bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric properties of Arabic-translated-related quality of life scales for people with parkinson disease: a scoping review
Authors: Azaiez Chiraz , Chalghaf Naser , Tannoubi Amayra , Guelmami Noomen , Srem-Sai Medina , Quansah Frank , Hagan John Elvis , Sneni Heifa , Boussayala Ghada , Ghalmi Imane , Lami Mazin Inhaier , Bragazzi Nicola Luigi , Mandigout Stephane , Ayed Choukri ben , Azaiez Fairouz
Published: September 2024

Background

Parkinson’s disease (PD) substantially contributes to poor functional outcomes, loss in productivity, and poor health-related quality of life (HRQoL). Despite the existence of various scales, there is a notable gap in existing HRQoL reviews with regard to the availability of Arabic validated scales. As a response to this gap, the aim of our scoping review is to identify validated scales, focusing on their psychometric validation procedures, to contribute valuable insights to the understanding of HRQoL among the Arabic-speaking people with PD.

Methods

A scoping review was conducted at the end of December 2022, using the Medline and Embase databases. The focus of this review was on examining the psychometric properties and validation procedures of included scales. Articles were included in the full-text screening process if they focused on people with PD of any age, included a scale measuring HRQoL in Arabic, and were written in English, French, or Arabic.

Results

After applying inclusion/exclusion criteria, 10 studies were selected to analyze HRQoL scales validated in people with PD. However, the PDQ-39 is the only HRQol PD specific scales validated in the Arabic language. Five studies validated in people with PD were identified in the context of instrument validation (3 generic, 1 specific validated in 2 studies).

Conclusion

There are several HRQoL measurement scales for people with PD. However, only one specific HRQoL instrument has been validated in Arabic for people with PD. For the remaining instruments identified they were just used in people with PD without being validated in this population.
Programming Bordetella pertussis lipid A to promote adjuvanticity
Authors: Fathy Mohamed Yasmine , Fernandez Rachel C.
Published: September 2024

Background

Bordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines.

Results

This work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs).

Conclusion

These findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis.
Seed priming with graphene oxide improves salinity tolerance and increases productivity of peanut through modulating multiple physiological processes
Authors: Yan Ning , Cao Junfeng , Wang Jie , Zou Xiaoxia , Yu Xiaona , Zhang Xiaojun , Si Tong
Published: September 2024

Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes.
Targeting the NLRP3 inflammasome in cochlear macrophages protects against hearing loss in chronic suppurative otitis media
Authors: Schiel Viktoria , Bhattacharya Ritwija , Gupta Ankur , Eftekharian Kourosh , Xia Anping , Santa Maria Peter L
Published: September 2024

The activation of the NLRP3 inflammasome has been linked to several inflammatory and autoinflammatory diseases. Despite cases of potential hearing improvement in immune-mediated diseases, direct evidence of the efficacy of targeting this mechanism in the inner ear is still lacking. Previously, we discovered that macrophages are associated with Sensorineural Hearing loss (SNHL) in Chronic Suppurative Otitis Media (CSOM), the leading cause of this permanent hearing loss in the developing world and incurring costs of $4 to $11 billion dollars in the United States. However, the underlying mechanism remained unknown. Here, we investigate how macrophages drive permanent hearing loss in CSOM. We first confirmed the occurrence of NLRP3 inflammasome activation in cochlear macrophages in CSOM. We then revealed that Outer Hair Cells (OHCs) were protected in CSOM by macrophage depletion and subsequently confirmed the same protection in the NLRP3 knockout condition. Furthermore, we showed that therapeutic inhibition of NLRP3 inflammasome activation and downstream inhibition of IL-1β protects OHCs in CSOM. Collectively, our data demonstrates that the main driver for hearing loss in CSOM is NLRP3 inflammasome activation in cochlear macrophages and this is therapeutically targetable, leading the way for the development of interventions to prevent the leading cause of permanent hearing loss and a costly disease in the developed world.
Hybrid-3D robotic suite in spine and trauma surgery - experiences in 210 patients
Authors: Haida Dominik M. , Mohr Peter , Won Sae-Yeon , Möhlig Thorsten , Holl Mike , Enk Thorsten , Hanschen Marc , Huber-Wagner Stefan
Published: September 2024

Background

In modern Hybrid ORs, the synergies of navigation and robotics are assumed to contribute to the optimisation of the treatment in trauma, orthopaedic and spine surgery. Despite promising evidence in the area of navigation and robotics, previous publications have not definitively proven the potential benefits. Therefore, the aim of this retrospective study was to evaluate the potential benefit and clinical outcome of patients treated in a fully equipped 3D-Navigation Hybrid OR.

Methods

Prospective data was collected (March 2022- March 2024) after implementation of a fully equipped 3D-Navigation Hybrid OR (“Robotic Suite”) in the authors level 1 trauma centre. The OR includes a navigation unit, a cone beam CT (CBCT), a robotic arm and mixed reality glasses. Surgeries with different indications of the spine, the pelvis (pelvic ring and acetabulum) and the extremities were performed. Spinal and non-spinal screws were inserted. The collected data was analysed retrospectively. Pedicle screw accuracy was graded according to the Gertzbein and Robbins (GR) classification.

Results

A total ofn = 210 patients (118 m:92f) were treated in our 3D-Navigation Hybrid OR, with 1171 screws inserted. Among these patients, 23 patients (11.0%) arrived at the hospital via the trauma room with an average Injury Severity Score (ISS) of 25.7. There were 1035 (88.4%) spinal screws inserted at an accuracy rate of 98.7% (CI95%: 98.1-99.4%; 911 GR-A & 111 GR-B screws). The number of non-spinal screws were 136 (11.6%) with an accuracy rate of 99.3% (CI95%: 97.8-100.0%; 135 correctly placed screws). This resulted in an overall accuracy rate of 98.8% (CI95%: 98.2-99.4%). The robotic arm was used in 152 cases (72.4%), minimally invasive surgery (MIS) was performed in 139 cases (66.2%) and wound infection occurred in 4 cases (1,9%). Overall, no revisions were needed.

Conclusion

By extending the scope of application, this study showed that interventions in a fully equipped 3D-Navigation Hybrid OR can be successfully performed not only on the spine, but also on the pelvis and extremities. In trauma, orthopaedics and spinal surgery, navigation and robotics can be used to perform operations with a high degree of precision, increased safety, reduced radiation exposure for the OR-team and a very low complication rate.
A psychosocial bouldering intervention improves the well-being of young refugees and adolescents from the host community in Lebanon: results from a pragmatic controlled trial
Authors: Luttenberger Katharina , Baggenstos Beat , Najem Charbel , Sifri Charles , Lewczuk Piotr , Radegast Anne , Rosenbaum Simon
Published: September 2024

Background

Mental health and psychosocial support (MHPSS) is increasingly considered vital for addressing the needs of displaced communities. The mental health of young people in Lebanon, including members of the host community and refugees, has been severely affected by multiple crises. Physical activity (PA) is an effective means for enhancing mental health, but evidence of PA’s impact on mental health among forcibly displaced populations is still emerging and often varies widely across studies.

Method

In this waitlist-controlled study, we examined the effectiveness of an 8-week psychosocial bouldering group intervention offered by the nonprofit organization ClimbAID on psychological well-being, distress, self-efficacy, and social cohesion in a group of mostly Syrian refugee adolescents residing in the Bekaa Valley, Lebanon. The intervention consisted of 8 sessions and took place once a week for 2 h in a group of up to 12 adolescents with 2 trained facilitators and up to 2 volunteers, supervised by a climbing instructor and a social worker. Multilevel analyses were performed for all outcomes.

Results

233 people were included in the study. The dropout rate was approximately 33%. The IG improved significantly more than the waitlist group in terms of overall mental well-being and psychological distress. Group allocation was a significant predictor of improvements in mental well-being and psychological distress and showed a trend toward predicting self-efficacy. There was no positive impact of the intervention on social cohesion.

Conclusions

Even in complex humanitarian settings of forced displacement, a psychosocial bouldering intervention reduces psychological distress and increases well-being in a mixed group of host and refugee youth in Bekaa, Lebanon.

Trial registration

Prospectively registered with ISRCTN 13005983, registered April 1st, 2022.
In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma
Authors: Krug Adrien , Saidane Aymen , Martinello Chiara , Fusil Floriane , Michels Alexander , Buchholz Christian J. , Ricci Jean-Ehrland , Verhoeyen Els
Published: September 2024

Background

For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human disease and allows to evaluate new treatments. As in human AITL, the murine CD4+ follicular helper T (Tfh) cells are drivers of the malignancy. Therefore, chimeric antigen receptor (CAR) T cell therapy might represent a new therapeutic option.

Methods

To prevent fratricide among CAR T cells when delivering an CD4-specific CAR, we used a lentiviral vector (LV) encoding an anti-CD4 CAR, allowing exclusive entry into CD8 T cells.

Results

These anti-CD4CAR CD8-targeted LVs achieved in murine AITL biopsies high CAR-expression levels in CD8 T cells. Malignant CD4 Tfh cells were eliminated from the mAITL lymphoma, while the CAR + CD8 T cells expanded upon encounter with the CD4 receptor and were shaped into functional cytotoxic cells. Finally, in vivo injection of the CAR + CD8-LVs into our preclinical AITL mouse model carrying lymphomas, significantly prolonged mice survival. Moreover, the in vivo generated functional CAR + CD8 T cells efficiently reduced neoplastic T cell numbers in the mAITL tumors.

Conclusion

This is the first description of in vivo generated CAR T cells for therapy of a T cell lymphoma. The strategy described offers a new therapeutic concept for patients suffering from CD4-driven T cell lymphomas.
Annotation of epilepsy clinic letters for natural language processing
Authors: Fonferko-Shadrach Beata , Strafford Huw , Jones Carys , Khan Russell A. , Brown Sharon , Edwards Jenny , Hawken Jonathan , Shrimpton Luke E. , White Catharine P. , Powell Robert , Sawhney Inder M. S. , Pickrell William O. , Lacey Arron S.
Published: September 2024

Background

Natural language processing (NLP) is increasingly being used to extract structured information from unstructured text to assist clinical decision-making and aid healthcare research. The availability of expert-annotated documents for the development and validation of NLP applications is limited. We created synthetic clinical documents to address this, and to validate the Extraction of Epilepsy Clinical Text version 2 (ExECTv2) NLP pipeline.

Methods

We created 200 synthetic clinic letters based on hospital outpatient consultations with epilepsy specialists. The letters were double annotated by trained clinicians and researchers according to agreed guidelines. We used the annotation tool, Markup, with an epilepsy concept list based on the Unified Medical Language System ontology. All annotations were reviewed, and a gold standard set of annotations was agreed and used to validate the performance of ExECTv2.

Results

The overall inter-annotator agreement (IAA) between the two sets of annotations produced a per item F1 score of 0.73. Validating ExECTv2 using the gold standard gave an overall F1 score of 0.87 per item, and 0.90 per letter.

Conclusion

The synthetic letters, annotations, and annotation guidelines have been made freely available. To our knowledge, this is the first publicly available set of annotated epilepsy clinic letters and guidelines that can be used for NLP researchers with minimum epilepsy knowledge. The IAA results show that clinical text annotation tasks are difficult and require a gold standard to be arranged by researcher consensus. The results for ExECTv2, our automated epilepsy NLP pipeline, extracted detailed epilepsy information from unstructured epilepsy letters with more accuracy than human annotators, further confirming the utility of NLP for clinical and research applications.
Trade-related infrastructure and bilateral trade flows: evidence from Nigeria and its trading partners
Authors: Wahab Bashir Adelowo
Published: September 2024

This study examines the relative impacts of transport and information and communications technology (ICT) components of trade-related infrastructure on bilateral trade flows between Nigeria and its major trading partners. An augmented standard gravity model that featured variables for the transport infrastructure component and the ICT component was estimated using bilateral trade data on 22 major trading partners of Nigeria for the period 2005–2021. The panel instrumental variables technique, precisely pooled two-stage least squares technique leveraged on fixed and random effects models, was used for the analysis. The findings show that the two components of trade-related infrastructure, transportation and information and communication technology (ICT) have a significant impact on trade flows between Nigeria and its trading partners. In the exports model, the differential impact of the transport infrastructure component is higher than the ICT component, but the differential impact of the ICT component is greater in the imports model. This suggests that the efficient provision of both transport and ICT infrastructure facilitates trade, while the inefficient provision of either or both hinders it. Therefore, greater attention must be placed on improving both components.
Navigating wellness through integration: coping strategies for depression among Syrian refugees in Norway
Authors: Brea Larios Dixie
Published: September 2024

Background

Refugees frequently face the challenges of adapting to unfamiliar environments and new cultural contexts. Such adaptations emphasize the importance of coping strategies during resettlement and for individuals to successfully integrate in the new communities. Particularly for Syrian refugees in Norway, many of whom have escaped war and conflict, understanding their ways of coping with mental health problems, such as depression, is pivotal.

Method

This study used a cross-sectional study design to explore the relationship between integration aspects and coping strategies for depression from the Syrian population living in Norway. Syrian participants (N = 96) answered questions from the Brief COPE, the Hopkins symptom checklist (HSCL-13), and the Immigration Policy Lab index (IPL-12/24).

Results

Hierarchical multiple regression analysis indicated that employing a problem-focused coping strategy was significantly associated with better psychological and social integration outcomes among Syrian refugees in Norwegian society.

Conclusion

The study suggests that certain aspects of integration, such as feeling a sense of belonging and actively seeking help, significantly improve mental health outcomes for Syrian refugees. Emphasizing problem-focused coping strategies could be vital in facilitating the successful integration of refugees into Norwegian society.
Monitoring corn stover processing by the fungus Ustilago maydis
Authors: Robertz Stefan , Philipp Magnus , Schipper Kerstin , Richter Paul , Miebach Katharina , Magnus Jorgen , Pauly Markus , Ramírez Vicente
Published: September 2024

A key aspect of sustainable bioeconomy is the recirculation of renewable, agricultural waste streams as substrates for microbial production of high-value compounds. One approach is the bioconversion of corn stover, an abundant maize crop byproduct, using the fungal maize pathogen Ustilago maydis. U. maydis is already used as a unicellular biocatalyst in the production of several industrially-relevant compounds using plant biomass hydrolysates. In this study, we demonstrate that U. maydis can grow using untreated corn stover as its sole carbon source. We developed a small-scale bioreactor platform to investigate U. maydis processing of corn stover, combining online monitoring of fungal growth and metabolic activity profiles with biochemical analyses of the pre- and post-fermentation residues. Our results reveal that U. maydis primarily utilizes soluble sugars i.e., glucose, sucrose and fructose present in corn stover, with only limited exploitation of the abundant lignocellulosic carbohydrates. Thus, we further explored the biotechnological potential of enhancing U. maydis´ lignocellulosic utilization. Additive performance improvements of up to 120 % were achieved when using a maize mutant with increased biomass digestibility, co-fermentation with a commercial cellulolytic enzyme cocktail, and exploiting engineered fungal strains expressing diverse lignocellulose-degrading enzymes. This work represents a key step towards scaling up the production of sustainable compounds from corn stover using U. maydis and provides a tool for the detailed monitoring of the fungal processing of plant biomass substrates.

Graphical abstract
Quantitative SPECT imaging of 155Tb and 161Tb for preclinical theranostic radiopharmaceutical development
Authors: Koniar Helena , McNeil Scott , Wharton Luke , Ingham Aidan , Van de Voorde Michiel , Ooms Maarten , Sekar Sathiya , Rodríguez-Rodríguez Cristina , Kunz Peter , Radchenko Valery , Rahmim Arman , Uribe Carlos , Yang Hua , Schaffer Paul
Published: September 2024

Background

Element-equivalent matched theranostic pairs facilitate quantitative in vivo imaging to establish pharmacokinetics and dosimetry estimates in the development of preclinical radiopharmaceuticals. Terbium radionuclides have significant potential as matched theranostic pairs for multipurpose applications in nuclear medicine. In particular, 155Tb (t1/2 = 5.32 d) and 161Tb (t1/2 = 6.89 d) have been proposed as a theranostic pair for their respective applications in single photon emission computed tomography (SPECT) imaging and targeted beta therapy. Our study assessed the performance of preclinical quantitative SPECT imaging with 155Tb and 161Tb. A hot rod resolution phantom with rod diameters ranging between 0.85 and 1.70 mm was filled with either 155Tb (21.8 ± 1.7 MBq/mL) or 161Tb (23.6 ± 1.9 MBq/mL) and scanned with the VECTor preclinical SPECT/CT scanner. Image performance was evaluated with two collimators: a high energy ultra high resolution (HEUHR) collimator and an extra ultra high sensitivity (UHS) collimator. SPECT images were reconstructed from photopeaks at 43.0 keV, 86.6 keV, and 105.3 keV for 155Tb and 48.9 keV and 74.6 keV for 161Tb. Quantitative SPECT images of the resolution phantoms were analyzed to report inter-rod contrast, recovery coefficients, and contrast-to-noise metrics.

Results

Quantitative SPECT images of the resolution phantom established that the HEUHR collimator resolved all rods for 155Tb and 161Tb, and the UHS collimator resolved rods ≥ 1.10 mm for 161Tb and ≥ 1.30 mm for 155Tb. The HEUHR collimator maintained better quantitative accuracy than the UHS collimator with recovery coefficients up to 92%. Contrast-to-noise metrics were also superior with the HEUHR collimator.

Conclusions

Both 155Tb and 161Tb demonstrated potential for applications in preclinical quantitative SPECT imaging. The high-resolution collimator achieves < 0.85 mm resolution and maintains quantitative accuracy in small volumes which is advantageous for assessing sub organ activity distributions in small animals. This imaging method can provide critical quantitative information for assessing and optimizing preclinical Tb-radiopharmaceuticals.
Silica infiltration as a strategy to overcome zirconia degradation
Authors: Alfrisany Najm M. , Somogyi-Ganss Eszter , Tam Laura E , Hatton Benjamin D. , Sodhi Rana N. S. , Yin Ling , De Souza Grace M.
Published: September 2024

The excellent clinical performance of yttria-partially stabilized zirconias (Y-SZs) makes them promising materials for indirect restorations. However, the Y-SZ phase stability is a concern, and infiltrating Y-SZs with a silica nanofilm may delay their degradation processes. In this study, we analyzed stabilities of silica-infiltrated zirconia surfaces after exposure to artificial aging (AA).

Four zirconia materials with different translucencies (n = 40) were used, including low translucency 3 mol% Y-SZ (3Y-LT, Ceramill ZI, Amann Girrbach); high translucency 4 mol% Y-SZ (4Y-HT, Ceramill Zolid); and two high translucency 5 mol% Y-SZs (5Y-HT, Lava Esthetic, 3M and 5Y-SHT, Ceramill Zolid, FX white). Sintered specimens were exposed to 40 cycles of silica (SiO2) through room temperature atomic layer deposition (RT-ALD) using tetramethoxysilane (TMOS) and ammonium hydroxide (NH4OH). AA was applied for 15 h in an autoclave (134°C, 2 bar pressure). Stabilities of zirconia-silica surfaces were characterized in terms of hardness and Young's modulus using nanoindentation techniques and crystalline contents using x-ray diffraction (XRD) analyses. Silica deposition was also characterized by X-ray photoelectron spectroscopy (XPS).

There was a significant effect of the interaction of materials and surface treatments on the hardness and Young's modulus values of zirconia-silica surfaces (p < 0.001). Silica deposition on zirconia surfaces improved the material resistance to degradation by AA.
A post-marketing study to evaluate the safety and immunogenicity of a quadrivalent influenza split-virion vaccine in elderly people aged 60 years and older
Authors: Kou Zengqiang , Li Xiaoyu , Liu Ti , Fan Bei , An Wenqi , An Wenjue , Dang Mingan , Zhang Ke , Tang Jingning , Zhu Nan , Pan Ruowen
Published: September 2024

Background

Influenza remains a global public health concern. Understanding the vaccination-induced response in an aging population, which is susceptible and at high risk, is essential for disease prevention and control. Here, we report findings on the safety and immunogenicity of a quadrivalent influenza split-virion vaccine (15 µg/subtype/0.5 ml/dose) (hereinafter referred to as the “quadrivalent influenza vaccine”) in a population aged ≥ 60 years.

Methods

This open-label, pragmatic post-marketing trial enrolled 1399 older adults to receive one dose of an approved commercially available quadrivalent influenza vaccine manufactured by Hualan Biological Bacterin Inc. (hereinafter referred to as “Hualan Bio”). Participants with contraindications for the vaccine were excluded, while poor health condition was acceptable. All vaccinated subjects experienced adverse events collection within 30 days and serious adverse events within 180 days post-vaccination. 25% subjects, selected randomly, underwent venous blood sampling pre-vaccination and 30 days after post-vaccination, for detecting antibody titers against each subtype of influenza virus by hemagglutination inhibition assay. The incidences of adverse events and antibody titers against each subtype of influenza virus were statistically analyzed using SAS 9.4.

Results

No grade 3 adverse reactions occurred within 30 days post-vaccination. The incidences of overall adverse reactions, local adverse reactions and systemic adverse reactions were 3.79%, 2.86% and 1.00%, respectively. No serious adverse reactions occurred within 180 days post-vaccination. There were 350 subjects who completed venous blood sampling pre-vaccination, among whom 348 subjects completed venous blood sampling at 30 days post-vaccination for immunogenicity assessment. With respect to hemagglutination inhibition antibodies against influenza viruses H1N1, H3N2, BV and BY subtypes, at 30 days post-vaccination, the seroconversion rates were 87.64%, 75.57%, 73.28% and 78.74%, respectively; the seropositive rates were 93.97%, 98.56%, 79.31% and 95.40%, respectively; and the geometric mean increase (GMI) in post-immunization/pre-immunization antibodies was 24.80, 7.26, 10.39 and 7.39, respectively.

Conclusion

One 15 µg/subtype dose of the vaccine had a good safety profile and elicited favorable immunogenicity among subjects aged ≥ 60 years. The results of this study indicate that Hualan Bio quadrivalent influenza vaccine strike balance between safety and immunogenicity, supporting unnecessity to increase dosage or inoculation frequency for further enhancing immunogenicity.

Trial registration

Registered on ClinicalTrials.gov. Registration number: NCT06334510. Registered on 28/03/2024 (retrospectively registered).
Moving forward: scaling-up the integration of an HIV and hypertension program in Akwa Ibom State, Nigeria
Authors: Mishra Shivani , Aifah Angela A. , Henry Daniel , Uzoigwe Nina , Udoh Ememobong Bassey , Idang Esther , Munagala Jahnavi , Onakomaiya Deborah , Kanneh Nafesa , Ekanem Anyiekere , Attah Eno Angela , Ogedegbe Gbenga , Ojji Dike
Published: September 2024

As people living with HIV experience increased life expectancy, there is a growing concern about the burden of comorbid non-communicable diseases, particularly hypertension. This brief describes the current policy landscape on the management of HIV and hypertension in Akwa Ibom State, Nigeria, stakeholder engagement meetings, and the resulting five policy recommendations rooted in an ongoing research study designed to integrate hypertension management into HIV care across primary health centers in the State. In order to identify the current gaps in integrated care, discussion sessions with three stakeholder groups (i.e., healthcare providers, patient advocacy groups, and policy makers) were held separately in November 2022. The discussions were purposed to brainstorm policy-level solutions for integrating hypertension into HIV treatment. After all the sessions were concluded, there were five recommendations provided by the stakeholders for integrating HIV and hypertension care in the Akwa Ibom State. Stakeholders unanimously agreed with the need to integrate hypertension care for HIV impacted communities in the State. Specifically, stakeholders recommended to: (1) engage retired community health nurses as mentors; (2) actively link communities to integrated care in clinics; (3) integrate hypertension management with HIV education; (4) expand health insurance accessibility; and (5) formally integrate hypertension management into primary healthcare centers in Akwa Ibom State.
Identification of novel likely pathogenic variant in CDH23 causing non-syndromic hearing loss, and a novel variant in OTOGL in an extended Iranian family
Authors: Mohammadi Aliasgar , Hoseinzadeh Marziyeh , Narrei Sina , Pourreza Mohammad Reza , Mohammadi Yousof , Norouzi Mahnaz , Sadeghian Ladan , Tabatabaiefar Mohammad Amin
Published: September 2024

Background

Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the GJB2 and GJB6 genes are among the most common causes of SNHL worldwide. Mutations in Cadherin 23 (CDH23) can cause Usher syndrome and/or non-syndromic hearing loss (NSHL).

Material and methods

In this study, the Whole Exome Sequencing (WES) was used to detect the cause of hearing loss in a large consanguineous Iranian family with two patients. All family members underwent a thorough Genotype–phenotype correlation assessment and co-segregation analysis to understand the inheritance pattern within the family. The candidate variants were further confirmed by Sanger sequencing. In addition, in silico analysis was performed to predict the functional impact of the variants; the interpretation of the variants was performed in accordance with the American College of Medical Genetics (ACMG) guidelines.

Results

WES results identified two novel variants, a homozygous missense variant in CDH23 (c.2961T > G) and a heterozygous splice site variant in OTOGL that was compatible with the autosomal recessive pattern of inheritance. Bioinformatics studies confirmed the pathogenic effects of novel variants. The c.2961T > G variant was classified as likely pathogenic.

Conclusions

The novel identified variant in the CDH23 was the cause of congenital profound progressive form of HL. Samples were not available from the second family to distinguish which variant is responsible for the molecular pathology of the disease. Further studies and functional examinations are suggested for investigating the role of OTOGL: c. 1863-1G > T in deafness.
Seismic fragility analysis of long-span rigid-frame bridge on mountainous soft clay site
Authors: Zhang Gao , Zhang Jin , Liu Yang , Cao Yating
Published: September 2024

In order to assess the damage condition of bridge components for a large-span rigid bridge in a soft clay site in a mountainous area in China southwest, a finite element model of a large-span rigid bridge is established based on the OpenSees software, and the joint probability density distribution function of the ground motion strength and seismic demand and the marginal distribution function of the ground motion are introduced into the kernel density function. As a basis to get the method of calculating the fragility of the bridge members, and the method is verified for its feasibility, on this basis, the damage condition of the bridge components are analyzed, and finally the damage condition of the bridge system are analyzed by the first-order bounds method and the improved PCM method (IPCM). The results showed that: (1) Kernel density method (KDE) can effectively calculate the damage probability of each component, for example, under ground motions with PGA equal to 0.2 g, the probability of slight damage of the 1# pier is 29%, that of the intermediate consolidation pier (2# pier ~ 4# pier) is about 90%; the probability of slight damage of the 1# bearing is 48%, and that of the 2# bearing is 87%. (2) Reasonable value of the expansion joints can effectively reduce the probability of main beam collision. In this investigation, the value is taken as 0.18 m ~ 0.24 m. (3) The bridge system is more likely to be damaged than a single component in the system, and the damage probability of a single component cannot be used as a criterion for the bridge system in the actual working condition. Comparing the first-order boundary law with the IPCM method, the IPCM method has higher accuracy.
Loss-of-function mutation in anthocyanidin reductase activates the anthocyanin synthesis pathway in strawberry
Authors: Xu Pengbo , Li Maobai , Ma Chao , Li Xinyu , Bai Peng , Lin Anqi , Wang Chong , Zhang Liqing , Kuang Huiyun , Lian Hongli
Published: September 2024

Fruit color substantially affects consumer preferences, with darker red strawberries being economically more valuable due to their higher anthocyanin content. However, the molecular basis for the dark red coloration remains unclear. Through screening of an ethyl methanesulfonate mutant library, we identified a rg418 mutant, that demonstrated anthocyanin accumulation during early fruit development stages. Furthermore, the ripening fruits of this mutant had higher anthocyanin content than wild-type (WT) fruits. An analysis of flavonoid content in WT and rg418 mutant fruits revealed substantial changes in metabolic fluxes, with the mutant exhibiting increased levels of anthocyanins and flavonols and decreased levels of proanthocyanidins. Bulked sergeant analysis sequencing indicated that the mutant gene was anthocyanidin reductase (ANR), a key gene in the proanthocyanidin synthesis pathway. Furthermore, transcriptome sequencing revealed the increased expression of MYB105 during the early development stage of mutant fruits, which promoted the expression of UFGT (UDP-glucose flavonoid 3-O-glucosyltransferase), a key gene involved in anthocyanin synthesis, thus substantially enhancing the anthocyanin content in the mutant fruits. Additionally, mutating ANR in a white-fruited strawberry variant (myb10 mutant) resulted in appealing pink-colored fruits, suggesting the diverse roles of ANR in fruit color regulation. Our study provides valuable theoretical insights for improving strawberry fruit color.
Somapacitan in Children Born SGA: 52-Week Efficacy, Safety, and IGF-I Response Results From the Phase 2 REAL5 Study
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Frystyk Jan , Kawai Masanobu , Kildemoes Rasmus Juul , Lemminger Anders Krogh , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko
Published: September 2024

Context

Somapacitan, a once-weekly reversible albumin-binding growth hormone (GH) derivative, is evaluated in short children born small for gestational age (SGA).

Objective

Evaluate efficacy, safety, tolerability as well as total and bioactive insulin-like growth factor I (IGF-I) response of once-weekly somapacitan compared to daily GH in children born SGA.

Methods

REAL5 is a randomized, multicenter, open-label, controlled phase 2 study comprising a 26-week main phase, a 26-week extension, and an ongoing 4-year safety extension (NCT03878446), conducted at 38 sites across 12 countries. A total of 62 GH-treatment-naïve, prepubertal short children born SGA were randomized; 61 completed 52-weeks of treatment. Patients were randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day), all administered subcutaneously.

Results

Estimated mean height velocity (HV; cm/year) at week 52 was 8.5, 10.4, and 10.7 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively, and 9.3 and 11.2 cm/year for daily GH 0.035 and 0.067 mg/kg/day, respectively. Dose-dependent increases in total IGF-I, as well as peak IGF-I bioactivity, were observed for both treatments and were similar between comparator groups. For somapacitan, exposure-response modeling indicated highest efficacy with 0.24 mg/kg/week after 52 weeks of treatment. Similar safety and tolerability were demonstrated across all groups.

Conclusion

A sustained dose-dependent growth response was demonstrated for somapacitan after 52 weeks of treatment. Overall, somapacitan 0.24 mg/kg/week provides similar efficacy, safety, and tolerability, as well as comparable bioactive and total IGF-I response, as daily GH (0.067 mg/kg/day) in children born SGA.
Data-Driven Strategies for Carbimazole Titration: Exploring Machine Learning Solutions in Hyperthyroidism Control
Authors: Reich Thilo , Bakirov Rashid , Budka Dominika , Kelly Derek , Smith James , Richardson Tristan , Budka Marcin
Published: September 2024

Background

University Hospitals Dorset (UHD) has more than 1000 thyroid patient contacts annually. These are primarily patients with autoimmune hyperthyroidism treated with carbimazole titration. Dose adjustments are made by a healthcare professional (HCP) based on the results of thyroid function tests, who then prescribes a dose and communicates this to the patient via letter. This is time consuming and introduces treatment delays. This study aimed to replace some time-intensive manual dose adjustments with a machine learning model to determine carbimazole dosing. This can in the future serve patients with rapid and safe dose determination and ease the pressures on HCPs.

Methods

Data from 421 hyperthyroidism patients at UHD were extracted and anonymized. A total of 353 patients (83.85%) were included in the study. Different machine learning classification algorithms were tested under several data processing regimes. Using an iterative approach, consisting of an initial model selection followed by a feature selection method, the performance was improved. Models were evaluated using weighted F1 scores and Brier scores to select the best model with the highest confidence.

Results

The best performance is achieved using a random forest (RF) approach, resulting in good average F1 scores of 0.731. A model was selected based on a balanced assessment considering the accuracy of the prediction (F1 = 0.751) and the confidence of the model (Brier score = 0.38).

Conclusion

To simulate a use-case, the accumulation of the prediction error over time was assessed. It was determined that an improvement in accuracy is expected if this model was to be deployed in practice.
Thyroid Hormone and Alzheimer Disease: Bridging Epidemiology to Mechanism
Authors: Escamilla Sergio , Salas-Lucia Federico
Published: September 2024

The identification of critical factors that can worsen the mechanisms contributing to the pathophysiology of Alzheimer disease is of paramount importance. Thyroid hormones (TH) fit this criterion. Epidemiological studies have identified an association between altered circulating TH levels and Alzheimer disease. The study of human and animal models indicates that TH can affect all the main cellular, molecular, and genetic mechanisms known as hallmarks of Alzheimer disease. This is true not only for the excessive production in the brain of protein aggregates leading to amyloid plaques and neurofibrillary tangles but also for the clearance of these molecules from the brain parenchyma via the blood-brain barrier and for the escalated process of neuroinflammation—and even for the effects of carrying Alzheimer-associated genetic variants. Suboptimal TH levels result in a greater accumulation of protein aggregates in the brain. The direct TH regulation of critical genes involved in amyloid beta production and clearance is remarkable, affecting the expression of multiple genes, including APP (related to amyloid beta production), APOE, LRP1, TREM2, AQP4, and ABCB1 (related to amyloid beta clearance). TH also affects microglia by increasing their migration and function and directly regulating the immunosuppressor gene CD73, impacting the immune response of these cells. Studies aiming to understand the mechanisms that could explain how changes in TH levels can contribute to the brain alterations seen in patients with Alzheimer disease are ongoing. These studies have potential implications for the management of patients with Alzheimer disease and ultimately can contribute to devising new interventions for these conditions.
Bone Marrow Adiposity Alterations in Postmenopausal Women With Type 2 Diabetes Are Site-Specific
Authors: Badr Sammy , Cotten Anne , Lombardo Daniela , Ruschke Stefan , Karampinos Dimitrios C , Ramdane Nassima , Genin Michael , Paccou Julien
Published: September 2024

Context

Bone marrow adiposity (BMAT) alterations in patients with type 2 diabetes mellitus (T2DM) may contribute to adverse bone effects.

Objective

Characterization of BMAT content and composition in patients with well-controlled T2DM.

Methods

This cross-sectional study included 2 groups of postmenopausal women: one with T2DM and the other without. The proton density fat fraction (PDFF) of the lumbar spine and proximal femur, comprising the femoral head, neck, and diaphysis, was assessed using chemical shift-based water-fat separation imaging (WFI). Magnetic resonance imaging with spectroscopy (1H-MRS) was performed in a subgroup of participants to confirm the PDFF measurements and determine the apparent lipid unsaturation level (aLUL) at the L3 vertebrae and femoral neck. The association of imaging-based PDFFs and aLUL between diabetes groups was investigated by adjusting for confounding factors using a linear mixed model.

Results

Among 199 participants, patients with T2DM (n = 29) were significantly heavier (P < .001) and had a higher bone mineral density (BMD) (P < .001 for all sites) than nondiabetic patients (n = 170). When PDFFs were compared after adjusting for age, body mass index (BMI), and BMD, the femoral head WFI-based PDFF was lower in patients with T2DM (mean [standard error] 88.0% [0.7] vs 90.6% [0.3], P < .001). Moreover, the aLUL at the L3 vertebrae was lower in patients with T2DM (n = 16) than in without (n = 97) (mean [standard error] 3.9% [0.1] vs 4.3% [0.1], P = .02).

Conclusion

The content and composition of BMAT are modified in postmenopausal women with T2DM and these changes occur at specific sites.
Pallidotomy – outdated procedure or modern therapeutic alternative? – a review
Authors: Pociecha Agnieszka , Kozikowska Marta , Kmak Bożena
Published: September 2024

Introduction and purpose
Pallidotomy is a neurosurgical procedure involving the ablation of the globus pallidus, resulting in reduced activity in this area of the brain. Pallidotomy is an irreversible stereotactic procedure performed only under local anesthesia. It was first used in the treatment of dyskinesias associated with Huntington's chorea, but its widespread application has been in Parkinson's disease. This method is increasingly less common in developed countries due to its replacement by deep brain stimulation (DBS); however, it remains an effective treatment, particularly in drug-resistant, idiopathic Parkinson's disease. Unilateral pallidotomy is considered safer than bilateral pallidotomy due to the risk of severe complications, and thus, the bilateral approach is not recommended.
Materials and methodsA comprehensive literature review was conducted through an extensive bibliographic search, with a primary focus on original research articles obtained from reputable databases such as PubMed, BioMed Central, Polish Medical Platform, and Google Scholar. The search was specifically targeted towards articles pertaining to Pallidotomy.
Conclusions
The study shows that pallidotomy is a well-established neurosurgical treatment primarily used in drug-resistant Parkinson's disease. It should only be performed in centers specializing in stereotactic procedures. Symptoms that respond best to pallidotomy are those that previously responded to treatment, such as rigidity and tremors. The replacement of pallidotomy by deep brain stimulation (DBS) is due to the increased safety, effectiveness, and the availability of bilateral and continuous stimulation. Bilateral pallidotomy leads to severe complications and is currently not recommended. Pallidotomy has become a procedure used in specific situations and may be an alternative surgical treatment when there are contraindications to deep brain stimulation.
Interpretation of «Reading Competence of a Primary Education Student» Definition in the Realities of New Ukrainian School
Authors:   State Institution Luhansk Taras Shevchenko National University, Pushko Vira , Pravova Ninel ,   State Institution Luhansk Taras Shevchenko National University
Published: September 2024

The article deals with the modern interpretation of «reading competence of a primary education student» definition, its content, and its structure in terms of implementing the ideas of New Ukrainian School. The importance of the process of forming the student’s ability to read with understanding in the lessons of language and literary education has been determined. Different interpretations of «reading competence» concept have been analyzed, their common and specific features, which led to the conclusion that the studied phenomenon is multifaceted, have been identified. It has been identified the tendency of scientists to understand reading competence more broadly – as a complex multicomponent phenomenon that covers the reader’s possession of a set of knowledge, skills, abilities, and value attitudes that allow one to effectively interact with various texts as part of everyday life and educational activities; the ability to understand, interpret, evaluate, reproduce and use texts, search for the necessary information in them, which is ensured by the results of previous mental development, the formation of intellectual operations in the student. The views of scientists on the components and elements of reading competence have been characterized. The most important factors influencing the effectiveness of the process of forming the reading competence of students have been identified. The importance of purposeful formation of motivational and value mechanisms of primary school students’ reading competence has been proved, taking into account the peculiarities of the educational process (distance / mixed forms of education) in the conditions of martial law.