bluuebunny/crossref_metadata_2025 huggingface dataset:
Immersive virtual reality for learning exoskeleton-like virtual walking: a feasibility study
Authors: Rodríguez-Fernández Antonio , den Berg Alex van , Cucinella Salvatore Luca , Lobo-Prat Joan , Font-Llagunes Josep M. , Marchal-Crespo Laura
Published: November 2024

Purpose

Virtual Reality (VR) has proven to be an effective tool for motor (re)learning. Furthermore, with the current commercialization of low-cost head-mounted displays (HMDs), immersive virtual reality (IVR) has become a viable rehabilitation tool. Nonetheless, it is still an open question how immersive virtual environments should be designed to enhance motor learning, especially to support the learning of complex motor tasks. An example of such a complex task is triggering steps while wearing lower-limb exoskeletons as it requires the learning of several sub-tasks, e.g., shifting the weight from one leg to the other, keeping the trunk upright, and initiating steps. This study aims to find the necessary elements in VR to promote motor learning of complex virtual gait tasks.

Methods

In this study, we developed an HMD-IVR-based system for training to control wearable lower-limb exoskeletons for people with sensorimotor disorders. The system simulates a virtual walking task of an avatar resembling the sub-tasks needed to trigger steps with an exoskeleton. We ran an experiment with forty healthy participants to investigate the effects of first- (1PP) vs. third-person perspective (3PP) and the provision (or not) of concurrent visual feedback of participants’ movements on the walking performance – namely number of steps, trunk inclination, and stride length –, as well as the effects on embodiment, usability, cybersickness, and perceived workload.

Results

We found that all participants learned to execute the virtual walking task. However, no clear interaction of perspective and visual feedback improved the learning of all sub-tasks concurrently. Instead, the key seems to lie in selecting the appropriate perspective and visual feedback for each sub-task. Notably, participants embodied the avatar across all training modalities with low cybersickness levels. Still, participants’ cognitive load remained high, leading to marginally acceptable usability scores.

Conclusions

Our findings suggest that to maximize learning, users should train sub-tasks sequentially using the most suitable combination of person’s perspective and visual feedback for each sub-task. This research offers valuable insights for future developments in IVR to support individuals with sensorimotor disorders in improving the learning of walking with wearable exoskeletons
Blood-brain barrier permeability increases with the differentiation of glioblastoma cells in vitro
Authors: Digiovanni Sabrina , Lorenzati Martina , Bianciotto Olga Teresa , Godel Martina , Fontana Simona , Akman Muhlis , Costamagna Costanzo , Couraud Pierre-Olivier , Buffo Annalisa , Kopecka Joanna , Riganti Chiara , Salaroglio Iris Chiara
Published: November 2024

Background

Glioblastoma multiforme (GBM) is an aggressive tumor, difficult to treat pharmacologically because of the blood-brain barrier (BBB), which is rich in ATP-binding cassette (ABC) transporters and tight junction (TJ) proteins. The BBB is disrupted within GBM bulk, but it is competent in brain-adjacent-to-tumor areas, where eventual GBM foci can trigger tumor relapse. How GBM cells influence the permeability of BBB is poorly investigated.

Methods

To clarify this point, we co-cultured human BBB models with 3 patient-derived GBM cells, after separating from each tumor the stem cell/neurosphere (SC/NS) and the differentiated/adherent cell (AC) components. Also, we set up cultures of BBB cells with the conditioned medium of NS or AC, enriched or depleted of IL-6. Extracellular cytokines were measured by protein arrays and ELISA. The intracellular signaling in BBB cells was measured by immunoblotting, in the presence of STAT3 pharmacological inhibitor or specific PROTAC. The competence of BBB was evaluated by permeability assays and TEER measurement.

Results

The presence of GBM cells or their conditioned medium increased the permeability to doxorubicin, mitoxantrone and dextran-70, decreased TEER, down-regulated ABC transporters and TJ proteins at the transcriptional level. These effects were higher with AC or their medium than with NS. The secretome analysis identified IL-6 as significantly more produced by AC than by NS. Notably, AC-conditioned medium treated with an IL-6 neutralizing antibody reduced the BBB permeability to NS levels, while NS-conditioned medium enriched with IL-6 increased BBB permeability to AC levels. Mechanistically, IL-6 released by AC GBM cells activated STAT3 in BBB cells. In turn, STAT3 down-regulated ABC transporter and TJ expression, increased permeability and decreased TEER. The same effects were obtained in BBB cells treated with STA-21, a pharmacological inhibitor of STAT3, or with a PROTAC targeting STAT3.

Conclusions

Our work demonstrates for the first time that the degree of GBM differentiation influences BBB permeability. The crosstalk between GBM cells that release IL-6 and BBB cells that respond by activating STAT3, controls the expression of ABC transporters and TJ proteins on BBB. These results may pave the way for novel therapeutic tools to tune BBB permeability and improve drug delivery to GBM.
Latent factors underlying the symptoms of adult-onset myotonic dystrophy type 1 during the clinical course
Authors: Zhang Yanan , Wallace Bailey , Cai Bo , Johnson Nicholas , Ciafaloni Emma , Venkatesh Yedatore Swamy , Westfield Christina , McDermott Suzanne
Published: November 2024

Background

Myotonic dystrophy type 1 (DM1) is a multisystem genetic disorder that classically presents with symptoms associated with myotonia, early onset cataracts, and muscular weakness, although the presentation and pattern of disease progression is quite varied. Presenting symptoms are well documented among adults with DM1. However, less is known about the co-occurrence of symptoms over time. We aimed to use factor analysis to explore the correlation pattern of signs and symptoms (S/S) that emerged during the clinical course.

Results

Clinical records of 228 individuals with adult onset DM1 were abstracted using the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) from a six-site cohort in the United States during an eight-year study period. Factor analysis was used to group the correlated S/S into latent factors. Three factors were identified. Group 1: ‘Facial Weakness/Myotonia’ includes the two most common S/S, as indicated by its name. Group 2: ‘Skeletal Muscle Weakness’ includes eight muscular S/S and is more frequently reported by males and those with older age at onset. Group 3: ‘Gastrointestinal distress/Sleepiness’ includes four non-muscular S/S and hand stiffness. The abstracted medical records reported that over 63% of individuals had S/S from all three groups. Associations of covariates with factor scores were also examined using linear regression. CTG repeat length was significantly positively associated with higher factor scores for all three factors.

Conclusions

This study identified three latent factors of S/S which accumulated during the clinical course of adult onset DM1.
Mapping the diagnostic odyssey of congenital disorders of glycosylation (CDG): insights from the community
Authors: Granjo Pedro , Pascoal Carlota , Gallego Diana , Francisco Rita , Jaeken Jaak , Moors Tristen , Edmondson Andrew C. , Kantautas Kristin A. , Serrano Mercedes , Videira Paula A. , dos Reis Ferreira Vanessa
Published: November 2024

Background

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases with heterogeneous presentations, leading to substantial diagnostic challenges, which are poorly understood. Therefore, this study aims to elucidate this diagnostic journey by examining families’ and professionals’ experiences.

Results and discussion

A questionnaire was designed for CDG families and professionals, garnering 160 and 35 responses, respectively. Analysis revealed the lack of seizures as a distinctive feature between PMM2-CDG (11.2%) with Other CDG (57.7%) at symptom onset. Hypotonia and developmental disability were prevalent symptoms across all studied CDG. Feeding problems were identified as an early onset symptom in PMM2-CDG (Cramer’s V (V) = 0.30, False Discovery Rate (FDR) = 3.8 × 10− 9), and hypotonia in all studied CDG (V = 0.34, FDR = 7.0 × 10− 3). The average time to diagnosis has decreased in recent years (now ~ 3.9 years), due to advancements namely the increased use of whole genome and exome sequencing. However, misdiagnoses remain prevalent (PMM2-CDG – 44.9%, non-PMM2-CDG – 64.8%). To address these challenges, we propose adapting medical training to increase awareness of CDG and other rare diseases, ongoing education for physicians, the development of educational resources for relevant medical units, and empowerment of families through patient organizations and support networks.

Conclusion

This study emphasizes the crucial role of community-centered research, and the insights families can offer to enhance CDG management. By pinpointing existing gaps and needs, our findings can inform targeted interventions and support systems to improve the lives of those impacted by CDG.
Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study
Authors: Jaeger B. , Hoytema van Konijnenburg E. , Groenveld M. A. , Langeveld M. , Wolf N. I. , Bosch A. M.
Published: November 2024

Background

Riboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital.

Methods

A systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing.

Results

EHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital.

Conclusions

By screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.
Paclitaxel- or sirolimus-coated balloons used for ArterioVEnous fistulas-2 (PAVE-2): study protocol for a randomised controlled trial to determine the efficacy of paclitaxel- or sirolimus-coated balloons in arteriovenous fistulas used for haemodialysis
Authors: Karunanithy Narayan , Norton Sam , Calder Francis , Das Neelanjan , Dooley Niamh , Hakobyan Lusine , Jones Robert , Padayache Soundrie , Spriggs Chloe , Steiner Kate , Suckling Rebecca , Robson Michael G.
Published: October 2024

Background

In view of the conflicting results from previous studies, the benefit of paclitaxel-coated balloons for arteriovenous fistulas is uncertain and equipoise remains. Although an industry-led trial testing the efficacy of sirolimus-coated balloons in AVFs is in progress, the benefit of sirolimus-coated balloons for arteriovenous fistulas is currently unknown. The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon fistuloplasty to preserve the patency of arteriovenous fistulae used for haemodialysis.

Methods

The study design is a multicentre randomised controlled trial. Following a successful plain balloon fistuloplasty, participants will be randomised to further treatment with a paclitaxel-coated balloon, a sirolimus-coated balloon, or an uncoated control balloon. We will recruit 642 patients, each with one or two treatment segments, over a 3-year period. Patients will remain in the trial and be followed up for 1 year. The primary endpoint is time to loss of treatment segment primary patency. Cox-proportional hazards models will be used to estimate hazard ratios for the time to loss of treatment segment primary patency for each treatment group relative to the control group. Analysis of the primary endpoint will be based on treatment segments rather than participants and a shared frailty will be estimated to account for the clustering of treatment segments within patients. Secondary endpoints are time to loss of primary patency at any treatment segment; time to end of access circuit primary patency; time to AVF abandonment; number of radiological or surgical interventions; adverse events; intima-media thickness and degree of stenosis at 3 months on ultrasound; and patient quality of life assessed by EQ-5D-5L and VASQoL.

Discussion

The three-armed design in this proposal will provide an answer on the efficacy of both paclitaxel- and sirolimus-coated balloons in the same trial. This trial is likely to provide a clear answer regarding the efficacy of drug-coated balloons for arteriovenous fistulas.

Trial registration

ISRCTN ISRCTN40182296. Registered on 4 August 2023.
Effectiveness of Virtual - Compensatory Cognitive Training (V-CCT) for improving cognition in persons with schizophrenia - a multi- centre randomized controlled trial
Authors: Sims Sonia , Kantipudi Suvarna Jyothi , Ashok Yogitha , Nisha B. , Gopal Subhashini , Joseph Elsa , Amritha S. , Venkatraman Lakshmi , Venkatasubramanian Pratiksha , Ramachandran Padmavati
Published: November 2024

Background

Cognitive deficits are the core component in persons with schizophrenia which impacts their socio-occupational functioning. Also, cognitive deficits cause significant impairment with the person’s quality of life [3]. Hence, targeting such a pivotal aspect in persons with schizophrenia through suitable interventions is very important. Developed countries have designed various cognitive remediation programs using computers involving high-end software which cannot be generalized to low-resource settings, like India, due to various factors including sociocultural factors, educational standards, and living standards of the patient population. Compensatory cognitive training (CCT) was developed to be “brief, practical, low-tech” and found to be effective in the west [9]. As there are no structured cognitive intervention modules in India, we have adapted the English CCT manual to be used for an urban population in Chennai, India. CCT was found to be feasible in face-to-face group sessions in our setting [12] and is found to be feasible and acceptable as virtual one–one intervention (unpublished data). Therefore, this study aims to evaluate the effectiveness of V-CCT in enhancing cognition and socio-occupational functioning.

Methods

The proposed study will be a multicenter assessor-blinded randomized controlled trial at two clinical sites in Chennai, India. The preparatory phase of the study would include translation of the manual to the local language, recruitment and training of research assistants, and pilot testing using the translated manual. The second phase will be the main randomized controlled trial (RCT), during which a total of 160 persons diagnosed with schizophrenia will be recruited from both sites. After obtaining informed consent, baseline assessments will be conducted on cognition, functioning, self-esteem, and quality of life. Participants will be randomly assigned to either the virtual CCT group or the control group using a computer-generated randomization table. End-line assessments will be conducted 6 weeks after the baseline by research assistants who are blinded to the randomization post-intervention.

Discussion

If V-CCT is found to be effective, it will be available for use in Tamil for persons with schizophrenia, and it will have an effect on their functioning, quality of life, and self-esteem.

Trial registration

The study is registered under Clinical trial registry-India (CTRI), and the registration number is CTRI/2024/04/065267. Registered on April 2024.
A novel stability-indicating chromatographic quantification of the antiparkinsonian drug safinamide in its pharmaceutical formulation employing HPTLC densitometry and ion-pair HPLC–DAD
Authors: Ibrahim Engy A. , Saad Samah S. , Hegazy Maha A. , Abdel Fattah Laila E. , Marzouk Hoda M.
Published: November 2024

Parkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC–DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively.
Ribosomal proteins in hepatocellular carcinoma: mysterious but promising
Authors: Su Qian , Sun Huizhen , Mei Ling , Yan Ying , Ji Huimin , Chang Le , Wang Lunan
Published: November 2024

Ribosomal proteins (RPs) are essential components of ribosomes, playing a role not only in ribosome biosynthesis, but also in various extra-ribosomal functions, some of which are implicated in the development of different types of tumors. As universally acknowledged, hepatocellular carcinoma (HCC) has been garnering global attention due to its complex pathogenesis and challenging treatments. In this review, we analyze the biological characteristics of RPs and emphasize their essential roles in HCC. In addition to regulating related signaling pathways such as the p53 pathway, RPs also act in proliferation and metastasis by influencing cell cycle, apoptosis, angiogenesis, and epithelial-to-mesenchymal transition in HCC. RPs are expected to unfold new possibilities for precise diagnosis and individualized treatment of HCC.
Semi-automated title-abstract screening using natural language processing and machine learning
Authors: Pilz Maximilian , Zimmermann Samuel , Friedrichs Juliane , Wördehoff Enrica , Ronellenfitsch Ulrich , Kieser Meinhard , Vey Johannes A.
Published: November 2024

Background

Title-abstract screening in the preparation of a systematic review is a time-consuming task. Modern techniques of natural language processing and machine learning might allow partly automatization of title-abstract screening. In particular, clear guidance on how to proceed with these techniques in practice is of high relevance.

Methods

This paper presents an entire pipeline how to use natural language processing techniques to make the titles and abstracts usable for machine learning and how to apply machine learning algorithms to adequately predict whether or not a publication should be forwarded to full text screening. Guidance for the practical use of the methodology is given.

Results

The appealing performance of the approach is demonstrated by means of two real-world systematic reviews with meta analysis.

Conclusions

Natural language processing and machine learning can help to semi-automatize title-abstract screening. Different project-specific considerations have to be made for applying them in practice.
Prediction of the R3 Test-Based Reactivity of Supplementary Cementitious Materials: A Machine Learning Approach Utilizing Physical and Chemical Properties
Authors: Yoon Jinyoung , Yonis Aidarus , Park Sungwoo , Rajabipour Farshad , Pyo Sukhoon
Published: November 2024

This study utilized machine learning (ML) models to investigate the effect of physical and chemical properties on the reactivity of various supplementary cementitious materials (SCMs). Six SCMs, including ground granulated blast furnace slag (GGBFS), pulverized coal fly ash (FA), and ground bottom ash (BA), underwent thorough material characterization and reactivity tests, incorporating the modified strength activity index (ASTM C311) and the R3 (ASTM C1897) tests. A data set comprising 46 entries, derived from both experimental results and literature sources, was employed to train ML models, specifically artificial neural network (ANN), support vector machine (SVM), and random forest (RF). The results demonstrated the robustness of the ANN model, achieving superior prediction accuracy with a testing mean absolute error (MAE) of 9.6%, outperforming SVM and RF models. The study classified SCMs into reactivity classes based on correlation analysis, establishes a comprehensive database linking material properties to reactivity, and identifies key input parameters for predictive modeling. While most SCMs exhibited consistent predictions across types, GGBFS displayed significant variations, prompting a recommendation for the inclusion of additional input parameters, such as fineness, to enhance predictive accuracy. This research provided valuable insights into predicting SCM reactivity, emphasizing the potential of ML models for informed material selection and optimization in concrete applications.
Effects and interactions of dietary lysine and apparent nitrogen corrected metabolizable energy on yellow-feathered broiler breeder hens
Authors: Wang Yibing , Wang Qin , Yao Xiangtian , Gou Zhongyong , Lin Xiajing , Luo Qili , Jiang Shouqun
Published: November 2024

Background

Dietary lysine and apparent nitrogen-corrected metabolizable energy (AMEn) are two key variables affecting the production of breeder hens. In this study, the effects and interactions of lysine and AMEn on yellow-feathered broiler breeder hens were investigated. A total of 720 30-week-old breeder hens were fed in a 5 (lysine: 0.56%, 0.68%, 0.80%, 0.92%, and 1.04%) × 2 (AMEn: 11.50 and 11.10 MJ/kg) factorial arrangement for 12 weeks. The productive performance, reproductive traits, biochemical variables of breeder hens, the amino acid concentration and quality of eggs, and the growth performance of offspring broilers were determined.

Result

(1) Dietary lysine had quadratic effects (P < 0.05) on laying rate, average daily egg mass and feed intake/egg mass of breeder hens; birds with 11.50 MJ/kg AMEn (high AMEn) had higher (P < 0.05) BW than those with 11.10 MJ/kg AMEn (low AMEn); (2) dietary lysine significantly affected on the relative ovarian weight (quadratic and linear), and numbers of large yellow follicles (LYF, quadratic); birds with high AMEn had longer fallopian tube and more LYF than those with low AMEn (P < 0.05); (3) dietary lysine had significant effects (linear and quadratic) on eggshell thickness and shell strength of eggs from breeder hens; birds with high AMEn had thinner eggshells and deeper yolk color than those with low AMEn (P < 0.05); (4) there were higher (P < 0.05) contents of protein and concentrations of all measured animo acids (AAs) in eggs from birds fed low AMEn; (5) supplementation with high AMEn to breeder hens significantly increased the hatchability of fertilized eggs; (6) neither dietary lysine level or AMEn affected growth performance of offspring broilers; (7) both dietary lysine level and AMEn significantly affected gonadotropin concentrations and biochemical variables of breeder hens.

Conclusions

Dietary lysine had significant influences on productive performance, reproductive traits, and egg quality of yellow-feathered breeder hens. Based on productive performance, the optimal levels of dietary lysine were 0.81% to 0.83%, while 0.71% to 72% lysine was enough to obtain the best quality of breeding eggs. High AMEn was more beneficial to breeder hens for reproductive traits and hatchability of the fertilized eggs, while it showed detrimental effects on eggshell thickness and AA concentrations of breeding eggs.
Vertical targeting of the PI3K/AKT pathway at multiple points is synergistic and effective for non-Hodgkin lymphoma
Authors: Kupcova Kristyna , Senavova Jana , Jura Filip , Herman Vaclav , Rajmonova Anezka , Pacheco-Blanco Mariana , Chrbolkova Tereza , Hamova Iva , Davis R. Eric , Havranek Ondrej
Published: November 2024

The phosphatidylinositol 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway is critically active in many cell types, both normal and neoplastic. Many small-molecule inhibitors targeting different levels of the PI3K/AKT pathway have been developed for cancer therapy, but their efficacy is reduced by compensatory pathway re-activation mechanisms, and their tolerability by toxic side effects. We studied this problem using cell lines representing diffuse large B-cell lymphoma (SUDHL-4 and OCI-Ly7), a genetically-encoded live-cell reporter of AKT activity, and 3 small-molecule inhibitors targeting different levels of the pathway: idelalisib (PI3Kδ), GSK2334470 (PDPK1), and ipatasertib (AKT). Half-maximal (IC50) concentrations of these inhibitors for AKT activity inhibition at 1 h, when used individually, were much lower than their IC50 values for reduction of viable cell number after 4 days. Time-course studies explained this discrepancy: AKT activity in the continuous presence of the inhibitors returned to normal after 24 h, and was supranormal after inhibitor removal. Combining all 3 inhibitors produced sustained inhibition of AKT activity, was broadly synergistic at reducing viable cell number, enabled substantially lower doses of each inhibitor to be used, and was enhanced further by the mTOR inhibitor rapamycin. Moreover, combined PDPK1 and AKT inhibition showed synergy with multiple different PI3K inhibitors. In a syngeneic mouse cell line model of lymphoma (A20), the triple combination showed antitumor activity and no evidence of toxicity. Our findings provide proof of concept suggesting further study of the safety and efficacy of low-dose multilevel PI3K/AKT pathway inhibition, for lymphoma and perhaps other cancers.
Rockery morphology based on quantitative analysis of shading
Authors: Wang Yuan , Pan Ben , Zhang Qingping
Published: November 2024

The rockeries of classical Chinese gardens are masterpieces of classical Chinese garden art and form a key element of garden heritage. Consequently, a quantitative study of “rockery shadows” is of considerable importance to the study of “rockery forms.” In this study, we selected the representative North Rockery in Zhanyuan Garden of Nanjing and Ruiyunfeng, Guanyunfeng, and Yulinglong as the objects of the study. This study aims to explore the shadow images of rockeries using image extraction and targeted quantitative analysis methods. Macroscopically, the overall shape of rockery shadows was described using fractal dimensions; microscopically, the aspect ratio, angle, and refinement indexes of each shadow based on each observation angle of the rockery were measured using the PAT-GEOM plug-in in ImageJ software. SPSS Statistics was used for the normal distribution test of the angular distribution data. Consequently, the shadow data of the North Rockery in Zhanyuan Garden and Ruiyunfeng, Guanyunfeng, and Yulinglong, respectively, were analyzed and compared, and four rockery-shadow laws were derived. Finally, the results were applied to the design of the rockery morphological translation based on quantitative analysis of the shadows. The approach presented here will enhance landscape design, support environmental planning, and preserve cultural heritage.
Transcriptomics-guided optimization of vitamins to enhance erythromycin yield in saccharopolyspora erythraea
Authors: Ke Xiang , Jiang Xing , Wang Shuohan , Tian Xiwei , Chu Ju
Published: November 2024

Comparative transcriptomics uncovered distinct expression patterns of genes associated with cofactor and vitamin metabolism in the high-yielding mutant strain Saccharopolyspora erythraea HL3168 E3, as compared to the wild-type NRRL 2338. An in-depth analysis was conducted on the effects of nine vitamins, and it was determined that thiamine pyrophosphate (TPP), vitamin B2, vitamin B6, vitamin B9, vitamin B12, and hemin are key enhancers in erythromycin production in E3, increasing the erythromycin titer by 7.96–12.66%. Then, the Plackett-Burman design and the path of steepest ascent were applied to further optimize the vitamin combination for maximum production efficiency, enhancing the erythromycin titer in shake flasks by 39.2%. Otherwise, targeted metabolomics and metabolic flux analysis illuminated how vitamin supplementation modulates the central carbon metabolism with notable effects on the TCA cycle and methionine synthesis to augment the provision of energy and precursors essential for erythromycin synthesis. This work highlights the capacity for precise vitamin supplementation to refine metabolic pathways, thereby boosting erythromycin production, and provides valuable directions for application on an industrial scale.

Graphical Abstract
A review of the application of in-vivo confocal microscopy on conjunctival diseases
Authors: Yu Mingyi , Liu Chang , Mehta Jodhbir S. , Liu Yu-Chi
Published: November 2024

Over the past few decades, the expanded applications of in-vivo confocal microscopy (IVCM) have greatly enhanced the knowledge of a variety of conjunctival diseases. IVCM allows non-invasively detailed observation of tarsal, palpebral and bulbar conjunctiva, from the superficial to the substantia propria at the cellular level. IVCM has been shown as a powerful tool for the assessment of morphological changes in both physiological and pathological conditions. High-resolution images of different cellular phenotypes, together with quantifiable results, open new insights into understanding the mechanisms of conjunctival diseases, as well as provide valuable and longitudinal information for the diagnosis and therapeutic evaluation. This review aims to provide an overview of the current knowledge on the applications of IVCM on conjunctival disorders, including aging changes, dry eye-related morphological changes, glaucoma and glaucoma surgery-related morphological changes, conjunctival neoplasm, pterygium, allergic conjunctivitis, trachomatous scarring, and the conjunctiva-associated lymphoid tissue (CALT) changes. In this review, we highlight the key findings of previous studies and discusses the current limitations and challenges of IVCM in assessing the structural characteristics of the conjunctiva. Furthermore, we consider possible future directions for unlocking the full potential of IVCM applications. The insights presented here will contribute to a more comprehensive understanding of the applications of IVCM in conjunctival diseases.
Development and feasibility of a sex- and gender-sensitive primary care intervention for patients with chronic non-cancer pain receiving long-term opioid therapy (GESCO): a study protocol
Authors: Kersting Christine , Just Johannes , Piotrowski Alexandra , Schmidt Alexandra , Kufeld Neele , Bisplinghoff Rebecca , Maas Michaela , Bencheva Veronika , Preuß Jordan , Wiese Birgitt , Weckbecker Klaus , Mortsiefer Achim , Thürmann Petra ,   on behalf of the GESCO study group, Duck Michaela , Schmiedl Sven , Bahrs Ottomar , Cegla Thomas , Elsenbruch Sigrid , Levenig Claudia , Hunger-Schoppe Christina , Kiessling Claudia , Klee Ulrich , Lauf Ursula , Scholz Brigitte , Moser Albine , Scherbaum Norbert , Specka Michael
Published: November 2024

Background

Chronic non-cancer pain (CNCP) is a common condition worldwide. The disease burden is influenced not only by pain itself, but also by psychiatric co-morbidities, which aggravate symptoms, generally negatively influence therapies, and may thereby lead to frustration, resignation, or withdrawal. A growing body of evidence suggests that sex and gender aspects influence CNCP management as the experience of pain, the emotions associated with it, and the expression of pain may differ between women and men. In addition, doctor-patient communication is known to be influenced by gender stereotypes. Despite there being evidence on such differences, current guidelines do not consider sex- and gender-sensitive approaches. In order to examine how to adequately address the diversity of the experience and processing of pain in patients of differing sex and gender, the GESCO study aims at developing and pilot testing a sex- and gender-sensitive intervention for patients with CNCP receiving long-term opioid therapy (LTOT) in primary care.

Methods

The development process is designed in accordance with the first two phases of the UK Medical Research Council. Phase I will iteratively explore, develop, and pilot the intervention’s modules using literature searches, interviews, and workshops involving stakeholders and experts. Phase II will pilot-test the novel intervention in a sample of 40 patients with CNCP under LTOT from ten general practices using an effectiveness-implementation hybrid design including a mixed-methods process evaluation focusing on implementation strategy criteria and a single-arm, pre-post comparison to determine preliminary effects in preparation for a larger effectiveness trial. The intervention will combine in-person educational sessions for general practitioners and tools to be used in patient care.

Discussion

The intervention aims to improve CNCP management in primary care by empowering practitioners to reflect on their attitudes towards pain and stereotypes. Besides sex and gender aspects, awareness of other factors that might affect the care process, such as age, social conditions, or culture, is also promoted. The intention is to develop a comprehensive care concept for CNCP that considers aspects relevant for sex- and gender-sensitive care which are transferrable to other health care fields as well.

Trial registration

German Clinical Trial Register DRKS00029980.
The financial benefits of health engagement programs to life insurers
Authors: Lee Hae Kang
Published: November 2024

Life insurance companies, as equity stakeholders in policyholders’ lives, have incentives to mitigate their health risks. I introduce a framework that enables life insurers to evaluate the financial viability of developing and implementing health engagement programs. By leveraging a proprietary big database of health and mortality information from a large U.S. life insurer, I use machine learning techniques to quantify the benefits and use a rational addiction model to calculate the costs associated with these programs. The estimated net benefit available to the life insurer from the smoking cessation program is USD 87 million and the aggregate benefit from including other chronic conditions is USD 872 million. I explore the broader application of this framework in a general health policy context.
Investigating differentiated instruction and the contributing factors to cater EFL students’ needs at the collegial level
Authors: Tajik Omid , Noor Shagofah , Golzar Jawad
Published: November 2024

Teaching language has challenges for many reasons, including learners’ backgrounds, learning styles, motivation, and socio-economic status. However, EFL students can benefit from differentiation across the learning continuum to a large extent. This study investigated Afghan EFL learners’ perceptions of differentiated instruction and the factors that contributed to catering to their needs. This study revolved around five main elements of differentiated instruction: learning environment, content, process, product, and assessment. In this study, a questionnaire was developed and distributed to 102 EFL students at Herat University, Afghanistan, to record their perceptions of differentiated instruction in their classes. Three teachers of the English department at the same university were also interviewed to understand their experiences implementing differentiated instruction and identify their tensions. Data from the survey and interviews highlight that while DI requires significant teacher commitment and time, properly designed classes catering to learner specifics can enhance efficiency and be reused in future heterogeneous settings. The study’s results suggested that it is practical to implement differentiated instruction in mixed-level, large, heterogeneous classrooms.
Amlodipine increases risk of primary open-angle glaucoma
Authors: Lehrer Steven , Rheinstein Peter H.
Published: November 2024

Background

The use of calcium channel blockers is associated with primary open-angle glaucoma (POAG) in a statistically meaningful but minor way. In general, those who had received calcium channel blocker medication were at a 23% increased risk of developing glaucoma in comparison to those who had never taken the antihypertensive drugs. We wished to confirm this association and examine POAG genes that might be involved, since the genetics has not yet been analyzed.

Methods

We used MedWatch and UK Biobank data to evaluate the effects of amlodipine on POAG and intraocular pressure (IOP). We analyzed three POAG-associated single-nucleotide polymorphisms: rs9913911, an intron variant in growth arrest-specific 7 (GAS7), one of the genes that influences IOP; rs944801, an intron variant within CDKN2B-AS1, and rs2093210, an intron variant within SIX6, known to be associated with vertical cup-disc ratio, an important optic nerve head parameter that is often used to define or diagnose glaucoma.

Results

Amlodipine use in MedWatch doubled the prevalence of POAG, from 0.0805 to 0.177%, a small but significant increase. Multivariate analysis by logistic regression of UK Biobank data revealed that POAG risk was significantly increased with age, male sex, major alleles of rs9913911 (GAS7) and rs944801 (CDKN2B-AS1), and minor allele of rs2093210 (SIX6). Amlodipine increased POAG risk by 16.1% (P = 0.032). Amlodipine has not been associated with increased IOP. We confirmed this lack of association and in addition found that GAS7, associated with IOP, was not associated with POAG risk and amlodipine. But CDKN2B-AS1 and SIX6, POAG genes not associated with IOP, were associated with POAG and amlodipine.

Conclusions

Amlodipine, a frequently prescribed drug and first line treatment for hypertension, has a potentially hazardous relationship with POAG. Knowledge of this link can guide the prescribing of alternate drugs for hypertensive individuals who have glaucoma or are at risk for it. Diuretics and β-blockers are not associated with POAG or increased IOP and could be substituted for amlodipine in hypertensive patients at risk POAG.

Trial registration

None.

Graphical Abstract
Assessing pain management in total joint arthroplasty using the Detroit interventional pain assessment scale—A prospective cohort study
Authors: Boggs Lauryn J. , Patel Ishan , Holyszko Melina , Little Bryan E. , Darwiche Hussein F. , Vaidya Rahul
Published: November 2024

Background

Total joint arthroplasty (TJA) is an effective treatment for end-stage osteoarthritis, but postoperative pain has been poorly managed. The purpose of this study was to (1) assess how much narcotic medication was prescribed after TJA; (2) assess if patients were satisfied with their pain management; (3) compare these same data between total hip arthroplasty (THA)/total knee arthroplasty (TKA); (4) compare these same data between preoperative opioid users/opioid-naïve patients.

Methods

An IRB-approved prospective study was conducted at a US academic joint replacement practice. Patients were evaluated by an independent observer at three weeks, three months, and six months postoperatively using the Detroit Interventional Pain Assessment (DIPA) scale. Patients verbally rated their pain with their current medication regimen as 0 (no pain), 1 (tolerable pain), or 2 (intolerable pain) on the DIPA scale. Narcotic usage was verified by the Michigan Automated Prescription System (MAPS). Patients were divided into THA, TKA, previously on opioids, and opioid-naïve groups. Provider efficiency scores reflected pain management satisfaction and were calculated as the percentage of patients reporting no pain or tolerable pain.

Results

Out of 200 patients, the percentage of patients using narcotics and their daily usage (MMEs) significantly decreased from 75.5% (27.5 MMEs) at three weeks to 42.9% (5.3 MMEs) at six months (P < 0.001). In 80% of patients, narcotics taken at six months were prescribed by outside providers. Significantly fewer patients used narcotics at six months for THA (15.4%) compared to TKA (52.7%) (P < 0.021). There was a significant difference in daily narcotic usage between patients who took narcotics preoperatively (22.9 MMEs) and opioid-naïve ones (13.4 MMEs) (P < 0.001). Provider efficiency scores were best at three weeks (76.6%) and three months (70%) but declined at six months (57.2%).

Conclusions

Narcotic tapering practices were observed as postoperative daily narcotic intake decreased across six months. However, outside providers prescribed 80% of narcotics at six months, necessitating a better-coordinated practice with surgeons. Patients taking preoperative narcotics experienced higher daily MME requirements than their opioid-naïve counterparts. In terms of the percentage of patients on narcotics, THA is a better procedure for tapering patients off narcotics by six months.
Business research on Industry 4.0: a systematic review using topic modelling approach
Authors: Islam Md Nazrul , Hossain Md Mofazzal , Ornob Md Shafayet Shahed
Published: November 2024

The number of theoretical and empirical literature on Industry 4.0 research has seen tremendous growth over the past few years. We seek to identify and classify the popular research topics published on Industry 4.0 in business and economics literature using a novel approach. First, we performed a co-occurrence analysis and found Industry 4.0 to have the strongest connection with innovation, implying the indispensability of innovation for the fourth industrial revolution. Further, we employed LDA-based topic modelling to identify the most frequent terms and labelled eight different topics based on the quantitative value of each term. Finally, we reviewed the relevant literature for each topic identified through the topic modelling process. Our literature review reveals that the concentration of existing literature is model-focussed. This study provides quantitative evidence of frequent occurrences of popular terms. We conclude that future studies should focus more on empirical measurement of the benefits of transiting towards the fourth industrial revolution.
Application of novel fabricated ballastless track on new designed long-span urban bridges
Authors: Yang Yi , Xin Tao , Li Qiuyi , Wang Sen , Dai Chuanqing , Kong Chao
Published: November 2024

Fabricated ballastless track has witnessed increasingly wide application in large-span bridges of municipal railways. The current ballastless track standard is applicable to bridges with a main span of 200 m to 400 m. For the main span is longer than 400 m, it is necessary to ensure the travelling safety and comfort on the fabricated tracks. In this study, static and dynamic analysis models of train-track-bridge are established to explore the influence of complex ambient temperature changes and concrete shrinkage and creep on bridge deformation, followed by the analysis of the deformation coordination between long-span bridge and fabricated ballastless tracks, thereby revealing the dynamic response of the train-track-bridge system under the complex influence of temperature. The results show that when a train runs at a speed of 160 km/h, the existing ballastless track design standard is still applicable to a bridge span of 688 m. Compared with CRTS type III track, the adoption of the novel prefabricated ballastless track on long-span urban bridges provides higher safety and greater comfort, with comprehensive power performance improved by more than 10%. This design comprehensively takes into account the deformation coordination and dynamic performance of the rail bridge, providing a basis for the design and application of fabricated ballastless tracks on long-span bridges of urban railways.
Customizing GPT for natural language dialogue interface in database access
Authors: Kim Jin-Dong , Okubo Kousaku
Published: November 2024

The paper presents Anatomy3DExplorer, a customized ChatGPT designed as a natural language dialogue interface for exploring 3D models of anatomical structures. It illustrates the significant potential of large language models (LLMs) as user-friendly interfaces for database access. Furthermore, it showcases the seamless integration of LLMs and database APIs, within the GPTS framework, offering a promising and straightforward approach.
Memorial
Authors: Monk Dave
Published: November 2024

Dave Ridyard, 1959–2024