yanni
Published: December 2022

Background

People’s health belief is an important factor affecting health behavior. However, there has been little use of the health belief model (HBM) in determining the pathway effect of patients’ beliefs on health behavior in dementia prevention in China. The aim of our study was to evaluate the impact of dementia prevention beliefs on health promoting lifestyle among Chinese adults.

Methods

A cross-sectional study was conducted on line by convenience sampling from January to March 2020. A survey about dementia prevention knowledge, health belief of dementia prevention and health-promoting lifestyle was completed by 1201 adults in China. Data was analyzed using a structural equation model with the analysis of moment program.

Results

The participants were aged 40.50 ± 12.72 years. About 70.3% of participants were female. The purposed model fit the data from the study well. Perceived barriers (total effect-0.322,P < 0.01) and perceived susceptibility (total effect -0.242,P < 0.01) had negative effects on lifestyle. Self-efficacy had promoting effects on lifestyle (total effect 0.207,P < 0.01). Perceived severity had positive effects both on perceived benefits (total effect 0.137,P < 0.01) and perceived barriers (total effect 0.202,P < 0.01), which had a contradictory effect in the formation of health belief. Perceived benefits, cues to action and self-efficacy played a partial mediating role between knowledge and health behavior. The belief of changing lifestyle to reduce the risk of dementia could explain 24.5% of health behavior (P < 0.05).

Conclusions

The findings indicate that in dementia prevention, dementia prevention health belief has important influences on health behavior. Community medical staff can develop targeted dementia prevention interventions based on the health belief model in the future.
Socioeconomic status and metabolic syndrome in Southwest Iran: results from Hoveyzeh Cohort Study (HCS)
Authors: Saki Nader , Hashemi Seyed Jalal , Hosseini Seyed Ahmad , Rahimi Zahra , Rahim Fakher , Cheraghian Bahman
Published: December 2022

Background

Socioeconomic status (SES) strongly predicts morbidity and premature mortality, especially for non-communicable diseases (NCDs). However, the effect of these factors on Metabolic Syndrome (MetS) is not clear yet. This study was conducted to assess the relationship between socioeconomic indicators and MetS.

Methods

In this prospective cohort study, 10,009 people aged 35–70 enrolled from May 2016 to August 2018. The MetS was defined according to The Standard National Cholesterol Education Program (NCEP)—adult treatment panel III (ATP III) or NCEP-ATP III criteria. Demographics and socioeconomic data were gathered face-to-face through trained interviews. Also, lab, anthropometrics, and blood pressure measurements were assayed for participants. Logistic regression was used to estimate the association between SES and MetS, adjusted for the potential confounding factors.

Results

The overall prevalence of MetS in the participants was 39.1%. The crude odds ratios were statistically significant for all the assessed variables (p < 0.05). After adjustment for age, sex, physical activity, smoking, and alcohol use as potential confounders, the results indicated significant direct independent associations between skill level (p = 0.006) and Townsend index (p = 0.002) with MetS. In contrast, no significant associations between educational level and wealth status with MetS.

Conclusion

The results of our study showed that SES is related to MetS. Among the four assessed SES indicators, skilled levels and Townsend score are strongly associated with MetS. We recommend considering people's SES when interventional programs are planned and conducted on MetS in similar communities.
Nocturnal sleep duration and bone mineral density: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2007–2014
Authors: Tang Yuchen , Liu Jinmin , Feng Zhiwei , Liu Zhongcheng , Wang Shenghong , Xia Yayi , Geng Bin
Published: December 2022

Background

This study aimed to investigate the association between sleep duration and bone mineral density (BMD) and determine whether vitamin D (VD) status influenced the association between sleep duration and BMD.

Methods

National Health and Nutrition Examination Survey 2007–2014 participants aged ≥ 40 years were included in this study. BMD testing was conducted with dual-energy X-ray absorptiometry examinations. Moreover, all individuals were divided into four groups according to self-reported nocturnal sleep duration (7–8 h; 6 h; < 6 h; and > 8 h). In addition, the differences in BMD between the normal sleep duration group and other groups were calculated using multiple linear regression models.

Results

Overall, the median age of the overall study population was 55.00 years old, with 46.97% of men distributed. Participants sleeping > 8 h/night had lower BMDs than those sleeping 7–8 h/night. Moreover, the association between unhealthy sleep duration (especially > 8 h/night) and low BMD was more pronounced in older individuals, men, postmenopausal women, and subjects with inadequate VD intakes (< 15.00 µg/day) or deficient/insufficient serum 25-hydroxyvitamin D (< 75.00 nmol/L).

Conclusions

In conclusion, unhealthy sleep duration, especially long sleep duration, was associated with decreased BMD, particularly among individuals aged > 60 years, men, or postmenopausal women. Moreover, VD status might influence the association between sleep duration and BMD, especially in the context of inadequate VD intake or deficient/insufficient serum 25-hydroxyvitamin D levels. However, given the limitations of the present study, further investigation is warranted to confirm this association and to explore potential mechanisms.
Comparison of magnetic resonance imaging findings in 880 temporomandibular disorder patients of different age groups: a retrospective study
Authors: Li Chuanjie , Zhang Qingbin
Published: December 2022

Background

Magnetic resonance imaging (MRI) findings of temporomandibular joint (TMJ) in temporomandibular disorder (TMD) patients of different ages are still unclear. The aim of this study was to analyze and compare the characteristics of MRI features of TMJs in different age groups.

Methods

A total of 1760 TMJs from 880 patients were included in the study and divided into three groups: ≤ 18Y (n = 195, 14.89 ± 2.35Y); 19-30Y (n = 475, 24.09 ± 3.23Y); and > 30Y (n = 210, 41.73 ± 10.45Y). T2-weighted image (T2WI) of MRI was obtained to evaluate the relationship between age and disc morphology, the degree of disc displacement, joint effusion, joint movement and changes of condylar bone morphology. Data were analyzed by Pearson Chi square test and Spearman correlation coefficient.

Results

There was no statistical difference between left and right sides in all age groups. Except condylar morphology (χ2 = 0.943, P = 0.624), there were significant differences in the distribution of disc morphology, disc position, joint effusion and joint motion among different age groups (χ2 = 24.450, χ2 = 24.829, χ2 = 19.855, χ2 = 39.259, respectively). There were significant differences in the distribution of the degree of anterior disc displacement, condyle morphology and joint effusion in different types of disc morphology among the different age groups (except for joint effusion in > 30Y), among which the first two were significantly correlated with the disc morphology.

Conclusions

The morphology and position of the articular disc changed significantly with age, but the proportion of abnormal condylar bone remained about 50%. The greater the degree of disc folding, the more prone to bone abnormalities.

Trial registration This study was retrospectively registered on 28/03/2022 and endorsed by the Ethics committee (LCYJ2022014).
Social networks, mobility, and HIV risk among women in the fishing communities of Lake Victoria
Authors: Nakamanya Sarah , Okello Elialilia S. , Kwena Zachary A. , Nanyonjo Gertrude , Bahemuka Ubaldo M. , Kibengo Freddie M. , Ssetaala Ali , Bukusi Elizabeth A. , Kapiga Saidi , Fast Patricia E. , Seeley Janet
Published: December 2022

Background

Population mobility is a demonstrated barrier to reducing HIV incidence. A clear understanding of social networks and their influence on mobility among women in the fishing communities of Lake Victoria may contribute to tailoring effective interventions that suit the needs of these mobile women.

Methods

A cross-sectional qualitative methods study was conducted to understand mobility patterns among women resident and or working in fishing communities of Lake Victoria in Kenya, Tanzania, and Uganda. The study was conducted in six fishing communities from March 2018 to June 2019. The communities were purposively selected, based on population size (1000 people or more) and HIV prevalence of > 15% among women aged 18 years or older who had lived in the fishing community for at least six months. In-depth interviews were conducted with 24 key informants and 72 women from the sites in the three countries. Questions focused on women’s social networks and other factors that fuelled or facilitated women’s mobility as well as challenges they faced due to mobility. Data analysis followed a thematic framework approach.

Results

Different social groupings/networks existed among women in the fishing communities of Lake Victoria. These included female sex workers, women fish processors/traders, women bar workers/owners, restaurant workers, and family networks. Networks encouraged mobility, supporting finding work opportunities, but also increased sexual risks through partner changes. The benefits of networks included information sharing, financial support, and group protection, especially against violence.

Conclusion

Social networks and groupings among women in the fishing communities of Lake Victoria could be useful in tailoring HIV prevention and HIV care interventions to suit the needs of these highly mobile populations.
Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro
Authors: Yakabe Mitsutaka , Hosoi Tatsuya , Sasakawa Hiroko , Akishita Masahiro , Ogawa Sumito
Published: December 2022

Background

Muscle disuse results in loss of skeletal muscle mass and function. Hochu-ekki-to (TJ-41; Bu-Zhong-Yi-Qi-Tang in Chinese) is an herbal medicinal formulation used to treat patients with frailty, fatigue and appetite loss. It has been suggested that two atrogenes, atrogin-1 and muscle Ring finger 1 (MuRF1), are ubiquitin ligases involved in disuse-induced muscle atrophy and that 5’ adenosine monophosphate-activated protein kinase (AMPK) is involved in skeletal muscle metabolism. Effects of TJ-41 on disuse-induced muscle atrophy are unclear.

Methods

We subjected differentiated C2C12 myotubes to serum starvation, then examined the effects of TJ-41 on atrogenes expression, AMPK activity and the morphology of the myotubes. Male C57BL/6J mice were subjected to tail-suspension to induce hindlimb atrophy. We administered TJ-41 by gavage to the control group and the tail-suspended group, then examined the effects of TJ-41 on atrogene expression, AMPK activity, and the muscle weight.

Results

Serum starvation induced the expression of atrogin-1 and MuRF1 in C2C12 myotubes, and TJ-41 significantly downregulated the expression of atrogin-1. Tail-suspension of the mice induced the expression of atrogin-1 and MuRF1 in skeletal muscle as well as its muscle atrophy, whereas TJ-41 treatment significantly downregulated the expression of atrogin-1 and ameliorated the loss of the muscle weight. In addition, TJ-41 also activated AMPK and inactivated Akt and mTOR in skeletal muscle in vivo.

Conclusion

TJ-41 inhibited atrogenes in an Akt-independent manner as well as activating AMPK in skeletal muscles in vivo, further implying the therapeutic potential of TJ-41 against disuse-induced muscle atrophy and other atrogenes-dependent atrophic conditions.
A mixed-methods program evaluation of the Alda Healthcare Experience- a program to improve healthcare team communication
Authors: Preis Heid , Dobias Mallory , Cohen Katherine , Bojsza Elizabeth , Whitney Clare , Pati Susmita
Published: December 2022

Background

Communication among interprofessional healthcare worker teams is critical to ensure a thriving and resilient workforce. We will evaluate the implementation and effectiveness of the Alda Healthcare Experience (AHE), a novel medical improvisation (improv) workshop designed to improve interprofessional communication skills among healthcare professionals. The AHE workshop includes a two-hour experiential training workshop led by an improv specialist and a clinical co-facilitator. In July 2022 we began implementing the AHE workshop by training 18 clinical co-facilitators who will co-facilitate the workshops for 550 healthcare workers from five hospital departments at Stony Brook University Hospital over the course of a year and a half. Using mixed-methods, we will conduct an Effectiveness-Implementation Hybrid Design project that includes an outcome evaluation (effectiveness) and a process evaluation (implementation).

Methods

Our outcome evaluation will assess the impact of the AHE workshop on short- and long-term improvement in interprofessional communication, stress, and professional fulfillment. The process evaluation component will examine programmatic, organizational, and individual facilitators or barriers to effective implementation of the AHE workshop. Qualitative methods will include dimensional analysis employing individual interviews of 20–40 AHE Project Participants, 5–10 Selected Informants, and all the clinical co-facilitators. Quantitative methods will use a quasi-experimental longitudinal design with an intervention group and surveillance of a control group (wait-list) and repeated assessments using validated instruments measuring communications skills, professional fulfillment, stress, burnout, uncertainty tolerance, and teamwork.

Discussion

Effective and efficient communication within healthcare teams is fundamental to building team cohesion that, in turn, supports individual resilience and builds positive organizational culture. The AHE program is an innovative approach to improve interprofessional healthcare communication and reduce healthcare worker burnout. In addition to institutional buy-in, rigorous evaluations of medical improv programs are necessary as a critical step in making such programs scalable.

Trial registration

N/A
An insight into misidentification of the small-subunit ribosomal RNA (18S rRNA) gene sequences of Theileria spp. as Theileria annulata
Authors: Nehra Anil Kumar , Kumari Ansu , Moudgil Aman Dev , Vohra Sukhdeep
Published: December 2022

Background

There had been isolated reports of the presence of novel Theileria annulata genotypes based on the 18S rRNA gene sequence data from India, Pakistan and Saudi Arabia; but, these studies were restricted to limited field samples. Additionally, no comparative study has been conducted on all the isolates of this parasite from different countries whose sequences are available in the nucleotide databases. Therefore, we aimed to study the genetic diversity of T. annulata based on all available nearly complete 18S rRNA gene sequences in the GenBank™. Out of a total of 312 gene sequences of T. annulata available in the NCBI database, only 70 nearly complete sequences (> 1527 bp) were used for multiple sequence alignment.

Results

The maximum likelihood tree obtained using TN93 + G + I model manifested two major clades. All the valid host-cell transforming Theileria species clustered in one clade. The T. annulata designated sequences occupying this clade clustered together, excluding two isolates (DQ287944 and EU083799), and represented the true T. annulata sequences (n = 54). DQ287944 and EU083799 exhibited close association with Theileria lestoquardi. In addition, 14 Indian sequences formed a large monophyletic group with published Theileria orientalis sequences. The broad range of sequence identity (95.8–100%) of T. annulata designated sequences indicated the presence of different Theileria spp. A closer analysis revealed the presence of three Theileria spp., namely, T. annulata, T. orientalis, and two isolates (DQ287944 and EU083799) closely related to T. lestoquardi. The true T. annulata sequences manifested 98.8–100% nucleotide identity within them. EU083799 and 14 misidentified Indian T. annulata sequences exhibited the highest similarity with T. lestoquardi (98.6–98.8%) and T. orientalis (98.0-99.9%) in comparison with the other Theileria spp. of domestic and wild ruminants.

Conclusion

In the course of analyzing the genetic diversity of T. annulata, we identified the nearly complete 18S rRNA gene sequences of other Theileria spp. that have not only been misidentified as T. annulata in the GenBank™, but are also published as T. annulata. Moreover, a high level of sequence conservation was noticed in the 18S rRNA gene of true T. annulata and T. orientalis sequences.
Nebulization of risedronate alleviates airway obstruction and inflammation of chronic obstructive pulmonary diseases via suppressing prenylation-dependent RAS/ERK/NF-κB and RhoA/ROCK1/MLCP signaling
Authors: Liu Di , Xu Wen , Tang Yuan , Cao Jingxue , Chen Ran , Wu Dingwei , Chen Hongpeng , Su Bo , Xu Jinfu
Published: December 2022

Background

Chronic obstructive pulmonary disease (COPD) is a progressive disorder that causes airway obstruction and lung inflammation. The first-line treatment of COPD is the bronchodilators of β2-agonists and antimuscarinic drugs, which can help control the airway obstruction, but the long-term use might render the drug tolerance. Bisphosphonates are widely used in osteoclast-mediated bone diseases treatment for decades. For drug repurposing, can delivery of a third generation of nitrogen-containing bisphosphonate, risedronate (RIS) ameliorate the progression of COPD?

Methods

COPD rats or mice models have been established through cigarette-smoking and elastase injection, and then the animals are received RIS treatment via nebulization. Lung deposition of RIS was primarily assessed by high-performance liquid chromatography (HPLC). The respiratory parameters of airway obstruction in COPD rats and mice were documented using plethysmography method and resistance-compliance system.

Results

High lung deposition and bioavailability of RIS was monitored with 88.8% of RIS input dose. We found that RIS could rescue the lung function decline of airspace enlargement and mean linear intercept in the COPD lung. RIS could curb the airway obstruction by suppressing 60% of the respiratory resistance and elevating the airway’s dynamic compliance, tidal volume and mid-expiratory flow. As an inhibitor of farnesyl diphosphate synthase (FDPS), RIS suppresses FDPS-mediated RAS and RhoA prenylation to obstruct its membrane localization in airway smooth muscle cells (ASMCs), leading to the inhibition of downstream ERK-MLCK and ROCK1-MLCP pathway to cause ASMCs relaxation. Additionally, RIS nebulization impeded pro-inflammatory cell accumulation, particularly macrophages infiltration in alveolar parenchyma. The NF-κB, tumor necrosis factor-alpha, IL-1β, IL-8, and IL-6 declined in microphages following RIS nebulization. Surprisingly, nebulization of RIS could overcome the tolerance of β2-agonists in COPD-rats by increasing the expression of β2 receptors.

Conclusions

Nebulization of RIS could alleviate airway obstruction and lung inflammation in COPD, providing a novel strategy for treating COPD patients, even those with β2-agonists tolerance.
Preventing early childhood transmission of hepatitis B in remote Aboriginal communities in northern Australia
Authors: Sullivan Richard P. , Davies Jane , Binks Paula , McKinnon Melita , Dhurrkay Roslyn Gundjirryiir , Hosking Kelly , Bukulatjpi Sarah Mariyalawuy , Locarnini Stephen , Littlejohn Margaret , Jackson Kathy , Tong Steven Y. C. , Davis Joshua S.
Published: December 2022

Background

Chronic hepatitis B is a public health concern in Aboriginal communities in the Northern Territory of Australia with prevalence almost four times the non-Aboriginal population. Infection is suspected to mainly occur in early life, however, the mode of transmission and vaccine effectiveness is not known in this population. WHO has set a target for hepatitis B elimination by 2030; elimination in this disproportionately affected population in Australia will require understanding of the modes of transmission and vaccine effectiveness.

Methods

We conducted the study at four very remote Aboriginal communities. We approached mothers who had chronic hepatitis B and had given birth between 1988 and 2013 for consent. We obtained hepatitis B serology, immunisation and birth details from the medical record. If both mother and child had hepatitis B viral DNA detected, we performed viral whole genome sequencing.

Results

We approached 45 women for consent, of whom 23 agreed to participate. We included 20 mothers and 38 of their children. Of the 20 included mothers, 5 (25%) had children who were hepatitis B immune by exposure and 3 (15%) had children with evidence of chronic hepatitis B infection at the time of assessment. Hepatitis B immunoglobulin (HBIg) had been given at birth in 29/38 (76.3, 95% CI 59.8–88.6) children, and 26 children (68.4, 95% CI 51.3–82.5) were fully vaccinated. Of the 3 children who had chronic hepatitis B, all had received HBIg at birth and two were fully vaccinated. Of the 5 who were immune by exposure, 4 had received HBIg at birth and one was fully vaccinated. Whole genome sequencing revealed one episode of definite mother to child transmission. There was also one definite case of horizontal transmission.

Conclusions

Chronic hepatitis B in this context is a sensitive issue, with a high proportion of women refusing consent. Although uncommon, there is ongoing transmission of hepatitis B to Aboriginal children in remote northern Australia despite vaccination, and this is likely occurring by both vertical and horizontal routes. Prevention will require ongoing investment to overcome the many barriers experienced by this population in accessing care.
Changes in physical activity outcomes in the Strong Hearts, Healthy Communities (SHHC-2.0) community-based randomized trial
Authors: Maddock Jay E. , Demment Margaret , Graham Meredith , Folta Sara , Strogatz David , Nelson Miriam , Ha Seong-Yeon , Eldridge Galen D. , Seguin-Fowler Rebecca A.
Published: December 2022

Background

Physical inactivity is a risk factor for numerous adverse health conditions and outcomes, including all-cause mortality. Aging rural women are at particular risk for physical inactivity based on environmental, sociocultural, and psychosocial factors. This study reports on changes in physical activity and associated factors from a multicomponent community-engaged intervention trial.

Methods

Strong Hearts, Healthy Communities 2.0 (SHHC-2.0) was a 24-week cluster (community) randomized controlled trial building on the results from the previous trial of SHHC-1.0. Rural women (n = 182) aged 40 and over living in 11 rural communities in upstate New York were recruited. The intervention consisted of twice-weekly experiential classes focused on exercise, nutrition, and civic engagement. Physical activity outcomes included accelerometry and self-report as well as related psychosocial measures at midpoint (12 weeks) and post-intervention (24 weeks). Data were analyzed using multilevel linear regression models with the community as the random effect.

Results

Compared to participants from the control communities, participants in the intervention communities showed a significant increase in objectively measured moderate to vigorous intensity physical activity: at 12 weeks (increase of 8.1 min per day, P < 0.001) and at 24 weeks (increase of 6.4 min per day; P = 0.011). Self-reported total MET minutes per week also increased: at 12 weeks (increase of 725.8, P = 0.003) and 24 weeks (increase of 955.9, P = 0.002). Several of the psychosocial variables also showed significant positive changes.

Conclusions

The SHHC-2.0 intervention successfully increased physical activity level and related outcome measures. Modifications made based upon in-depth process evaluation from SHHC-1.0 appear to have been effective in increasing physical activity in this at-risk population.

Trial registration

Clinicaltrials.gov: NCT03059472. Registered 23 February 2017.
Escalation of radiotherapy dose in large locally advanced drug-resistant gastrointestinal stromal tumors by multi-shell simultaneous integrated boost intensity-modulated technique: a feasibility study
Authors: Cui Haixia , Li Ying , Huang Wei , Lu Wenli , Yi Xin
Published: December 2022

Background

Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST.

Methods

7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P < 0.05).

Results

Compared with the Con-IMRT group, the EUD of GTV (EUDGTV) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB10-IMRT group and the SIB25-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU.

Conclusions

The proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.
Prevalence of cesarean sections in Swiss Bernese Mountain Dogs (2001–2020) and identification of risk factors
Authors: Schrank Magdalena , Sozzi Marco , Mollo Antonio
Published: December 2022

Background

Dystocia is an important limiting factor in animal breeding due to its cost, stress for the mother and risk of death for the neonates. Assessment of incidence and characteristics of dystocia and the inherent risk of Cesarean section are of major importance. The aim of the present study was to evaluate the reproductive performance of Bernese Mountain Dogs in Switzerland, with a particular focus on the prevalence of Cesarean sections due to dystocia, and identification of possible risk factors.

Results

The investigated population included 401 bitches, 207 sires, and 1127 litters. Litter size was significantly influenced by age and parity of the dam. Incidence of Cesarean section was 30.4%, with 2.0% of procedures being elective. History of previous Cesarean section, age of the dam, and a small litter size significantly influenced the risk for Cesarean section. The stillbirth rate was 12.0%, and the number of stillborn pups was significantly higher for litters delivered by Cesarean sections after birth of the first pup. The inbreeding coefficient had a low to non-significant impact on all reproductive parameters (e.g., litter size, number of stillborn pups).

Conclusion

The sample of Bernese Mountain Dogs of our study had an increased prevalence of Cesarean sections compared to the literature, and advanced age of the dam, litter size and prior Cesarean sections in the dam’s reproductive history was identified as significantly influencing factors. In order to improve pups’ survival rate, elective Cesarean section may be indicated in bitches that have had a previous Cesarean-section/s, are of advanced age, and/or have a small litter.
Progesterone modulates the DSCAM-AS1/miR-130a/ESR1 axis to suppress cell invasion and migration in breast cancer
Authors: Yadav Neelima , Sunder Roma , Desai Sanket , Dharavath Bhasker , Chandrani Pratik , Godbole Mukul , Dutt Amit
Published: December 2022

Background

A preoperative-progesterone intervention increases disease-free survival in patients with breast cancer, with an unknown underlying mechanism. We elucidated the role of non-coding RNAs in response to progesterone in human breast cancer.

Methods

Whole transcriptome sequencing dataset of 30 breast primary tumors (10 tumors exposed to hydroxyprogesterone and 20 tumors as control) were re-analyzed to identify differentially expressed non-coding RNAs followed by real-time PCR analyses to validate the expression of candidates. Functional analyses were performed by genetic knockdown, biochemical, and cell-based assays.

Results

We identified a significant downregulation in the expression of a long non-coding RNA, Down syndrome cell adhesion molecule antisense DSCAM-AS1, in response to progesterone treatment in breast cancer. The progesterone-induced expression of DSCAM-AS1 could be effectively blocked by the knockdown of progesterone receptor (PR) or treatment of cells with mifepristone (PR-antagonist). We further show that knockdown of DSCAM-AS1 mimics the effect of progesterone in impeding cell migration and invasion in PR-positive breast cancer cells, while its overexpression shows an opposite effect. Additionally, DSCAM-AS1 sponges the activity of miR-130a that regulates the expression of ESR1 by binding to its 3’-UTR to mediate the effect of progesterone in breast cancer cells. Consistent with our findings, TCGA analysis suggests that high levels of miR-130a correlate with a tendency toward better overall survival in patients with breast cancer.

Conclusion

This study presents a mechanism involving the DSCAM-AS1/miR-130a/ESR1 genomic axis through which progesterone impedes breast cancer cell invasion and migration. The findings highlight the utility of progesterone treatment in impeding metastasis and improving survival outcomes in patients with breast cancer.