bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Cardiac Resynchronization Therapy Response Using a Lead Placement Score Derived From 4-Dimensional Computed Tomography
Authors: Manohar Ashish , Colvert Gabrielle M. , Yang James , Chen Zhennong , Ledesma-Carbayo Maria J. , Kronborg Mads Brix , Sommer Anders , Nørgaard Bjarne L. , Nielsen Jens Cosedis , McVeigh Elliot R.
Published: August 2022

Background:

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure; however, 30% of patients do not respond to the treatment. We sought to derive patient-specific left ventricle maps of lead placement scores (LPS) that highlight target pacing lead sites for achieving a higher probability of CRT response.

Methods:

Eighty-two subjects recruited for the ImagingCRT trial (Empiric Versus Imaging Guided Left Ventricular Lead Placement in Cardiac Resynchronization Therapy) were retrospectively analyzed. All 82 subjects had 2 contrast-enhanced full cardiac cycle 4-dimensional computed tomography scans: a baseline and a 6-month follow-up scan. CRT response was defined as a reduction in computed tomography–derived end-systolic volume ≥15%. Eight left ventricle features derived from the baseline scans were used to train a support vector machine via a bagging approach. An LPS map over the left ventricle was created for each subject as a linear combination of the support vector machine feature weights and the subject’s own feature vector. Performance for distinguishing responders was performed on the original 82 subjects.

Results:

Fifty-two (63%) subjects were responders. Subjects with an LPS≤Q
1
(lower-quartile) had a posttest probability of responding of 14% (3/21), while subjects with an LPS≥ Q
3
(upper-quartile) had a posttest probability of responding of 90% (19/21). Subjects with Q
1
<LPS<Q
3
had a posttest probability of responding that was essentially unchanged from the pretest probability (75% versus 63%,
P
=0.2). An LPS threshold that maximized the geometric mean of true-negative and true-positive rates identified 26/30 of the nonresponders. The area under the curve of the receiver operating characteristic curve for identifying responders with an LPS threshold was 87%.

Conclusions:

An LPS map was defined using 4-dimensional computed tomography–derived features of left ventricular mechanics. The LPS correlated with CRT response, reclassifying 25% of the subjects into low probability of response, 25% into high probability of response, and 50% unchanged. These encouraging results highlight the potential utility of 4-dimensional computed tomography in guiding patient selection for CRT. The present findings need verification in larger independent data sets and prospective trials.
Presence of Coronary Endothelial Dysfunction, Coronary Vasospasm, and Adenosine-Mediated Vasodilatory Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries
Authors: Feenstra Rutger G.T. , Boerhout Coen K.M. , Woudstra Janneke , Vink Caitlin E.M. , Wittekoek Marianne E. , de Waard Guus A. , Appelman Yolande , Eringa Etto C. , Marques Koen M.J. , de Winter Robbert J. , Beijk Marcel A.M. , van de Hoef Tim P. , Piek Jan J.
Published: August 2022

Background:

Coronary function testing in patients with ischemia and nonobstructive coronary arteries (INOCA) commonly includes assessment of adenosine-mediated vasodilation and acetylcholine spasm provocation. The purpose of this study was to evaluate the diagnostic value of additional endothelial function testing for the diagnosis of vasomotor dysfunction in patients with INOCA.

Methods:

In this retrospective cohort study, we included patients with INOCA who underwent clinically indicated comprehensive coronary function testing. Endothelial dysfunction was defined as a <50% increase in coronary blood flow, determined by Doppler flow, and/or epicardial vasoconstriction compared to baseline, in response to low-dose acetylcholine. Coronary artery spasm (CAS) was defined as vasospastic angina or microvascular angina in response to coronary high-dose acetylcholine. An impaired adenosine-mediated vasodilation was defined as a coronary flow reserve <2.5 and/or hyperemic microvascular resistance ≥2.5.

Results:

Among all 110 patients, 79% had endothelial dysfunction, 62% had CAS, and 29% had an impaired adenosine-mediated vasodilation. Endothelial dysfunction was present in 80% of patients who tested positively for CAS and/or an impaired adenosine-mediated vasodilation. Endothelial function testing increases the diagnostic yield of coronary function testing that only incorporates adenosine testing and spasm provocation by 17% to 92%. Of patients with normal adenosine-mediated vasodilation and no inducible CAS, 68% had endothelial dysfunction.

Conclusions:

Concomitant endothelial dysfunction was prevalent in the vast majority of patients with INOCA with inducible CAS and/or an impaired adenosine-mediated vasodilation. In patients with INOCA without inducible CAS and normal adenosine-mediated vasodilation, two-thirds had endothelial dysfunction. These results indicate the relevance to perform endothelial function testing in patients with INOCA in view of its therapeutic implication.
Analysis of Pathways to Enhancing Facility Utilization under the Direct Health Facility Financing Reform in Tanzania
Authors: Osoro Otieno
Published: August 2022

Tanzania undertook the Direct Health Facility Financing (DHFF) programme in 2017 to improve health services in various aspects including facility utilization. This study analyzed the impact of expenditure as one factor that influences facility utilization using panel data from the Facility Financial Accounting and Reporting System and District Health Information System 2. The study specifically sought to identify the effect of various categories of expenditure and facility type on utilization. Findings revealed all expenditure items significantly impacted utilization up to given levels. Furthermore, dispensary utilization was lower than utilization at council hospitals. Expenditure on direct inputs had the largest impact on facility utilization, although expenditure on indirect inputs was also important. Given the findings, directing expenditure towards as many expenditures significantly impacts utilization. Furthermore, improving quality and range of services at dispensaries can enhance their utilization. Finally, spending on indirect inputs improves results by complementing direct inputs.
Pulmonary bleeding in racehorses: A gross, histologic, and ultrastructural comparison of exercise-induced pulmonary hemorrhage and exercise-associated fatal pulmonary hemorrhage
Authors: Rocchigiani Guido , Verin Ranieri , Uzal Francisco A. , Singer Ellen R. , Pregel Paola , Ressel Lorenzo , Ricci Emanuele
Published: August 2022

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition of Thoroughbred racehorses that is usually responsible for reduced performance, while exercise-associated fatal pulmonary hemorrhage (EAFPH) is characterized by severe pulmonary bleeding of unknown pathogenesis resulting in sudden death during strenuous exercise. The aim of the study was to characterize and compare anamnestic data together with pulmonary gross, histologic, and ultrastructural findings in racehorses with EIPH (n = 10), EAFPH (n = 10), and control horses (n = 5). No differences in anamnesis were identified between the 3 groups. Grossly cranial lobe reddening and edema scores were significantly more prevalent and severe in the EAFPH group compared with the EIPH and control groups. Histologically, hemorrhage scores were higher in the EAFPH group, while hemosiderophages, iron encrustations of collagen and elastin fibers, and vascular remodeling scores were significantly higher in EIPH group compared with the EAFPH and control groups. In all groups, caudal lung locations exhibited a significantly higher score for vascular remodeling, hemosiderophage accumulation, iron encrustation, and type II pneumocyte hyperplasia when compared with cranial, dorsal, and ventral locations. Ultrastructural analysis of perivascular collagen showed fibrils with significantly larger diameters in the EAFPH group compared with the EIPH group but not compared with the control group. This study demonstrates that lungs of horses that experienced EAFPH show significantly less vascular remodeling and other long-term pulmonary abnormalities that characterize horses with EIPH.
An overview of the history of wind turbine development: Part I—The early wind turbines until the 1960s
Authors: Gipe Paul , Möllerström Erik
Published: August 2022

We review the development of wind turbines for generating electricity from the late 19th century to the present, summarizing some key characteristics. We trace the move from two to four blade wind turbines to the three blades common today. We establish that it was not the governmental-funded wind programs with its large-scale prototypes of the 1970–80s that developed into the commercial turbines of today. Instead it was the small-scale Danish wind turbines, developed for an agricultural market, that developed into the commercial turbines of today. And we show that much of what we know today about wind turbine design was known by the 1930s and certainly well known by the late 1950s. This work is divided into two parts: the first part takes up the development from the first electricity producing wind turbines through to the 1960s and a second part on development from the 1970s onward.
The Roles of Information Valence, Media Literacy and Perceived Information Quality on the Association Between Frequent Social Media Exposure and COVID-19 Vaccination Intention
Authors: Xin Meiqi , Luo Sitong , Wang Suhua , Zhao Junfeng , Zhang Guohua , Li Lijuan , Li Liping , Lau Joseph Tak-Fai
Published: August 2022

Purpose

This study aimed to examine the associations between frequent exposure to positive/negative information about vaccine efficacy/safety on social media and intention of COVID-19 vaccination, and to test if media literacy and perceived information quality would moderate such associations.

Design

A multi-city cross-sectional survey.

Setting

At five universities in different regions of China.

Subjects

6922 university students (a response rate of 72.3%).

Measures

frequency of exposure to social media information about COVID-19 vaccination, media literacy, perceived information quality, intention of COVID-19 vaccination, and sociodemographic characteristics.

Analysis

Logistic regression analysis was conducted to test main and interaction effects.

Results

Higher exposure to positive information about vaccine efficacy (adjusted odds ratio [AOR] = 1.30, P < .001) and vaccine safety (AOR = 1.27, P < .001) were positively associated with vaccination intention. No significant associations were shown between exposure to negative information about vaccine efficacy/safety and vaccination intention. Higher net exposure to negative vs positive information was negatively associated with vaccination intention (AOR = .82, P < .001). High media literacy was further found to attenuate the effect of negative information exposure and strengthen that of positive information exposure. Perceived information quality was not a significant moderator.

Conclusion

The valence of social media information regarding the efficacy and safety of COVID-19 vaccines and individuals’ media literacy jointly shaped COVID-19 vaccination intention. The findings can inform the development of effective health promotion strategies for enhancing COVID-19 vaccination.
Contemporary present-tense fiction: Crossing boundaries in narrative
Authors: Ikeo Reiko
Published: August 2022

The use of the present tense as the primary narrative tense has become a commonly encountered phenomenon in contemporary fiction. The textual effects of the use of the present narrative tense, however, have not yet been fully explored. This paper first reviews how the use of tenses contributes to constructing narrative worlds, focusing on three facets of narrative: the relationship between the narrator and the narrated, time frames within the narrative and characters’ discourse embedded in narrative. Then, using corpus data which includes both present- and past-tense fiction, I will show that the boundaries and distinctions which are consistently taken for granted in past-tense narrative can be blurred, crossed within narratorial structures and partly expanded at a meta-textual level from written discourse to spoken discourse.
Development of the Blackfeet Community Hospice Project: Pilot Workshop
Authors: Colclough Yoshiko , Brown Gary M
Published: August 2022

Taboo perception on talking about death and dying among American Indians/Alaska Natives is prevalent. This suppressive value makes hospice introduction difficult, leading hospice disparity. Working together by using a community-based participatory research approach over a decade, we conducted a 6-hour workshop including information sharing and group activities. The purpose of the study was to investigate the community readiness for end-of-life knowledge by conducting a public workshop. We used pre- and post-workshop surveys with Likert-type responses to five questions to assess the effect of workshop in end-of-life knowledge. Thirty individuals participated the workshop; 80% of them reported their knowledge increase on at least one question. While the survey had concerns, positive participant responses indicated readiness and appropriateness to use workshops to increase end-of-life knowledge.
Fat stigma and body objectification: A text analysis approach using social media content
Authors: Wanniarachchi Vajisha U , Scogings Chris , Susnjak Teo , Mathrani Anuradha
Published: August 2022

This study investigates how female and male genders are positioned in fat stigmatising discourses that are being conducted over social media. Weight-based linguistic data corpus, extracted from three popular social media (SM) outlets, Twitter, YouTube and Reddit, was examined for fat stigmatising content. A mixed-method analysis comprising sentiment analysis, word co-occurrences and qualitative analysis, assisted our investigation of the corpus for body objectification themes and gender-based differences. Objectification theory provided the underlying framework to examine the experiential consequences of being fat across both genders. Five objectifying themes, namely, attractiveness, physical appearance, lifestyle choices, health and psychological well-being, emerged from the analysis. A deeper investigation into more facets of the social interaction data revealed overall positive and negative attitudes towards obesity, which informed on existing notions of gendered body objectification and weight/fat stigmatisation. Our findings have provided a holistic outlook on weight/fat stigmatising content that is posted online which can further inform policymakers in planning suitable props to facilitate more inclusive SM spaces. This study showcases how lexical analytics can be conducted by combining a variety of data mining methods to draw out insightful subject-related themes that add to the existing knowledge base; therefore, has both practical and theoretical implications.
Qatar's multi-actors sports strategy: Diplomacy, critics and legitimisation
Authors: Søyland Håvard Stamnes , Moriconi Marcelo
Published: August 2022

Drawing on official documents and empirical examples, this article analyses Qatar's sports strategy to gain attraction and generate soft power globally. The paper shows how the country based has efficiently used sport as a mean for modernisation, diplomacy and soft power, through a strategy based in the participation of national and foreign actors and institutions. While Qatar's sports diplomacy has been very ambitious, the newfound global attention has led to an increased scrutiny regarding national internal policies. This has resulted in massive criticism regarding corruption allegations and several reports of labour abuses towards the migrant workers in the country. In consequence, critics consider Qatar as an example of sportswashing, which is understood as a deliberate use of sports soft power in seeking to alter a tarnished global reputation. We claim that the Qatari strategy, even having a bit of both, can be used to generate a positive context for social development and we describe how the county has managed to engage foreign actors and institutions to counter external denounces. The context created by successful sports diplomacy strategies and evidence-based external critics might generate an adequate ecosystem to promote substantial cultural and political changes, respect for human rights and individual freedom. In this context, western countries, sport institutions and external actors play (or not) a crucial legitimator role, and so does money.
Ulna hook plate osteosynthesis for ulna head fracture associated with distal radius fracture
Authors: Gauthier Morgan , Beaulieu Jean-Yves , Nichols Lucille , Hannouche Didier
Published: August 2022

Background

Distal ulna head or neck fracture is commonly associated with distal radius fracture. Treatment of these fractures remains controversial. Plate osteosynthesis is commonly performed. The purpose of this study was to observe clinical and radiological outcomes in ulna hook plate osteosynthesis for distal ulna fracture associated with distal radius fracture.

Materials and methods

This retrospective study between 2010 and 2018 included patients presenting combined displaced distal ulna fracture and distal radius fracture who were treated with ulna hook plate osteosynthesis. Patient evaluation included pain measurement with the visual analog scale, wrist range of motion, grip and pinch strengths, Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score, and Mayo wrist score. Preoperative radiographs were reviewed to classify the distal ulna fracture according to Biyani. Bone union was evaluated on postoperative X-rays. At final follow-up, the usual radiographic parameters were measured and distal radioulnar joint (DRUJ) osteoarthritis was assessed.

Results

A total of 48 patients were included. Mean age was 63 years old and mean follow-up was 28 months. According to the Biyani classification, there were 12 type I, 4 type II, 8 type III, and 24 type IV distal ulna fractures. Wrist flexion was 60°, extension 57°, pronation 85°, and supination 80°. Grip strength was 21 kg (86% of the uninjured opposite side). Pinch strength was 6.6 kg (92% of the uninjured opposite side). Clinical scores were very good to excellent, with a mean Q-DASH of 12 and a Mayo wrist score of 90. Discomfort or pain due to the implant that required implant removal was reported in 29%, and was higher in younger patients. Nonunion was observed in two cases and secondary implant displacement in one case. These three cases required secondary intervention with ulna head resection, which was higher in Biyani type IV. DRUJ osteoarthritis was observed in 12 patients (31%) and was higher in older patients.

Conclusions

Ulna hook plate fixation gives good clinical results and a high rate of fracture union, but complications are common. Implant irritation is a frequent complication, especially in young patients, and often requires implant removal.

Level of evidence: IV
Nutrition or nature: using elementary flux modes to disentangle the complex forces shaping prokaryote pan-genomes
Authors: Garza Daniel R. , von Meijenfeldt F. A. Bastiaan , van Dijk Bram , Boleij Annemarie , Huynen Martijn A. , Dutilh Bas E.
Published: August 2022

Background

Microbial pan-genomes are shaped by a complex combination of stochastic and deterministic forces. Even closely related genomes exhibit extensive variation in their gene content. Understanding what drives this variation requires exploring the interactions of gene products with each other and with the organism’s external environment. However, to date, conceptual models of pan-genome dynamics often represent genes as independent units and provide limited information about their mechanistic interactions.

Results

We simulated the stochastic process of gene-loss using the pooled genome-scale metabolic reaction networks of 46 taxonomically diverse bacterial and archaeal families as proxies for their pan-genomes. The frequency by which reactions are retained in functional networks when stochastic gene loss is simulated in diverse environments allowed us to disentangle the metabolic reactions whose presence depends on the metabolite composition of the external environment (constrained by “nutrition”) from those that are independent of the environment (constrained by “nature”). By comparing the frequency of reactions from the first group with their observed frequencies in bacterial and archaeal families, we predicted the metabolic niches that shaped the genomic composition of these lineages. Moreover, we found that the lineages that were shaped by a more diverse metabolic niche also occur in more diverse biomes as assessed by global environmental sequencing datasets.

Conclusion

We introduce a computational framework for analyzing and interpreting pan-reactomes that provides novel insights into the ecological and evolutionary drivers of pan-genome dynamics.
Identification of long non-coding RNAs and microRNAs involved in anther development in the tropical Camellia oleifera
Authors: Kong Lingshan , Zhuo Yanjing , Xu Jieru , Meng Xiangxu , Wang Yue , Zhao Wenxiu , Lai Hanggui , Chen Jinhui , Wang Jian
Published: August 2022

Background

Explored the molecular science of anther development is important for improving productivity and overall yield of crops. Although the role of regulatory RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), in regulating anther development has been established, their identities and functions in Camellia oleifera, an important industrial crop, have yet not been clearly explored. Here, we report the identification and characterization of genes, lncRNAs and miRNAs during three stages of the tropical C. oleifera anther development by single-molecule real-time sequencing, RNA sequencing and small RNA sequencing, respectively.

Results

These stages, viz. the pollen mother cells stage, tetrad stage and uninucleate pollen stage, were identified by analyzing paraffin sections of floral buds during rapid expansion periods. A total of 18,393 transcripts, 414 putative lncRNAs and 372 miRNAs were identified, of which 5,324 genes, 115 lncRNAs, and 44 miRNAs were differentially accumulated across three developmental stages. Of these, 44 and 92 genes were predicted be regulated by 37 and 30 differentially accumulated lncRNAs and miRNAs, respectively. Additionally, 42 differentially accumulated lncRNAs were predicted as targets of 27 miRNAs. Gene ontology enrichment indicated that potential target genes of lncRNAs were enriched in photosystem II, regulation of autophagy and carbohydrate phosphatase activity, which are essential for anther development. Functional annotation of genes targeted by miRNAs indicated that they are relevant to transcription and metabolic processes that play important roles in microspore development. An interaction network was built with 2 lncRNAs, 6 miRNAs and 10 mRNAs. Among these, miR396 and miR156 family were up-regulated, while their targets, genes (GROWTH REGULATING FACTORS and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE genes) and lncRNAs, were down-regulated. Further, the trans-regulated targets of these lncRNAs, like wall-associated kinase2 and phosphomannose isomerase1, are involved in pollen wall formation during anther development.

Conclusions

This study unravels lncRNAs, miRNAs and miRNA-lncRNA-mRNA networks involved in development of anthers of the tropical C. oleifera lays a theoretical foundation for further elucidation of regulatory roles of lncRNAs and miRNAs in anther development.
Primary care physicians’ knowledge and attitudes about obesity, adherence to treatment guidelines and association with confidence to treat obesity: a Swedish survey study
Authors: Carrasco Daniel , Thulesius Hans , Jakobsson Ulf , Memarian Ensieh
Published: August 2022

Background

Obesity is a chronic disease with increasing prevalence. We aimed to explore primary care physicians’ knowledge and attitudes about obesity and how knowledge and attitudes are associated with confidence and adherence to obesity guidelines and barriers to obesity treatment.

Methods

A questionnaire survey was sent by e-mail to 1642 primary care physicians in four regions in Sweden. The survey focused on the physicians’ knowledge, attitudes towards obesity, confidence in obesity management, adherence to obesity guidelines and barriers to optimal care. We created different statistical indices for knowledge, attitudes and adherence. To analyse the correlation between these indices, we used linear regression analyses.

Results

Replies from 235 primary care physicians yielded a response rate of 14.3%. Most physicians answered correctly that obesity is a disease (91%), that obesity regulation sits in the hypothalamus (70%) and that obesity is due to disorders of appetite regulation (69%). However, 44% of the physicians thought that the most effective weight reduction method for severe obesity was lifestyle changes; 47% believed that obesity is due to lack of self-control, 14% mentioned lack of motivation and 22% stated laziness. Although 97% believed that physicians can help individuals with obesity and 56% suggested that obesity treatment should be prioritised, 87% of the physicians expressed that losing weight is the patients’ responsibility. There was a positive association between higher knowledge and better adherence to obesity guidelines (B = 0.07, CI 0.02–0.12, p-value = 0.005) and feeling confident to suggest medication (p < 0.001) or bariatric surgery (p = 0.002). While 99% of the physicians felt confident to discuss lifestyle changes, 67% and 81% were confident to suggest medication or bariatric surgery, respectively. Respondents perceived that the greatest barrier in obesity management was lack of time (69%) and resources (49%).

Conclusion

There was a positive association between Swedish primary care physicians’ knowledge and adherence to obesity guidelines and being more confident to suggest obesity treatment. Yet, many physicians had an ambivalent attitude towards obesity management.
Analysis of pregnancy outcomes following surgical treatment of cesarean scar pregnancy
Authors: Xu Zongxu , Sheng Chengcheng , Yang Qing , Wang Jun
Published: August 2022

Purpose

To investigate the surgical treatment approaches for patients with Cesarean scar pregnancy (CSP) and the effects on subsequent pregnancy.

Methods

CSP patients admitted to Shengjing Hospital of China Medical University from January 2013 to December 2018 were retrospectively analyzed to collect their clinical characteristics, and follow-up of postoperative pregnancies.

Results

A total of 1126 CSP patients were enrolled in this study, including 595 (52.84%) CSP type I, 415 (36.86%) CSP type II, and 116 (10.30%) CSP type III cases. There were significant differences between the three types of patients in terms of β-HCG levels, gestational sac diameter, clinical symptoms and presence of fetal heartbeat at diagnosis (P < 0.01). Among these, 89.90% of CSP type I, 88.90% of CSP type II and 50% of CSP type III patients were treated with hysteroscopic lesion excision, 7.9% of CSP type I and 2.2% of CSP type II patients underwent ultrasound-monitored curettage, and the remaining patients underwent lesion excision and and simultaneous repair of excised lesions by different routes (trans-laparoscopic, transabdominal or transvaginal methods). And 5.55% of CSP type I, 22.65% of CSP type II and 43.10% of CSP type III patients were treated with adjunctive uterine artery embolization (UAE). The patients were followed up for more than 2 years after surgery. Among the 166 re-pregnancies, 58 (34.94%) were normal pregnancies, 17 patients reoccurred with CSP, the recurrent rate of CSP was 10.24%. All 58 normal pregnancies were terminated by cesarean section, with a mean gestational week of delivery of (38.36 ± 2.25) weeks, a mean birth weight of (3228.45 ± 301.96)g, and the postnatal Apgar score was (9.86 ± 0.23) points at 1 min and all 5 min were 10 points. Logistic regression analysis suggested that the number of previous cesarean deliveries was a risk factor for recurrent CSP (RCSP) (OR = 10.82, 95% CI: 2.52–46.50, P = 0.001).

Conclusions

The type of CSP is related to β-HCG values, presence of fetal heartbeat, gestational sac diameter and clinical symptoms. Hysteroscopic therapy is a commonly used surgical procedure and UAE is often used as an adjuvant treatment. For subsequent pregnancies, the number of previous cesarean deliveries is a risk factor for recurrent CSP.
Construction of a novel model based on cell-in-cell-related genes and validation of KRT7 as a biomarker for predicting survival and immune microenvironment in pancreatic cancer
Authors: Song Jianlu , Ruze Rexiati , Chen Yuan , Xu Ruiyuan , Yin Xinpeng , Wang Chengcheng , Xu Qiang , Zhao Yupei
Published: August 2022

Background

Pancreatic cancer (PC) is a highly malignant tumor featured with high intra-tumoral heterogeneity and poor prognosis. Cell-in-cell (CIC) structures have been reported in multiple cancers, and their presence is associated with disease progression. Nonetheless, the prognostic values and biological functions of CIC-related genes in PC remain poorly understood.

Methods

The sequencing data, as well as corresponding clinicopathological information of PC were collected from public databases. Random forest screening, least absolute shrinkage, and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to construct a prognostic model. The effectiveness and robustness of the model were evaluated using receiver operating characteristic (ROC) curves, survival analysis and establishing the nomogram model. Functional enrichment analyses were conducted to annotate the biological functions. The immune infiltration levels were evaluated by ESTIMATE and CIBERSORT algorithms. The expression of KRT7 (Keratin 7) was validated by quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) staining. The CIC formation, cell clusters, cell proliferation, migration and invasion assays were applied to investigate the effects of silencing the expression of KRT7.

Results

A prognostic model based on four CIC-related genes was constructed to stratify the patients into the low- and high-risk subgroups. The high-risk group had a poorer prognosis, higher tumor mutation burden and lower immune cell infiltration than the low-risk group. Functional enrichment analyses showed that numerous terms and pathways associated with invasion and metastasis were enriched in the high-risk group. KRT7, as the most paramount risk gene in the prognostic model, was significantly associated with a worse prognosis of PC in TCGA dataset and our own cohort. High expression of KRT7 might be responsible for the immunosuppression in the PC microenvironment. KRT7 knockdown was significantly suppressed the abilities of CIC formation, cell cluster, cell proliferation, migration, and invasion in PC cell lines.

Conclusions

Our prognostic model based on four CIC-related genes has a significant potential in predicting the prognosis and immune microenvironment of PC, which indicates that targeting CIC processes could be a therapeutic option with great interests. Further studies are needed to reveal the underlying molecular mechanisms and biological implications of CIC phenomenon and related genes in PC progression.
Effects of a theory-based training program with follow-up home visits on self-management behavior, glycemic index, and quality of life among Iranian patients with type 2 diabetes mellitus
Authors: Kaveh Mohammad Hossein , Montazer Maryam , Karimi Masoud , Hassanzadeh Jafar
Published: August 2022

Background

Uncontrolled diabetes is an important public health problem that endangers the quality of life of patients. Promoting self-management through well-planned training is an essential strategy to control diabetes effectively. This study aimed to examine the effects of a training program based on social cognitive theory (SCT) on self-management behavior, glycemic index, and quality of life among patients with type 2 diabetes mellitus.

Methods

This is a quasi-experimental study with a pretest–posttest design. The statistical population included 106 adults with type 2 diabetes mellitus assigned to the intervention and control groups [n1 = n2 = 53], who received services from two urban health centers. A multi-method, SCT-based training program consisting of six 60–80-min sessions was run, followed by 2–3 follow-up home visits [once a month for each participant] for the intervention group. The data were collected before and three months after the intervention and were analyzed in SPSS 19.

Results

Before the intervention, there was no significant difference between the two groups regarding the main variables. After the intervention, there was a significant increase in the intervention group's mean scores of knowledge, self-efficacy, social support, outcome expectations, self-regulation, self-management behavior, glycemic index, and quality of life. There were no significant changes in these constructs in the control group after the intervention. The regression analysis results indicated that social cognitive theory and self-management could explain the variance in quality of life [adjusted R-squared = 0.476].

Conclusions

The findings support the effectiveness of the multi-method, SCT-based educational intervention in improving self-management behaviors, glycemic index, and quality of life among patients with type 2 diabetes mellitus. It is suggested that the quality of type 2 diabetes care programs should be promoted. However, further research is needed to evaluate the long-term outcomes.
Awakening the control of the ankle dorsiflexors in the post-stroke hemiplegic subject to improve walking activity and social participation: the WAKE (Walking Ankle isoKinetic Exercise) randomised, controlled trial
Authors: Ferry Béatrice , Compagnat Maxence , Yonneau Jules , Bensoussan Laurent , Moucheboeuf Geoffroy , Muller François , Laborde Bertrand , Jossart Anne , David Romain , Magne Julien , Marais Loïc , Daviet Jean-Christophe
Published: August 2022

Background

Stroke is the leading cause of acquired disability in France. While 90% of patients recover the ability to walk, it is often limited with a steady speed of approximately 0.7 m/s. This limitation of walking activity is partly related to a decrease in strength associated with more or less significant spasticity. In particular, it seems that the strength of the dorsiflexor muscles is directly related to walking speed. We hypothesise that a protocol based on gestural repetition targeted at the ankle during the subacute phase potentiates the recovery of motor control, improving walking activity, and participates in recovering better social participation.

Methods

An estimated total of 60 patients with subacute stroke will be recruited to participate in this multicentre, interventional, prospective, randomised controlled trial.

All participants will benefit from conventional rehabilitation. In addition, the experimental group will take part in an ankle isokinetic rehabilitation programme for 6 weeks (at least 25 sessions). The control group will receive the same duration of conventional rehabilitation.

The primary outcome measure will be a 10-m walking speed at post-intervention. Secondary outcomes will include social participation, walking spatio-temporal parameters, and dorsiflexor strength. Outcome measurements will be taken at baseline, immediately after treatment (6 weeks), then at 6 months and 1 year of follow-up.

Discussion

This study aims to provide scientific evidence that a protocol based on an early over-solicitation of the ankle dorsiflexor muscles to promote their “awakening” can serve to achieve a more effective walking activity, which in turn encourages social participation following discharge from the hospital.

This protocol should also help optimise physical medicine and rehabilitation practices: the more systematic use of the isokinetic dynamometer as a technique associated with, and integrated into the conventional rehabilitation protocol would allow an objective evaluation of the rehabilitation benefits and should increase the rehabilitation gain in central nervous system disorders.

Trial registration

Limoges University Hospital is the sponsor of this research (Unique Protocol ID: 87RI18_0010)

This research is supported by the French Ministry of Health (PHRC 2020-A03328-31) and is conducted with the support of DGOS (PHRC interregional – GIRCI SOHO).

The study protocol was approved by the French Human Subjects Protection Review Board (Comité de Protection des Personnes Nord-Ouest III) on February 23, 2021.

The trial was registered in the ClinicalTrials.gov registry (NCT04800601) on March 16, 2021.
MiR-942-5p targeting the IFI27 gene regulates HCT-8 cell apoptosis via a TRAIL-dependent pathway during the early phase of Cryptosporidium parvum infection
Authors: Xie Fujie , Zhang Yajun , Li Juanfeng , Sun Lulu , Zhang Longxian , Qi Meng , Zhang Sumei , Jian Fuchun , Li Xiaoying , Li Junqiang , Ning Changsheng , Wang Rongjun
Published: August 2022

Background

MicroRNAs (miRNAs) are involved in the regulation of both the innate and adaptive immune response to Cryptosporidium parvum infection. We previously reported that C. parvum upregulated miR‑942‑5p expression in HCT‑8 cells via TLR2/TLR4‑NF‑κB signaling. In the present study, the role of miRNA-942-5p in the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated HCT-8 cell apoptosis induced by C. parvum was investigated.

Methods

Quantitative real-time polymerase chain reaction, western blotting, flow cytometry, and immunofluorescence were used for analysis.

Results

Forced expression of miRNA-942-5p resulted in decreased apoptosis and an increased C. parvum burden in HCT-8 cells. The opposite results were observed using the suppressed expression of miRNA-942-5p. The miRNA-942-5p led to the translational suppression of IFI27 gene through targeting the 3’-untranslated region of the IFI27 gene. Moreover, overexpression of the IFI27 gene produced a high apoptotic ratio and low C. parvum burden. In contrast, a low apoptotic ratio and a high C. parvum burden were observed following downregulation of the IFI27 gene. Both miR-942-5p and the IFI27 gene influenced TRAIL and caspase-8 expression induced by C. parvum in HCT-8 cells. Moreover, TRAIL promoted HCT-8 cell apoptosis in a concentration-dependent manner.

Conclusions

These data suggested that C. parvum induced the downregulation of IFI27 via relief of miR-942-5p-mediated translational suppression. IFI27 downregulation was affected the burden of C. parvum by regulating HCT-8 cell apoptosis through TRAIL-dependent pathways. Future studies should determine the mechanisms by which C. parvum infection increases miR-942-5p expression and the role of miR-942-5p in hosts' anti-C. parvum immunity in vivo.

Graphical Abstract
Serum granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in patients with active radiographic axial spondyloarthritis and persists despite anti-TNF treatment
Authors: Papagoras Charalampos , Tsiami Styliani , Chrysanthopoulou Akrivi , Mitroulis Ioannis , Baraliakos Xenofon
Published: August 2022

Background

Accumulating evidence supports the role of monocytes and neutrophils in radiographic axSpA (r-axSpA). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a growth factor for both leukocyte lineages and a pro-inflammatory cytokine activating myeloid cells and promoting osteoclastogenesis. It acts through the JAK-STAT pathway. We measured serum GM-CSF and markers of bone metabolism in patients with r-axSpA before and after anti-TNF treatment.

Methods

Patients with active r-axSpA despite treatment with NSAIDs, all eligible for treatment with a biologic agent, were recruited. Healthy donors were sampled as controls. Serum was collected before (baseline) and after 4–6 months (follow-up) of anti-TNF treatment and the following molecules were measured with ELISA: GM-CSF, sclerostin (SOST), and dickkopf-1 (Dkk-1).

Results

Twelve r-axSpA patients (7 males, 5 females, median age 37 years) with a median disease duration of 1 year and 16 age- and sex-matched controls were included. At baseline, patients had mean BASDAI 6.3±2 and ASDAS 3.2±0.7, which decreased to 4.1±1.7 and 2.2±0.6 at follow-up, respectively. At baseline, r-axSpA patients had significantly higher mean serum levels of GM-CSF (150 vs 62pg/ml, p=0.049), significantly lower Dkk-1 (1228 vs 3052pg/ml, p=0.001), but similar levels of SOST (369 vs 544pg/ml, p=0.144) compared to controls. Anti-TNF treatment did not affect GM-CSF, Dkk-1, or SOST levels. Spearman correlation analysis showed that GM-CSF correlated positively with ASDAS at baseline (r=0.61, p=0.039), while no correlations were identified between bone markers (Dkk-1, SOST) on one hand and GM-CSF or disease activity indices on the other.

Conclusions

GM-CSF is increased in patients with active AS and strongly correlates with disease activity. TNF inhibition does not affect GM-SCF levels, despite improving disease activity. GM-CSF may represent an important pathway responsible for residual inflammation during TNF blockade, but also a potential target of JAK inhibitors, explaining their efficacy in r-axSpA.
A duodenal gastrointestinal stromal tumor mimicking a pancreatic neuroendocrine tumor: a case report
Authors: Inoue Masashi , Ohmori Ichiro , Watanabe Atsuhiro , Kajikawa Ryujiro , Kajiwara Ryotaro , Sawada Hiroyuki , Miyamoto Kazuaki , Ikeda Masahiro , Toyota Kazuhiro , Sadamoto Seiji , Takahashi Tadateru
Published: August 2022

Background

Duodenal gastrointestinal stromal tumors are rare. If tumor growth is extraluminal and involves the head of the pancreas, the diagnosis of a duodenal gastrointestinal stromal tumor is difficult.

Case presentation

A 44-year-old Japanese woman was referred to our hospital with anemia. An enhanced computed tomography scan showed a hypervascular mass 30 mm in diameter, but the origin of the tumor, either the duodenum or the head of the pancreas, was unclear. Upper gastrointestinal endoscopy revealed bulging accompanied by erosion and redness in part of the duodenal bulb. Mucosal biopsy was not diagnostic. Endoscopic ultrasound fine-needle aspiration was difficult to perform because a pulsating blood vessel was present in the region to be punctured. These findings led to a diagnosis of pancreatic neuroendocrine tumor invasion to the duodenum. The patient underwent pancreaticoduodenectomy. Histologically, the tumor was made up of spindle-shaped cells immunohistochemically positive for c-Kit and CD34. The tumor was ultimately diagnosed as a duodenal gastrointestinal stromal tumor.

Conclusion

Extraluminal duodenal gastrointestinal stromal tumors are rare and mimic pancreatic neuroendocrine tumors. Endoscopic ultrasound fine-needle aspiration is useful for preoperative diagnosis, but it is not possible in some cases. Intraoperative diagnosis based on a completely resected specimen of the tumor may be useful for modifying the surgical technique.
Long noncoding RNA LIPH-4 promotes esophageal squamous cell carcinoma progression by regulating the miR-216b/IGF2BP2 axis
Authors: Xiao Yuhang , Tang Jinming , Yang Desong , Zhang Baihua , Wu Jie , Wu Zhining , Liao Qianjin , Wang Hui , Wang Wenxiang , Su Min
Published: August 2022

Introduction

Esophageal squamous cell carcinoma (ESCC) represents a major malignancy with poor clinical outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of multiple cancers. However, how lncRNAs are involved in ESCC is currently undefined.

Methods

LIPH-4 levels in ESCC tissue specimens and cells were assessed by qRT-PCR. The biological function of LIPH-4 was examined in cell and animal studies, applying CCK-8, EdU, colony formation and flow cytometry assays as well as xenograft model experiments. The underlying mechanisms of action of LIPH-4 were explored through bioinformatics, luciferase reporter assay, RNA-immunoprecipitation assay and immunoblot.

Results

We identified a novel lncRNA, LIPH-4, which showed elevated amounts in ESCC tissues and positive correlations with increased tumor size and poor prognosis in ESCC patients. Functional studies showed that LIPH-4 promoted the growth, mediated cell cycle progression and inhibited apoptosis in ESCC cells in vitro, and promoted tumor growth in mice. In terms of mechanism, LIPH-4 could bind to miR-216b and act as a competing endogenous RNA (ceRNA) to induce the expression of miR-216’s target gene IGF2BP2. LIPH-4 played an oncogenic role in ESCC through the miR-216b/IGF2BP2 axis.

Conclusions

This study suggested that LIPH-4 functions as a novel oncogenic lncRNA by acting as a ceRNA for miR-216b to regulate IGF2BP2, indicating LIPH-4 likely constitutes a prognostic biomarker and therapeutic target in ESCC.
Warming up for a better fever: a randomized pilot study in pediatric oncology
Authors: Krafft Hanno S. , Raak Christa K. , Jenetzky Ekkehart , Zuzak Tycho J. , Längler Alfred , Martin David D.
Published: August 2022

Background

Fever in children is a major problem in pediatric oncology. Usual management leads to immediate antibiotic and antipyretic therapy, although there is consensus that antipyretic therapy should not be utilized with the sole aim of reducing body temperature. Increased body temperature during fever appears to be an effective modifier in terms of viral replication and enhanced host defense mechanisms against pathogens. Therefore, it might be beneficial to support febrile patients by applying gentle heat during the onset of fever to help the body to reach its new thermoregulatory set point.

Methods

A randomized pilot study over 6 months will be conducted in a pediatric oncology department in an academic hospital in Germany. This study is a preparation for a multicenter clinical trial with two parallel groups concerning the efficacy of heat application vs. treatment as usual. One of the inclusion criteria is body temperatures ≥ 38.0 °C inn= 24 cases of patients receiving chemotherapy aged 18 months to 17 years. The first intervention consists of gentle heat application with hot water bottles at any sign of illness and onset of fever. The aim is to achieve a warm periphery equilibrated to trunk temperature of less than 0.5 °C. The second intervention is the avoidance of antipyretics. The control group receives the standard antipyretic treatment from the participating hospital. The purposes of this pilot study are proof of principle of intervention, evaluation of safety, feasibility, definition of endpoints, and to receive basic data for sample size calculation and needed resources.

Discussion

The main goal is to improve the care of children with cancer by providing the best possible support for febrile episodes. If fever support by heat reduces discomfort, administration of antipyretics and maybe even antibiotics, this would be an advancement in oncological fever management. This pilot study is intended to provide a basis for a main, multicenter, randomized trial and demonstrate the practicability of heat application in febrile patients in pediatric oncology.

Trial registration

German Clinical Trials Register (DRKS),DRKS00028273. Registered on 14 April 2022