bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate immunodeficiencies: a group of primary immunodeficiencies predisposing exclusively to common diseases
Authors: Refaat Marwa , Oujane Chaymae , Kholaiq Halima , Aadam Zahra , Errami Abderrahmane , Baghad Bouchra , Boussetta Soufiane , El Kettani Assiya , Benhsaien Ibtihal , Ailal Fatima , Bourhanbour Asmaa Drissi , El Bakkouri Jalila , Bousfiha Ahmed Aziz
Published: November 2024

Background

Innate immune deficiencies can impair both cellular and humoral immune responses. In contrast, other immune functions may appear normal, leading to increased susceptibility to specific pathogens, such as severe viral infections or Mendelian Susceptibility to Mycobacterial Disease (MSMD). Studying these deficiencies is essential for understanding the pathophysiology of these infectious diseases.

Main body

While primary immunodeficiencies (PIDs) generally cause vulnerability to multiple infections, innate immunodeficiencies increase susceptibility to specific pathogens, despite normal immune responses to others. Patients with these deficiencies show normal immunoglobulins and lymphocyte subpopulations, complicating diagnosis. This review highlights genetic susceptibility to mycobacteria, pneumococci, herpes simplex virus, and candidiasis, emphasizing recognizing this subset of PIDs.

Conclusion

This review highlights the diverse spectrum of genetic mutations contributing to defects in innate and intrinsic immunity, including Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis, and predispositions to invasive bacterial and viral infections. Identifying key mutations in pathprovideh such as TLR3, IFN signaling, and IL-17A/F immunity provides valuable insights into the pathogenesis of these conditions. Our findings underscore the need for early genetic diagnosis and targeted interventions, particularly in regions with high undiagnosed cases, to reduce the morbidity and mortality associated with defects in innate and intrinsic immunity.
Assessment of gastrointestinal symptoms in neurologically impaired children with PEG using peptide versus casein based formulae
Authors: Tarek Sara , Eskander Ayman E. , Younis Alaa Mohamed , Salama Christine G. , ElNaggar Walaa
Published: November 2024

Background

Nutritional interventions are a key strategy for sustaining general health in children with neurological impairment. Whey-based formulae have been shown to reduce gastroesophageal reflux and accelerate gastric emptying. Casein protein, on the other hand, precipitates in the stomach's acidic environment, slowing down gastric emptying.

Methods

This is a prospective observational study that included 34 children with severe neurological impairment between 2–14 years old of both sexes who underwent percutaneous endoscopic gastrostomy (P.E.G) tube insertion, gastrointestinal dysfunction symptoms and nutritional status were compared after 6 months between those fed either peptide-based (100% whey) or casein-based formula. We aimed in the current study to determine whether peptide-based formula reduces gastroesophageal reflux episodes and improves symptoms of poor feeding tolerance compared to casein-based formula, and to evaluate the impact of both formulae on the nutritional status of those children.

Results

Using peptide-based, 100% whey protein formula was associated with improved feeding tolerance and reduced gastrointestinal issues such as constipation (p-value = 0.016), reflux, and vomiting episodes (p-value = 0.034). Unlike patients who obtained the casein-based formula, patients who received the peptide-based formula exhibited significant improvement in swallowing ability 6 months after PEG insertion when compared to pre-insertion (p-value = 0.002).

Conclusion

Whey-based formula is better recommended for neurologically impaired children who have poor swallowing abilities, constipation, reflux, and vomiting episodes.
Molecular modeling and implications of Biochanin A on ghrelin and IGF-1/myostatin signaling in radiation triggered cachexia
Authors: Shaheen Aya , Gheita Heba A. , Karam Heba M. , Zaher Nashwa H. , El-Sabbagh Walaa A.
Published: November 2024

Background

Cachexia, a loss of appetite and body weight as a result of systemic inflammation, considered one of the unavoidable side effects of radiation therapy. Controlling ghrelin (Ghr) levels could assist in alleviating this condition by improving appetite, promoting energy storage, and reducing cytokines’ generation. This study aimed to explore the effect of Biochanin A (BCA), a natural bioactive isoflavone, in alleviating radiation-cachexic syndrome.

Results

Molecular docking study of BCA demonstrated strong fitting with more binding interactions than megestrol acetate (MA), a commonly prescribed medication for cachexia, into Ghr active binding site. Accordingly, irradiated rats were treated with BCA or MA, with body weight monitoring. Force swimming test (FST) was carried out followed by gastrocnemius muscle weighting and histological examination. Biochemical assay of Ghr, TNF-α, insulin growth factor-1 (IGF-1), myostatin (Mst), lactate dehydrogenase (LDH), and brain serotonin (5-HT) level, were carried in order to estimate the possible action pathway of BCA. Results showed that BCA improved weight gain and histological muscle bundle arrangement. Although, BCA and MA significantly reduced serum TNF-α by 25.6% and 24.2%, respectively, only BCA maintained normal IGF-1and Mst levels, whose balance is necessary to avoid skeletal muscle loss, the main mark of cachexia. Moreover, BCA showed tissue injury mitigation with normal energy expenditure by significantly suppressing LDH (20.5%) and maintaining normal 5-HT level.

Conclusion

By preserving the appropriate IGF-1 and MST metabolic balance and keeping muscle homeostasis, BCA, with its high Ghr binding interaction and anti-inflammatory properties, could have an impact on radiation cachectic syndrome.
Development and optimization of multivesicular gefitinib liposomal transdermal system employing lipoid S100 for breast cancer: pharmacokinetics, bioavailability, and skin irritation studies in Wistar rats
Authors: Patel Jyoti S. , Raghavendra Nulgumnalli Manjunathaiah , Sajeev Kumar B.
Published: November 2024

Background

Conventional therapies in cancer treatment face challenges including drug resistance, lack of specificity, and severe adverse reactions. This study explores the potential of liposomal transdermal delivery systems as an alternative to current therapies with improved BA and PK. The objective of the study was to formulate gefitinib liposomes by thin film hydration technique (TFH) using lipoid S100. A central composite design (CCD) was used to develop and optimize GEF-LIP-TDDs and to analyze the optimum concentrations of the selected variables (phospholipid, cholesterol) in liposomal formation. The model fitting was performed using Design-Expert (Stat-Ease, Ver 13). The GEF liposomes were evaluated for %EE, mean particle size and PDI. The optimized liposomes were fabricated as a transdermal patch by mercury substrate method and evaluated for %drug content, in vitro diffusion, in vivo biodistribution (PK and BA), and skin irritation studies in female Albino Wistar rats. The stability of the optimized transdermal patch was also assessed for 3 months.

Results

The CCD model was significant with F-value of 37.97, P-value of 0.0500 and R2 of 0.9644. The average vesicle size, PDI, and ZP of GEF-LIPs (F1–F13) were found to be between 112.8 to 373.7 nm, 0.186 to 0.510 and − 3.69 to − 82.2 mV, respectively. F3-GEF-LIP exhibited a mean vesicle size of 96.07 nm, ZP of − 46.06 mV, and a PDI of 0.423. F3-GEF-LIP demonstrated exceptional %EE (97.79) and sustained release effect (%CDR, 83.32) following a diffusion-controlled mechanism. TEM images confirmed liposomes of multivesicular type (MVV, < 100 nm). Importantly, optimized F3-GEF-LIP-TD showed no signs of edema in Wistar rats. The biodistribution of F3-GEF-LIP-TD was similar to pure GEF and was higher in the liver (p < 0.05). The BA of F3-GEF-LIP-TD was observed to be 74.05 ± 0.11% in comparison with oral GEF-LIP (65.25 ± 0.08%) and pure GEF (58.10 ± 0.17%).

Conclusion

TFH technique offers stable liposomes with high reproducibility. Our findings imply that GEF-LIP-TD provides enhanced BA and tissue distribution and can be considered as a substitution for orals or in combination for treating breast cancer. Lipoid S100 is a potential lipid for developing stable multivesicular nanoliposomes.

Graphical abstract
Chrna2-driven CRE Is Expressed in Beige Adipocytes
Authors: Zhu Kezhou , Liu Shanshan , Huang Yunying , Zhang Biyang , Houssein Nadia , Wu Jun
Published: November 2024

Significant research interest has been focused on beige adipocytes, the activation of which improves glucose and lipid homeostasis, therefore representing new therapeutic opportunities for metabolic diseases. Various Cre/Lox-based strategies have been used to investigate the developmental history of beige adipocytes and how these cells adapt to environmental changes. Despite the significant advancement of our understanding of beige adipocyte biology, much of the molecular insights of the beige adipocyte, including its origin and cell type-specific function, remain to be further illustrated. It has previously been shown that Chrna2 (cholinergic receptor nicotinic alpha 2 subunit) has selective functionality in beige adipocytes. In this study, we explore the Chrna2-Cre-driven reporter expression in mouse beige adipocytes in vivo and in vitro. Our findings indicate that Chrna2-Cre expression is present selectively in multiple locular beige adipocytes in subcutaneous inguinal white adipose tissue (iWAT) and differentiated stromal vascular fraction from iWAT. Chrna2-Cre expression was detected in iWAT of young pups and mice after cold exposure where a significant number of beige adipocytes are present. Chrna2-Cre-driven reporter expression is permanent in iWAT postlabeling and can be detected in the iWAT of adult mice or mice that have been housed extensively at thermoneutrality after cold exposure, even though only “inactive dormant” beige adipocytes are present in these mice. Chrna2-Cre expression can also be increased by rosiglitazone treatment and β-adrenergic activation. This research, therefore, introduces the Chrna2-Cre line as a valuable tool for tracking the development of beige adipocytes and investigating beige fat function.
Neurological Surgery Manpower Training and Density in Islamic Republic of Iran: A Population Study
Authors: Aarabi Bizhan , Tabatabaei Seyed Mahmood , Farrokhi Majid Reza , Khalili Hosseinali , Nejat Farideh , Samini Fariborz , Akhtar-Danesh Noori
Published: November 2024

BACKGROUND AND OBJECTIVES:

Significant disparities in worldwide neurosurgical training and workforce distribution are prominent primarily in low-income and middle-income countries. Although Iran is considered a lower middle–income country, neurosurgical density and distribution in Iran has surpassed the recommended ratio of 1 neurosurgeon for every 100 000 population. The objective was to determine neurological surgery density and distribution in Iran and the factors significant in the relative success in training and allocation of neurosurgeons in Iran.

METHODS:

Review of PubMed and administration of site surveys of multiple data sources including Neurosurgical Society of Iran, Iranian Board of Neurological Surgery, Medical Council of Islamic Republic of Iran, Universities of Medical Sciences in Iran, and Ministry of Health and Higher Education of Iran.

RESULTS:

Over the 72-year period from 1952 to 2024, 1200 neurosurgeons have been trained and distributed in 31 provinces in Iran, attaining a ratio of 1.4/100 000 population. All but 40 neurosurgeons were trained after 1981, which coincided with the Iran-Iraq War. Decentralization of medical and neurosurgical residency training programs, resolving the immediate need for neurosurgeons managing penetrating traumatic brain and spinal cord injuries during the 1980 to 1988 Iran-Iraq War, and active participation of legislative and executive branches of government in solving health care disparities were major factors in meeting the needs of the country. At the present time, more than 555 neurosurgeons are practicing in Tehran Province, a proportion of 3.8 neurosurgeons for every 100 000 population, which indicates an element of disparity in density distribution across Iranian land.

CONCLUSION:

Legislative initiatives and government support of public health care delivery and decentralization of medical and residency training programs after the Iran-Iraq War and introduction of the Ministry of Health and Medical Education are considered the main reasons for the relative success in meeting the neurosurgical demand and manpower density. Still, further adjustment of distribution of manpower is needed.
The ClearPoint Prism® Laser Ablation System: A New Platform for Laser Interstitial Thermal Therapy (LITT) in Neuro-Oncology
Authors: Wilson Hannah , Dhawan Sanjay , Do Truong Huy , Jones Samuel H. , Chen Clark C.
Published: November 2024

BACKGROUND AND OBJECTIVES:

Laser interstitial thermal therapy (LITT) has advanced the surgical treatment of brain cancer. However, technical constraints in the first-generation laser ablation systems limit the full potential of this technology. The ClearPoint Prism® Laser Ablation System was developed to overcome many of these limitations, including a larger ablation window, a faster refresh rate for magnetic resonance thermometry, and integration with an MRI-compatible stereotactic system. This system was US Food and Drug Administration–cleared for neurosurgical use in 2022.

METHODS:

As an IDEAL Stage 1 study, we prospectively followed the first 3 patients who underwent LITT using the ClearPoint Prism® Laser Ablation System in the United States to establish feasibility and safety of this technology platform.

RESULTS:

Three patients underwent procedures involving MRI-guided needle biopsy followed by LITT. The radial error of stereotaxis relative to the intended target ranged from 0.8 to 1.6 mm (with a median of 1.0 mm). Definitive diagnosis was achieved in all cases. The average time required to establish the trajectories was 98.7 ± 16.6 minutes. The average time required to perform the biopsy and LITT was 110 ± 19.3 minutes. These times are not statistically different from our published results for comparable procedures using other available LITT systems. The average LITT time required to achieve ablation of >1 cm radius was 49 seconds (range: 29-133 seconds). There were no procedural complications. All patients were discharged home by postoperative day 3. The postoperative MRIs demonstrated expected ablation findings consistent with intraoperative thermometric assessment. With a median follow-up of 219 days (range: 185-259 days), there were no 30-day readmission, 90-day emergency visits, or wound complications.

CONCLUSION:

In this study, we introduced the design rationale for the ClearPoint Prism® Laser Ablation System, theoretical considerations for its technical merits relative to other existing systems, and to share our initial experience.
A Scoping Review on Vestibulopathy After Microsurgical Resection of Vestibular Schwannoma—The Forgotten Symptom
Authors: Bambakidis Evangeline , Mowry Sarah , Amin-Hanjani Sepideh
Published: November 2024

BACKGROUND AND OBJECTIVES:

Although half of patients with vestibular schwannoma (VS) experience some form of vestibular dysfunction, it is rarely the most prominent symptom. The effect of VS resection on preexisting vestibulopathy remains poorly understood. Our objective was to perform a scoping review to elucidate the incidence and role of postoperative vestibulopathy after microsurgery (MS) as it relates to long-term quality of life (QOL) and predictors of recovery and to identify optimal management of vestibulopathy as a presenting symptom.

METHODS:

Studies were identified using the PubMed database published in the English language peer-reviewed recent literature (2000-2023) using MeSH and tiab terms, and additional studies identified from a secondary review of reference lists.

RESULTS:

Thirty-one articles were selected and reviewed. The literature quotes a wide range for the incidence of postoperative vestibulopathy after MS (4%-100%). Persistent vertigo universally demonstrates a strong negative effect on long-term QOL. Potential predictors of poor vestibular compensation include sex, advanced age, and tumor size. Few studies examine postoperative vertigo compared with preoperative baseline. Studies are inconsistent and variable in their use of measurement tools to assess vestibulopathy and QOL. Improvement in baseline vestibulopathy can be seen in long-term post-MS, particularly in patients with severe or disabling vertigo, although outcomes relative to other treatment modalities are otherwise similar.

CONCLUSION:

Further understanding of predictors and comparative management strategies for vestibulopathy would be valuable in addressing an important negative influence on QOL in patients with VS. Prospective studies factoring preoperative baseline and using standardized measurement tools are needed.
The role of therapeutic MicroRNA in arteriogenesis process in limb ischemia: A systematic review
Authors: Ismail Muhamad Taufik , Anggrahini Dyah Wulan , Haryana Sofia Mubarika , Setianto Budi Yuli
Published: November 2024

Background Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral artery disease (PAD) and has poor clinical outcomes. Recently, stimulating arteriogenesis has been proposed to improve clinical outcomes. Several studies have shown that miRNAs have beneficial effects on limb ischemia related to arteriogenesis. This study aimed to review the roles of therapeutic miRNAs in the arteriogenesis of limb ischemia. Methods A systematic search was conducted through July 2021 using the PubMed, Scopus, and ScienceDirect databases. Two authors independently assessed studies that investigated the role of miRNAs in the arteriogenesis of limb ischemia, both in vivo and in clinical studies. Results All selected studies were in vivo studies, with a total of 36 articles and 28 types of miRNAs. miRNAs potentially regulate arteriogenesis by targeting different targets. The following miRNAs were upregulated to enhance arteriogenesis: miRNA-126-3p, -93, -675, -143-3p, -130a, -210, -146b, -21, -let-7g, -132/212, -150, and 155. Meanwhile, microRNAs needed to be downregulated, namely: miRNA-939-5p, -503, -199a-5p, -146a, -92a, -14q32 microRNA gene cluster, -15a/16, -100, -133a, -139-5p, -223, -352, -615-5p, -15b/5p, -124-3p, and 29a. MiRNA-126 was the most studied miRNA, and SPRED1 was the most common target of microRNA. However, the included studies showed high heterogeneity in terms of inducing hindlimb ischemia, the timing of administration, and the method used for evaluating arteriogenesis. Moreover, most studies presented unclear or high-risk bias. Conclusion MicroRNA application in a preclinical model of hindlimb ischemia has beneficial effects on arteriogenesis. This result indicates that miRNAs might be potentially beneficial in patients with CLTI. Registration The review protocol was registered with PROSPERO under registration number CRD42024484988.
Teaching Self-efficacy and Teaching Methods in the Aquatic Environment
Authors: Fonseca-Pinto Rita , Moreno-Murcia Juan Antonio
Published: November 2024

Background Studies have shown that perceived self-efficacy can influence teachers’ emotional state, thoughts and behaviours, and students’ learning. It’s also an important referential of professional satisfaction. In turn, teaching methodologies influence motor learning, as well as psychological, cognitive and social learning, with different impacts on human development and learning retention, levels of intrinsic motivation and continuity of practice in order to support a healthy lifestyle. Research on aquatic educators and teaching methodologies is scarce and at the same time necessary according to the view that aquatic literacy is an integral part of physical literacy and the only possibility of being more able to interact with this environment. Methods In this study we used an online questionnaire, aimed at aquatic professionals, which was answered voluntarily and anonymously to measure the prevalence of the use of different teaching methodologies, the comprehensive aquatic method and the perception of teacher self-efficacy. It has been deposited and can be consulted at https://doi.org/10.6084/m9.figshare.27316242.v1. Results All methods can generate a feeling of self-efficacy in teachers despite having different results, with the methodologies that involve students more actively (cognitivist and constructivist) being those that generate a greater feeling of self-efficacy in teachers. MAC is a method that is more closely related to methodologies focused on active student participation and, consequently, it is a method that generates a high perception of self-efficacy in teachers. Conclusions Levels of self-efficacy influence professional satisfaction, teacher physical, mental and emotional health, as well as student learning. Is recommended that aquatic professionals give prevalence to the cognitivist and constructivist teaching methodologies being MAC a privileged methodological approach for promoting active lifestyle habits throughout life.
Interventions targeting the reduction or discontinuation of long-term use of benzodiazepine receptor agonists: protocol for an overview of systematic reviews
Authors: Coteur Kristien , Ryan Cristín , Smith Susan M , Sheaf Greg , DeWert Marjorie , Gardner David , Cadogan Cathal
Published: November 2024

Background Benzodiazepine receptor agonists (BZRAs) are commonly prescribed to treat anxiety and insomnia. Although guidelines recommend limiting prescriptions to short-term use (<4 weeks), BZRAs are often continued long-term. Due to the associated risks (e.g. memory impairment, falls/fractures), it is recommended that long-term BZRA use should be discontinued. Several systematic reviews have studied the effectiveness of pharmacological and non-pharmacological interventions targeting long-term BZRA use; however, an overview of the evidence across intervention types and healthcare settings is lacking. Aim To identify and narratively synthesise systematic reviews that assess the effectiveness of interventions targeting the reduction or discontinuation of long-term BZRA use. Methods An overview of systematic reviews will be conducted. Five electronic databases (MEDLINE, Embase, Web of Science, PsycINFO, CINAHL) will be searched for systematic reviews of randomised controlled trials of interventions targeting the reduction or discontinuation of long-term BZRA use in adults in any setting. All types and combinations of interventions are eligible for inclusion (e.g. psychosocial interventions, pharmacological interventions). Interventions will be evaluated against usual care. Article screening and data extraction will be conducted by two reviewers independently. Overlap in primary publications will be assessed by calculating the corrected covered area and graphically represented. Methodological quality of included reviews will be assessed using the AMSTAR-2 tool. Results will be synthesised narratively. The certainty of evidence will be assessed using the GRADE approach. Conclusions This overview of reviews will narratively synthesise the evidence from systematic reviews of the effectiveness of interventions targeting long-term BZRA use. The review will provide an extensive overview of the existing evidence, which will inform future research and policy decisions about interventions for reducing and discontinuing long-term BZRA use.
Parametrizing analog multi-compartment neurons with genetic algorithms
Authors: Stock Raphael , Kaiser Jakob , Müller Eric , Schemmel Johannes , Schmitt Sebastian
Published: November 2024

Background Finding appropriate model parameters for multi-compartmental neuron models can be challenging. Parameters such as the leak and axial conductance are not always directly derivable from neuron observations but are crucial for replicating desired observations. The objective of this study is to replicate the attenuation behavior of an excitatory postsynaptic potential (EPSP) traveling along a linear chain of compartments on the analog BrainScaleS-2 neuromorphic hardware platform. Methods In the present publication we use genetic algorithms to find suitable model parameters. They promise parameterization without domain knowledge of the neuromorphic substrate or underlying neuron model. To validate the results of the genetic algorithms, a comprehensive grid search was conducted. Furthermore, trial-to-trial variations in the analog system are counteracted utilizing spike-triggered averaging. Results and conclusions The algorithm successfully replicated the desired EPSP attenuation behavior in both single and multi-objective searches illustrating the applicability of genetic algorithms to parameterize analog neuromorphic hardware.
Organophosphate and carbamate susceptibility profiling of Anopheles gambiae sl. across different ecosystems in southern Benin
Authors: Dossou Camille , Tchigossou Genevieve , Koto Massioudou , Atoyebi Seun Michael , Tossou Eric , Adanzounon Danahé , Ateutchia Ngouanet Sandra , Sina Haziz , Djègbè Innocent , Gbankoto Adam , Wondji Charles , Djouaka Rousseau
Published: November 2024

Background To overcome the spread of high pyrethroid resistance in the main malaria vectors and malaria disease persistence, it is crucial to look for effective and better resistance management strategies. Understanding the phenotypic profile of Anopheles gambiae sl. against alternatives insecticides like organophosphates and carbamates is crucial. Methods Anopheles larvae and pupae were collected from the breeding sites in rice fields, pineapple crop areas, and peri-urban areas. WHO susceptibility tests were conducted on unfed female mosquitoes aged 3–5 days old. Mosquitoes were exposed to malathion 5%, pirimiphos-methyl 0.25%, and bendiocarb 0.1% using the standard WHO protocol. Polymerase chain reaction (PCR) techniques were used to detect species, kdr and Ace-1 mutations. Results Anopheles gambiae sl. from Sèdjè-Dénou rice field population was resistant to bendiocarb (0.1%) with a mortality rate of 72.2% whereas Anopheles gambiae sl. populations from Zinvié-Dokomey (rice field), Zè-Tozounmè (pineapple field), and Adjagbo (peri-urban area) were suspected to be resistant with mortality rates of 90%, 93.5%, 95.4% respectively. However, all of them were susceptible to organophosphates (malathion and pirimiphos-methyl) with a mortality rate of 100%. PCR assay revealed that 100% of the mosquitoes tested were Anopheles coluzzii. The frequencies of Ace-1R mutation in all Anopheles coluzzii populations tested were low (3–27%). Conclusions Organophosphates (malathion and pirimiphos-methyl) have maintained their efficacy against Anopheles coluzzii populations from Sèdjè-Dénou (rice field), Zè Tozounmè (pineapple field), Zinvié Dokomey (rice field), or Adjagbo (peri-urban area). The good efficacy of these organophosphates against Anopheles coluzzii populations from the southern part of Benin are observed in the current study. The use of pirimiphos-methyl for IRS in this part of the country would be a successful alternative for malaria control in this area.
Evaluation of a six-minute walk test in the DE50-MD canine model of Duchenne muscular dystrophy and its effect on blood-borne biomarkers
Authors: Riddell Dominique , Harron Rachel , Hildyard John , Wells Dominic , Piercy Richard
Published: November 2024

Background Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease caused by mutations in the dystrophin gene resulting in cycles of muscle degeneration, inflammation and regeneration. The 6-minute walk test (6MWT) is a key functional outcome measure for DMD patient clinical trials and has been adapted for use in animal models of the disease. The DE50-MD dog model of DMD closely reflects the DMD patient phenotype prior to loss of ambulation. For pre-clinical trials using this model, functional outcome measures must be established. Methods This longitudinal study compared distance walked in a 6MWT by DE50-MD and WT control dogs and assessed the utility of the 6MWT as a functional biomarker. Dogs underwent two 6MWTs conducted approximately 48-hours apart, at 3, 6, 9, 12, 15 and 18 months of age. In addition, we evaluated the stability of selected blood-borne biomarkers in 12-month old DE50-MD and WT dogs 0, 3, 6, 24 and 48 hours following a 6MWT. Results DE50-MD dogs exhibited significantly shorter 6-minute walk distance (6MWD) than WT dogs at all timepoints (P<0.05), with no difference in 6MWD between the first and second 6MWT. C-C motif chemokine ligand 2 (CCL2), myomesin-3 (MYOM3) and myostatin (MSTN) were biomarkers of the DE50-MD phenotype that remained unchanged in DE50-MD dogs following the 6MWT, while creatine kinase (CK) activity significantly increased 3-hours following the test in DE50-MD dogs but remained unchanged in WT dogs. Conclusions The 6MWT effectively discriminates DE50-MD from WT dogs aged 3-18 months and a single 6MWT is sufficient for future studies. Serum MYOM3, CCL2 and MSTN are good biomarkers of the DE50-MD phenotype that are unaffected by this relatively low level exertion.
Energia odnawialna w województwie zachodniopomorskim
Authors: Igliński Bartłomiej , Kiełkowska Urszula , Pietrzak Michał , Skrzatek Mateusz
Published: November 2024

The book presents the current status and prospects for the development of renewable energy in the West Pomeranian Voivodeship. The voivodeship can cover 100% of its energy needs from renewable energy and additionally be an exporter of this energy.
Zakład ubezpieczeń jako pokrzywdzony z art. 49 § 3 Kodeksu postępowania karnego
Authors: Gołdyn-Badowiec Renata
Published: November 2024

This monograph is a study concerning the issue of participation in criminal proceedings of an insurance company as an injured party to the extent to which it has covered the damage caused to the injured party by a crime or is obliged to cover it. The addressed subject refers to the issues related to, among others, the right of the injured party, i.e. the insurance company, to a fair criminal trial, its representation in criminal proceedings, its rights in criminal proceedings as an injured party under Article 49 § 3 of the Code of Criminal Procedure, its pursuit of civil-law claims in criminal proceedings under the provision of Article 49 § 3 of the Code of Criminal Procedure, the obligation of the perpetrator of a traffic accident to compensate for damage in the context of the insurance company's obligation to compensate for damage under third party liability insurance for motor vehicle owners or the impact of the curtailment benefit on the position of the insurance company as an injured party in criminal proceedings. The book also presents proposals for legislative solutions in the context of the continued validity of the provision of Article 49 § 3 of the Code of Criminal Procedure or the possibility of pursuing civil-law claims by an insurance company in criminal proceedings.   The considerations undertaken in this monograph refer not only to the analysis of regulations of broadly understood criminal law, but also civil law (both substantive law and, in some considerations, procedural law), with particular emphasis on business insurance law.  In the context of the right of the injured party, i.e. the insurance company, to a fair criminal trial, the norms of constitutional and international law (primarily the European Convention on Human Rights), as well as the rulings of the European Court of Human Rights and the Constitutional Tribunal, have been considered. The book also contains the current views of the doctrine and a rich collection of case law, collected in one place, as well as the results of case file research on the participation of the insurance company in criminal proceedings as an injured party under the provisions of Article 49 § 3 of the Code of Criminal Procedure.
AI-BASED AUTOMATED VARUS/VALGUS ALIGNMENT MEASUREMENT IN STANDARD KNEE RADIOGRAPHS
Authors: Cullen D. , Thompson P. , Johnson D. , Lindner C.
Published: November 2024

Introduction

Accurate assessment of alignment in pre-operative and post-operative knee radiographs is important for planning and evaluating knee replacement surgery. Existing methods predominantly rely on manual measurements using long-leg radiographs, which are time-consuming to perform and are prone to reliability errors. In this study, we propose a machine-learning-based approach to automatically measure anatomical varus/valgus alignment in pre-operative and post-operative standard AP knee radiographs.

Method

We collected a training dataset of 816 pre-operative and 457 one-year post-operative AP knee radiographs of patients who underwent knee replacement surgery. Further, we have collected a separate distinct test dataset with both pre-operative and one-year post-operative radiographs for 376 patients. We manually outlined the distal femur and the proximal tibia/fibula with points to capture the knee joint (including implants in the post-operative images). This included point positions used to permit calculation of the anatomical tibiofemoral angle. We defined varus/valgus as negative/positive deviations from zero. Ground truth measurements were obtained from the manually placed points. We used the training dataset to develop a machine-learning-based automatic system to locate the point positions and derive the automatic measurements. Agreement between the automatic and manual measurements for the test dataset was assessed by intra-class correlation coefficient (ICC), mean absolute difference (MAD) and Bland-Altman analysis.

Result

Analysing the agreement between the manual and automated measurements, ICC values were excellent pre-/post-operatively (0.96, CI: 0.94-0.96) / (0.95, CI: 0.95-0.96). Pre-/post-operative MAD values were 1.3°±1.4°SD / 0.7°±0.6°SD. The Bland-Altman analysis showed a pre-/post-operative mean difference (bias) of 0.3°±1.9°SD/-0.02°±0.9°SD, with pre-/post-operative 95% limits of agreement of ±3.7°/±1.8°, respectively.

Conclusion

The developed machine-learning-based system demonstrates high accuracy and reliability in automatically measuring anatomical varus/valgus alignment in pre-operative and post-operative knee radiographs. It provides a promising approach for automating the measurement of anatomical alignment without the need for long-leg radiographs.

Acknowledgements

This research was funded by the Wellcome Trust [223267/Z/21/Z].
CASPASES-1/-8 AND CHONDROCYTES: DRUG TARGET EFFECT AND OSTEOARTHRITIS PATHOLOGY
Authors: Mei J. , Pasoldt A. , Matalova E. , Graessel S.
Published: November 2024

Introduction

Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration, inflammation, and pain. Current treatments provide only symptomatic relief, necessitating novel molecular targets. The caspase family, known for its roles in apoptosis and inflammation regulation, may additionally influence crucial processes for cartilage homeostasis such as differentiation and proliferation. However, the specific roles of individual caspases in OA pathogenesis remain unclear. This study aims to investigate the involvement of the caspase family in OA and as potential targets for therapy, with a focus on caspase-1 and -8.

Method

Chondrocytes from both healthy and OA donors were cultured in 2D and 3D culture models and stimulated with TNF-α or IL-1β. The expression and activation of caspase-1 and -8 was assessed using RT-PCR, ELISA. Transcriptome analysis of OA and healthy cartilage samples, along with Mendelian randomization (MR) analysis were conducted to explore the involvement of caspase family in OA and to assess its potential as therapeutic targets.

Result

Higher expression levels of caspase-1, -8 were observed in OA cartilage compared to healthy cartilage. TNF-α stimulation increased their expression in both healthy and OA chondrocytes, while IL-1β had limited impact. Caspase-8 expression was causally associated with knee OA in MR analysis, suggesting a potential therapeutic target. The caspase-1 inhibitor VX-765 mildly reduced chondrocyte viability, with no significant effect in the presence of TNF-α. While the caspase-8 inhibitor Z-IETD-FMK exhibited slight enhancements in cell viability, these improvements were not statistically significant. Nevertheless, its effectiveness significantly increased in the presence of TNF-α.

Conclusion

This study highlights the involvement of caspase-1 and caspase-8 in OA pathology, with caspase-8 emerging as a potential therapeutic target for knee OA treatment. Further investigation into the roles of caspase-1 and -8 in OA pathophysiology, including the efficacy and potential side effects of their corresponding inhibitors, is warranted.

Acknowledgements

Funding Inter-Action/Inter-Excellence project (BTHA-JC-2022-36/LUABA22019)
ENHANCING BIOMECHANICAL SPINE MODELS WITH NON-LINEAR RHYTHMS
Authors: Lund M. , Shayestehpour H.
Published: November 2024

Introduction

This research aims to enhance the control of intricate musculoskeletal spine models, a critical tool for comprehending both healthy and pathological spinal conditions. State-of-the-art musculoskeletal spine models incorporate segments for all vertebra, each possessing 3 degrees-of-freedom (DOF). Manually defining the posture with this amount of DOFs presents a significant challenge. The prevalent method of equally distributing the spine's overall rotation among the vertebrae often proves to be an inadequate assumption, particularly when dealing with the entire spine.

Method

We have engineered a comprehensive non-linear spine rhythm and the requisite tools for its implementation in widely utilized musculoskeletal modelling software (1). The rhythm controls lateral bending, axial rotation, and flexion/extension. The mathematical and implementation details of the rhythm are beyond this abstract, but it's noteworthy that the implementation accommodates non-linear rhythms. This means, for example, that one set of rhythm coefficients is used for flexion and another for extension. The rhythm coefficients, which distinguish the movement along the spine, were derived from a review of spine literature. The values for spine and vertebra range-of-motion (ROM) vary significantly in published studies, and no complete dataset was found in any single study. Consequently, the rhythm presented here is a composite, designed to provide the most consistent and average set of rhythm coefficients.

Result

The novel spine rhythm simplifies the control of detailed spine models, accommodating varying amounts of input data. It allows for the specification of only the overall motion or the posture at a more detailed level (i.e., lumbar, thoracic, neck). The tools and rhythm coefficients are publicly available on GitHub.

Conclusion

The innovative spine rhythm enhances the usability of cutting-edge spine models. For flexion/extension of the spine, it introduces a non-linear rhythm, exhibiting distinct behaviour between flexion and extension - a feature not previously observed in musculoskeletal spine models.

1) The AnyBody Modeling System
PREOPERATIVE PREDICTORS OF HIP ABDUCTOR FOR GAIT SPEED IMPROVEMENT AFTER TOTAL HIP ARTHROPLASTY FOR PATIENTS WITH OSTEOARTHRITIS
Authors: Yasuda T. , Ota S. , Mitsuzawa S. , Yamashita S. , Tsukamoto Y. , Takeuchi Hi. , Onishi E.
Published: November 2024

Introduction

A recent study to identify clinically meaningful benchmarks for gait improvement after total hip replacement (THA) has shown that the minimum clinically important improvement (MCII) in gait speed after THA is 0.32 m/sec. Currently, it remains to be investigated what preoperative factors link to suboptimal recovery of gait function after THA. This study aimed to identify preoperative lower-limb muscle predictors for gait speed improvement after THA for hip osteoarthritis.

Method

This study enrolled 58 patients who underwent unilateral primary THA. Gait speed improvement was evaluated as the subtraction of preoperative speed from postoperative speed at 6 months after THA. Preoperative muscle composition of the glutei medius and minimus (Gmed+min) and the gluteus maximus (Gmax) was evaluated on a single axial computed tomography slice at the bottom end of the sacroiliac joint. Cross-sectional area ratio of individual composition to the total muscle was calculated.

Result

The females (n=45) showed smaller total cross-sectional areas of the gluteal muscles than the males (n=13). Gmax in the females showed lower lean muscle mass area (LMM) and higher ratios of the intramuscular fat area and the intramuscular adipose tissue area to the total muscle area (TM) than that in the males. Regression analysis revealed that LMM/TM of Gmed+min may correlate negatively with postoperative improvement in gait speed. Receiver operating characteristic curve analysis for prediction of MCII in gait speed at ≥ 0.32 m/sec resulted in the highest area under the curve for Gmax TM with negative correlation. The explanatory variables of hip abductor muscle composition predicted gait speed improvement after THA more precisely in the females compared with the total group of both sexes.

Conclusion

Preoperative Gmax TM could predict gait speed MCII after THA. Preoperative muscle composition should be evaluated separately based on sexes for achievement of clinically important improvement in gait speed after THA.
Food Insecurity among Women Involved in the Criminal Legal System and Members of their Risk Network
Authors: Robles Jessica , Kershaw Trace , Meyer Jaimie P.
Published: November 2024

Abstract: Background. People affected by the criminal legal system face significant challenges accessing food assistance. Methods. We estimated the prevalence of food insecurity among women involved in the criminal legal system (WICL) and members of their risk network using a secondary analysis. Results. Among 104 participants, over one-third were food insecure, 97% of whom lived in an economically disadvantaged ZIP Code. Compared with those who were not food-insecure (N=67), people who were food-insecure (N=37) were more often married, unemployed, and had a severe psychiatric disorder. In bivariate and multivariate models, food insecurity was associated with the same factors and not with race/ethnicity, education, number of dependents, monthly income, or type of CL involvement. Conclusion. Among WICL, we found widely prevalent food insecurity. In an economically disadvantaged ZIP Code, food insecurity compounds other social determinants to drive health disparities. Eliminating policies that restrict access to food assistance is important for ensuring that WICL can meet basic subsistence needs.
Wavelength optimization of fine optical surface defect detection based on FDTD
Authors: Wang Shaowen , Lan Wu , Wang Shiling , Liu Dong , Guo Shiwei , Wang Xulongqi , Jin Bingwen , Deng Zhiji , Cheng Miao , Liu Ming , Fu Zhewei
Published: November 2024

Due to the similar order of magnitude of the defect size and the detection wavelength, when detecting micro-/nano-scale defects on the surface of a fine optical component, the intense modulation of the optical field poses challenges in correlating imaging widths of defects with actual widths. A dark-field scattering imaging (DFSI) model, based on the finite difference time domain (FDTD) method, is established to study the imaging for triangular and circular section defects and investigate the influence of wavelength on defect width detection. Simulated results indicate that a shorter wavelength of the light source in a DFSI detection system leads to a larger mapping range between the imaging width and the actual defect width, which makes calibration less difficult. A DFSI detection system for micro-/nano-scale surface defects on optical components is built to test defects with rectangular cross-sections on a calibration board. The defect widths estimated from the experimental and simulated results are in good agreement, with a root-mean-square error (RMSE) of 0.11 µm.
Complex-valued generative adversarial network for real-time and high-quality computer-generated holography
Authors: Qin Haifeng , Han Chao , Shi Xuan , Gu Tao , Sun Kangsheng
Published: November 2024

Real-time generation of high-quality phase-only hologram (POH) is a critical challenge in holographic display. Deep learning-based computer-generated holography (CGH) offers innovative solutions to this challenging problem. In this paper, a complex-valued generative adversarial network (CV-GAN) is proposed for the real-time generation of high-quality POHs. Firstly, a complex-valued U-shaped network (U-Net) is designed as the generator of CV-GAN, which is able to process complex-valued data directly, thereby improving the learning efficiency of the network. Secondly, a complex-valued sub-pixel convolution up-sampling strategy is proposed and an adversarial learning mechanism is established to enhance the fitting ability of the network. Finally, the band-limited angular spectrum method is embedded into the neural network, allowing the CV-GAN to be trained in an unsupervised manner. The proposed algorithm generates high-quality 1920 × 1072 resolution POHs with an average peak-signal-to-noise ratio (PSNR) of 33.68 dB and an average structural similarity index measure (SSIM) of 0.95 at a speed of 51.63 frames per second (FPS) on the DF2K validation dataset. Both numerical reconstructions and optical experiments demonstrate that CV-GAN exhibits excellent fitting ability and lightweight network architecture, capable of generating high-quality POHs efficiently.
Concentrations of potentially toxic metals and trace elements in pregnant women and association with birth outcomes: A cross-sectional study in Malawi
Authors: Mwapasa Mphatso , Xu Shanshan , Chakhame Bertha Magreta , Maluwa Alfred , Röllin Halina , Choko Augustine , Huber Sandra , Odland Jon Øyvind
Published: November 2024

Potentially toxic metals and trace elements have been used in Malawi for a long time. However, data on exposure to these elements by susceptible groups like pregnant women and its associations with reproductive health outcomes in Malawi and southern hemisphere is limited. We investigated the concentrations of potentially toxic metals as well as trace elements in pregnant women and assessed the relationship between the levels these elements in maternal blood and sociodemographic factors, dietary habits and birth outcomes. Maternal data was collected from 605 pregnant women. Provider administered questionnaire was used to collect data on maternal sociodemographic factors, life style and immediate birth outcomes. Maternal venous blood samples were collected from 506 pregnant women in southern Malawi between August 2020 and July 2021. An inductively coupled plasma mass spectrometry (ICP-MS) technique was used to analyse maternal blood samples for concentrations of arsenic (As), copper (Cu), lead (Pb), mercury (Hg), nickel (Ni), selenium (Se) and zinc (Zn). Maternal age emerged as the primary predictor for Cu (p = 0.023), As (p = 0.034) and Hg (p = 0.013) blood concentrations, followed by area of residence, which had significant impact on Ni (p = 0.024) and As (p < 0.001) concentrations. High maternal blood concentrations of Ni were associated with increased birth weight (p = 0.047), birth length (p = 0.026), head circumference (p = 0.029) and gestational age (p = 0.035). Negative associations were observed between maternal whole blood total arsenic (combining organic and inorganic As) concentration and neonatal birth length (p = 0.048) and head circumferences (p < 0.001). Similarly, higher maternal blood Pb concentrations were associated with smaller head circumference (p = 0.002) and birth weight (p = 0.016). This study demonstrates the need to introduce biomonitoring studies in Malawi and countries with similar settings in the global south.