bluuebunny/crossref_metadata_2025 huggingface dataset:
User testing to modify the MyHealthyGut digital health application for inflammatory bowel disease
Authors: Erlich Madeline , Lindblad Sarah , Haskey Natasha , Clarkin Darlene Higbee , Dong Taojie , Harvie Ruth , Lunken Genelle , Pirnack Jess , Jacobson Kevan
Published: September 2023

Introduction

Inflammatory bowel disease, characterized by chronic intestinal inflammation, can be subcategorized into Crohn's disease and ulcerative colitis. The treatment for these conditions is unique to each patient and may include lifestyle changes, pharmaceutical intervention, and surgery. Lifestyle changes, such as dietary intervention, are a cornerstone of inflammatory bowel disease symptom management. Given the daily burden of this disease, self-management is paramount in coping with and/or minimizing symptoms. The MyHealthyGut application, successfully proven to be a self-management tool for celiac disease, shows promise for use in an inflammatory bowel disease patient population.

Objective

To conduct user testing to gather valuable insights for the development of an IBD-focused version of the existing MyHealthyGut app.

Methods

Participants included inflammatory bowel disease patients and healthcare practitioners. Participants used the application for a 2-week period, followed by participation in a focus group or individual interview to provide feedback. Qualitative questionnaires were administered verbally and feedback was recorded. Thematic analysis techniques were used for data quantification and analysis.

Results

15 participants were recruited and enrolled. Of these, 14 participants took part in the focus group and/or individual interviews. The feedback suggested changes related to clinical uses, food and symptom tracking, ease of use, and educational content. All (100%) participants reported that they would either use the application themselves or recommend it to patients, once their suggestions were implemented.

Conclusion

Through user testing and feedback collection, priorities for app modification were identified. Areas for modification in the app functions and features, ease of use, and content were identified. Once updated to meet the needs of inflammatory bowel disease patients, the MyHealthyGut app may be a useful tool for IBD self-management.
Computational Communication Methods for Examining Problematic News-Sharing Practices on Facebook at Scale
Authors: Angus Daniel , Bruns Axel , Hurcombe Edward , Harrington Stephen , (Jane) Tan Xue Ying
Published: September 2023

Social media, in general, and Facebook in particular, have been clearly identified as important platforms for the dissemination of mis- and disinformation and related problematic content. However, the patterns and processes of such dissemination are still not sufficiently understood. We detail a novel computational methodology that focusses on the identification of high-profile vectors of “fake news” and other problematic information in public Facebook spaces. The method enables examination of networks of content sharing that emerge between public pages and groups, and external sources, and the study of longitudinal dynamics of these networks as interests and allegiances shift and new developments (such as the COVID-19 pandemic or the US presidential elections) drive the emergence or decline of dominant themes. Through a case study of content captured between 2016 and 2021, we demonstrate how this methodology allows the development of a new and more comprehensive picture of the overall impact of “fake news,” in all its forms, on contemporary societies.
Identifying Themes of Right-Wing Extremism in Hindutva Discourse on Twitter
Authors: Ghasiya Piyush , Ahnert Georg , Sasahara Kazutoshi
Published: September 2023

Hindutva, the core political ideology of India’s current ruling party, the Bharatiya Janata Party (BJP), seeks to transform constitutionally secular India into a Hindu Rashtra (“Hindu nation”). Although Hindutva has all of the features of right-wing extremism (RWE), it is nevertheless viewed as an insular sociopolitical phenomenon, due to the Eurocentric nature of RWE discourse. Recent theoretical and analytical research has sought to showcase the similarity between RWE and Hindutva, but empirical research on their relationship has been largely absent. To fill this gap, in our study, we collected 15 million tweets and used network analysis to identify prominent themes of RWE—including exclusionary nationalism, conspiracy theories, and anti-minority violence and hate speech—among the supporters of Hindutva and the BJP. Furthermore, in our toxicity analysis (performed to understand which themes produced higher levels of toxicity), we found that Hindi-language tweets related to conspiracy theories and anti-minority violence or hate speech were more toxic than English-language tweets. Given that the growing global presence and normalization of RWE-based ideas and movements are sources of concern for everyone invested in the idea of liberal democratic society, our research broadens the discussion on RWE to include the Indian context and invites researchers to further investigate Hindutva from the perspective of RWE.
Midterm Outcomes of Operatively and Nonoperatively Managed Achilles Tendon Ruptures in Young Adults
Authors: Ge Laurence , Saunders Noah , Betts Dakota , Holmes James R. , Walton David M. , Talusan Paul G.
Published: September 2023

Background:

There continues to be controversy regarding treatment options for Achilles tendon ruptures (ATR). The aim of our study is to compare outcomes between operatively and nonoperatively managed Achilles ruptures in young adults (age 18-30 years), which has not been previously evaluated.

Methods:

At a single institution, all patients aged 18-30 years at time of injury who underwent treatment for an acute ATR from 2014 to 2021 were evaluated. Medical records were reviewed to collect demographics, dates of injury and treatment, smoking status, body mass index (BMI), Charlson Comorbidity Index (CCI), rate of deep venous thrombosis (DVT) after treatment, and rate of rerupture. Patients then completed Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) questionnaires. Mann-Whitney nonparametric testing was used to evaluate for any statistical differences in PROMIS scores.

Results:

Sixty-six operative patients qualified and 28 (42%) participated. Thirty-seven nonoperative patients qualified and 14 (38%) participated. All patients had a CCI of 0. One patient in the operative cohort and 2 in the nonoperative reported active smoking. In the operative and nonoperative cohorts, respectively, the average age was 24.4 and 27.8 years; average BMI 26.5 (SD = 4.8) and 27.3 (SD = 4.3, P = .52); DVT rates 4 (6.1%) and 2 (5.4%); and rerupture rates 2 (3.0%) and 1 (2.7%), respectively. PROMIS scores did not differ in the operative and nonoperative groups: PROMIS PF mean of 60.4 (SD = 9.8) and 62.9 (SD = 9.1), respectively ( P = .33); as well as PROMIS PI mean of 44.6 (SD = 5.9) and 43.9 (SD = 6.5), respectively ( P = .59).

Conclusion:

This study should be interpreted with the understanding that we had a considerable loss to follow-up rate. In the study cohort, we found that young adults with ATR may be considered for either operative or nonoperative management. Rates of DVT, rates of rerupture, and PROMIS scores were not dissimilar between the 2 cohorts.

Level of Evidence:

Level III, retrospective cohort study.
Vibration-based temporary monitoring of a 253 m tall skew-plan building in Istanbul
Authors: Celik Ozan Cem , Budak Erhan , Sucuoğlu Halûk
Published: September 2023

A 253 m tall office building in Istanbul with a parallelogram footprint, which has 62 stories in total, 54 tower stories above and 8 podium stories below grade, was monitored using 92 channels of accelerometers deployed on 20 different floors for about 4 days. The structural system of the building consists of reinforced concrete (RC) core shear walls with peripheral composite columns and two-story tall RC outriggers between floors 29 and 31. First 12 natural vibration periods and mode shapes of the building together with the modal directions for the translational modes were identified from the ambient vibration records. These dynamic properties were reproduced with the three-dimensional finite element model developed using gross section properties for all structural members without a need for model updating. The fundamental period of the building at the time of testing, 5.3 s, is expected to lengthen to 5.9 s and 7.8 s upon cracking in structural members for the prescribed service-level and design-level evaluations, respectively, in line with the recent performance-based design guidelines for tall buildings. Damping ratios for the first six vibration modes, with median values of 0.6% and coefficients of variation in the order of 0.3–0.4, were identified through statistical analysis using the random decrement technique. The simulated peak floor accelerations, when the building was subjected to the 2019 Mw 5.8 Marmara Sea earthquake ground motions recorded in the vicinity of the building, showed that ASCE 7-16 in-structure floor acceleration amplifications are exceeded at the lower floors but not reached at the upper floors.
Characterization of the mitochondrial Huso huso genome and new aspects of its organization in the presence of tandem repeats in 12S rRNA
Authors: Dadkhah Khadijeh , Mianji Ghodrat Rahimi , Barzegar Ali , Farhadi Ayoub
Published: September 2023

Background

The sturgeon group has been economically significant worldwide due to caviar production. Sturgeons consist of 27 species in the world. Mitogenome data could be used to infer genetic diversity and investigate the evolutionary history of sturgeons. A limited number of complete mitogenomes in this family were sequenced. Here, we annotated the mitochondrial Huso huso genome, which revealed new aspects of this species.

Results

In this species, the mitochondrial genome consisted of 13 genes encoding proteins, 22tRNA and 2rRNA, and two non-coding regions that followed other vertebrates. In addition, H. huso had a pseudo-tRNA-Glu between ND6 and Cytb and a 52-nucleotide tandem repeat with two replications in 12S rRNA. This duplication event is probably related to the slipped strand during replication, which could remain in the strand due to mispairing during replication. Furthermore, an 82 bp repeat sequence with three replications was observed in the D-loop control region, which is usually visible in different species. Regulatory elements were also seen in the control region of the mitochondrial genome, which included termination sequences and conserved regulatory blocks. Genomic compounds showed the highest conservation in rRNA and tRNA, while protein-encoded genes and nonencoded regions had the highest divergence. The mitochondrial genome was phylogenetically assayed using 12 protein-encoding genes.

Conclusions

In H. huso sequencing, we identified a distinct genome organization relative to other species that have never been reported. In recent years, along with the advancement in sequencing identified more genome rearrangements. However, it is an essential aspect of researching the evolution of the mitochondrial genome that needs to be recognized.
De novo assembly and annotation of the singing mouse genome
Authors: Smith Samantha K. , Frazel Paul W. , Khodadadi-Jamayran Alireza , Zappile Paul , Marier Christian , Okhovat Mariam , Brown Stuart , Long Michael A. , Heguy Adriana , Phelps Steven M.
Published: September 2023

Background

Developing genomic resources for a diverse range of species is an important step towards understanding the mechanisms underlying complex traits. Specifically, organisms that exhibit unique and accessible phenotypes-of-interest allow researchers to address questions that may be ill-suited to traditional model organisms. We sequenced the genome and transcriptome of Alston’s singing mouse (Scotinomys teguina), an emerging model for social cognition and vocal communication. In addition to producing advertisement songs used for mate attraction and male-male competition, these rodents are diurnal, live at high-altitudes, and are obligate insectivores, providing opportunities to explore diverse physiological, ecological, and evolutionary questions.

Results

Using PromethION, Illumina, and PacBio sequencing, we produced an annotated genome and transcriptome, which were validated using gene expression and functional enrichment analyses. To assess the usefulness of our assemblies, we performed single nuclei sequencing on cells of the orofacial motor cortex, a brain region implicated in song coordination, identifying 12 cell types.

Conclusions

These resources will provide the opportunity to identify the molecular basis of complex traits in singing mice as well as to contribute data that can be used for large-scale comparative analyses.
Genome-wide landscape of runs of homozygosity and differentiation across Egyptian goat breeds
Authors: Sallam Ahmed M. , Reyer Henry , Wimmers Klaus , Bertolini Francesca , Aboul-Naga Adel , Braz Camila U. , Rabee Alaa Emara
Published: September 2023

Understanding the genomic features of livestock is essential for successful breeding programs and conservation. This information is scarce for local goat breeds in Egypt. In the current study, genomic regions with selection signatures were identified as well as runs of homozygosity (ROH), genomic inbreeding coefficients (FROH) and fixation index (FST) were detected in Egyptian Nubian, Damascus, Barki and Boer goat breeds. A total of 46,268 SNP markers and 337 animals were available for the genomic analyses. On average, 145.44, 42.02, 87.90 and 126.95 ROHs were detected per individual in the autosomal genome of the respective breeds. The mean accumulative ROH lengths ranged from 46.5 Mb in Damascus to 360 Mb in Egyptian Nubian. The short ROH segments (< 2 Mb) were most frequent in all breeds, while the longest ROH segments (> 16 Mb) were exclusively found in the Egyptian Nubian. The highest average FROH was observed in Egyptian Nubian (~ 0.12) followed by Boer (~ 0.11), while the lowest FROH was found in Damascus (~ 0.05) and Barki breed (~ 0.03). The estimated mean FST was 0.14 (Egyptian Nubian and Boer), 0.077 (Egyptian Nubian and Barki), 0.075 (Egyptian Nubian and Damascus), 0.071 (Barki and Boer), 0.064 (Damascus and Boer), and 0.015 (Damascus and Barki), for each pair of breeds. Interestingly, multiple SNPs that accounted for high FST values were observed on chromosome 6 in regions harboring ALPK1 and KCNIP4. Genomic regions overlapping both FST and ROH harbor genes related to immunity (IL4R, PHF23, GABARAP, GPS2, and CD68), reproduction (SPATA2L, TNFSF12, TMEM95, and RNF17), embryonic development (TCF25 and SOX15) and adaptation (MC1R, KDR, and KIT), suggesting potential genetic adaptations to local environmental conditions. Our results contribute to the understanding of the genetic architecture of different goat breeds and may provide valuable information for effective preservation and breeding programs of local goat breeds in Egypt.
Function and autophagy of monocyte-derived dendritic cells is affected by hepatitis B virus infection
Authors: Xu Hua , Kang Juan , Zhong Shan , Chen Min , Hu Peng , Ren Hong , Zhou Zhi , Lei Yu
Published: September 2023

Background

The role of dendritic cells and the autophagy state of dendritic cells in the immune response of hepatitis B virus (HBV) infection was still controversial. In this study, we carefully examined the phenotype, function and autophagy pathway of dendritic cells in HBV infection.

Methods

Monocyte-derived dendritic cells from healthy blood donors and patients with chronic HBV infection were stimulated by lipopolysaccharide, supernatant of HepG2.2.15 cells or supernatant of HepG2 cells respectively. Phenotype of dendritic cells was examined by flow cytometry and cytokines secretion was detected by enzyme-linked immunosorbent assay. Autophagy related proteins were detected by western blot and immunofluorescence analysis.

Results

Our results showed that the expression of both major histocompatibility complex II molecules and co-stimulated molecules including cluster of differentiation antigen 80, cluster of differentiation antigen 86 in the monocyte-derived dendritic cells from patients with chronic HBV infection was significantly higher than that from healthy donors when cultured with supernatant of HepG2.2.15 cells. The amount of cytokines, including tumour necrosis factor-α, interleukin-10 and interleukin-12, secreted by monocyte-derived dendritic cells from patients with chronic HBV infection was also significantly higher than that from healthy donors when stimulate by HBV. Interestingly, the expression level of autophagy-related proteins including autophagy-related protein5 and associated protein 1 light chain in dendritic cells from patients with chronic HBV infection was significantly increased when compared with that from healthy donors when re-exposed to HBV.

Conclusions

Our results indicated that dendritic cells from patients with chronic HBV infection could intensively present antigen and express co-stimulatory molecules. The increased activation of dendritic cells might be related to the enhanced autophagy of dendritic cells in HBV infection.
Genealogical tracing of Olea europaea species and pedigree relationships of var. europaea using chloroplast and nuclear markers
Authors: Mariotti Roberto , Belaj Angjelina , de la Rosa Raúl , Muleo Rosario , Cirilli Marco , Forgione Ivano , Valeri Maria Cristina , Mousavi Soraya
Published: September 2023

Background

Olive is one of the most cultivated species in the Mediterranean Basin and beyond. Despite being extensively studied for its commercial relevance, the origin of cultivated olive and the history of its domestication remain open questions. Here, we present a genealogical and kinship relationships analysis by mean of chloroplast and nuclear markers of different genera, subgenus, species, subspecies, ecotypes, cultivated, ancient and wild types, which constitutes one of the most inclusive research to date on the diversity within Olea europaea species. A complete survey of the variability across the nuclear and plastid genomes of different genotypes was studied through single nucleotide polymorphisms, indels (insertions and deletions), and length variation.

Results

Fifty-six different chlorotypes were identified among the Oleaceae family including Olea europaea, other species and genera. The chloroplast genome evolution, within Olea europaea subspecies, probably started from subsp. cuspidata, which likely represents the ancestor of all the other subspecies and therefore of wild types and cultivars. Our study allows us to hypothesize that, inside the subspecies europaea containing cultivars and the wild types, the ancestral selection from var. sylvestris occurred both in the eastern side of the Mediterranean and in the central-western part of Basin. Moreover, it was elucidated the origin of several cultivars, which depends on the introduction of eastern cultivars, belonging to the lineage E1, followed by crossing and replacement of the autochthonous olive germplasm of central-western Mediterranean Basin. In fact, our study highlighted that two main ‘founders’ gave the origin to more than 60% of analyzed olive cultivars. Other secondary founders, which strongly contributed to give origin to the actual olive cultivar diversity, were already detected.

Conclusions

The application of comparative genomics not only paves the way for a better understanding of the phylogenetic relationships within the Olea europaea species but also provides original insights into other elusive evolutionary processes, such as chloroplast inheritance and parentage inside olive cultivars, opening new scenarios for further research such as the association studies and breeding programs.
Pseudoaneurysm of the mitral-aortic intervalvular fibrosa: a rare case after percutaneous transluminal coronary angioplasty
Authors: Xie Debo , Jiang Lulu , Zhang Jun , Li Xin , Guo Yanli
Published: September 2023

Background

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is an uncommon but potentially life-threatening condition. The most common pathogenic factors of P-MAIVF are infective endocarditis and surgical valve operation. Here, we report a rare case of P-MAIVF which occurred one year after percutaneous transluminal coronary angioplasty (PTCA).

Case presentation

A 31-year-old man developed a P-MAIVF one year after PTCA. Transthoracic echocardiography (TTE) revealed a pseudoaneurysm between the aortic root and the left atrium. Three-dimensional transesophageal echocardiography (3D-TEE) clearly demonstrated the orifice of the pseudoaneurysm. This case was initially diagnosed by ultrasound, and the prognosis was good after surgical repair.

Conclusions

We report a rare case of P-MAIVF that occurred one year after PTCA.
Echocardiography-based machine learning algorithm for distinguishing ischemic cardiomyopathy from dilated cardiomyopathy
Authors: Zhou Mei , Deng Yongjian , Liu Yi , Su Xiaolin , Zeng Xiaocong
Published: September 2023

Background

Machine learning (ML) can identify and integrate connections among data and has the potential to predict events. Heart failure is primarily caused by cardiomyopathy, and different etiologies require different treatments. The present study examined the diagnostic value of a ML algorithm that combines echocardiographic data to automatically differentiate ischemic cardiomyopathy (ICM) from dilated cardiomyopathy (DCM).

Methods

We retrospectively collected the echocardiographic data of 200 DCM patients and 199 ICM patients treated in the First Affiliated Hospital of Guangxi Medical University between July 2016 and March 2022. All patients underwent invasive coronary angiography for diagnosis of ICM or DCM. The data were randomly divided into a training set and a test set via 10-fold cross-validation. Four ML algorithms (random forest, logistic regression, neural network, and XGBoost [ML algorithm under gradient boosting framework]) were used to generate a training model for the optimal subset, and the parameters were optimized. Finally, model performance was independently evaluated on the test set, and external validation was performed on 79 patients from another center.

Results

Compared with the logistic regression model (area under the curve [AUC] = 0.925), neural network model (AUC = 0.893), and random forest model (AUC = 0.900), the XGBoost model had the best identification rate, with an average sensitivity of 72% and average specificity of 78%. The average accuracy was 75%, and the AUC of the optimal subset was 0.934. External validation produced an AUC of 0.804, accuracy of 78%, sensitivity of 64% and specificity of 93%.

Conclusions

We demonstrate that utilizing advanced ML algorithms can help to differentiate ICM from DCM and provide appreciable precision for etiological diagnosis and individualized treatment of heart failure patients.
Public transit stop density is associated with walking for exercise among a national sample of older adults
Authors: Twardzik Erica , Falvey Jason R. , Clarke Philippa J. , Freedman Vicki A. , Schrack Jennifer A.
Published: September 2023

Background

Walking is the primary and preferred mode of exercise for older adults. Walking to and from public transit stops may support older adults in achieving exercise goals. This study examined whether density of neighborhood public transit stops was associated with walking for exercise among older adults.

Methods

2018 National Health and Aging Trends Study (NHATS) data were linked with the 2018 National Neighborhood Data Archive, which reported density of public transit stops (stops/mile2) within participants’ neighborhood, defined using census tract boundaries. Walking for exercise in the last month was self-reported. The extent to which self-reported public transit use mediated the relationship between density of neighborhood public transit stops and walking for exercise was examined. Covariates included sociodemographic characteristics, economic status, disability status, and neighborhood attributes. National estimates were calculated using NHATS analytic survey weights.

Results

Among 4,836 respondents with complete data, 39.7% lived in a census tract with at least one neighborhood public transit stop and 8.5% were public transit users. The odds of walking for exercise were 32% higher (OR = 1.32; 95% confidence interval: 1.08, 1.61) among respondents living in a neighborhood with > 10 transit stops per mile compared to living in a neighborhood without any public transit stops documented. Self-reported public transit use mediated 24% of the association between density of neighborhood public transit stops and walking for exercise.

Conclusions

Density of neighborhood public transit stops was associated with walking for exercise, with a substantial portion of the association mediated by self-reported public transit use. Increasing public transit stop availability within neighborhoods may contribute to active aging among older adults.
Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19
Authors: Van Singer Mathias , Brahier Thomas , Koch Jana , Hugli Pr. Olivier , Weckman Andrea M. , Zhong Kathleen , Kain Taylor J. , Leligdowicz Aleksandra , Bernasconi Enos , Ceschi Alessandro , Parolari Sara , Vuichard-Gysin Danielle , Kain Kevin C. , Albrich Werner C. , Boillat-Blanco Noémie
Published: September 2023

Background

A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation.

Methods

This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement.

Results

373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%.

Conclusion

The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.
Effect of virtual reality combined with repetitive transcranial magnetic stimulation on musculoskeletal pain and motor development in children with spastic cerebral palsy: a protocol for a randomized controlled clinical trial
Authors: Li Xin , Huang Zefan , Lu Tijiang , Liang Juping , Guo Haibin , Wang Lixia , Chen Zhengquan , Zhou Xuan , Du Qing
Published: September 2023

Purpose

This trial aims to investigate the efficacy and safety of virtual reality (VR) combined with repetitive transcranial magnetic stimulation (rTMS) for improving musculoskeletal pain and motor development in children with unilateral spastic cerebral palsy (CP).

Methods

This study protocol is for a randomized controlled trial consisting of 2 treatment sessions (3 days/week for 4 weeks in each session, with a 1-week interval between sessions). We will recruit children aged 3–10 years with unilateral spastic CP (Gross Motor Function Classification System level I or II). Participants will be randomly divided into 3 groups: the VR + rTMS group (immersive VR intervention, rTMS and routine rehabilitation therapy), rTMS group (rTMS and routine rehabilitation therapy), and control group (sham rTMS and routine rehabilitation therapy). VR therapy will involve a daily 40-minute movement training session in a fully immersive environment. rTMS will be applied at 1 Hz over the primary motor cortex for 20 min on the contralateral side. The stimulation intensity will be set at 90% of the resting motor threshold, with 1200 pulses applied. A daily 60-minute routine rehabilitation therapy session including motor training and training in activities of daily living will be administered to all participants. The primary outcome will be pain intensity, assessed by the Revised Face, Legs, Activity, Cry, and Consolability Scale (R-FLACC). The secondary outcomes will include motor development, evaluated by the 66-item version of the Gross Motor Function Measure (GMFM-66) and Fine Motor Function Measure (FMFM); balance capacity, measured by the interactive balance system; activities of daily living; and quality of life, measured by the Barthel index and the Chinese version of the Cerebral Palsy Quality of Life scale for Children (C-CP QOL-Child). Safety will be monitored, and adverse events will be recorded during and after treatment.

Discussion

Combined application of VR therapy and rTMS may reveal additive effects on pain management and motor development in children with spastic CP, but further high-quality research is needed. The results of this trial may indicate whether VR therapy combined with rTMS achieves a better analgesic effect and improves the motor development of children with spastic CP.

Trial registration

Registration number: ChiCTR230069853. Trial registration date: 28 March 2023. Prospectively registered.
Assessing the safety and activity of cabozantinib combined with lanreotide in gastroenteropancreatic and thoracic neuroendocrine tumors: rationale and protocol of the phase II LOLA trial
Authors: Corti Francesca , Brizzi Maria Pia , Amoroso Vito , Giuffrida Dario , Panzuto Francesco , Campana Davide , Prinzi Natalie , Milione Massimo , Cascella Tommaso , Spreafico Carlo , Randon Giovanni , Oldani Simone , Leporati Rita , Scotto Giulia , Pulice Iolanda , Stocchetti Benedetta Lombardi , Porcu Luca , Coppa Jorgelina , Di Bartolomeo Maria , de Braud Filippo , Pusceddu Sara
Published: September 2023

Background

Well-differentiated (WD) neuroendocrine tumors (NETs) are a group of rare neoplasms with limited therapeutic options. Cabozantinib is an inhibitor of multiple tyrosine kinases with a pivotal role in NET pathogenesis, including c-MET and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2). LOLA is the first prospective phase II trial aiming to assess the safety and activity of cabozantinib combined with lanreotide in WD NETs of gastroenteropancreatic (GEP), thoracic and of unknown origin.

Methods

This is a multicenter, open-label, double-cohort, non comparative, non-randomized, three-stage phase II trial. Eligible patients have to meet the following inclusion criteria: diagnosis of advanced or metastatic, progressive, non-functioning WD thoracic NETs, GEP-NETs or NETs of unknown origin with Ki67 ≥ 10%; positive 68 Ga-PET uptake or somatostatin receptor 2 immunohistochemical (IHC) stain; maximum 1 prior systemic regimen for metastatic disease. Two cohorts will be considered: pNETs and carcinoids (typical or atypical lung and thymus NETs, gastro-intestinal NETs or NETs of unknown origin). In stage I, the primary objective is to find the optimal dose of cabozantinib in combination with lanreotide and to evaluate the safety of the combination (percentage of patients experiencing grade 3–5 toxicities according to NCI-CTCAE version 5.0). Starting dose of cabozantinib is 60 mg/day continuously, plus lanreotide 120 mg every 28 days. In stage II and III, co-primary endpoints are safety and overall response rate (ORR) according to RECIST version 1.1. The uninteresting antitumor activity is fixed in ORR ≤ 5%. Secondary endpoints are progression-free survival and overall survival. Exploratory objectives include the assessment of c-MET, AXL and VEGFR2 IHC expression, to identify predictive or prognostic tissue biomarkers. Enrolment started in July 2020, with an expected trial duration of 42 months comprehensive of accrual, treatment and follow-up. Considering a drop-out rate of 5%, the maximum number of enrolled patients will be 69.

Discussion

Supported by a solid rationale, the trial has the potential to generate milestone data about the synergistic effects of cabozantinib plus lanreotide in a group of NET patients with relatively aggressive disease and limited therapeutic options.

Trial registration

LOLA is registered at ClinicalTrials.gov (NCT04427787) and EudraCT (2019–004506-10).
Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2
Authors: Xu Yahong , Zhu Yongjie , Wu Zhenru , Li Shengfu , Shao Mingyang , Tao Qing , Xu Qing , Chen Yuwei , Shu Yuke , Chen Menglin , Zhou Yongjie , Shi Yujun
Published: September 2023

Background

Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages.

Methods

Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6−/−) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells.

Results

We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC.

Conclusion

In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.
Effectiveness of wheelchair skills training for improving manual wheelchair mobility in children and adolescents: protocol for a multicenter randomized waitlist-controlled trial
Authors: Best K. L. , Rushton P. W. , Sheriko J. , Arbour-Nicitopoulos K. P. , Dib T. , Kirby R. L. , Lamontagne M. E. , Moore S. A. , Ouellet B. , Routhier F.
Published: September 2023

Background

Self-directed mobility during childhood can influence development, social participation, and independent living later in life. For children who experience challenges with walking, manual wheelchairs (MWCs) provide a means for self-directed mobility. An effective MWC skills training program exists for adults, but controlled trials have not yet been documented in children and adolescents. This paper outlines the protocol for a multi-centre randomized wait-list controlled trial. The primary objective is to test the hypothesis that children and adolescents who receive MWC skills training will have higher MWC skills capacity compared to children and adolescents in the control group who receive usual care. The secondary objectives are to explore the influence of MWC skills training in children and adolescents (MWC use self-efficacy and satisfaction with participation in meaningful activities), and parents (perceived MWC skills); and to measure retention three months later.

Methods

A multi-centre, parallel-group, single-blind randomized wait-list controlled trial will be conducted. A sample of 60 children and adolescents who use MWCs will be recruited in rehabilitation centres, specialized schools, and the communities of three Canadian cities. Participants will be randomized (1:1) to the experimental (Wheelchair Skills Training Program [WSTP]) or wait-list control group (usual care). Performance-based and self-report measures will be completed at baseline (T1), three months (post-intervention, T2), and three months post-intervention (T3). The primary outcome will be MWC skills capacity post-intervention. Secondary outcomes will be MWC use self-efficacy and satisfaction with participation of the child/adolescent, and parent-perceived MWC skills. The WSTP will consist of 12 sessions, 45–60 min each, delivered 1–2 times per week by trained personnel with health professions education. Training will be customized according to the child’s baseline skills and participation goals that require the use of the MWC. The wait-list control group will receive usual care for 3 months and then receive the WSTP after completing T2 evaluations. Data will be analysed using ANCOVA (controlling for baseline scores).

Discussion

MWC skills training may be one way to improve self-directed mobility and related outcomes for children and adolescents. The results of this multi-centre randomized wait-list controlled trial will allow for the effectiveness of the intervention to be evaluated in a variety of clinical contexts and geographical regions.

Trial registration

ClinicalTrials.gov: NCT05564247, Version October 3, 2022.
Delayed diagnosis of pediatric intra-articular epithelioid sarcoma: a case report and literature review
Authors: Zhang Ranran , Liu Jia , Liu Lin , Lin Yi , Zhang Qiuye
Published: September 2023

Background

Epithelioid sarcoma (ES) is a rare form of mesenchymal malignancy that rarely occurs in children. Only seven cases of intra-articular epithelioid sarcoma have been reported in the medical literature.

Case presentation

In this report, we presented the case of a 13-year-old girl with a delayed diagnosis of ES in the left knee. Her initial diagnosis was mistaken for Pigmented Villonodular Synovitis (PVNS) but ruled out later by the first biopsy. However, the lesion rapidly regrew again after arthroscopy, raising suspicions of malignancy. A comprehensive histochemistry examination was conducted again, leading to the diagnosis of INI-1 negative epithelioid sarcoma. Unfortunately, the girl passed away seven months later due to early metastasis of the tumor.

Conclusion

Careful consideration should be given to the differential diagnosis of pediatric patients presenting with monoarthritis. This report highlights the importance of early and accurate diagnosis and underscores the necessity for effective treatments for epithelioid sarcoma. Surgical resection or radical surgery is recommended, while novel treatment strategies targeting EZH2 show promise.
Medical service utilization by children with physical or brain disabilities in South Korea
Authors: Yoo Sunyong , Choi Ja Young , Yang Shin-seung , Koh Seong-Eun , Jeong Myeong-Hyeon , Song Min-Keun
Published: September 2023

Background

Children with physical or brain disabilities experience several functional impairments and declining health complications that must be considered for adequate medical support. This study investigated the current medical service utilization of children expressing physical or brain disabilities in South Korea by analyzing medical visits, expenses, and comorbidities.

Methods

We used a database linked to the National Rehabilitation Center of South Korea to extract information on medical services utilized by children with physical or brain disabilities, the number of children with a disability, medical visits for each child, medical expenses per visit, total medical treatment cost, copayments by age group, condition severity, and disability type.

Results

Brain disorder comorbidities significantly differed between those with mild and severe disabilities. Visits per child, total medical treatment cost, and copayments were higher in children with severe physical disabilities; however, medical expenses per visit were lower than those with mild disabilities. These parameters were higher in children with severe brain disabilities than in mild cases. Total medical expenses incurred by newborns to three-year-old children with physical disorders were highest due to increased visits per child. However, medical expenses per visit were highest for children aged 13–18.

Conclusion

Medical service utilization varied by age, condition severity, and disability type. Severe cases and older children with potentially fatal comorbidities required additional economic support. Therefore, a healthcare delivery system for children with disabilities should be established to set affordable medical costs and provide comprehensive medical services based on disability type and severity.
Exposure to pesticides and the risk of hypothyroidism: a systematic review and meta-analysis
Authors: Sirikul Wachiranun , Sapbamrer Ratana
Published: September 2023

Background

Knowledge surrounding the association between exposure to pesticides and hypothyroidism is inconsistent and controversial.

Methods

The aim of present study was, therefore, to review scientific evidence systematically and conduct a meta-analysis into the contribution of exposure to pesticides to hypothyroidism. PubMed, Scopus, Web of Science, and Google Scholar were searched. The findings are presented as OR, HR, PR, IRR, and 95% confidence interval (95%CI). A fixed-effect model using the inverse-variance method and random-effects inverse-variance model with DerSimonian-Laird method were used for estimating the pooled estimates. Cochran Q and I2 tests were used to confirm the heterogeneity of selected studies.

Results

Twelve studies were included in the systematic review, and 9 studies in the meta-analysis. Epidemiological evidence suggested that exposure to insecticides including organochlorines, organophosphates, and pyrethroids increased risk of hypothyroidism (adjusted odds ratio (aOR) = 1.23, 95%CI = 1.14, 1.33 for organochlorines, aOR = 1.12, 95%CI = 1.07, 1.17 for organophosphates, aOR = 1.15, 95%CI = 1.03, 1.28 for pyrethroids). Exposure to herbicides also increased risk of hypothyroidism (aOR = 1.06, 95%CI = 1.02, 1.10). However, exposure to fungicides and fumigants was not found to be associated with hypothyroidism.

Conclusion

To increase current knowledge and confirm evidence to date future research needs to center on large-scale longitudinal epidemiological and biological studies, examination of dose–response relationships, the controlling of relevant confounding variables, using standardized and high sensitivity tools, and investigating the effects of environmental exposure.
A qualitative study examining young peoples’ perceptions and adherence to COVID-19 public health guidelines in Ireland
Authors: Breslin Tara M. , Galvin Rose , Foran Aoife Mare , Muldoon Orla T.
Published: September 2023

Background

Public health measures are the main intervention to stop the spread of COVID-19. They rely on the adherence to everyday health behaviors, and depend on those at high and low personal risk of serious disease to comply. Young people are crucial to stemming community transmission, and are often living in shared housing and at a stage of their lives with more economic uncertainty than older groups. Public health messaging has relied on the mantra that we are ‘in it together,’ despite very diverse experiences of the pandemic across different groups. The central aim of this research is to understand and optimize young peoples’ engagement with public health guidelines with the view to improve future adherence with public health initiatives.

Method

Twelve young people were interviewed as part of this research, ranging from 18 to 24 years. Interviewees were chosen to ensure that there was a diverse range of opinions within the participant pool. Interviews were semi-structured with open questions and the flexibility to explore the topics of interest that arose. All interviews were fully transcribed and analyzed using thematic analysis.

Results

This study found that participants deemed the consequences of lockdown a greater threat than infection with SARS-COV-2. Participants expressed concerns about the government’s handling of the pandemic. Some felt young peoples’ interests were not represented by authorities. There were concerns that messaging was inaccurate, difficult to understand, and filled with statistical and medical jargon. These perceptions underpinned a sense that the guidelines could be broken in good conscience as well as result in accidental breaches of the guidelines. Though wider community factors were often cited as having a positive influence on health behavior, differences and division were seen to inspire trust or adherence.

Conclusion

These findings provide an insight into the psychological, financial and physical difficulties young people face as a consequence of pandemic public health measures and lockdowns in particular. They highlight the need for better communication with young people to support and embed trust in authorities and the scientific and political community.
Raptor mediates the selective inhibitory effect of cardamonin on RRAGC-mutant B cell lymphoma
Authors: Liu Ying , Zhu Yanting , Chen Huajiao , Zhou Jintuo , Niu Peiguang , Shi Daohua
Published: September 2023

Background

mTORC1 (mechanistic target of rapamycin complex 1) is associated with lymphoma progression. Oncogenic RRAGC (Rag guanosine triphosphatase C) mutations identified in patients with follicular lymphoma facilitate the interaction between Raptor (regulatory protein associated with mTOR) and Rag GTPase. It promotes the activation of mTORC1 and accelerates lymphomagenesis. Cardamonin inhibits mTORC1 by decreasing the protein level of Raptor. In the present study, we investigated the inhibitory effect and possible mechanism of action of cardamonin in RRAGC-mutant lymphoma. This could provide a precise targeted therapy for lymphoma with RRAGC mutations.

Methods

Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Protein expression and phosphorylation levels were determined using western blotting. The interactions of mTOR and Raptor with RagC were determined by co-immunoprecipitation. Cells overexpressing RagC wild-type (RagCWT) and RagC Thr90Asn (RagCT90N) were generated by lentiviral infection. Raptor knockdown was performed by lentivirus-mediated shRNA transduction. The in vivo anti-tumour effect of cardamonin was assessed in a xenograft model.

Results

Cardamonin disrupted mTOR complex interactions by decreasing Raptor protein levels. RagCT90N overexpression via lentiviral infection increased cell proliferation and mTORC1 activation. The viability and tumour growth rate of RagCT90N-mutant cells were more sensitive to cardamonin treatment than those of normal and RagCWT cells. Cardamonin also exhibited a stronger inhibitory effect on the phosphorylation of mTOR and p70 S6 kinase 1 in RagCT90N-mutant cells. Raptor knockdown abolishes the inhibitory effects of cardamonin on mTOR. An in vivo xenograft model demonstrated that the RagCT90N-mutant showed significantly higher sensitivity to cardamonin treatment.

Conclusions

Cardamonin exerts selective therapeutic effects on RagCT90N-mutant cells. Cardamonin can serve as a drug for individualised therapy for follicular lymphoma with RRAGC mutations.