bluuebunny/crossref_metadata_2025 huggingface dataset:
The beneficial effects of simultaneous supplementation of Lactobacillus reuteri and calcium fluoride nanoparticles on ovariectomy-induced osteoporosis
Authors: Rahmani Dibachehr , Faal Bahareh , Zali Hakimeh , Tackallou Saeed Hesami , Niknam Zahra
Published: September 2023

Background

The development of new strategies to inhibit and/or treat osteoporosis as a chronic systemic disease is one of the most crucial topics. The present study aimed to investigate the simultaneous effects of calcium fluoride nanoparticles (CaF2 NPs) and lactobacillus reuteri ATCC PTA 6475 (L. reuteri) against osteoporosis in an ovariectomized rat model (OVX).

Methods

In this study, 18 matured Wistar female rats were randomly assigned into 6 groups, including control, OVX, sham, OVX + L. reuteri, OVX + CaF2 NPs, and OVX + L. reuteri + CaF2 NPs. We used OVX rats to simulate post-menopausal osteoporosis, and the treatments were begun two weeks before OVX and continued for four weeks. All groups’ blood samples were collected, and serum biomarkers (estrogen, calcium, vitamin D3, and alkaline phosphatase (ALP)) were measured. The tibia and Femur lengths of all groups were measured. Histopathological slides of tibia, kidney, and liver tissues were analyzed using the Hematoxylin and Eosin staining method.

Results

Our results revealed that dietary supplementation of L. reuteri and CaF2 NPs in low doses for 6 weeks did not show adverse effects in kidney and liver tissues. The tibial and femoral lengths of OVX rats as well as the population of osteoblasts and osteocytes and newly generated osteoid in the tibia remarkably increased in the combination therapy group. Moreover, there was a significant increase in serum estrogen levels and a significant decrease in serum calcium and alkaline phosphatase levels in combination treatment groups compared to the OVX groups not receiving the diet.

Conclusions

Our results suggest the favorable effects of the simultaneous supplementation of L. reuteri and CaF2 NP to reduce post-menopausal bone loss.

Graphical abstract
Examination of residency program websites for the use of gendered language and imagery
Authors: Read Catherine E. , Tracz Jovanna A. , Mhaimeed Nour , Mainville Rylie N. , Elzie Carrie A.
Published: September 2023

Background

Significant disparity in gender distribution exists among medical specialties. Residency program websites are a main source of preliminary program information for candidates, and website content may influence a prospective applicant’s sense of belongingness within a particular program. Given the importance of the residency program website as a recruiting tool, this study sought to examine and compare the presence of gendered language and imagery on residency program websites across various specialties.

Methods

A list of words considered masculine or feminine was used to evaluate residency program websites of the two most male-dominated specialties (orthopedic and thoracic surgery), female-dominated specialties (pediatrics and obstetrics and gynecology), and gender-balanced specialties (dermatology and family medicine) in the United States in 2022. Forty-five residency programs were randomly selected from each specialty across different regions of the US, with the exception of thoracic surgery of which there are only 33 programs. Masculine and feminine words were evaluated using a parsing and scraping program. Representation of female and male-presenting team members in photos on program websites was also evaluated.

Results

Masculine wording occurred more frequently in male-dominated specialties compared to gender-balanced (p = 0.0030), but not female-dominated specialties (p = 0.2199). Feminine language was used more frequently in female-dominated compared to male dominated fields (p = 0.0022), but not gender balanced (p = 0.0909). The ratio of masculine-to-feminine words used was significantly higher in male-dominated specialties compared to both gender-balanced (p < 0.0001) and female-dominated specialties. (p < 0.0001). There was an average of 1, 7, and 10 female-presenting residency team members pictured on each male-dominated, gender balanced, and female-dominated specialty RPW respectively, with significantly more female-presenting team members pictured in the photographs on female-dominated specialty websites when compared to male-dominated and gender-balanced specialty websites (p < 0.0001, p = 0.014).

Conclusions

The use of gendered language and female representation in photographs varies significantly across specialties and is directly correlated with gender representation within the specialty. Given that students’ perceptions of specialty programs may be affected by the use of language and photos on residency program websites, programs should carefully consider the language and pictures depicted on their program websites.
CNN-Res: deep learning framework for segmentation of acute ischemic stroke lesions on multimodal MRI images
Authors: Gheibi Yousef , Shirini Kimia , Razavi Seyed Naser , Farhoudi Mehdi , Samad-Soltani Taha
Published: September 2023

Background

Accurate segmentation of stroke lesions on MRI images is very important for neurologists in the planning of post-stroke care. Segmentation helps clinicians to better diagnose and evaluation of any treatment risks. However, manual segmentation of brain lesions relies on the experience of neurologists and is also a very tedious and time-consuming process. So, in this study, we proposed a novel deep convolutional neural network (CNN-Res) that automatically performs the segmentation of ischemic stroke lesions from multimodal MRIs.

Methods

CNN-Res used a U-shaped structure, so the network has encryption and decryption paths. The residual units are embedded in the encoder path. In this model, to reduce gradient descent, the residual units were used, and to extract more complex information in images, multimodal MRI data were applied. In the link between the encryption and decryption subnets, the bottleneck strategy was used, which reduced the number of parameters and training time compared to similar research.

Results

CNN-Res was evaluated on two distinct datasets. First, it was examined on a dataset collected from the Neuroscience Center of Tabriz University of Medical Sciences, where the average Dice coefficient was equal to 85.43%. Then, to compare the efficiency and performance of the model with other similar works, CNN-Res was evaluated on the popular SPES 2015 competition dataset where the average Dice coefficient was 79.23%.

Conclusion

This study presented a new and accurate method for the segmentation of MRI medical images using a deep convolutional neural network called CNN-Res, which directly predicts segment maps from raw input pixels.
Prevalence and predictors of asymptomatic malaria infection in Boricha District, Sidama Region, Ethiopia: implications for elimination strategies
Authors: Dabaro Desalegn , Birhanu Zewdie , Adissu Wondimagegn , Yilma Daniel , Yewhalaw Delenasaw
Published: September 2023

Background

Malaria remains a major public health threat in Ethiopia despite the tremendous progress made towards the 2030 elimination targets. The silent transmission of asymptomatic infection is one of the factors that enhance the persistence of the disease as a public health issue and impedes efforts to eliminate malaria. Thus, this study aimed at investigating the prevalence and risk factors of asymptomatic malaria infection in Boricha district, Sidama region of Ethiopia.

Methods

A community-based cross-sectional study was conducted in eight selected kebeles (smallest administrative unit) in Boricha district. Representative households were chosen using a multi-stage sampling technique. A total of 573 participants were included in the study. Malaria diagnosis was performed using rapid diagnostic test (RDT) and microscopy. A structured questionnaire was administered to collect socio-demographic information. Epi data 3.1 was employed for data entry, and SPSS version 25 was used for analysis.

Results

Of the 573 asymptomatic participants tested, 6.1% were found to be positive by RDT and 4.0% by microscopy. Participants aged under 5 years (AOR = 1.57, 95% CI 0.46–5.39) and 5–14 years old (AOR = 2.42, 95% CI 1.08–5.40), Insecticide-treated net utilization (AOR = 8.41; 95% CI 1.09–65.08), travel history (AOR = 6.85, 95% CI 2.32–20.26) and living in a house with windows (AOR = 2.11, 95% CI 1.02–4.36) were significantly associated with the asymptomatic malaria infection.

Conclusion

The findings of this study revealed that prevalence of asymptomatic malaria infection was higher in the study area. As a result, rigorous implementation of existing interventions, such as vector control and anti-malaria drugs, is strongly recommended. In addition, devising new ones that are suited to the contextual situations is highly suggested.
Capturing emergency dispatch address points as geocoding candidates to quantify delimited confidence in residential geolocation
Authors: Klaus Christian A. , Henry Kevin A. , Il’yasova Dora
Published: September 2023

Background

In response to citizens’ concerns about elevated cancer incidence in their locales, US CDC proposed publishing cancer incidence at sub-county scales. At these scales, confidence in patients’ residential geolocation becomes a key constraint of geospatial analysis. To support monitoring cancer incidence in sub-county areas, we presented summary metrics to numerically delimit confidence in residential geolocation.

Results

We defined a concept of Residential Address Discriminant Power (RADP) as theoretically perfect within all residential addresses and its practical application, i.e., using Emergency Dispatch (ED) Address Point Candidates of Equivalent Likelihood (CEL) to quantify Residential Geolocation Discriminant Power (RGDP) to approximate RADP. Leveraging different productivity of probabilistic, deterministic, and interactive geocoding record linkage, we simultaneously detected CEL for 5,807 cancer cases reported to North Carolina Central Cancer Registry (NC CCR)- in January 2022. Batch-match probabilistic and deterministic algorithms matched 86.0% cases to their unique ED address point candidates or a CEL, 4.4% to parcel site address, and 1.4% to street centerline. Interactively geocoded cases were 8.2%. To demonstrate differences in residential geolocation confidence between enumeration areas, we calculated sRGDP for cancer cases by county and assessed the existing uncertainty within the ED data, i.e., identified duplicate addresses (as CEL) for each ED address point in the 2014 version of the NC ED data and calculated ED_sRGDP by county. Both summary RGDP (sRGDP) (0.62–1.00) and ED_sRGDP (0.36–1.00) varied across counties and were lower in rural counties (p < 0.05); sRGDP correlated with ED_sRGDP (r = 0.42, p < 0.001). The discussion covered multiple conceptual and economic issues attendant to quantifying confidence in residential geolocation and presented a set of organizing principles for future work.

Conclusions

Our methodology produces simple metrics – sRGDP – to capture confidence in residential geolocation via leveraging ED address points as CEL. Two facts demonstrate the usefulness of sRGDP as area-based summary metrics: sRGDP variability between counties and the overall lower quality of residential geolocation in rural vs. urban counties. Low sRGDP for the cancer cases within the area of interest helps manage expectations for the uncertainty in cancer incidence data. By supplementing cancer incidence data with sRGDP and ED_sRGDP, CCRs can demonstrate transparency in geocoding success, which may help win citizen trust.
Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials
Authors: Wretlind Asger , Curovic Viktor Rotbain , de Zawadzki Andressa , Suvitaival Tommi , Xu Jin , Zobel Emilie Hein , von Scholten Bernt Johan , Ripa Rasmus Sejersten , Kjaer Andreas , Hansen Tine Willum , Vilsbøll Tina , Vestergaard Henrik , Rossing Peter , Legido-Quigley Cristina
Published: September 2023

Background

Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of CVD. Reducing lipotoxic lipids with an antidiabetic drug therapy could be a path towards precision medicine approaches for the treatment of complications to diabetes. In this post-hoc study, an investigation was carried out on the effect of liraglutide on CVD-risk associated ceramides in two randomized clinical trials including participants with type 2 diabetes (T2D).

Methods

This study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1.8 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses.

Results

In the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer (p < 0.05) compared to placebo. None of the remaining ceramides showed statistically significant changes in response to liraglutide treatment compared to placebo. Significant changes in ceramides were not found after 12-weeks of liraglutide treatment in the LirAlbu12 trial. Mediation analyses showed that weight loss did not affect ceramide reduction.

Conclusions

It was demonstrated that treatment with liraglutide resulted in a reduction in C16 Cer and C24:1 Cer after 26 weeks of treatment. These findings suggest the GLP-1RA can be used to modulate ceramides in addition to its other properties.

Trial registration

Clinicaltrial.gov identifier: NCT02545738 and NCT03449654.
18F-FDG-PET/CT-based machine learning model evaluates indeterminate adrenal nodules in patients with extra-adrenal malignancies
Authors: Cao Lixiu , Zhang Dejiang , Yang Haoxuan , Xu Wengui , Liu Yongliang
Published: September 2023

Background

To assess the value of an 18F-FDG-positron emission tomography/computed tomography (PET/CT)-based machine learning model for distinguishing between adrenal benign nodules (ABNs) and adrenal metastases (AMs) in patients with indeterminate adrenal nodules and extra-adrenal malignancies.

Methods

A total of 303 patients who underwent 18F-FDG-PET/CT with indeterminate adrenal nodules and extra-adrenal malignancies from March 2015 to June 2021 were included in this retrospective study (training dataset (n = 182): AMs (n = 97), ABNs (n = 85); testing dataset (n = 121): AMs (n = 68), ABNs (n = 55)). The clinical and PET/CT imaging features of the two groups were analyzed. The predictive model and simplified scoring system for distinguishing between AMs and ABNs were built based on clinical and PET/CT risk factors using multivariable logistic regression in the training cohort. The performances of the predictive model and simplified scoring system in both the training and testing cohorts were evaluated by the areas under the receiver operating characteristic curves (AUCs) and calibration curves. The comparison of AUCs was evaluated by the DeLong test.

Results

The predictive model included four risk factors: sex, the ratio of the maximum standardized uptake value (SUVmax) of adrenal lesions to the mean liver standardized uptake value, the value on unenhanced CT (CTU), and the clinical stage of extra-adrenal malignancies. The model achieved an AUC of 0.936 with a specificity, sensitivity and accuracy of 0.918, 0.835, and 0.874 in the training dataset, respectively, while it yielded an AUC of 0.931 with a specificity, sensitivity, and accuracy of 1.00, 0.735, and 0.851 in the testing dataset, respectively. The simplified scoring system had comparable diagnostic value to the predictive model in both the training (AUC 0.938, sensitivity: 0.825, specificity 0.953, accuracy 0.885; P = 0.5733) and testing (AUC 0.931, sensitivity 0.735, specificity 1.000, accuracy 0.851; P = 1.00) datasets.

Conclusions

Our study showed the potential ability of a machine learning model and a simplified scoring system based on clinical and 18F-FDG-PET/CT imaging features to predict AMs in patients with indeterminate adrenal nodules and extra-adrenal malignancies. The simplified scoring system is simple, convenient, and easy to popularize.
Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms
Authors: Niu Kaiyi , Shi Yanlong , Lv Qingpeng , Wang Yizhu , Chen Jiping , Zhang Wenning , Feng Kung , Zhang Yewei
Published: September 2023

Ubiquitination is one of the most significant post-translational modifications that regulate almost all physiological processes like cell proliferation, autophagy, apoptosis, and cell cycle progression. Contrary to ubiquitination, deubiquitination removes ubiquitin from targeted protein to maintain its stability and thus regulate cellular homeostasis. Ubiquitin-Specific Protease 12 (USP12) belongs to the biggest family of deubiquitinases named ubiquitin-specific proteases and has been reported to be correlated with various pathophysiological processes. In this review, we initially introduce the structure and biological functions of USP12 briefly and summarize multiple substrates of USP12 as well as the underlying mechanisms. Moreover, we discuss the influence of USP12 on tumorigenesis, tumor immune microenvironment (TME), disease, and related signaling pathways. This study also provides updated information on the roles and functions of USP12 in different types of cancers and other diseases, including prostate cancer, breast cancer, lung cancer, liver cancer, cardiac hypertrophy, multiple myeloma, and Huntington's disease. Generally, this review sums up the research advances of USP12 and discusses its potential clinical application value which deserves more exploration in the future.
Semiautomated pipeline for quantitative analysis of heart histopathology
Authors: Droste Patrick , Wong Dickson W. L. , Hohl Mathias , von Stillfried Saskia , Klinkhammer Barbara M. , Boor Peter
Published: September 2023

Background

Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software.

Methods

We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis.

Results

In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available.

Conclusions

In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples.
Treat-to-target strategies for the management of familial Mediterranean Fever in children
Authors: Ehlers Lisa , Rolfes Elisabeth , Lieber Mareike , Müller Dominik , Lainka Elke , Gohar Faekah , Klaus Günter , Girschick Hermann , Hörstermann Jana , Kümmerle-Deschner Jasmin , Brunner Jürgen , Palm-Beden Katharina , Tenbrock Klaus , von Wrangel Lusine , Faßhauer Maria , Blank Norbert , Trauzeddel Ralf , von Stuckrad Anne Sae Lim , Higgins Sonja , Welzel Tatjana , Lutz Thomas , Hentgen Véronique , Foell Dirk , Wittkowski Helmut , Kallinich Tilmann
Published: September 2023

Background

The objective of this initiative was to develop a treat-to-target (T2T) approach for the management of patients with Familial Mediterranean Fever (FMF), including the definition of a complex treatment target, and establish strategies that improve patient care and long-term outcome.

Methods

An initial set of statements as well as a flow chart visualising the proposed concept was developed. To adapt the preliminary statements to the current state of knowledge, a systematic literature search was performed and the modified statements were subject to a Delphi approach. To ensure the applicability of the statements in daily practice, an online survey was conducted among paediatric rheumatologists in Germany. In addition, data from the national AID-NET registry were analysed with respect to therapeutic response.

Results

This T2T initiative yielded a total of 26 statements guiding FMF management with respect to diagnosis, treatment targets, treatment strategies and monitoring. The online survey identified cut-off values for inflammatory markers indicating treatment intensification and appropriate measures in case of colchicine intolerance or non-adherence. The analysis of data derived from the national AID-NET showed that colchicine therapy was successfully terminated in 61% of patients (27 out of 44) with heterozygous MEFV mutations. Multidimensional treatment targets incorporating objective and subjective reported outcome measures were developed. These provide the basis for stratifying patients into the following treatment paths: continue colchicine, persisting attacks / inflammation, colchicine intolerance, persisting arthritis, colchicine reduction and adjustment/reduction of biologics.

Conclusions

The proposed consensus treatment plan for the management of FMF incorporates multidimensional targets allowing transparent treatment decisions, which will promote personalised disease management and increase adherence to therapy.
Extended interval dosing of ocrelizumab modifies the repopulation of B cells without altering the clinical efficacy in multiple sclerosis
Authors: Rodriguez-Mogeda Carla , van Lierop Zoë Y. G. J. , van der Pol Susanne M. A. , Coenen Loet , Hogenboom Laura , Kamermans Alwin , Rodriguez Ernesto , van Horssen Jack , van Kempen Zoé L. E. , Uitdehaag Bernard M. J. , Teunissen Charlotte E. , Witte Maarten E. , Killestein Joep , de Vries Helga E.
Published: September 2023

Background

Recent studies suggest that extended interval dosing of ocrelizumab, an anti-B cell therapy, does not affect its clinical effectiveness in most patients with multiple sclerosis (MS). However, it remains to be established whether certain B cell subsets are differentially repopulated after different dosing intervals and whether these subsets relate to clinical efficacy.

Methods

We performed high-dimensional single-cell characterization of the peripheral immune landscape of patients with MS after standard (SID; n = 43) or extended interval dosing (EID; n = 37) of ocrelizumab and in non-ocrelizumab-treated (control group, CG; n = 28) patients with MS, using mass cytometry by time of flight (CyTOF).

Results

The first B cells that repopulate after both ocrelizumab dosing schemes were immature, transitional and regulatory CD1d+CD5+B cells. In addition, we observed a higher percentage of transitional, naïve and regulatory B cells after EID in comparison with SID, but not of memory B cells or plasmablasts. The majority of repopulated B cell subsets showed an increased migratory phenotype, characterized by higher expression of CD49d, CD11a, CD54 and CD162. Interestingly, after EID, repopulated B cells expressed increased CD20 levels compared to B cells in CG and after SID, which was associated with a delayed repopulation of B cells after a subsequent ocrelizumab infusion. Finally, the number of/changes in B cell subsets after both dosing schemes did not correlate with any relapses nor progression of the disease.

Conclusions

Taken together, our data highlight that extending the dosing interval of ocrelizumab does not lead to increased repopulation of effector B cells. We show that the increase of CD20 expression on B cell subsets in EID might lead to longer depletion or less repopulation of B cells after the next infusion of ocrelizumab. Lastly, even though extending the ocrelizumab interval dosing alters B cell repopulation, it does not affect the clinical efficacy of ocrelizumab in our cohort of patients with MS.
Unraveling the interplay between daily life fatigue and physical activity after subarachnoid hemorrhage: an ecological momentary assessment and accelerometry study
Authors: de Vries Elisabeth A. , Heijenbrok-Kal Majanka H. , van Kooten Fop , Giurgiu Marco , Ribbers Gerard M. , van den Berg-Emons Rita J.G. , Bussmann Johannes B.J.
Published: September 2023

Background

Fatigue is one of the most commonly reported symptoms after subarachnoid hemorrhage (SAH) and is indirectly associated with physical activity (PA). Associations between fatigue and PA are primarily examined based on conventional measures (i.e. a single fatigue score or average PA levels), thereby assuming that fatigue and PA do not fluctuate over time. However, levels of fatigue and PA may not be stable and may interrelate dynamically in daily life. Insight in direct relationships between fatigue and PA in daily life, could add to the development of personalized rehabilitation strategies. Therefore we aimed to examine bidirectional relationships between momentary fatigue and PA in people with SAH.

Methods

People (n = 38) with SAH who suffer from chronic fatigue were included in an observational study using Ecological Momentary Assessment (EMA) and accelerometry. Momentary fatigue was assessed on a scale from 1 to 7 (no to extreme fatigue), assessed with 10–11 prompts per day for 7 consecutive days using EMA with a mobile phone. PA was continuously measured during this 7-day period with a thigh-worn Activ8 accelerometer and expressed as total minutes of standing, walking, running and cycling in a period of 45 min before and after a momentary fatigue prompt. Multilevel mixed model analyses including random effects were conducted.

Results

Mean age was 53.2 years (SD = 13.4), 58% female, and mean time post SAH onset was 9.5 months (SD = 2.1). Multilevel analyses with only time effects to predict fatigue and PA revealed that fatigue significantly (p < 0.001) increased over the day and PA significantly (p < 0.001) decreased. In addition, more PA was significantly associated with higher subsequent fatigue (β = 0.004, p < 0.05) and higher fatigue was significantly associated with less subsequent PA (β=-0.736, p < 0.05). Moreover, these associations significantly differed between participants (p < 0.001).

Conclusions

By combining EMA measures of fatigue with accelerometer-based PA we found that fatigue and PA are bidirectionally associated. In addition, these associations differ among participants. Given these different bidirectional associations, rehabilitation aimed at reducing fatigue should comprise personalized strategies to improve both fatigue and PA simultaneously, for example by combining exercise therapy with cognitive behavioral and/or energy management therapy.
Developing a serious game for gaze stability rehabilitation in children with vestibular hypofunction
Authors: Ortega Solís José , Reynard Pierre , Spruyt Karen , Bécaud Cécile , Ionescu Eugen , Thai-Van Hung
Published: September 2023

Background

Children with vestibular hypofunction (VH) may have gaze instability, balance disorders, and delayed postural-motor development. Gaze stabilization exercises (GSE) are designed to improve dynamic visual acuity (DVA). We aimed to assess the acceptability of a serious game prototype called Kid Gaze Rehab (KGR) designed to implement GSE training in children with VH, combined with traditional vestibular rehabilitation. Effects on DVA and motor performance were also analyzed.

Methods

Twelve children (6 to 9 years old) were included. Sessions were held at the hospital twice a week, for 5 weeks. An adapted French version of The Child Simulator Sickness Questionnaire (SSQ) and the Face Scale Pain-Revised (FPS-R) were used to assess pain in the cervical region and undesirable side effects after each session. Vestibular and motor function parameters (active and passive DVA and Movement Assessment Battery for Children–Second Edition, MABC-2) were assessed before and after the training.

Results

All children included completed the 10 sessions. The FPS-R visual analog scale and SSQ showed good cervical tolerance and no oculomotor or vegetative adverse effects nor spatial disorientation. After training, active DVA scores were significantly improved for the right, left, and up directions (p < 0.05). Passive DVA scores were significantly improved for the left and down directions (p < 0.01 and p < 0.05, respectively). MABC-2 scores were improved in the balance and ball skill sections (p < 0.05).

Conclusion

An innovative pediatric training method, the use of a dedicated serious game for gaze stabilization was well-tolerated as a complement to conventional vestibular rehabilitation in children with VH. Moreover, both DVA and motor performance were found to improve in the study sample. Although replication studies are still needed, serious game-based training in children with VH could represent a promising rehabilitation approach for years to come.

Trial registration

The study was conducted in accordance with the Declaration of Helsinki and approved by an Institutional Review Board (local ethics committee, CPP Sud-Est IV, ID 2013–799). The study protocol was registered on ClinicalTrials.gov (NCT04353115).
Traditional knowledge 10 min far from Barcelona: ethnobotanical study in the Llobregat river delta (Catalonia, NE Iberian Peninsula), a heavily anthropized agricultural area
Authors: Marín Jon , Garnatje Teresa , Vallès Joan
Published: September 2023

Background

The right floodplain at the Llobregat river delta (Catalonia, NE Iberian Peninsula) constitutes an agricultural periurban area adjacent to Barcelona, which has remained ethnobotanically unexplored until now. This area comprises a very heavily anthropized mosaic of soil uses—urban, industrial, natural, agricultural—including the Agricultural Park of Baix Llobregat. The main aim of this work has been to collect and analyze the ethnoflora of this area in order to fill a gap in the ethnobotanical knowledge in industrialized areas.

Methods

The followed methodology has been based on semi-structured interviews. The obtained data have been qualitatively and quantitatively analyzed and compared with other studies.

Results

Data have been gathered from 83 informants. The interviewed informants referred 1965 use reports from 292 taxa, including both non-cultivated and cultivated species, from 85 botanical families. Among those, 451 were referred to medicinal uses, 1247 to food uses and 267 to other uses. In the present study, 779 vernacular names have been reported for 287 taxa. In addition to medicinal and food uses, this study significantly enhances our understanding of some agrosilvopastoral uses of plants, artistic use of plants and insights into folk functional foods. In this regard, we propose a novel quantitative ethnobotany index (the folk functional food index) to assess the relative significance of taxa employed as folk functional foods.

Conclusions

The findings of this study highlight the enduring presence of ethnobotanical knowledge in this periurban agricultural region and underscore the significance of its preservation.
Definitive irradiation as a first treatment strategy for primary and metastatic sites of newly diagnosed IVB cervical cancer that presented with synchronous oligometastases
Authors: Li Junyun , Wang Ying , Huo Lanqing , Huang Xiaodan , Shi Liu , Huang Lin , Chen Kai , Cao Xinping
Published: September 2023

Background

The present study identified survival and progression-free rates and evaluated prognostic factors for IVB stage cervical cancer in patients that presented with synchronous oligometastases (sync-oligometastases) who received definitive irradiation for primary and metastatic sites.

Methods

The study retrospectively included 60 patients with newly diagnosed stage IVB cervical cancer. Patients received definitive radiation for both primary and metastatic sites through Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) followed by three dimensional-intracavitary/interstitial brachytherapy at our institution between July 2014 to December 2020. All patients were staged based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 guidelines. Overall survival (OS), progression-free survival (PFS), and patient prognostic factors were analyzed.

Results

The 60 patients who received curative-intent irradiation for primary and metastatic sites showed a 5-year OS rate of 51.4% and a 5-year PFS rate of 25.9%. The median PFS was 52.3 months, and the median OS had not been reached. Lymphatic metastases had a better OS compared with hematogenous metastases (3-year OS rates: 57.2% vs. 20%, p = 0.017). Patients with one metastasis site showed a more favorable prognosis than patients with ≥ 2 metastases sites (3-year OS rates: 60.4% vs. 20.6%, p = 0.003). Patients that presented with tumors larger than 4 cm in diameter before treatment demonstrated a poorer prognosis (5-year OS rates: 41.2% vs. 65.2%, p = 0.029; 5-year PFS rates: 10.4% vs. 53.7%, p = 0.021).

Conclusion

Definitive irradiation for both primary and oligo-metastatic sites for selected IVB patients is a feasible treatment strategy. Metastatic type, number of metastatic sites, and pre-treatment tumor diameter were significant prognostic factors. Neoadjuvant chemotherapy, the lymph nodal metastatic type (supraclavicular or inguinal), and number of lymphatic metastatic sites failed to reach statistical significance as prognostic factors.
Identification of histidine kinase inhibitors through screening of natural compounds to combat mastitis caused by Streptococcus agalactiae in dairy cattle
Authors: Pathak Rajesh Kumar , Kim Jun-Mo
Published: September 2023

Background

Mastitis poses a major threat to dairy farms globally; it results in reduced milk production, increased treatment costs, untimely compromised genetic potential, animal deaths, and economic losses. Streptococcus agalactiae is a highly virulent bacteria that cause mastitis. The administration of antibiotics for the treatment of this infection is not advised due to concerns about the emergence of antibiotic resistance and potential adverse effects on human health. Thus, there is a critical need to identify new therapeutic approaches to combat mastitis. One promising target for the development of antibacterial therapies is the transmembrane histidine kinase of bacteria, which plays a key role in signal transduction pathways, secretion systems, virulence, and antibiotic resistance.

Results

In this study, we aimed to identify novel natural compounds that can inhibit transmembrane histidine kinase. To achieve this goal, we conducted a virtual screening of 224,205 natural compounds, selecting the top ten based on their lowest binding energy and favorable protein–ligand interactions. Furthermore, molecular docking of eight selected antibiotics and five histidine kinase inhibitors with transmembrane histidine kinase was performed to evaluate the binding energy with respect to top-screened natural compounds. We also analyzed the ADMET properties of these compounds to assess their drug-likeness. The top two compounds (ZINC000085569031 and ZINC000257435291) and top-screened antibiotics (Tetracycline) that demonstrated a strong binding affinity were subjected to molecular dynamics simulations (100 ns), free energy landscape, and binding free energy calculations using the MM-PBSA method.

Conclusion

Our results suggest that the selected natural compounds have the potential to serve as effective inhibitors of transmembrane histidine kinase and can be utilized for the development of novel antibacterial veterinary medicine for mastitis after further validation through clinical studies.
A comparison of the effects of occupation-based interventions with and without responsibility feedback and conventional interventions on participation in people with idiopathic Parkinson’s disease: study protocol for a randomized controlled trial
Authors: Meimandi Mahsa , Azad Akram , Ghani Jafar Haj , HojabriFard Fatemeh , von Rosen Philip , Alizadeh Naeeme Haji , Taghizadeh Ghorban
Published: September 2023

Background

Parkinson’s disease (PD) is a neurodegenerative disorder with debilitating motor and non-motor symptoms which affect participation in meaningful occupations. Occupation-based interventions can improve participation in people with PD. Evidence for incorporating structured and intensive occupational therapy by considering the concept of responsibility is lacking for this population. This trial will compare the effects of occupation-based interventions with and without responsibility feedback and conventional interventions on participation in people with idiopathic PD.

Methods

A total of 45 people with PD, between 35 and 85 years old and Hoehn and Yahr stages between I to III, will be recruited from movement disorder centers for this three-armed study. Participants will be randomized into three groups (occupation-based interventions with responsibility feedback, occupation-based interventions without responsibility feedback, and conventional interventions). All participants will receive intervention for 24 sessions during a period of 12 weeks (2 sessions per week). The primary outcome measure will be participation satisfaction. Participation frequency and restriction, self-perceived performance, performance satisfaction, motivation, volition, sense of agency, responsibility, physical activity, community integration, activities of daily living (ADL), instrumental ADL, upper extremity function, balance, fatigue, and quality of life will be measured as secondary outcome measures. All outcomes will be measured at baseline, session 9, session 17, post-intervention (week 13), and follow-up (week 25).

Discussion

This home-based high-intensity, structured, client-centered, and occupation-based intervention will be conducted by utilizing the concept of responsibility. This proposed trial may result in enhanced participation that would benefit other motor and non-motor symptoms in people living with PD. Findings from this proposed study are expected to expand the knowledge of clinicians and help them in evidence-based decision-making processes.

Trial registration

Iranian Registry of Clinical Trials IRCT20140304016830N13. Registered on August 19, 2022
A randomised controlled trial in preterm infants comparing prophylactic with selective “less invasive surfactant administration” (pro.LISA)
Authors: Göpel Wolfgang , Rausch Tanja K. , Mitschdörfer Barbara , Mader Silke , Herting Egbert , König Inke R. , Stichtenoth Guido ,   on behalf of the pro.LISA study group, Höhn Thomas , Stein Anja , Bayer Hagen , Schmidtke Susanne , Naust Barabara , Roll Claudia , Franz Axel , Wolff Moritz , Siemes Anna , Schneider Katja , Dieks Jana Katharina , Fuchs Hans , Körner Thorsten , Schroth Michael , Dohle Frank , Völkl Thomas , Härtel Christoph , Bejo Levente , Schneider Welfhard
Published: September 2023

Background

Respiratory distress syndrome is the main cause of mortality and morbidity in preterm infants. “Less invasive surfactant administration” (LISA), which describes intratracheal surfactant administration to spontaneously breathing infants via a small diameter tube, is recommended as the first-line treatment in preterm infants with more than 30% supplemental oxygen. Prophylactic use of LISA in preterm infants with less than 30% supplemental oxygen was not tested in randomised controlled trials yet, and long-term outcome data of the procedure are scarce.

Methods

Preterm infants with a gestational age between 25 weeks + 0 days and 28 weeks + 6 days who are breathing spontaneously on continuous positive airway pressure with supplemental oxygen at or below 30% in the first hour of life will be randomised to a prophylactic LISA treatment with 100–200 mg surfactant intratracheally per kilogramme bodyweight (intervention group) or will continue the continuous positive airway pressure treatment (control group). Participants will have follow-up until age 5 years. At that time, the children will be tested by spirometry, and forced expiratory volume within 1-s z-scores will be compared between the intervention and control groups as the primary outcome parameter of the trial. Secondary endpoints include additional lung function parameters, endurance, motor development, intelligence, and sensitivity for infectious lung diseases. Short-term safety assessment will be done after completed enrolment (n = 698) and discharge of all infants. This safety assessment will include in-hospital mortality and short-term complications.

Discussion

Robust data concerning the possible long-term benefits of prophylactic LISA treatment are lacking. The current observational data from the German Neonatal Network indicate that approximately 50% of preterm infants with supplemental oxygen at or below 30% within the first hour of life are treated with LISA. The pro.LISA trial will provide short- and long-term outcomes of preterm infants receiving prophylactic treatment and will clarify if prophylactic treatment should be given to all preterm infants or if the current practice of selective treatment if supplemental oxygen exceeds 30% is more appropriate.

Trial registration

German Clinical Trials Register DRKS00028086. Prospectively registered on 8 February 2022.
A health-risk assessment method for the preventive protection of metal cultural relics using improved rank correlation analysis and AHP fuzzy synthetic evaluation
Authors: Li Dandan , Zhou Hao , Xu Fangyuan , Yan Ying , Wu Laiming , Cai Lankun
Published: September 2023

This paper presents an innovative health-risk assessment methodology for the preventive protection of metal cultural relics in museums, which is based on the improved rank correlation analysis and AHP fuzzy synthetic evaluation (Relics—AHP—FSE). The approach combines the established ABC method for analyzing the pertinent environmental risk level. In this study, metal cultural relics are introduced as the research subjects. Based on the current scientific knowledge and requirements reported in international norms, a three-level index framework for assessing the health-risk is established in a hierarchical manner, and the quantitative indicators with typical correlations are proposed. The Relics—AHP—FSE approach is applied to the results of the 2022 temporary exhibition “Zhaizi China: Henan Xia, Shang and Zhou Dynasties civilization exhibition” of Shanghai Museum (China), a renowned institution boasting a significant collection of invaluable relics. In addition, the study accomplishes a scientific and practical health-risk assessment of relics. By utilizing online monitoring data and employing the expert judgment method, this study presents a comprehensive method for assessing the health-risk of metal cultural relics efficiently and conveniently. This cultural heritage protection method is specifically for safeguarding cultural relics exhibited in museums, developed in close collaboration with conservation scientists.
Forming Groups in a Large-Enrollment Biology Class: Group Permanence Matters More than Group Size
Authors: Connell Georgianne L. , Donovan Deborah A. , Theobald Elli J.
Published: September 2023

Students in permanent groups reported better attitudes towards working in groups and had higher group exam scores compared to students in nonpermanent groups. Students in larger groups had higher group exam scores but attitudes towards working in groups were not affected by group size.
A systematic review of repeatability and reproducibility studies of diffusion tensor imaging of cervical spinal cord
Authors: Al-shaari Hussein , J Fulford , R Meertens , CJ Heales
Published: September 2023

Objectives:

Diffusion tensor imaging (DTI) techniques are being studied as a possible diagnostic and predictive tool for the evaluation of cervical spinal cord disease. This systematic review aims to evaluate the previous DTI studies that specifically investigated the repeatability and reproducibility of DTI in the cervical spinal cord.

Methods and materials:

A search in the PubMed, Scopus, Web of Science and Ovid electronic databases was conducted for articles published between January 1990 and February 2022 that related to the repeatability and reproducibility of DTI in evaluating the cervical spinal cord using one of the following measurements: the intraclass correlation coefficient (ICC) and/or the coefficient of variation (CV), and/or Bland-Altman (BA) differences analysis methods. DTI studies that presented full statistical analysis of repeatability and/or reproducibility tests of the cervical spinal cord in peer-reviewed full-text publications published in journals were included. Articles that included at least one of the keywords within the titles or abstracts were identified. Additional full-text papers were found by searching the citations and reference lists of related articles. This review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Risk of bias was evaluated with 13 criteria weighted toward methodological quality of reported studies using the QuADS assessment criteria. This assessment only included full-text articles written in English.

Results:

A total of 11 studies were included and assessed for different characteristics, including sample size,(3–34) re-test time interval (<1 h to >3 months), test-retest reproducibility scores and acquisition method. Six studies used ICC which ranged from poor (ICC<0.37) to excellent reproducibility (ICC 0.91–0.99). Four studies reported an overall CV lower than 40% for all DTI metrics. Three studies reported the Bland-Altman (BA) differences and reported a minimum percentage showing no strong differences between repeated measurements. Quantitative analysis was not undertaken due to heterogeneity of methods. Repeatability and reproducibility measures were generally found to be good.

Conclusion:

This study revealed that the application of DTI and its related measures in a clinical setting in the assessment of cervical spinal cord changes is feasible and reproducible. However, cervical spinal cord DTI suffers from some existing limitations that prevent it from being routinely used in research and clinical settings.

Advances in knowledge:

DTI with its parametric maps provide broad evaluation of the tissue structure of axonal white matter and are being studied as a possible diagnostic and predictive tool for the assessment of cervical spinal cord (CSC) disease.