bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opening the “black box” of organizational coaching for implementation
Authors: Fleddermann Kathryn , Jacobson Nora , Horst Julie , Madden Lynn M , Haram Eric , Molfenter Todd 
Published: February 2023

AbstractBackgroundOrganizational coaching to promote the implementation of evidence-informed interventions is becoming more popular in healthcare organizations. In order to open the “black box” of coaching for implementation, we first developed, then tested the rigor and utility of a model of coaching for implementation.MethodsInterviews with nine experienced coaches were conducted and inductively coded to develop a model of coaching for implementation. Later, forty coaching calls with behavioral health organizations in Ohio, Wisconsin, and Florida were analyzed with directed content analysis using a priori codes based on this model.ResultsThe coaching work that occurred during these calls aligned closely with the model of coaching for implementation developed by our team. Most coaching work was devoted to building capacity; almost as much work focused on building relationships. Very little coaching work was dedicated to building sustainability. Use of tools for organizational change and implementation remained relatively consistent across all coaching periods.ConclusionUnderstanding what occurs during a successful coaching intervention will improve the effectiveness of coaching as an implementation strategy. Future research should focus on which processes and patterns make coaching more likely to promote specific implementation outcomes.
Postabortion and safe abortion care coverage, capacity, and caseloads during the global gag rule policy period in Ethiopia and Uganda
Authors: Stillman Melissa , Kibira Simon P. S. , Shiferaw Solomon , Makumbi Fredrick , Seme Assefa , Sully Elizabeth A. , Ha Lilian , Giorgio Margaret 
Published: February 2023

Abstract
Background
Abortion-related complications contribute to preventable maternal mortality, accounting for 9.8% of maternal deaths globally, and 15.6% in sub-Saharan Africa. High-quality postabortion care (PAC) can mitigate the negative health outcomes associated with unsafe abortion. While the expanded Global Gag Rule policy did not prohibit the provision of PAC, other research has suggested that over-implementation of the policy has resulted in impacts on these services. The purpose of this study was to assess health facilities’ capacity to provide PAC services in Uganda and PAC and safe abortion care (SAC) in Ethiopia during the time in which the policy was in effect.

Methods
We collected abortion care data between 2018 and 2020 from public health facilities in Ethiopia (N = 282) and Uganda (N = 223). We adapted a signal functions approach to create composite indicators of health facilities’ capacity to provide basic and comprehensive PAC and SAC and present descriptive statistics documenting the state of service provision both before and after the GGR went into effect. We also investigate trends in caseloads over the time-period.

Results
In both countries, service coverage was high and improved over time, but facilities’ capacity to provide basic PAC services was low in Uganda (17.8% in 2019) and Ethiopia (15.0% in 2020). The number of PAC cases increased by 15.5% over time in Uganda and decreased by 7% in Ethiopia. Basic SAC capacity increased substantially in Ethiopia from 66.7 to 82.8% overall, due in part to an increase in the provision of medication abortion, and the number of safe abortions increased in Ethiopia by 9.7%.

Conclusions
The findings from this analysis suggest that public health systems in both Ethiopia and Uganda were able to maintain essential PAC/SAC services during the GGR period. In Ethiopia, there were improvements in the availability of safe abortion services and an overall improvement in the safety of abortion during this time-period. Despite loss of partnerships and potential disruptions in referral chains, lower-level facilities were able to expand their capacity to provide PAC services. However, PAC caseloads increased in Uganda which could indicate that, as hypothesized, abortion became more stigmatized, less accessible and less safe.
Integrative single-cell RNA-seq and ATAC-seq analysis of myogenic differentiation in pig
Authors: Cai Shufang , Hu Bin , Wang Xiaoyu , Liu Tongni , Lin Zhuhu , Tong Xian , Xu Rong , Chen Meilin , Duo Tianqi , Zhu Qi , Liang Ziyun , Li Enru , Chen Yaosheng , Li Jianhao , Liu Xiaohong , Mo Delin 
Published: February 2023

Abstract
Background
Skeletal muscle development is a multistep process whose understanding is central in a broad range of fields and applications, from the potential medical value to human society, to its economic value associated with improvement of agricultural animals. Skeletal muscle initiates in the somites, with muscle precursor cells generated in the dermomyotome and dermomyotome-derived myotome before muscle differentiation ensues, a developmentally regulated process that is well characterized in model organisms. However, the regulation of skeletal muscle ontogeny during embryonic development remains poorly defined in farm animals, for instance in pig. Here, we profiled gene expression and chromatin accessibility in developing pig somites and myotomes at single-cell resolution.

Results
We identified myogenic cells and other cell types and constructed a differentiation trajectory of pig skeletal muscle ontogeny. Along this trajectory, the dynamic changes in gene expression and chromatin accessibility coincided with the activities of distinct cell type-specific transcription factors. Some novel genes upregulated along the differentiation trajectory showed higher expression levels in muscular dystrophy mice than that in healthy mice, suggesting their involvement in myogenesis. Integrative analysis of chromatin accessibility, gene expression data, and in vitro experiments identified EGR1 and RHOB as critical regulators of pig embryonic myogenesis.

Conclusions
Collectively, our results enhance our understanding of the molecular and cellular dynamics in pig embryonic myogenesis and offer a high-quality resource for the further study of pig skeletal muscle development and human muscle disease.
Immunotherapies in rare cancers
Authors: Vivekanandhan Sneha , Bahr Deborah , Kothari Ashish , Ashary Mohammed Ali , Baksh Mizba , Gabriel Emmanuel 
Published: February 2023

AbstractCancer remains a leading cause of death worldwide, placing a significant burden on healthcare systems as well as the global economy. Rare cancers comprise a group of about 200 cancers that individually occur at extremely low frequencies. In the United States (US), their frequency is approximately 15 cases per 100,000 people, and it is even lower in Europe with approximately 6 cases per 100,000 people. However, combined their frequency of occurrence is much higher than any singular cancer. Cancer treatment and management has tremendously improved in the last decade, particularly with the administration of immune-based therapies. The four most prevalent immune-based therapies are (1) the use of immune-checkpoint inhibitors, (2) macrophage therapy, (3) Chimeric Antigen Receptor (CAR) T cell therapy, and (4) neoantigen-based therapies. In our review, we discuss these various aproaches and their implementation in the treatment of a variety of rare cancers. Furthermore, we discuss their limitations and potential strategies to overcome them to enhance the therapeutic efficacy of these approaches. Finally, our article presents the future directions and other additional immune therapies that may be incorporated into the treatment of rare cancers.
Impact of total cerebral small vessel disease score on ophthalmic artery morphologies and hemodynamics
Authors: Wang Jia-lin , Cheng Xue-ru , Meng Zhao-yang , Wang Yan-ling 
Published: February 2023

Abstract
Background
Cerebral small vessel disease (CSVD) is a systemic disease, affecting not only the brain, but also eyes and other organs. The total CSVD score is a tool for comprehensive evaluation of brain lesions in patients with CSVD. The ophthalmic artery (OA) is a direct response to ocular blood flow. However, little is known about the correlation between CSVD and characteristics of OA. We investigated the OA morphologies and hemodynamics in patients with CSVD and the correlation between these changes and the total CSVD score.

Methods
This cross-sectional observational study included 34 eyes from 22 patients with CSVD and 10 eyes from 5 healthy controls. The total CSVD score was rated according to the CSVD signs on magnetic resonance imaging. OA morphological characteristics were measured on the basis of 3D OA model reconstruction. OA hemodynamic information was calculated using computational fluid dynamics simulations.

Results
The total CSVD score negatively correlated with the OA diameter, blood flow velocity, and mass flow ratio (all P < 0.05). After adjusting for potential confounding factors, the total CSVD score was still independently correlated with the OA blood velocity (β = − 0.202, P = 0.005). The total CSVD score was not correlated with OA angle (P > 0.05). The presence of cerebral microbleeds and enlarged perivascular spaces was correlated with the OA diameter (both P < 0.01), while the lacunar infarcts and white matter hyperintensities were correlated with the OA blood velocity (both P < 0.001).

Conclusions
The decrease of the blood velocity in the OA was associated with the increase in the total CSVD score. The changes of the OA diameter and velocity were associated with the presence of various CSVD signs. The findings suggest that more studies are needed in the future to evaluate CSVD by observing the morphologies and hemodynamics of OA.
Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis
Authors: Peng Cheng , Zhang Yanxiu , Lang Xueyan , Zhang Yao 
Published: February 2023

Abstract
Background
Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics.

Methods
DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function.

Results
MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function.

Conclusions
This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions.
Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids
Authors: Srimongkol Atthapol , Laosillapacharoen Natanan , Saengwimol Duangporn , Chaitankar Vijender , Rojanaporn Duangnate , Thanomchard Thanastha , Borwornpinyo Suparerk , Hongeng Suradej , Kaewkhaw Rossukon 
Published: February 2023

Abstract
Background
Recurrence of retinoblastoma (RB) following chemoreduction is common and is often managed with local (intra-arterial/intravitreal) chemotherapy. However, some tumors are resistant to even local administration of maximum feasible drug dosages, or effective tumor control and globe preservation may be achieved at the cost of vision loss due to drug-induced retinal toxicity. The aim of this study was to identify drugs with improved antitumor activity and more favorable retinal toxicity profiles via screening of potentially repurposable FDA-approved drugs in patient-derived tumor organoids.

Methods
Genomic profiling of five RB organoids and the corresponding parental tissues was performed. RB organoids were screened with 133 FDA-approved drugs, and candidate drugs were selected based on cytotoxicity and potency. RNA sequencing was conducted to generate a drug signature from RB organoids, and the effects of drugs on cell cycle progression and proliferative tumor cone restriction were examined. Drug toxicity was assessed with human embryonic stem cell-derived normal retinal organoids. The efficacy/toxicity profiles of candidate drugs were compared with those of drugs in clinical use.

Results
RB organoids maintained the genomic features of the parental tumors. Sunitinib was identified as highly cytotoxic against both classical RB1-deficient and novel MYCN-amplified RB organoids and inhibited proliferation while inducing differentiation in RB. Sunitinib was a more effective suppressor of proliferative tumor cones in RB organoids and had lower toxicity in normal retinal organoids than either melphalan or topotecan.

Conclusion
The efficacy and retinal toxicity profiles of sunitinib suggest that it could potentially be repurposed for local chemotherapy of RB.
HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway
Authors: Liu Yunzhi , Xu Qishan , Deng Fan , Zheng Zhuojun , Luo Jialiang , Wang Ping , Zhou Jia , Lu Xiao , Zhang Liyun , Chen Zhengliang , Zhang Qifan , Chen Qingyun , Zuo Daming 
Published: February 2023

Abstract
Background
Hepatic inflammation is a common initiator of liver diseases and considered as the primary driver of hepatocellular carcinoma (HCC). However, the precise mechanism of inflammation-induced HCC development and immune evasion remains elusive and requires extensive investigation. This study sought to identify the new target that is involved in inflammation-related liver tumorigenesis.

Methods
RNA-sequencing (RNA-seq) analysis was performed to identify the differential gene expression signature in primary human hepatocytes treated with or without inflammatory stimulus. A giant E3 ubiquitin protein ligase, HECT domain and RCC1-like domain 2 (HERC2), was identified in the analysis. Prognostic performance in the TCGA validation dataset was illustrated by Kaplan–Meier plot. The functional role of HERC2 in HCC progression was determined by knocking out and over-expressing HERC2 in various HCC cells. The precise molecular mechanism and signaling pathway networks associated with HERC2 in HCC stemness and immune evasion were determined by quantitative real-time PCR, immunofluorescence, western blot, and transcriptomic profiling analyses. To investigate the role of HERC2 in the etiology of HCC in vivo, we applied the chemical carcinogen diethylnitrosamine (DEN) to hepatocyte-specific HERC2-knockout mice. Additionally, the orthotopic transplantation mouse model of HCC was established to determine the effect of HERC2 during HCC development.

Results
We found that increased HERC2 expression was correlated with poor prognosis in HCC patients. HERC2 enhanced the stemness and PD-L1-mediated immune evasion of HCC cells, which is associated with the activation of signal transducer and activator of transcription 3 (STAT3) pathway during the inflammation-cancer transition. Mechanically, HERC2 coupled with the endoplasmic reticulum (ER)-resident protein tyrosine phosphatase 1B (PTP1B) and limited PTP1B translocation from ER to ER-plasma membrane junction, which ameliorated the inhibitory role of PTP1B in Janus kinase 2 (JAK2) phosphorylation. Furthermore, HERC2 knockout in hepatocytes limited hepatic PD-L1 expression and ameliorated HCC progression in DEN-induced mouse liver carcinogenesis. In contrast, HERC2 overexpression promoted tumor development and progression in the orthotopic transplantation HCC model.

Conclusion
Our data identified HERC2 functions as a previously unknown modulator of the JAK2/STAT3 pathway, thereby promoting inflammation-induced stemness and immune evasion in HCC.
A NEw MOdel of individualized and patient-centered follow-up for women with gynecological cancer (the NEMO study)—protocol and rationale of a randomized clinical trial
Authors: Bergholdt Stinne Holm , Hansen Dorte Gilsaa , Johnsen Anna Thit , Boman Bo Snedker , Jensen Pernille Tine 
Published: February 2023

Abstract
Background
Follow-up programs for gynecological cancer patients are currently under revision. There is limited evidence that traditional follow-up and clinical examinations improve survival in an early-stage gynecological setting. Further, traditional follow-up programs fail to accommodate the patient’s need for psychosocial and sexual supportive care and to actively involve patients and their relatives in the follow-up process. Individualized programs may replace traditional routine follow-up with fixed intervals and length. Focusing on alarm-symptoms and self-reporting may ensure detection of recurrence while allowing a continuous attention to the patient’s well-being and return to daily life.
In this study, a nurse-led, individualized, and need-based intervention with a specific focus on patient empowerment is tested against a standard physician-led model primarily focusing on the detection of recurrence.

Methods
The study is designed as a clinical, randomized trial conducted in one of four national onco-gynecological centers in Denmark. Patients with early-stage cervical or endometrial cancer are eligible for inclusion. The intervention group undergoes individualized, nurse-led follow-up supporting patient empowerment including repeated use of electronic patient-reported outcome measures (ePROMs) before each contact as a dialogue support tool. The follow-up contacts are mainly conducted by telephone. All project nurses attended a special training program before project start and are all well-educated and dedicated onco-gynecological nurses. The control group receives standard, physician-led, follow-up without use of ePROMs or specific focus on empowerment.
The effect of the intervention is evaluated by questionnaires completed by patients at baseline (3 months after surgery) and 12, 18, and 36 months after surgery. Outcomes include empowerment using the Skill and technique subscale of the HEI-Q questionnaire as the primary outcome while fear of cancer recurrence and health-related quality of life as well as the remaining subscales of the HEI-Q represent secondary outcomes. Data is collected by use of the REDCap technology, which also provides a customized visual support function for the dialogue tool.

Discussion
This study will provide new information about follow-up in early-stage gynecological cancer settings and thereby contribute to improvement of future follow-up programs. Importantly, the study will provide knowledge about the impact of specific focus on patient empowerment in follow-up programs and, further, how to facilitate empowerment among patients.

Trial registration
The study is registered at clinicaltrials.gov: ID no. NCT03838861. Registered on 6 February 2019.
Protocol version 2, issue date 21 November 2022.
Prophylactic effect of retromuscular mesh placement during loop ileostomy closure on incisional hernia incidence—a multicentre randomised patient- and observer-blind trial (P.E.L.I.O.N trial)
Authors: Müller Sven , Weyhe Dirk , Herrle Florian , Horvath Philipp , Bachmann Robert , von Ehrlich-Treuenstätt Viktor , Heger Patrick , Nasir Nadir , Klose Christina , Ritz Alexander , Sander Anja , Grohmann Erich , Dörr-Harim Colette , Mihaljevic André L. 
Published: February 2023

Abstract
Background
Incisional hernia is a frequent complication following loop ileostomy reversal. Incisional hernias are associated with morbidity, loss of health-related quality of life and costs and warrant the investigation of prophylactic measures. Prophylactic mesh implantation at the time of surgical stoma reversal has shown to be a promising and safe method to prevent incisional hernias in this setting. However, the efficacy of this method has not yet been investigated in a large multicentre randomised-controlled trial (RCT) with adequate external validity. The P.E.L.I.O.N. trial will evaluate the efficacy of prophylactic mesh reinforcement after loop ileostomy closure in decreasing the rate of incisional hernia versus standard closure alone.

Methods
P.E.L.I.O.N. is a multicentre, patient- and observer-blind RCT. Patients undergoing loop ileostomy closure will undergo intraoperative 1:1 randomisation into either abdominal wall closure with a continuous slowly absorbable suture in small-stitch technique without mesh reinforcement (control group) or abdominal wall closure with an additional reinforcement with a retromuscular non-absorbable, macro-pore (pore size ≥ 1000 μm or effective porosity >0%) light-weight monofilament or mixed structure mesh. A total of 304 patients (152 per group) will need to be randomised in the study. Based on inclusion and exclusion criteria, 1,014 patients are expected to be screened for eligibility in order to recruit the necessary number of patients. The primary endpoint will be the frequency of incision hernias within 24 months according to the European Hernia Society definition. Secondary endpoints will be the frequency of surgical site occurrences (including surgical site infections, wound seromas and hematomas, and enterocutaneous fistulas), postoperative pain, the number of revision surgeries and health-related quality of life. Safety will be assessed by measuring postoperative complications ≥ grade 3 according to the Dindo-Clavien classification.

Discussion
Depending on the results of the P.E.L.I.O.N. trial, prophylactic mesh implantation could become the new standard for loop ileostomy reversal.

Trial registration
DRKS00027921, U1111-1273-4657