bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse Career Fairs in Rural Areas for Postsecondary Transitions for Students With Disabilities
Authors: Hogg Jennifer A. , Courtade Ginevra
Published: October 2024

For students with disabilities in rural locations, there can be unique barriers related to postsecondary transition. Reverse Career Fairs (RCFs), wherein employers take the role of attendees and students with disabilities focus on showcasing their skills and talents, are one way to provide U.S. students with experiences that support evidence-based predictors of post-school outcomes. An option for navigating these barriers is described through a framework used to foster postsecondary transitions for students with disabilities in rural settings through the implementation of RCFs. RCFs provide inclusive postsecondary opportunities by restructuring traditional approaches to career exploration and promoting meaningful connections between students with disabilities and prospective employers. A framework identifying key role groups and phases in facilitating an RCF and pilot results of one Special Education Regional Technical Assistance Center are provided.
Genetic and clinical spectrum of SAMD9 and SAMD9L syndromes: from variant interpretation to patient management
Authors: Sahoo Sushree S. , Erlacher Miriam , Wlodarski Marcin W.
Published: October 2024

Sterile alpha motif domain–containing protein 9 (SAMD9) and SAMD9-like (SAMD9L) are paralogous genes encoding antiviral proteins that negatively regulate cell proliferation. Heterozygous germ line gain-of-function (GoF) SAMD9/9L variants cause multisystem syndromes with variable manifestations. The unifying features are cytopenia, immunodeficiency, infections, bone marrow failure, myelodysplasia, and monosomy 7. Nonhematopoietic presentations can affect almost every organ system. Growth impairment and adrenal insufficiency are typical in SAMD9, whereas progressive neurologic deficits characterize SAMD9L. Most patients (>90%) carry germ line missense GoF variants. A subgroup of patients presenting with SAMD9L-associated inflammatory disease carry frameshift-truncating variants that are also GoF. Somatic genetic rescue occurs in two-third of patients or more and involves monosomy 7, which may spontaneously disappear (transient monosomy 7) or progress to myelodysplastic syndrome (MDS)/leukemia, and adaptive clones with somatic SAMD9/9L compensatory mutations or uniparental disomy 7q (UPD7q), both associated with remission. This manuscript examines the clinical and genetic spectrum, therapies, and outcome based on 243 published patients compiled in our registry, with additional genetic information on 62 unpublished cases. We consolidate the diverse clinical manifestations and diagnostic challenges of SAMD9/9L syndromes to enhance recognition and improve patient care. We highlight the knowledge gaps in pathomechanisms and emphasize the importance of genetic surveillance assessing disease remission vs disease progression. Insights are provided into variant curation and the necessity of testing for somatic SAMD9/9L mutations and UPD7q. Multidisciplinary care in specialized centers is critical to manage these complex disorders. Future natural history studies, especially in patients with monosomy 7, will help formulate evidence-based surveillance protocols and optimize transplant timing and outcomes.
Patient-managed interventions for adults with bronchiectasis: evidence, challenges and prospects
Authors: Spinou Arietta , Lee Annemarie L. , O'Neil Brenda , Oliveira Ana , Shteinberg Michal , Herrero-Cortina Beatriz
Published: October 2024

Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes.
The deadly dance of alveolar macrophages and influenza virus
Authors: David Camille , Verney Charles , Si-Tahar Mustapha , Guillon Antoine
Published: October 2024

Influenza A virus (IAV) is one of the leading causes of respiratory infections. The lack of efficient anti-influenza therapeutics requires a better understanding of how IAV interacts with host cells. Alveolar macrophages are tissue-specific macrophages that play a critical role in lung innate immunity and homeostasis, yet their role during influenza infection remains unclear. First, our review highlights an active IAV replication within alveolar macrophages, despite an abortive viral cycle. Such infection leads to persistent alveolar macrophage inflammation and diminished phagocytic function, alongside direct mitochondrial damage and indirect metabolic shifts in the alveolar micro-environment. We also discuss the “macrophage disappearance reaction”, which is a drastic reduction of the alveolar macrophage population observed after influenza infection in mice but debated in humans, with unclear underlying mechanisms. Furthermore, we explore the dual nature of alveolar macrophage responses to IAV infection, questioning whether they are deleterious or protective for the host. While IAV may exploit immuno-evasion strategies and induce alveolar macrophage alteration or depletion, this could potentially reduce excessive inflammation and allow for the replacement of more effective cells. Despite these insights, the pathophysiological role of alveolar macrophages during IAV infection in humans remains understudied, urging further exploration to unravel their precise contributions to disease progression and resolution.
Physiological phenotyping of transpiration response to vapour pressure deficit in wheat
Authors: Moritz Anna , Eckert Andreas , Vukasovic Stjepan , Snowdon Rod , Stahl Andreas
Published: October 2024

Background

Precision phenotyping of short-term transpiration response to environmental conditions and transpiration patterns throughout wheat development enables a better understanding of specific trait compositions that lead to improved transpiration efficiency. Transpiration and related traits were evaluated in a set of 79 winter wheat lines using the custom-built “DroughtSpotter XXL” facility. The 120 l plant growth containers implemented in this phenotyping platform enable gravimetric quantification of water use in real-time under semi-controlled, yet field-like conditions across the entire crop life cycle.

Results

The resulting high-resolution data enabled identification of significant developmental stage-specific variation for genotype rankings in transpiration efficiency. In addition, for all examined genotypes we identified the genotype-specific breakpoint in transpiration in response to increasing vapour pressure deficit, with breakpoints ranging between 2.75 and 4.1 kPa.

Conclusion

Continuous monitoring of transpiration efficiency and diurnal transpiration patterns enables identification of hidden, heritable genotypic variation for transpiration traits relevant for wheat under drought stress. Since the unique experimental setup mimics field-like growth conditions, the results of this study have good transferability to field conditions.
Is alcohol use disorder associated with higher rates of depression and anxiety among people with new onset type 2 diabetes? A cohort study using linked primary care data in England
Authors: Cook Sarah , Osborn David , Mathur Rohini , Forbes Harriet , Parekh Ravi , Maini Arti , Neves Ana Luisa , Gnani Shamini , Beaney Thomas , Walters Kate , Saxena Sonia , Quint Jennifer K.
Published: October 2024

Introduction

Depression and alcohol use disorder (AUD) in people living with Type 2 diabetes mellitus (T2DM) are associated with worse health outcomes. AUD is strongly associated with depression and anxiety, but it is not known how these conditions cluster in people with T2DM. We investigated rates of new episodes of depression and anxiety following T2DM diagnosis in people with and without prior AUD among an English primary care population.

Methods

The study population was people diagnosed with T2DM between 2004 and 2019. We used the Clinical Practice Research Datalink (CPRD) Aurum database and linked Hospital Episode Statistics Admitted Patient Care (HES APC) and Office for National Statistics (ONS) mortality data. We examined incidence of new episodes of anxiety or depression in people with T2DM with and without AUD. AUD was defined as any of i) clinical diagnosis; ii) alcohol withdrawal; or iii) chronic alcohol-related harm (physical or mental) using SNOMED-CT or ICD-10 codes. People were excluded if they had codes for depression/anxiety 12 months prior to T2DM diagnosis. Poisson regression models were fitted adjusting sequentially for a) age, gender, calendar time; b) region, Index of Multiple Deprivation, ethnicity, body mass index, smoking status, Charlson co-morbidity index; and c) history of a mental health condition.

Results

Our study population was 479,447 people of whom 10,983 (2.3%) had an AUD code prior to T2DM diagnosis.

After adjusting for all measured confounders except history of a mental health condition, IRR for depression was 2.00 (95% CI 1.93, 2.06) for people with AUD compared to without AUD. This reduced to 1.45 (95% CI 1.41, 1.50) after further adjustment for history of a mental health condition.

Findings for anxiety were substantially similar to those for depression (adjusted for all measured confounders except history of a mental health condition, IRR 2.08 95% CI 1.99, 2.18 fully adjusted IRR 1.48 95% CI 1.41, 1.55).

Conclusions

People with AUD have over double the rates of depression and anxiety following T2DM diagnosis than those without AUD. This was only partially explained by pre-existing diagnoses of mental health conditions. A holistic approach incorporating mental health support is needed to improve health outcomes for people with AUD who develop T2DM.

Trial registration

Not applicable.
The ability of Austrian registered physiotherapists to recognize serious pathology
Authors: Janssen Jessie , Lackenbauer Wolfgang , Gasselich Simon , Lickel Martina Edda , Schabel Lars , Beikircher Reinhard , Keip Christian , Wieser Manfred , Selfe James , Mazuquin Bruno , Yeowell Gillian
Published: October 2024

Background

Serious pathology masking as musculoskeletal conditions is rare, still it is pertinent that physiotherapists can recognise it. This ability has been investigated internationally, however the decision-making skills of registered Austrian physiotherapists has not been examined. The aim of this study was to assess the ability of registered Austrian physiotherapists to make accurate keep-refer decisions based on clinical vignettes.

Methods

In this national survey registered Austrian (self-)employed physiotherapists were recruited and completed 12 clinical vignettes. Correctly answered vignettes were listed as percentages.

Results

479 physiotherapists participated in the study. The response rate of the self-employed physiotherapists was 8.0%. On average participants classified 70.5% of the musculoskeletal cases, 79.4% of the non-critical medical cases, and 53.3% of the critical medical cases correctly.

Conclusion

This study suggests that, despite the limitations of using written clinical vignettes, registered Austrian physiotherapists welcome additional training to improve their skills in identifying serious pathology. Targeted training and educational programs including new and more detailed educational clinical vignettes relevant for non-direct access countries are needed to enhance physiotherapists’ diagnostic skills and decision-making processes.
Therapeutic alliance and suicidal ideation in brief cognitive behavioral therapy for outpatients
Authors: Melzer Laura , Forkmann Thomas , Friedrich Sören , Teismann Tobias
Published: October 2024

Objective

The therapeutic alliance is central to psychotherapy. However, research on the relationship between alliance and suicidality is scarce. We examined whether pretreatment suicidality is associated with an impaired alliance formation in brief cognitive behavioral therapy (CBT) and whether the therapeutic alliance is associated with change in suicidal ideation (difference between pretreatment and posttreatment assessment).

Methods

N = 643 outpatients (64% female; age: M[SD] = 37.09[13.15], range: 18–73 years), received 12 sessions of manual-based short-term CBT for primary diagnosis treatment. Using self-report questionnaires, suicidal ideation and behavior were assessed before and after therapy, patient-rated therapeutic alliance was assessed after the fourth session and posttreatment. We performed correlation analyses and two hierarchical linear regressions, unadjusted and adjusted for possible confounding variables (age, gender, lifetime suicide attempts and depression).

Results

Pretreatment suicidal ideation was not predictive of the quality of the early alliance. In addition, the therapeutic alliance was not predictive of change in suicidal ideation.

Conclusions

In the outpatient setting, no association was found between therapeutic alliance and suicidality. Future studies should investigate therapeutic alliance as a predictor of prospective suicidal behavior in different clinical settings.
Perceptions of sedentary behaviour in people with severe asthma: a qualitative study
Authors: Urroz Guerrero Paola D , Gibson Peter G , Lewthwaite Hayley , Majellano Eleanor , Hiles Sarah A , McDonald Vanessa M
Published: October 2024

People with severe asthma often lead sedentary lifestyles, which adversely affects overall health and asthma-specific outcomes. To inform future sedentary behaviour- interventions, this study aimed to explore perceptions of sedentary behaviour among people with severe asthma. Adults (≥ 18 years) with severe asthma (n = 21) participated in face-to-face interviews. Participants were asked open-ended questions about factors influencing their sitting behaviour. A thematic analysis was conducted on phrases and sentences relevant to sedentary behaviour. Participants were predominantly females (62%), with controlled asthma (median [Q1, Q3]: ACQ6 0.5 [0.2,1.8]) and receiving monoclonal antibody therapy (71%). Almost half of the participants were not meeting the physical activity guidelines (47%) and were sedentary (10.8 [9.7, 11.4] hours of sedentary behaviour per day). The analysis generated four main themes: (1) Sedentary behaviour often stems from habits and routines, (2) Asthma and associated health issues contribute to sedentary behaviour, (3) Participants’ responsibilities influence their activity levels, and; (4) Participants’ conscious balance between being physically active and sedentary. The results of this qualitative study offers insights into the perspectives of people with severe asthma regarding sedentary behaviour, highlighting the identification of strategies that can be implemented to improve sedentary behaviour in this population.
The association between ADAMTS14/rs4747096 gene polymorphism and some risk factors and knee osteoarthritis
Authors: Elshaarawy Ghada A. , Salama Iman I. , Salama Somaia I. , Abdelrahman Amany H. , Hassan Mirhane , Eissa Eman , Ismail Sherif , Eldeeb Sherif E. , Ahmed Doaa E. , Elhariri Hazem , Elgohary Rasmia , Abdelmohsen Aida M. , Fouad Walaa A. , Raslan Hala M.
Published: October 2024

Knee osteoarthritis (KOA) is an important cause of disability in the world and it denotes a public health defiance of the upcoming years.

Aim To examine the connection between ADAMTS14 gene rs4747096 polymorphism and KOA and to assess risk factors associated with KOA.

Methods A case control study was conducted on 158 patients with KOA and 120 controls with comparable age and sex randomly recruited from National Research Centre employees. All participants were subjected to full history taking, assessment of KOA severity using WOMAC scoring system, and thorough clinical examination. Blood sample was collected for detection of ADAMTS14/rs4747096 gene polymorphism.

Results The frequency of ADAMTS14 gene rs4747096 genotypes among patients with KOA was 73.5% for AA, 25.7% for AG, and 0.7% for GG compared to controls 963%, 31.3%, and 5.6% respectively and the frequency of alleles among patients was 86.4% for A and 78.7% for G compared to controls (78.7% and 21.3% respectively, P < 0.05. The study found that the median levels of total WOMAC score and its domains were significantly higher among KOA patients than controls. The logistic regression analysis revealed that age ≥ 50 years, BMI ≥ 35, and long standing at work were predictive factors for KOA (P < 0.05). Regarding different genetic patterns, only the A recessive pattern of inheritance was found to be a predictive risk factor for KOA.

Conclusion For ADAMTS14 rs4747096 genotype, the AA and AG genotypes significantly increased the risk of KOA. The recessive pattern of inheritance, older age, morbid obesity, and prolonged standing at work were the predictive risk factors for KOA. Further studies with larger sample size are encouraged to investigate the mechanism by which this genotype can affect the development of KOA.
Regenerative potentials of bone marrow mesenchymal stem cells derived exosomes or its combination with zinc in recovery of degenerated circumvallate papilla following surgical bilateral transection of glossopharyngeal nerve in rats
Authors: Salem Eman Mohamed , Rizk Hamdy , Abouelela Yara S. , Prince Abdelbary , Tohamy Adel Fathy , Lasheen Nawal A. , Ezzat Bassant A. , Mostafa Sana
Published: October 2024

Background

Taste buds’ innervation is necessary to sustain their cell turnover, differentiated taste buds and nerve fibers in circumvallate papilla (CVP) disappear following glossopharyngeal nerve transection. Normally, taste buds recover to baseline number in about 70 days. Bone marrow stem cell (BM-MSC) derived exosomes or their combination with Zinc chloride are used to assess their potential to speed up the regeneration process of CVP following bilateral deafferentation.

Methods

Twenty-eight male Sprague-Dawley rats were randomly divided into four groups; Group I: subjected to sham operation followed by IP injection of saline. The other experimental groups (II, III and IV) were subjected to surgical bilateral transection of glossopharyngeal nerve. Group II received single IP injection of saline. Group III received single IV injection of BM-MSC-derived exosomes (100 µg). Group IV received single IV injection of BM-MSC-derived exosomes and single IP injection of zinc chloride (5 mg/kg). After 28 days, CVP was dissected and prepared for histological and histomorphometric analysis, RT-PCR for cytokeratin 8 gene expression, ELISA to assess protein level of brain-derived neurotrophic factor, redox state analysis of malondialdehyde and glutathione content, followed by statistical analysis.

Results

Histopathologically, group II exhibited great tissue damage with marked reduction in taste buds and signs of degeneration in the remaining ones. Group III was close to control group with marked improvement in taste buds’ number and structure. Group IV showed inferior results when compared to group III, with many immature taste buds and signs of degeneration. Statistical results showed that groups I and III have significantly higher values than groups II and IV regarding taste buds’ number, cytokeratin 8, and reduced glutathione. However, malondialdehyde demonstrated high significant values in group IV compared to groups I and III. Regarding brain-derived neurotrophic factor, group III had significantly higher values than group II.

Conclusion

BM-MSC-derived exosomes have superior regenerative potentials in acceleration of CVP and nerve healing following bilateral transection of glossopharyngeal nerve in contrary to its combination with zinc chloride.

Graphical Abstract
A modified multiple-criteria decision-making approach based on a protein-protein interaction network to diagnose latent tuberculosis
Authors: Ayalvari Somayeh , Kaedi Marjan , Sehhati Mohammadreza
Published: October 2024

Background

DNA microarrays provide informative data for transcriptional profiling and identifying gene expression signatures to help prevent progression of latent tuberculosis infection (LTBI) to active disease. However, constructing a prognostic model for distinguishing LTBI from active tuberculosis (ATB) is very challenging due to the noisy nature of data and lack of a generally stable analysis approach.

Methods

In the present study, we proposed an accurate predictive model with the help of data fusion at the decision level. In this regard, results of filter feature selection and wrapper feature selection techniques were combined with multiple-criteria decision-making (MCDM) methods to select 10 genes from six microarray datasets that can be the most discriminative genes for diagnosing tuberculosis cases. As the main contribution of this study, the final ranking function was constructed by combining protein-protein interaction (PPI) network with an MCDM method (called Decision-making Trial and Evaluation Laboratory or DEMATEL) to improve the feature ranking approach.

Results

By applying data fusion at the decision level on the 10 introduced genes in terms of fusion of classifiers of random forests (RF) and k-nearest neighbors (KNN) regarding Yager’s theory, the proposed algorithm reached a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. Finally, with the help of cumulative clustering, the genes involved in the diagnosis of latent and activated tuberculosis have been introduced.

Conclusions

The combination of MCDM methods and PPI networks can significantly improve the diagnosis different states of tuberculosis.

Clinical trial number

Not applicable.
Patient perspectives on health care models in cardiac surgery: a qualitative evaluation
Authors: Schmid Mona Elisabeth , Stumm Jannik , Stock Sina , Girdauskas Evaldas
Published: October 2024

Background

The implementation of ERAS represents a promising solution to improve treatment efficiency and facilitate patient involvement. This innovative care model aims to optimize recovery processes following surgeries by adopting a holistic, interprofessional approach. At our hospital, ERAS was implemented in minimally invasive heart valve surgery, offering two distinct ERAS models. Additionally, there is also the standard of care without ERAS. The objective of the study is to gain insight into patient satisfaction and perceived differences across these various care models.

Methods

Patients were interviewed using semi-structured interviews approximately two to three months after undergoing surgery. The data were analysed using qualitative content analysis in accordance with the methodology proposed by Kuckartz. Four main categories were established: Preoperative care, postoperative care and communication, patient participation and involvement, and rehabilitation and post-clinical course.

Results

Comprehensive preoperative education and seamless communication throughout the perioperative care journey were identified as fundamental to patient satisfaction and optimal care processes. Patients in the ERAS + model reported higher overall satisfaction with their care compared to patients in the standard of care and ERAS groups.

Conclusion

Preoperative education establishes the foundation for patients’ subsequent behaviours and expectations regarding their treatment. Physical activity, nutrition, and mental health are significant aspects. The active involvement and participation of patients and their families in the treatment process facilitated superior postoperative care, intensive physiotherapy, mental support, and faster recovery. A functional flow of information throughout the entire care process is vital. Moreover, having a dedicated point of contact had a beneficial impact on patients´ well-being. The integration of innovative ERAS concepts, which encompass interprofessional preoperative patient education and psychosomatic support, represents a promising approach from a patient perspective, offering benefits to a broad spectrum of cardiac surgical patients.
Improving genetic testing pathways for transthyretin amyloidosis in France: challenges and strategies
Authors: Hebrard Bérénice , Babonneau Marie-Lise , Charron Philippe , Consolino Emilie , Dauriat Benjamin , Dupin-Deguine Delphine , Fargeaud Dominique , Farrugia Agnès , Giguet-Valard Anna-Gaëlle , Guijarro Damien , Inamo Jocelyn , Jeanneteau Julien , Mazzella Jean-Michaël , Michon Claire-Cécile , Millat Gilles , Mouquet Frédéric , Oghina Silvia , Pereon Yann , Poinsignon Vianney , Pompougnac Julie , Proukhnitzky Julie , Schaefer Elise , Sturtz Franck , Trosdorf Mathilde , Auguste Anne , Canali Giorgia , Combes Alexandre , Funalot Benoît , Damy Thibaud
Published: October 2024

Transthyretin amyloidosis (ATTR) is a severe and rare disease characterized by the progressive deposition of misfolded transthyretin proteins, causing irreversible organ damage. Transthyretin amyloidosis can present as a hereditary ATTR or acquired wild-type ATTR form. Genetic testing is critical for determining a hereditary predisposition and subsequently initiating appropriate family screening. In France, strict regulations govern genetic testing that aim to protect patients and their families affected by hereditary diseases such as ATTR. However, challenges persist in establishing an effective genetic testing pathway. A multidisciplinary group of French experts convened to discuss the challenges associated with an ATTR genetic diagnosis and to propose improvement strategies. Key challenges include the lack of pathway standardization, communication gaps between healthcare professionals (HCPs) and patients, and difficulties in complying with regulatory requirements. Concerns about patient data safety and outsourced testing quality further complicate matters. Proposed strategies included the development of stakeholder mapping tools for HCPs and patients, educational programs to improve literacy on genetic testing regulations, increase disease awareness among medical geneticists and genetic counselors, and strengthening HCP-patient communication through educational materials. These initiatives aim to streamline the genetic testing pathway, enhance compliance with regulations, and ultimately provide optimal support for patients and families with ATTR.
Concomitant sarcoidosis, psoriasis, and eczema – immune patterns on the skin
Authors: Sitaru Sebastian , Zink Alexander , Biedermann Tilo , Steimle-Grauer Susanne Annette
Published: October 2024

Sarcoidosis is a rare and elusive chronic inflammatory disease. It can manifest itself in any organ, but preferentially affects the lungs and the skin. Our case of an elderly woman with cutaneous and pulmonary sarcoidosis presented with exacerbated itchy, scaly skin changes to our department. The clinical and histopathological findings were consistent with sarcoidosis and eczematized psoriasis. The case represents a unique presentation of sarcoidosis with cutaneous involvement and poses diagnostic and therapeutic challenges due to overlapping clinical features and histology covering the three diagnoses. We discuss the immunological complexities underlying this overlap and resulting possible treatment options, highlighting the role of dermatology in systemic autoimmune diseases involving the skin and the need for pathophysiology-based tailored management approaches in these diseases.
Targeted hematopoietic stem cell depletion through SCF-blockade
Authors: Chan Yan Yi , Ho Pui Yan , Dib Carla , Swartzrock Leah , Rayburn Maire , Willner Hana , Ko Ethan , Ho Katie , Down Julian D. , Wilkinson Adam C. , Nakauchi Hiro , Denis Morgane , Cool Taylor , Czechowicz Agnieszka
Published: October 2024

Background

Hematopoietic stem cell transplantation (HSCT) is a curative treatment for many diverse blood and immune diseases. However, HSCT regimens currently commonly utilize genotoxic chemotherapy and/or total body irradiation (TBI) conditioning which causes significant morbidity and mortality through inducing broad tissue damage triggering infections, graft vs. host disease, infertility, and secondary cancers. We previously demonstrated that targeted monoclonal antibody (mAb)-based HSC depletion with anti(α)-CD117 mAbs could be an effective alternative conditioning approach for HSCT without toxicity in severe combined immunodeficiency (SCID) mouse models, which has prompted parallel clinical αCD117 mAbs to be developed and tested as conditioning agents in clinical trials starting with treatment of patients with SCID. Subsequent efforts have built upon this work to develop various combination approaches, though none are optimal and how any of these mAbs fully function is unknown.

Methods

To improve efficacy of mAb-based conditioning as a stand-alone conditioning approach for all HSCT settings, it is critical to understand the mechanistic action of αCD117 mAbs on HSCs. Here, we compare the antagonistic properties of αCD117 mAb clones including ACK2, 2B8, and 3C11 as well as ACK2 fragments in vitro and in vivo in both SCID and wildtype (WT) mouse models. Further, to augment efficacy, combination regimens were also explored.

Results

We confirm that only ACK2 inhibits SCF binding fully and prevents HSC proliferation in vitro. Further, we verify that this corresponds to HSC depletion in vivo and donor engraftment post HSCT in SCID mice. We also show that SCF-blocking αCD117 mAb fragment derivatives retain similar HSC depletion capacity with enhanced engraftment post HSCT in SCID settings, but only full αCD117 mAb ACK2 in combination with αCD47 mAb enables enhanced donor HSC engraftment in WT settings, highlighting that the Fc region is not required for single-agent efficacy in SCID settings but is required in immunocompetent settings. This combination was the only non-genotoxic conditioning approach that enabled robust donor engraftment post HSCT in WT mice.

Conclusion

These findings shed new insights into the mechanism of αCD117 mAb-mediated HSC depletion. Further, they highlight multiple approaches for efficacy in SCID settings and optimal combinations for WT settings. This work is likely to aid in the development of clinical non-genotoxic HSCT conditioning approaches that could benefit millions of people world-wide.
Quantitative proteomic profiling reveals sexual dimorphism in the retina and RPE of C57BL6 mice
Authors: Jang Geeng-Fu , Crabb John S. , Grenell Allison , Wolk Alyson , Campla Christie , Luo Shiming , Ali Mariya , Hu Bo , Willard Belinda , Anand-Apte Bela
Published: October 2024

Background

Sex as a biological variable is not a common consideration in molecular mechanistic or preclinical studies of retinal diseases. Understanding the sexual dimorphism of adult RPE and retina under physiological conditions is an important first step in improving our understanding of sex-based physio-pathological mechanisms.

Methods

Isobaric tags for relative and absolute quantitation (iTRAQ) were used for quantitative proteomics of male and female mouse retina and RPE (10 mice of each sex for each tissue type). Differentially expressed proteins were subjected to Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA).

Results

Differential expression analysis identified 21 differentially expressed proteins in the retina and 58 differentially expressed proteins in the RPE. Ingenuity pathway analysis identified the top canonical pathways differentially activated in the retina to be calcium transport I, nucleotide excision repair, molecular transport and cell death and survival. In the RPE, the top canonical pathways were calcium signaling, dilated cardiomyopathy signaling, actin cytoskeletal signaling and cellular assembly and organization.

Conclusions

These results provide insights into sex differences in the retina and RPE proteome of mice and begin to shed clues into the sexual dimorphism seen in retinal diseases.
Single-cell analysis of nasal epithelial cell development in domestic pigs
Authors: Wang Wenqian , Liu Ruiling , Zhong Qiu , Cao Yunlei , Qi Jiaxin , Li Yuchen , Yang Qian
Published: October 2024

The nasal mucosa forms a critical barrier against the invasion of respiratory pathogens. Composed of a heterogeneous assortment of cell types, the nasal mucosa relies on the unique characteristics and complex intercellular dynamics of these cells to maintain their structural integrity and functional efficacy. In this study, single-cell RNA sequencing (scRNA-seq) of porcine nasal mucosa was performed, and nineteen distinct nasal cell types, including nine epithelial cell types, five stromal cell types, and five immune cell types, were identified. The distribution patterns of three representative types of epithelial cells (basal cells, goblet cells, and ciliated cells) were subsequently detected by immunofluorescence. We conducted a comparative analysis of these data with published human single-cell data, revealing consistent differentiation trajectories among porcine and human nasal epithelial cells. Specifically, basal cells serve as the initial stage in the differentiation process of nasal epithelial cells, which then epithelial cells. This research not only enhances our understanding of the composition and transcriptional signature of porcine nasal mucosal cells but also offers a theoretical foundation for developing alternative models for human respiratory diseases.
Volume-based selection in Pinus pinaster Aiton breeding: evaluating resistance to Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle and wood properties
Authors: Torres-Sánchez Esteban , Acosta Juan José , Hodge Gary R. , Prada Eva , Menéndez-Gutiérrez María , Díaz Raquel
Published: October 2024

Key message

Genetic parameter estimates at age 12 years for trunk volume in Pinus pinaster displayed low to moderate heritability for growth and stem form, whereas wood properties showed high heritability. No correlation was detected between resistance to the nematode Bursaphelenchus xylophilus and growth, stem form, or wood properties. However, certain families stood out, showing favorable values across all traits, including resistance to the nematode.

Context

The breeding program for Pinus pinaster should advance towards a second-generation breeding population based on volume, stem form, and resistance to Bursaphelenchus xylophilus, with the challenge of incorporating novel traits of importance.

Aims

We focused on assessing the genetic parameters of growth, stem form, wood properties, and resistance to B. xylophilus as well as exploring the relationship between these traits.

Methods

We evaluated 116 half-sib families at three ages (7, 12, and 17 years) in seven progeny trials established in 2005, analyzing growth, stem form, and wood traits. Resistance to B. xylophilus was assessed in 91 of the 116 half-sib families at age 2 by artificial inoculation tests under greenhouse conditions.

Results

Advancing the selection age to 12 years proved to be feasible for volume selection in Galician P. pinaster. All traits, including resistance to B. xylophilus, showed potential for genetic improvement. Remarkably, resistance to B. xylophilus was not correlated to any other trait.

Conclusion

Excluding the most susceptible families to B. xylophilus from the Galician P. pinaster breeding program would not result in a significant decrease in volume, stem form, or wood properties.
New generalized Jacobi–Galerkin operational matrices of derivatives: an algorithm for solving the time-fractional coupled KdV equations
Authors: Ahmed H. M.
Published: October 2024

The present paper investigates a new method for computationally solving the time-fractional coupled Korteweg–de Vries equations (TFCKdVEs) with initial boundary conditions (IBCs). The method utilizes a set of generalized shifted Jacobi polynomials (GSJPs) that adhere to the specified initial and boundary conditions (IBCs). Our approach involves constructing operational matrices (OMs) for both ordinary derivatives (ODs) and fractional derivatives (FDs) of the GSJPs we employ. We subsequently employ the collocation spectral method using these OMs. This method successfully converts the TFCKdVEs into a set of algebraic equations, greatly simplifying the task. In order to assess the efficiency and precision of the proposed numerical technique, we utilized it to solve two distinct numerical instances.
Grazing exclusion promotes soil organic carbon accumulation in Tibetan grasslands with lower temperatures
Authors: Zhang Guangru , Tan Xiangping , He Jinhong , Luo Dengnan , Zeng Xiang , Liang Minqi , Cao Ruochen , Peng Siyuan , Li Pan , Tao Long , Ibrahim Muhammed Mustapha , Hu Zhongmin
Published: October 2024

Background

Grazing exclusion is a practical approach to restore vegetation in degraded grasslands and enhance soil organic carbon (SOC) sequestration. However, the dynamics and drivers of SOC in grasslands after grazing exclusion have not been well documented, especially in ecosystems with cold climates.

Methods

Here, we established 14 paired treatments (grazing exclusion vs. free-grazing) along a 600-km transect in the northeastern zone of the Qinghai-Tibet Plateau. After six years, we analyzed vegetation biomass dynamics and measured the soil physicochemical properties and organic C concentration across three depths (0–10, 10–20, and 20–30 cm).

Results

Grazing exclusion significantly increased above- and belowground biomass (139.85% and 43.30%, respectively), pH (1.38%), total phosphorus (3.29%), nitrate nitrogen (18.03%), and ammonium nitrogen (17.81%), but significantly decreased soil bulk density (2.43%) and clay content (10.49%), particularly in 0–30 cm. Specifically, SOC concentrations positively responded to grazing exclusion (0–10 cm) in 9 of the 14 sites evaluated. The effects of grazing exclusion on SOC concentrations were significantly higher in areas with a mean annual temperature (MAT) below 0 °C compared to those in sites with a high MAT (> 0 °C). The SOC concentrations significantly correlated with the mean annual precipitation (MAP) in both treatments, but these correlations diminished with increasing soil depth. Ridge regression analysis showed that soil chemical properties (e.g., total nitrogen and phosphorus) positively influenced SOC accumulation, while MAT negatively influenced it after grazing exclusion. Path analysis further revealed that MAT indirectly regulated SOC dynamics via soil chemical properties.

Conclusions

Our study highlights that grazing exclusion results in an asynchronous SOC and plant biomass accumulation and may be more beneficial for SOC sequestration in Qinghai-Tibet Plateau grasslands with lower temperatures. Also, humid climates promote SOC concentration in alpine grasslands. These results could help develop management practices and policies that promote sustainable grassland management.
Young people’s civic engagement in Italy: evidence on grade 8 students from the international civic and citizenship education study (ICCS) 2016
Authors: Damiani Valeria , Caponera Elisa , Losito Bruno , Palmerio Laura , Agrusti Gabriella
Published: October 2024

Civic engagement represents a key aspect of a democratic society and is itself a multidimensional construct. Research has shown that the promotion of civic engagement is an important component of civic and citizenship education intended in a broad sense, pertaining to formal, non-formal and informal learning situations. Within a national scenario characterised by increasing levels of general institutional disaffection and a lack of electoral and political involvement, the recent reform in the area of civic and citizenship education (Law 92/2019) has led to lively debates on the status of its implementation in Italian schools and recent research at the national level has highlighted the lack of activities to promote students’ engagement. This study further investigates the ICCS 2016 findings on civic engagement of Italian students with two objectives: to identify possible groups of Italian eighth-grade students on the basis of their level of civic engagement and to examine the associations among these groups and some key factors reflecting school contexts and students’ attitudes and behaviours. To reach these goals, the data analyses encompassed a latent profile analysis and a logistic regression model. The latent profile analysis allowed the identification of three groups of Italian students: disengaged, moderately engaged and engaged students. The results of the regression model showed that engaged students were characterised by a higher level of citizenship self-efficacy. These findings confirm those of previous research on the key role of internal self-efficacy in promoting students’ civic engagement.
Integrating Big Data, Artificial Intelligence, and motion analysis for emerging precision medicine applications in Parkinson’s Disease
Authors: Dipietro Laura , Eden Uri , Elkin-Frankston Seth , El-Hagrassy Mirret M. , Camsari Deniz Doruk , Ramos-Estebanez Ciro , Fregni Felipe , Wagner Timothy
Published: October 2024

One of the key challenges in Big Data for clinical research and healthcare is how to integrate new sources of data, whose relation to disease processes are often not well understood, with multiple classical clinical measurements that have been used by clinicians for years to describe disease processes and interpret therapeutic outcomes. Without such integration, even the most promising data from emerging technologies may have limited, if any, clinical utility. This paper presents an approach to address this challenge, illustrated through an example in Parkinson’s Disease (PD) management. We show how data from various sensing sources can be integrated with traditional clinical measurements used in PD; furthermore, we show how leveraging Big Data frameworks, augmented by Artificial Intelligence (AI) algorithms, can distinctively enrich the data resources available to clinicians. We showcase the potential of this approach in a cohort of 50 PD patients who underwent both evaluations with an Integrated Motion Analysis Suite (IMAS) composed of a battery of multimodal, portable, and wearable sensors and traditional Unified Parkinson's Disease Rating Scale (UPDRS)-III evaluations. Through techniques including Principal Component Analysis (PCA), elastic net regression, and clustering analysis we demonstrate how this combined approach can be used to improve clinical motor assessments and to develop personalized treatments. The scalability of our approach enables systematic data generation and analysis on increasingly larger datasets, confirming the integration potential of IMAS, whose use in PD assessments is validated herein, within Big Data paradigms. Compared to existing approaches, our solution offers a more comprehensive, multi-dimensional view of patient data, enabling deeper clinical insights and greater potential for personalized treatment strategies. Additionally, we show how IMAS can be integrated into established clinical practices, facilitating its adoption in routine care and complementing emerging methods, for instance, non-invasive brain stimulation. Future work will aim to augment our data repositories with additional clinical data, such as imaging and biospecimen data, to further broaden and enhance these foundational methodologies, leveraging the full potential of Big Data and AI.
Heatmap analysis of modeled coastal tsunamis using different bathymetry data resolutions
Authors: Felix Raquel , Hubbard Judith , Wilson Kaya , Switzer Adam
Published: October 2024

We examined how variations in the horizontal resolution of bathymetry influence the behavior of modeled tsunamis at shallow depths nearshore. This was done using the Cornell Multi-grid Coupled Tsunami Model (COMCOT) to simulate tsunamis with resampled bathymetric data at resolutions of 5, 10, 20, 30, 40, 50, 100, 200, and 300 meters, derived from 1-m resolution NOAA coastal LiDAR data sets (at water depths of less than or equal to 30 m) and soundings. In total, we utilized 1,080 data sets, comprising 9 resolutions across 30 sets at 4 different sites. In addition, we included the 15-arc second grid ($$\sim$$
∼
455 m) 2021 GEBCO data for comparison. We initiated a 5-m high tsunami wave offshore and propagated it towards the coast, then used the resulting maximum wave heights for each resolution to quantify the differences across varying resolutions. Using the 5 m bathymetry as the reference model, we observed that data sets with 10–50 m resolutions can reproduce tsunamis reasonably well. The maximum heights are overestimated by less than or equal to 5% or underestimated by less than or equal to 10%, and the first wave arrival time is $$\sim$$
∼
10% earlier than expected. Coarser bathymetries show an increasing trend of height underestimation, with the GEBCO model underestimating it by as much as 70%. Coarser bathymetry models have more variable first wave arrival time, with waves arriving up to 20% later or up to 10% earlier than expected. Overall, a reasonably accurate result can be achieved using a bathymetric resolution in the 10 m–50 m range, and is achievable with reasonable computational efficiency (at least 80% faster than simulations using the 5 m model on high-performance computing). This study highlights the importance of shallow bathymetry data quality in the numerical modeling of tsunami propagation.