bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptualisation of severe and enduring anorexia nervosa: a qualitative meta-synthesis
Authors: Kiely Laura , Conti Janet , Hay Phillipa
Published: August 2023

Background

Severe and enduring anorexia nervosa (SE-AN) is amongst the most impairing of all mental illnesses. Collective uncertainties about SE-AN nosology impacts treatment refinement. Qualitative research, particularly lived experience literature, can contribute to a process of revision and enrichment of understanding the SE-AN experience and further develop treatment interventions. Poor outcomes to date, as evidenced in clinical trials and mortality for people with SE-AN (1 in 20) demonstrate the need for research that informs conceptualisations and novel treatment directions. This interpretative, meta-ethnographic meta-synthesis aimed to bridge this gap.

Methods

A systematic search for qualitative studies that explored the AN experiences of people with a duration of greater than 3 years was undertaken. These studies included those that encompassed phenomenology, treatment experiences and recovery.

Results

36 papers, comprising 382 voices of SE-AN experiences informed the meta-ethnographic findings. Four higher order constructs were generated through a synthesis of themes and participant extracts cited in the extracted papers: (1) Vulnerable sense of self (2) Intra-psychic processes (3) Global impoverishment (4) Inter-psychic temporal processes. Running across these meta-themes were three cross cutting themes (i) Treatment: help versus harm, (ii) Shifts in control (iii) Hope versus hopelessness. These meta-themes were integrated into conceptualisations of SE-AN that was experienced as a recursive process of existential self-in-relation to other and the anorexia nervosa trap.

Conclusions

The alternative conceptualisation of SE-AN proposed in this paper poses a challenge to current conceptualisations of AN and calls for treatments to engage with the complex intra and inter-psychic processes of the SE-AN, more fully. In doing so, clinicians and researchers are asked to continue to be bold in testing novel ideas that may challenge our own rigidity and attachment to dominant paradigms to best serve the individual person with SE-AN. The ‘global impoverishment of self’, found in this synthesis of AN experiences, should inform proposed diagnostic criteria for SE-AN.
Longitudinal analysis of cigar use patterns among US youth and adults, 2013–2019
Authors: Jensen Jessica King , Stoddard Gregory J. , Delnevo Cristine D. , Merten Julie W. , Azagba Sunday
Published: August 2023

Background

Cigars are available in a range of pack quantities, which contrasts regulations requiring cigarettes to be sold in packs of 20 or greater. Smaller packages may be associated with increases in initiation while larger packs may lead consumers to smoke more. The purpose of this study was to inform pack quantity regulations by examining whether usual cigar pack quantity purchased was associated with use, initiation, and discontinuation among youth and adults for four cigar types: premium cigars, large cigars, cigarillos, and filtered cigars.

Methods

We analyzed waves 1–5 (2013–2019) of the adult and waves 2–5 (2014–2019) of the youth Population Assessment of Tobacco and Health (PATH) Study. Samples included those responding to the item on pack quantity and providing data at all waves (adults: premium cigars [N = 536], large cigars [N = 1,272], cigarillos [N = 3,504], filtered cigars [N = 1,281]; youth: premium cigars [N = 55], large cigars [N = 217], cigarillos [N = 1514], filtered cigars [N = 266]). Generalized estimating equation models examined the population-averaged effects of pack quantity on cigar use, initiation, and discontinuation.

Results

Adult pack quantity was positively associated with the days used per month for premium cigars (b: 0.23, 95% CI: 0.11, 0.34), large cigars (b: 0.17, 95% CI: 0.08, 0.25), cigarillos (b: 0.12, 95% CI: 0.003, 0.24), and filtered cigars (b: 0.07, 95% CI: 0.04, 0.10), and positively associated with amount smoked per day for all cigar types. Youth pack quantity was positively associated with days used per month for premium cigars (b: 0.88, 95% CI: 0.33, 1.43), large cigars (b: 0.79, 95% CI: 0.43, 1.15), and cigarillos (b: 0.17, 95% CI: 0.01, 0.34). Adult initiation was associated with pack quantity for filtered cigars (b: -2.22, 95% CI: -4.29, -0.13), as those who initiated purchased smaller pack quantities compared to those who did not initiate that wave. Pack quantity was not associated with discontinuation for adults or youth.

Conclusions

Cigar use increased as usual pack quantity purchased increased across cigar types for youth and adults. Small increases in pack quantity (e.g., one additional cigar) are likely to result in consuming less than one additional day per month, though larger increases (e.g., 10 additional cigars per pack) may result in greater use.
Factors associated with physical function in patients after surgery for soft tissue sarcoma in the thigh
Authors: Fukushima Takuya , Okita Yusuke , Watanabe Noriko , Yokota Shota , Nakano Jiro , Kawai Akira
Published: August 2023

Purpose

This study aimed to examine the validity of the timed up and go test (TUGT), which is a representative, objective, and functional assessment that can evaluate walking speed, strength, and balance, and determine the significant factors associated with physical dysfunction in the early postoperative period in patients with soft tissue sarcomas (STSs).

Methods

This retrospective, single-center, observational study conducted at the National Cancer Center Hospital included 54 patients with STSs in the thigh who underwent surgery. The Musculoskeletal Tumor Society (MSTS) score, which subjectively evaluates the affected limb, was evaluated at discharge, and TUGT was performed preoperatively and at discharge. Higher scores indicated good limb function in the MSTS score and poor performance in the TUGT. Spearman’s correlation analysis was performed to identify the relationship between the MSTS score and TUGT. A receiver operating characteristic curve was used to calculate the cut-off value of the change in pre- and postoperative TUGT for an MSTS score of ≥ 80%. To examine the significant factors associated with physical dysfunction, multivariate regression analysis was performed using the change in pre- and postoperative TUGT as the dependent variable.

Results

Postoperative TUGT and the change in pre- and postoperative TUGT were significantly associated with the MSTS score. The cut-off value for the change in pre- and postoperative TUGT for acceptable affected lower-limb function was 3.7 s. Furthermore, quadriceps muscle resection was significantly associated with the change in pre- and postoperative TUGT in the early postoperative period.

Conclusions

TUGT could be a useful objective evaluation tool for postoperative patients with STSs. The cut-off value for the change in TUGT can be used to monitor postoperative recovery. If recovery is prolonged, a rehabilitation program can be designed according to the severity of the functional impairment in muscle strength, balance, or gait. In addition, sufficient information should be obtained regarding the presence or absence of quadriceps resection, which has a significant impact on postoperative performance.
“This is really something: same place, same day result, same day treatment” women’s experiences of testing positive for HPV and receiving same-day treatment in Papua New Guinea: an interpretative phenomenological analysis
Authors: Camara Hawa , Nosi Somu , Munnull Gloria , Badman Steven G , Bolgna John , Kuk Joseph , Mola Glen DL , Guy Rebecca , Vallely Andrew J. , Kelly-Hanku Angela
Published: August 2023

Introduction

Human papillomavirus (HPV) testing is transforming cervical screening globally. The World Health Organization (WHO) now recommends same-day HPV screen-and-treat for primary cervical screening in low- and middle-income countries (LMIC) but there is a lack of evidence on women’s lived experience of testing positive for oncogenic HPV and receiving same-day treatment. This study aimed to address this knowledge gap among women participating in a same-day HPV screen-and-treat (HPV S&T) program in Papua New Guinea.

Methods

As part of a larger qualitative study, this paper explores the lived experiences of 26 women who tested positive for oncogenic HPV and were treated the same day. We analysed the data using the interpretative phenomenological analysis method. All data were managed using Nvivo 12.5.

Results

The interpretative phenomenological analysis led to three superordinate themes: 1) facing and alleviating initial worries, (2) transforming the disclosure process, and (3) connecting to their faith. Women’s experiences of the same day HPV screen-and-treat were framed by initial emotional reactions to their positive HPV test result, and having access to treatment on the same day, which helped address their worries and fears, and transformed their experience of disclosing their test result and subsequent treatment to family and friends.

Conclusion

This study shows that, while women experience similar initial emotional reactions, undergoing same day treatment quickly resolved the women’s worries, making this program highly acceptable. Overall, women’s engagement in the program confirmed its high acceptability and cultural congruence, leaving women feeling empowered and hopeful about their future, and the future of all Papua New Guinea women.
Association between depressive symptoms of mothers and eating behaviors of school-going children in Urban Bangladesh: A cross-sectional study
Authors: Sultana Sharmin , Muhammad Faisal , Chowdhury ABM Alauddin , Tasnim Tasmia , Haque Md. Imdadul , Hasan BakiBillah Abul , Hossain Md. Kamrul , Zaman Sanjana , Delwer Hossain Hawlader Mohammad , Chowdhury Moniruddin
Published: August 2023

Objective

This study aimed to investigate the association between depressive symptoms among mothers and the eating behaviors of their school-going children in Urban Bangladesh.

Materials and methods

This analytical cross-sectional study was conducted in the context of the urban area of Bangladesh. A multistage sampling technique was applied to select 324 children’s mothers in Dhaka City. Data were collected from both city corporation settings in Dhaka, Bangladesh. Semi-structured questionnaires were used in this study. We estimated the depressive symptoms among mothers using the Zung Self-Rating Depression Scale. We examined the association of mothers of school-going children’s socio-demographic variables and eating behaviors of school-going children with their mother’s depression by using chi-square and evaluating the impact of these variables on mothers’ depression through univariate and multivariate binary logistic regression.

Results

In our study, 57.7% of the mothers of school-going children had depressive symptoms, and 42.3% had no depressive symptoms. The study explored that consuming fewer vegetables (AOR = 0.237, 95% CI: 0.099–0.569), taking fewer fruits (AOR = 0.177, 95% CI: 0.093–0.337), and interestingly, taking fast food less than 4 days per week (AOR = 3.024, 95% CI: 1.517–6.031) were significantly associated with mothers’ depressive symptoms.

Conclusion

Mothers with depressive symptoms of school-going children in Dhaka city are alarmingly high as a grave concern. The eating behaviors of children are associated with their mothers’ depressive symptoms. With an aim to build rigorous awareness on depression and child’s healthy eating behaviors, it is imperative to arrange health education and awareness related programs.
Panax quinquefolius saponins combined with dual antiplatelet therapy enhanced platelet inhibition with alleviated gastric injury via regulating eicosanoids metabolism
Authors: Wang Wenting , Song Lei , Yang Lin , Li Changkun , Ma Yan , Xue Mei , Shi Dazhuo
Published: August 2023

Background

Panax quinquefolius saponin (PQS) was shown beneficial against platelet adhesion and for gastroprotection. This study aimed to investigate the integrated efficacy of PQS with dual antiplatelet therapy (DAPT) on platelet aggregation, myocardial infarction (MI) expansion and gastric injury in a rat model of acute MI (AMI) and to explore the mechanism regarding arachidonic acid (AA)-derived eicosanoids metabolism.

Methods

Wistar rats were subjected to left coronary artery occlusion to induce AMI model followed by treatment with DAPT, PQS or the combined therapy. Platelet aggregation was measured by light transmission aggregometry. Infarct size, myocardial histopathology was evaluated by TTC and H&E staining, respectively. Gastric mucosal injury was examined by scanning electron microscope (SEM). A comprehensive eicosanoids profile in plasma and gastric mucosa was characterized by liquid chromatography-mass spectrometer-based lipidomic analysis.

Results

PQS+DAPT further decreased platelet aggregation, lessened infarction and attenuated cardiac injury compared with DAPT. Plasma lipidomic analysis revealed significantly increased synthesis of epoxyeicosatrienoic acid (EET) and prostaglandin (PG) I2 (potent inhibitors for platelet adhesion and aggregation) while markedly decreased thromboxane (TX) A2 (an agonist for platelet activation and thrombosis) by PQS+DAPT, relative to DAPT. DAPT induced overt gastric mucosal damage, which was attenuated by PQS co-administration. Mucosal gastroprotective PGs (PGE2, PGD2 and PGI2) were consistently increased after supplementation of PQS+DAPT.

Conclusions

Collectively, PQS+DAPT showed synergistic effect in platelet inhibition with ameliorated MI expansion partially through upregulation of AA/EET and AA/PGI2 synthesis while suppression of AA/TXA2 metabolism. PQS attenuated DAPT-induced gastric injury, which was mechanistically linked to increased mucosal PG production.
An ex vivo model for education and training of bilateral cleft lip surgery
Authors: Lutz Rainer , Kesting Marco Rainer , Weber Manuel , Olmos Manuel , Tasyürek Deniz , Möst Tobias , Bürstner Jan , Schulz Katja Leonie
Published: August 2023

Background

Bilateral cleft lip surgery is very challenging and requires a high level of skill, knowledge and experience. Existing high-fidelity simulation models that can be used by novice cleft surgeons to gain experience and expand their knowledge are rare and expensive. In this study, we developed a bilateral cleft lip model using porcine snout discs, which are available anywhere and inexpensive.

Methods

Anatomic reference points of a patient with a bilateral cleft lip were superimposed with landmarks of the porcine snout disc on a foil template. The template was used to construct an ex vivo bilateral cleft lip model. Surgery was performed on the model according to Millard and the surgical steps were photodocumented analogous to two clinical cases of bilateral cleft lip surgery. The suitability of the model was further tested by twelve participants and evaluated using self-assessment questionnaires.

Results

The bilateral cleft lip ex vivo model made of a porcine snout disc proved to be a suitable model with very low cost and ease of fabrication, as the template is reusable on any snout disc. The Millard procedure was successfully performed and the surgical steps of the lip plasty were simulated close to the clinical situation. Regarding the nasal reconstruction, the model lacks three-dimensionality. As a training model, it enhanced the participants comprehension of cleft surgery as well as their surgical skills. All participants rated the model as valuable for teaching and training.

Conclusions

The porcine snout discs can be used as a useful ex vivo model for bilateral cleft lip surgery with limitations in the construction of the nose, which cannot be realistically performed with the model due to anatomical differences with humans. Benefits include a realistic tissue feel, the simulation of a multi-layered lip construction, a wide and rapid availability and low cost. This allows the model to be used by novice surgeons also in low-income countries. It is therefore useful as a training model for gaining experience, but also as a model for refining, testing and evaluating surgical techniques for bilateral lip plasty.
Simulation video: a tool to evaluate communications skills in radiologist residents
Authors: Ding Ning , Hu Ge , Wang Xuan , Sun Hao , Song Lan , Chen Yu , Zhang Daming , Xue Huadan , Jin Zhengyu
Published: August 2023

Background

Effective communication is a crucial component of radiology resident training, and many different aspects need to be explored when teaching and evaluating communication skills. To ensure that radiology residents’ communication skill levels can be measured accurately, a standardized evaluation tool has been introduced. In twenty hospitals in Beijing, simulation videos have been developed as a way to assess the communication skills of radiology residents during their certification exams, to minimize evaluating biases. This study aims to assess the performance of a simulation video model in evaluating communications skills compared to the standard patient model.

Methods

This is a retrospective observational study. The performance of standard patient and simulation video models was evaluated through an eight-year examination of communication skills in radiology residents. From 2014 to 2021, communications skill tests were administered to 1003 radiology residents in 20 hospitals in Beijing. The standardized patient (SP) model was applied in 2014, and simulation videos were used from 2015 to 2021. The difficulty and discrimination radio of the tests were evaluated. The subjective survey for candidates on two models of communication skills evaluation was performed and analyzed.

Results

The simulation video model evaluation demonstrated stable difficulty (ranging from 0.92 to 0.98) and discrimination ratio (ranging from 0.37 to 0.49), except for minor exceptions of discrimination in 2019 (0.58) and 2020 (0.20). Furthermore, the Kruskal-Wallis H test revealed no significant differences in average scores between 2016 (93.9 ± 4.6) and 2018 (94.5 ± 4.2), 2016 and 2019 (97.3 ± 3.9), 2017 (97.0 ± 5.6) and 2019, 2017 and 2020 (97.7 ± 4.7), as well as 2019 and 2020 exams (all p ≥ 0.05). In addition, candidates who responded to the survey preferred the simulation video model (with a 77.2% response rate), with 62.7% choosing it over the SP model for communication skills evaluation.

Conclusion

The simulation video demonstrated a stable and better acceptable construct for assessing radiology residents’ communication skills.
Exploring unfinished nursing care among nursing students: a discussion paper
Authors: Palese Alvisa , Chiappinotto Stefania , Bayram Aysun , Sermeus Walter , Suhonen Riitta , Papastavrou Evridiki
Published: August 2023

Background

In line with the impetus traceable among the nursing staff, studies regarding the perception of Unfinished Care among students have increased in recent years as also recommended by some policy documents in the consideration that, as future members of the staff, they are expected to raise concerns about failures in the standards of care. However, no discussion of their methodological requirements has been provided to date. The aim of this study is to debate Unfinished Care explorations among nursing students and developing recommendations.

Methods

A Rapid Review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, followed by a scientific discussion based on empirical evidence that emerged from the review combined with expert knowledge. Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases were searched up to May 2022.

Results

In the last five years, seven studies have been conducted by researchers affiliated at the university level, involving from 18 to 737 undergraduate students across Europe. By critically analysing their key aspects, there are derived some recommendations in conducting investigations in this field as, (a) the hidden meaning of Unfinished Care investigations among students by also deciding which concept is mostly appropriate to investigate; (b) the need of establishing alliances with the clinical settings in order to involve them in such explorations; (c) more complex research methods capable of exploring this issue among students by promoting learning outcomes and not only a simple data collection; and (e) the influences of these explorations on students’ wellbeing, as well as on ethical implications and that regarding the relationship between the healthcare services and the universities.

Conclusion

Policymakers consider students to be key informants of the quality of nursing care issues witnessed during their clinical placements. The related emerging line of research is intriguing because of the underlying methodological, ethical and system complexities that need to be addressed according to some considerations.
Roles and therapeutic potential of different extracellular vesicle subtypes on traumatic brain injury
Authors: Dong Xinlong , Dong Jing-fei , Zhang Jianning
Published: August 2023

Traumatic brain injury (TBI) is a leading cause of injury-related disability and death around the world, but the clinical stratification, diagnosis, and treatment of complex TBI are limited. Due to their unique properties, extracellular vesicles (EVs) are emerging candidates for being biomarkers of traumatic brain injury as well as serving as potential therapeutic targets. However, the effects of different extracellular vesicle subtypes on the pathophysiology of traumatic brain injury are very different, or potentially even opposite. Before extracellular vesicles can be used as targets for TBI therapy, it is necessary to classify different extracellular vesicle subtypes according to their functions to clarify different strategies for EV-based TBI therapy. The purpose of this review is to discuss contradictory effects of different EV subtypes on TBI, and to propose treatment ideas based on different EV subtypes to maximize their benefits for the recovery of TBI patients.
NEK8 regulates colorectal cancer progression via phosphorylating MYC
Authors: Cao Beibei , Zhang Kailun , Pan Changjie , Dong Yifei , Lu Feng
Published: August 2023

Radiotherapy and chemotherapy remain the mainstay of treatment for colorectal cancer (CRC), although their efficacy is limited. A detailed understanding of the molecular mechanisms underlying CRC progression could lead to the development of new therapeutic strategies. Although it has been established that MYC signaling is dysregulated in various human cancers, direct targeting MYC remains challenging due to its "undruggable" protein structure. Post-translational modification of proteins can affect their stability, activation, and subcellular localization. Hence, targeting the post-translational modification of MYC represents a promising approach to disrupting MYC signaling. Herein, we revealed that NEK8 positively regulates CRC progression by phosphorylating c-MYC protein at serine 405, which exhibited enhanced stability via polyubiquitination. Our findings shed light on the role of NEK8/MYC signaling in CRC progression, offering a novel and helpful target for colorectal cancer treatment.
Short-chain fatty acids in diseases
Authors: Zhang Dan , Jian Yong-Ping , Zhang Yu-Ning , Li Yao , Gu Li-Ting , Sun Hui-Hui , Liu Ming-Di , Zhou Hong-Lan , Wang Yi-Shu , Xu Zhi-Xiang
Published: August 2023

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases.
A new perspective on mesenchymal stem cell-based therapy for liver diseases: restoring mitochondrial function
Authors: Cen Yelei , Lou Guohua , Qi Jinjin , Zheng Min , Liu Yanning
Published: August 2023

Mesenchymal stem cells (MSCs) have emerged as a promising alternative treatment for liver disease due to their roles in regeneration, fibrosis inhibition, and immunoregulation. Mitochondria are crucial in maintaining hepatocyte integrity and function. Mitochondrial dysfunction, such as impaired synthesis of adenosine triphosphate (ATP), decreased activity of respiratory chain complexes, and altered mitochondrial dynamics, is observed in most liver diseases. Accumulating evidence has substantiated that the therapeutic potential of MSCs is mediated not only through their cell replacement and paracrine effects but also through their regulation of mitochondrial dysfunction in liver disease. Here, we comprehensively review the involvement of mitochondrial dysfunction in the development of liver disease and how MSCs can target mitochondrial dysfunction. We also discuss recent advances in a novel method that modifies MSCs to enhance their functions in liver disease. A full understanding of MSC restoration of mitochondrial function and the underlying mechanisms will provide innovative strategies for clinical applications.
Use of a toolbox of tailored evidence-based interventions to improve children’s physical activity and cardiorespiratory fitness in primary schools: results of the ACTIPROS cluster-randomized feasibility trial
Authors: Brandes Berit , Sell Louisa , Buck Christoph , Busse Heide , Zeeb Hajo , Brandes Mirko
Published: August 2023

Background

School-based physical activity (PA) promotion is usually conducted by providing one specific intervention. In contrast, the ACTIvity PROmotion via Schools (ACTIPROS) toolbox provides a set of twelve evidence-based PA interventions serving different domains of the Health Promoting Schools framework that primary schools can select according to their requirements. In this study, we tested the feasibility of the toolbox approach in primary schools.

Methods

A two-arm cluster-randomized feasibility trial at primary schools (n = 5 intervention schools [IS], n = 5 control schools) located in the Federal State of Bremen, Germany, was conducted. Children’s habitual PA (GENEActiv, Activinsights Ltd.) and motor skills (Deutscher Motorik Test; DMT) were measured at the beginning (t0: Sept and Oct 2021) and at the end of the school year (t1: June and July 2022). Between Oct 2021 and July 2022, the ACTIPROS toolbox was implemented at IS. Teachers documented intervention choices and implementation within a short questionnaire (SIQ) at t1.

Results

IS successfully implemented at least one intervention of the toolbox. In total, seven out of twelve possible interventions were selected. Two schools decided to replace an intervention with another during the trial. Results of the SIQ indicated that IS tended to choose similar interventions while implementation frequency was highly different. N = 429 students from two classes per school were recruited. The mean consent rate was 75.1% (n = 322). At t0 and t1, n = 304 (94.4%) and n = 256 (79.3%) of consented children took part in the DMT, respectively. The accelerometry sample included one class per participating school. At t0 and t1, n = 166 and n = 151 devices were handed out to students and n = 133 (80.1%) and n = 106 (70.2%) valid records could be retrieved, respectively. Linear mixed models showed an intervention effect of 15.5 min (95% CI: 4.5; 26.6) in children’s daily MVPA at IS between t0 and t1 compared to controls.

Conclusions

All IS were able to implement at least one intervention from the toolbox, and unsuitable interventions were successfully replaced in a timely manner, highlighting the feasibility of implementing the ACTIPROS toolbox. Good consent rates for accelerometer and motor skills data were achieved. Results indicate a substantial increase in MVPA associated with the ACTIPROS toolbox and need to be tested in a larger sample.

Trial registration

German Clinical Trials Register DRKS00025840.
Inhibition of serum- and glucocorticoid-induced kinase 1 ameliorates hydrocephalus in preclinical models
Authors: Hochstetler Alexandra , Smith Hillary , Reed Makenna , Hulme Louise , Territo Paul , Bedwell Amanda , Persohn Scott , Perrotti Nicola , D’Antona Lucia , Musumeci Francesca , Schenone Silvia , Blazer-Yost Bonnie L.
Published: August 2023

Background

Hydrocephalus is a pathological accumulation of cerebrospinal fluid (CSF), leading to ventriculomegaly. Hydrocephalus may be primary or secondary to traumatic brain injury, infection, or intracranial hemorrhage. Regardless of cause, current treatment involves surgery to drain the excess CSF. Importantly, there are no long-term, effective pharmaceutical treatments and this represents a clinically unmet need. Many forms of hydrocephalus involve dysregulation in water and electrolyte homeostasis, making this an attractive, druggable target.

Methods

In vitro, a combination of electrophysiological and fluid flux assays was used to elucidate secretory transepithelial electrolyte and fluid flux in a human cell culture model of the choroid plexus epithelium and to determine the involvement of serum-, glucocorticoid-induced kinase 1 (SGK1). In vivo, MRI studies were performed in a genetic rat model of hydrocephalus to determine effects of inhibition of SGK1 with a novel inhibitor, SI113.

Results

In the cultured cell line, SI113 reduced secretory transepithelial electrolyte and fluid flux. In vivo, SI113 blocks the development of hydrocephalus with no effect on ventricular size of wild-type animals and no overt toxic effects. Mechanistically, the development of hydrocephalus in the rat model involves an increase in activated, phosphorylated SGK1 with no change in the total amount of SGK1. SI113 inhibits phosphorylation with no changes in total SGK1 levels in the choroid plexus epithelium.

Conclusion

These data provide a strong preclinical basis for the use of SGK1 inhibitors in the treatment of hydrocephalus.
Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy
Authors: Jan I-Shiow , Ch’ang Hui Ju
Published: August 2023

Despite combination chemotherapy demonstrating a positive effect on survival, the clinical outcomes of pancreatic adenocarcinoma (PDAC) remain poor. Radiotherapy was previously a component of the curative treatment of PDAC. Advances in imaging and computer sciences have enabled the prescription of higher dosage of radiation focused on tumours with minimal toxicity to normal tissue. However, the role of radiotherapy has not been established in the curative treatment of localized PDAC because of the conflicting results from large prospective trials. Most studies have demonstrated improved locoregional control but no survival benefit from additional chemoradiotherapy (CRT) in addition to chemotherapy for resectable, borderline or locally advanced PDAC. The improved locoregional control enabled by CRT does not cause extended survival because of rapid distant progression in a significant proportion of patients with PDAC. Several single-institute studies of prescribing intensive chemotherapy with modern ablative radiotherapy for locally advanced PDAC have demonstrated extended survival with an acceptable safety profile. In an analysis after long-term follow-up, the PREOPANC study demonstrated a survival benefit from neoadjuvant gemcitabine-based CRT in resected PDAC relative to upfront surgery followed by adjuvant gemcitabine only. These observations indicated that the role of radiotherapy in PDAC should be evaluated in a subgroup of patients without rapid distant progression because systemic therapy for PDAC remains underdeveloped. We reviewed critical imaging, tissue, liquid and clinical biomarkers to differentiate the heterogeneous biologic spectra of patients with PDAC to identify those who may benefit the most from local radiotherapy. Exclusion of patients with localised PDAC who develop distant progression in a short time and undergo extended upfront chemotherapy for over 4 months may enable the identification of a survival benefit of local radiotherapy. Though promising, the effectiveness of biomarkers must be validated in a multi-institutional prospective study of patients with PDAC receiving CRT or not receiving CRT.
Locally advanced thymoma; does neoadjuvant chemotherapy make a difference?
Authors: Abdel Jalil Riad , Abdallah Farah A. , Obeid Zeinab , Harb Ahmad Khaled , Abou Chaar Mohamad K. , Shannies Tariq Bassem , El-Edwan Ahed , Haddad Hussam , Ghraibeh Azza , Abu-Shanab Ahmad
Published: August 2023

Background

Regardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety.

Methods

Demographic and clinical data from patients who presented to a tertiary cancer center between January 2015–October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue.

Results

A total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm3 (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4–125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy.

Conclusions

The exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.
Performance of urinary C–C motif chemokine ligand 14 for the prediction of persistent acute kidney injury: a systematic review and meta-analysis
Authors: Chen Yih‑Ting , Pan Heng-Chih , Hsu Cheng-Kai , Sun Chiao-Yin , Chen Chun-Yu , Chen Yi-Hung , Hsu Heng-Jung , Wu I-Wen , Wu Vin-Cent , Hoste Eric
Published: August 2023

Background

Urinary C–C motif chemokine ligand 14 (CCL14) has been described as an effective marker for delayed recovery of acute kidney injury (AKI), yet its efficacy has been found to vary between different trials. The goal of this research was to assess the predictive performance of urinary CCL14 as a marker for persistent AKI.

Methods

In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to April 2023 for studies of adults (> 18 years) that reported the diagnostic performance of urinary CCL14. The sensitivity, specificity, number of events, true positive, and false positive results were extracted and evaluated. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence.

Results

We included six studies with 952 patients in this meta-analysis. The occurrence of persistent AKI among these patients was 39.6% (377/952). The pooled sensitivity and specificity results of urinary CCL14 in predicting persistent AKI were 0.81 (95% CI 0.72–0.87) and 0.71 (95% CI 0.53–0.84), respectively. The pooled positive likelihood ratio (LR) was 2.75 (95% CI 1.63–4.66), and the negative LR was 0.27 (95% CI 0.18–0.41). The HSROC with pooled diagnostic accuracy was 0.84.

Conclusion

Our results suggest that urinary CCL14 can be used as an effective marker for predicting persistent AKI.
A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial
Authors: Wu Xin , Yu Hailin , Bai Yongrui , Hou Yanli , Lou Weihua , Wang Xipeng , Zhu Tao , Zhang Yuyang , Hu Weiguo , Xue Xiaohong , Zhu Zhiling , Xiang Libing , Li Jiarui , Fang Xuhong , Gao Shujun , Feng Hua , Diao Wenjing , Zhang Hongwei , Du Ming , Yan Weili , Qiu Ling , Feng Hao , Zhu Shurong , Du Yan , Jiang Hua
Published: August 2023

Background

Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial.

Methods/design

This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements.

Discussion

The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method.

Trial registration

ClinicalTrials.gov, NCT04939831, retrospectively registered on 25 June 2021.
Iguratimod attenuated fibrosis in systemic sclerosis via targeting early growth response 1 expression
Authors: Shen Lichong , Yin Hanlin , Sun Li , Zhang Zhiliang , Jin Yuyang , Cao Shan , Fu Qiong , Fan Chaofan , Bao Chunde , Lu Liangjing , Zhan Yifan , Xu Xiaojiang , Chen Xiaoxiang , Yan Qingran
Published: August 2023

Background

The early growth response 1 (EGR1) is a central transcription factor involved in systemic sclerosis (SSc) pathogenesis. Iguratimod is a synthesized anti-rheumatic disease-modifying drug, which shows drastic inhibition to EGR1 expression in B cells. This study is aiming to investigate the anti-fibrotic effect of iguratimod in SSc.

Methods

EGR1 was detected by immunofluorescence staining real-time PCR or western blot. Iguratimod was applied in EGR1 overexpressed or knockdown human dermal fibroblast, bleomycin pre-treated mice, tight skin 1 mice, and SSc skin xenografts. RNA sequencing was performed in cultured fibroblast and xenografts to identify the iguratimod regulated genes.

Results

EGR1 overexpressed predominantly in non-immune cells of SSc patients. Iguratimod reduced EGR1 expression in fibroblasts and neutralized changes of EGR1 response genes regulated by TGFβ. The extracellular matrix (ECM) production and activation of fibroblasts were attenuated by iguratimod while EGR1 overexpression reversed this effect of iguratimod. Iguratimod ameliorated the skin fibrosis induced by bleomycin and hypodermal fibrosis in TSK-1 mice. Decreasing in the collagen content as well as the density of EGR1 or TGFβ positive fibroblasts of skin xenografts from naïve SSc patients was observed after local treatment of iguratimod.

Conclusion

Targeting EGR1 expression is a probable underlying mechanism for the anti-fibrotic effect of iguratimod.
Transposable elements as essential elements in the control of gene expression
Authors: Gebrie Alemu
Published: August 2023

Interspersed repetitions called transposable elements (TEs), commonly referred to as mobile elements, make up a significant portion of the genomes of higher animals. TEs contribute in controlling the expression of genes locally and even far away at the transcriptional and post-transcriptional levels, which is one of their significant functional effects on gene function and genome evolution. There are different mechanisms through which TEs control the expression of genes. First, TEs offer cis-regulatory regions in the genome with their inherent regulatory features for their own expression, making them potential factors for controlling the expression of the host genes. Promoter and enhancer elements contain cis-regulatory sites generated from TE, which function as binding sites for a variety of trans-acting factors. Second, a significant portion of miRNAs and long non-coding RNAs (lncRNAs) have been shown to have TEs that encode for regulatory RNAs, revealing the TE origin of these RNAs. Furthermore, it was shown that TE sequences are essential for these RNAs' regulatory actions, which include binding to the target mRNA. By being a member of cis-regulatory and regulatory RNA sequences, TEs therefore play essential regulatory roles. Additionally, it has been suggested that TE-derived regulatory RNAs and cis-regulatory regions both contribute to the evolutionary novelty of gene regulation. Additionally, these regulatory systems arising from TE frequently have tissue-specific functions. The objective of this review is to discuss TE-mediated gene regulation, with a particular emphasis on the processes, contributions of various TE types, differential roles of various tissue types, based mostly on recent studies on humans.
Students’ COVID-19 vaccine behaviors, intentions, and beliefs at a US Native American-Serving Nontribal Institution (NASNTI)
Authors: Dutta Tapati , Agley Jon , Xiao Yunyu , Golzarri-Arroyo Lilian , Ali Sumayyah
Published: August 2023

Objective

Multiple national and international studies of college student COVID-19 vaccination have been recently published, providing important descriptive information and a conceptual basis to inform future decisions about infectious disease prevention in higher education settings. Yet almost no research has examined Native American-Serving Nontribal Institutions (NASNTIs), which occupy a unique space in US higher education in terms of structure and students served. To address that gap, this report describes results from a two-wave cross-sectional survey administered at a NASNTI in Durango, Colorado, as part of a larger study of COVID-19 campus response. Surveys were administered prior to (wave one) and following (wave two) statewide availability of the COVID-19 vaccine for ages 16+. Comparisons between waves used Cramer’s V and Mann-Whitney U tests.

Results

A total of 283 students responded to wave one, and 186 responded to wave two. Notable results included a self-reported COVID-19 vaccination rate (40.1%) at wave one that far exceeded parallel national rates. Injunctive and disjunctive normative beliefs were also less supportive of vaccination among the unvaccinated at wave two compared to wave one. Findings from this study should be considered in the context of all available evidence and not used to make inferences in isolation.
Feasibility and therapeutical potential of local intracerebral encapsulated cell biodelivery of BDNF to AppNL−G−F knock-in Alzheimer mice
Authors: Tambaro Simone , Mitra Sumonto , Gera Ruchi , Linderoth Bengt , Wahlberg Lars U. , Darreh-Shori Taher , Behbahani Homira , Nilsson Per , Eriksdotter Maria
Published: August 2023

Background

Alzheimer’s disease (AD) is an age-related disease characterized by altered cognition, neuroinflammation, and neurodegeneration against which there is presently no effective cure. Brain-derived neurotrophic factor (BDNF) is a key neurotrophin involved in the learning and memory process, with a crucial role in synaptic plasticity and neuronal survival. Several findings support that a reduced BDNF expression in the human brain is associated with AD pathogenesis. BDNF has been proposed as a potential therapy for AD, but BDNF has low brain penetration. In this study, we used an innovative encapsulated cell biodelivery (ECB) device, containing genetically modified cells capable of releasing BDNF and characterized its feasibility and therapeutic effects in the novel App knock-in AD mouse model (AppNL−G−F).

Methods

ECB’s containing human ARPE-19 cells genetically modified to release BDNF (ECB-BDNF devices) were stereotactically implanted bilaterally into hippocampus of 3-month-old AppNL−G−F mice. The stability of BDNF release and its effect on AD pathology were evaluated after 1, 2-, and 4-months post-implantation by immunohistochemical and biochemical analyses. Exploratory and memory performance using elevated plus maze (EPM) and Y-maze test were performed in the 4-months treatment group. Immunological reaction towards ECB-BDNF devices were studied under ex vivo and in vivo settings.

Results

The surgery and the ECB-BDNF implants were well tolerated without any signs of unwanted side effects or weight loss. ECB-BDNF devices did not induce host-mediated immune response under ex vivo set-up but showed reduced immune cell attachment when explanted 4-months post-implantation. Elevated BDNF staining around ECB-BDNF device proximity was detected after 1, 2, and 4 months treatment, but the retrieved devices showed variable BDNF release. A reduction of amyloid-β (Aβ) plaque deposition was observed around ECB-BDNF device proximity after 2-months of BDNF delivery.

Conclusions

The result of this study supports the use of ECB device as a promising drug-delivery approach to locally administer BBB-impermeable factors for treating neurodegenerative conditions like AD. Optimization of the mouse-sized devices to reduce variability of BDNF release is needed to employ the ECB platform in future pre-clinical research and therapy development studies.