bluuebunny/crossref_metadata_2025 huggingface dataset:
Glioneuronal tumor in an autosomal-dominant polycystic kidney disease patient: a case report and literature review
Authors: Qupp Salem K. , Zeidan Mohammad M. , Nimer Hafez
Published: June 2024

Introduction:

The association between primary brain tumors, such as glioneuronal tumors, with autosomal-dominant polycystic kidney disease (ADPKD) remains poorly understood, with only two cases reported excluding this one. This case of an ADPKD patient diagnosed with a rosette-forming glioneuronal tumor highlights an exceptionally rare potential association warranting further investigation.

Case presentation:

A 28-year-old male with ADPKD presented with progressive ataxia, dizziness, and headache. MRI revealed a cerebellar mass and obstructive hydrocephalus. Surgical resection and histopathological examination confirmed the diagnosis of a rosette-forming glioneuronal tumor. Postoperatively, the patient showed significant symptom improvement.

Discussion:

The interplay between genetics and glioneuronal development is complex and underexplored. While most glioneuronal arise sporadically, rare genetic syndromes may predispose individuals to these tumors. Additionally, although more than 70 cases of ADPKD with concurrent tumors were reported, the literature on this specific association remains limited.

Conclusion:

This case underscores the need for heightened awareness of potential associations between ADPKD and tumors such as glioneuronal tumors. With limited literature on this subject, further research is imperative to understand the underlying mechanisms and clinical implications. Enhancing our knowledge in this area can improve patient outcomes and management strategies.
Symptomatic Unilateral Carotid Artery Disease
Authors: Melanis Konstantinos , Athanasaki Athanasia , Bakola Eleni , Chondrogianni Maria , Lazaris Andreas , Akrivaki Alexandra , Triantafyllou Alexandros Stavros , Kotsali-Peteinelli Vasiliki , Bonakis Anastasios , Paraskevas George P. , Tsivgoulis Georgios
Published: June 2024

Introduction:

Symptomatic carotid artery disease (CAD) represents an uncommon but treatable cause of corticobasal syndrome.

Case Report:

We present the clinical details and successful management of a previously healthy 77-year-old patient who presented with 1-year cognitive dysfunction, alien limb syndrome, limb kinetic apraxia, and ipsilateral cortical sensory deficit, fulfilling the criteria of the diagnosis of probable corticobasal syndrome. Imaging modalities, including magnetic resonance imaging and time-of-flight magnetic resonance angiography, revealed acute external borderzone infarcts of the right hemisphere due to symptomatic CAD causing near occlusion of the vessel. The patient underwent a right carotid endarterectomy, leading to a marked improvement in mobility and neuropsychological evaluation.

Conclusion:

This case highlights the importance of swift diagnosis of symptomatic CAD in patients with corticobasal syndrome. Moreover, it emphasizes the efficacy of carotid endarterectomy in achieving symptom improvement in such cases.
Prevalence, Associated Factors, and Outcomes of Severe Acute Kidney Injury in Pediatric Acute Liver Failure: Single-Center Retrospective Study, 2003–2017
Authors: Alexander Emma C. , Saxena Romit , Singla Raman , Douiri Abdel , Deep Akash
Published: June 2024

OBJECTIVES:

Our aim was to determine the prevalence and explanatory factors associated with outcomes in children with acute liver failure (ALF) admitted to the PICU, who also develop severe acute kidney injury (AKI).

DESIGN:

Retrospective cohort, 2003 to 2017.

SETTING:

Sixteen-bed PICU in a university-affiliated tertiary care hospital.

PATIENTS:

Admissions to the PICU with ALF underwent data review of the first week and at least 90-day follow-up. Patients with stages 2–3 AKI using the British Association of pediatric Nephrology definitions, or receiving continuous renal replacement therapy (CRRT) for renal indications, were defined as severe AKI. We excluded ALF cases on CRRT for hepatic-only indications.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Baseline characteristics, proportion with severe AKI, illness severity and interventions, and outcomes (i.e., transplant, survival with native liver, overall survival, duration of PICU stay, and mechanical ventilation). Ninety-four children with ALF admitted to the PICU were included. Over the first week, 29 had severe AKI, and another eight received CRRT for renal/mixed reno-hepatic indications; hence, the total severe AKI cohort was 37 of 94 (39.4%). In a multivariable logistic regression model, peak aspartate aminotransferase (AST) and requirement for inotropes on arrival were associated with severe AKI. Severe AKI was associated with longer PICU stay and duration of ventilation, and lower spontaneous survival with native liver. In another model, severe AKI was associated with greater odds of mortality (odds ratio 7.34 [95% CI, 1.90–28.28],p= 0.004). After 90 days, 3 of 17 survivors of severe AKI had serum creatinine greater than the upper limit of normal for age.

CONCLUSIONS:

Many children with ALF in the PICU develop severe AKI. Severe AKI is associated with the timecourse of PICU admission and outcome, including survival with native liver. Future work should look at ALF goal directed renoprotective strategies at the time of presentation.
Evaluation of Treatment Outcomes of Prostate Cancer Patients With Lymph Node Metastasis Treated With Definitive Radiotherapy
Authors: Onal Cem , Guler Ozan Cem , Erpolat Petek , Hurmuz Pervin , Sutera Philip , Deek Matthew P. , Elmali Aysenur , Yilmaz Melek Tugce , Koken Ummu Habibe , Yavuz Melek , Ozyigit Gokhan , Tran Phuoc T.
Published: June 2024

Purpose

We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT).

Patients and Methods

A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis.

Results

The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence.

Conclusions

ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT.
Bioinformatics Study on Mechanism of Postnatal Development of Craniofacial Bone
Authors: Shang Guangling , Lei Liu , Peng Changliang
Published: June 2024

Objective:

The postnatal development of craniofacial bone plays a crucial role in shaping the overall structure and functionality of the skull and face. Understanding the underlying mechanisms of this intricate process is essential for both clinical and research purposes. In this study, the authors conducted a bioinformatics analysis using the Gene Expression Omnibus database to investigate the molecular pathways and regulatory networks involved in the postnatal development of craniofacial bone.

Methods:

In this study, the online Gene Expression Omnibus microarray expression profiling data set GSE27976 was used to identify differentially expressed genes (DEGs) in different age groups. Protein-Protein Interaction network analyses, functional enrichment, and hub genes analysis were performed. The differences in immune infiltration and microenvironment among different types of cells were also analyzed.

Results:

In total, 523 DEGs, including 287 upregulated and 236 downregulated genes, were identified. GO and KEGG analysis showed that the DEGs were significantly enriched in multiple signaling pathways, such as skeletal system morphogenesis, osteoblast differentiation, and stem cell differentiation. Immune infiltration and microenvironment characteristics analysis showed that there were significant differences in fibroblasts, mesenchymal stem cell, osteoblast, stroma score, and microenvironment score between the two groups. Five hub genes, including IGF1, IL1B, ICAM1, MMP2, and brain-derived neurotrophic factor, were filled out.

Conclusion:

The findings of this study showed a significant shift in gene expression towards osteogenesis during the first 12 months after birth. These findings emphasize the critical role of the postnatal period in craniofacial bone development and provide valuable insights into the molecular mechanisms underlying this process.
Management of Constricted Upper Arch and Protruded Premaxilla in a 2-Year-Old Patient With Unrepaired BCLP
Authors: Zhang Jingjing , Yi Biao , Ma Lian
Published: June 2024

The paper presented the treatment procedure of a 2-year-old patient with unrepaired bilateral cleft lip and palate (BCLP). Complicated situation included severely protruded premaxilla and constricted upper dental arch, possibly related to delayed treatment of cleft lip and palate. Orthodontic expansion lasted for 8 months, including using fan-type expander for 3 months. After that, premaxillary osteotomy was performed to reset the premaxilla, and 4 months later, simultaneous repair of cleft lip and palate was taken. Follow-up evaluation in 5.5 years revealed acceptable language development and craniofacial profile, and maxillary growth was satisfactory. The treatment procedure of this patient provided an exploratory protocol for those patients with unrepaired BCLP who suffered from deteriorated preaxillary protrusion and constricted upper arch.
Hyaline Fibromatosis Syndrome: Early Outcomes Following Major Craniofacial Mass Excision
Authors: Chaisrisawadisuk Sarut , Rattana-arpa Sirirat , Vathanophas Vannipa , Sathienkijkanchai Achara
Published: June 2024

Hyaline fibromatosis syndrome (HFS) is a rare congenital disorder characterized by abnormal hyaline deposition within soft tissues. Hyaline fibromatosis syndrome manifests in 2 distinct forms: (1) infantile systemic hyalinosis and (2) juvenile hyaline fibromatosis. Infantile systemic hyalinosis, the more severe form, typically emerges in early childhood with extensive systemic involvement. In contrast, juvenile HFS is less severe, allowing patients to survive into adulthood. Common clinical manifestations include thickened skin, hyperpigmented patches, gingival hypertrophy, skin nodules, and progressive severe joint contractures, leading to significant morbidity and potential mortality. This case report describes a 7-year-old child who was diagnosed with HFS and presented with a very large, ulcerated, rapidly expanding craniofacial mass. The patient underwent successful treatment involving a multidisciplinary medical team and strategic surgical intervention, achieving favorable postoperative outcomes.
Late Treatment With Autologous Expanded Regulatory T-cell Therapy After Alemtuzumab Induction Is Safe and Facilitates Immunosuppression Minimization in Living Donor Renal Transplantation
Authors: Brook Matthew O. , Hennessy Conor , Hester Joanna , Hammad Salim , Alzhrani Alaa , Rombach Ines , Dutton Susan , Lombardi Giovanna , Wood Kathryn J. , Friend Peter , Harden Paul N. , Issa Fadi
Published: June 2024

Background.

The TWO Study (Transplantation Without Overimmunosuppression) aimed to investigate a novel approach to regulatory T-cell (Treg) therapy in renal transplant patients, using a delayed infusion protocol at 6 mo posttransplant to promote a Treg-skewed lymphocyte repopulation after alemtuzumab induction. We hypothesized that this would allow safe weaning of immunosuppression to tacrolimus alone. The COVID-19 pandemic led to the suspension of alemtuzumab use, and therefore, we report the unique cohort of 7 patients who underwent the original randomized controlled trial protocol. This study presents a unique insight into Treg therapy combined with alemtuzumab and is therefore an important proof of concept for studies in other diseases that are considering lymphodepletion.

Methods.

Living donor kidney transplant recipients were randomized to receive autologous polyclonal Treg at week 26 posttransplantation, coupled with weaning doses of tacrolimus, (Treg therapy arm) or standard immunosuppression alone (tacrolimus and mycophenolate mofetil). Primary outcomes were patient survival and rejection-free survival.

Results.

Successful cell manufacturing and cryopreservation until the 6-mo infusion were achieved. Patient and transplant survival was 100%. Acute rejection-free survival was 100% in the Treg-treated group at 18 mo after transplantation. Although alemtuzumab caused a profound depletion of all lymphocytes, including Treg, after cell therapy infusion, there was a transient increase in peripheral Treg numbers.

Conclusions.

The study establishes that delayed autologous Treg therapy is both feasible and safe, even 12 mo after cell production. The findings present a new treatment protocol for Treg therapy, potentially expanding its applications to other indications.
Prey size reflected in tooth wear: a comparison of two wolf populations from Sweden and Alaska
Authors: Schulz-Kornas Ellen , Skiba Mirella H. , Kaiser Thomas M.
Published: June 2024

Ingesta leaves distinct patterns on mammalian teeth during mastication. However, an unresolved challenge is how to include intraspecific variability into dietary reconstruction and the biomechanical aspects of chewing. Two extant populations of the grey wolf (Canis lupus), one from Alaska and one from Sweden, were analysed with consideration to intraspecific dietary variability related to prey size depending on geographical origin, sex and individual age as well as tooth function. Occlusal enamel facets of the upper fourth premolars, first molars and the second lower molar were analysed via three-dimensional surface texture analysis. The Swedish wolves displayed facets characterized by higher peaks and deeper, more voluminous dales, featuring an overall rougher surface than the wolves from Alaska. Compared to females, the Swedish male wolves had a slightly larger dale area and hill volume on their facets. Upper fourth premolars are smoother and had higher values in texture direction compared to upper first molars. The upper first molars were rougher than the occluding lower second molars and were characterized by larger and deeper dales. We find evidence supporting intraspecific dietary segregation, and antagonistic asymmetry in occlusal wear signatures. The data offer new insights into the roles of apex predators like the grey wolf.
The thermal ‘Buddha Board’—application of microstructured polyolefin films for variable thermal infrared transparency materials
Authors: Sun Xiaoruo , Ali Mehbab , Jalali Shima , Vaheb Abolfazl , Asad Asad , Dolez Patricia I. , Hogan James D. , Sameoto Dan
Published: June 2024

In this study, we explore the innovative application of biological principles of scattering foams and structural colouration of white materials to manipulate the transmission properties of thermal infrared (IR) radiation, particularly within the 8–14 μm wavelength range in polyolefin materials. Inspired by the complex skin of organisms such as chameleons, which can dynamically change colour through structural alterations, as well as more mundane technologies such as Buddha Boards and magic water colouring books, we are developing methods to control thermal IR transmission using common thermoplastic materials that are semi-transparent to thermal IR radiation. Polyethylene and polypropylene, known for their versatility and cost-effectiveness, can be engineered into microstructured sheets with feature sizes spanning from 5 to 100 μm. By integrating these precisely moulded microstructures with index-matching fluids, specifically IR transparent oils, we achieve a reversible modification of the thermal transmission properties. This novel approach not only mimics the adaptive functionality of natural systems but also offers a practical and scalable solution for dynamic thermal management. Our results indicate a promising pathway for the development of new materials that can adapt their IR properties in real time, paving the way for smarter thermal management solutions via radiative emission/absorption.
Driving macro-scale transformations in three-dimensional-printed biopolymers through controlled induction of molecular anisotropy at the nanoscale
Authors: Mogas-Soldevila Laia , Duro-Royo Jorge , Lizardo Daniel , Hollyer George G. , Settens Charles M. , Cox Jordan M. , Overvelde Johannes T. B. , DiMasi Elaine , Bertoldi Katia , Weaver James C. , Oxman Neri
Published: June 2024

Motivated by the need to harness the properties of renewable and biodegradable polymers for the design and manufacturing of multi-scale structures with complex geometries, we have employed our additive manufacturing platform that leverages molecular self-assembly for the production of metre-scale structures characterized by complex geometries and heterogeneous material composition. As a precursor material, we used chitosan, a chemically modified form of chitin, an abundant and sustainable structural polysaccharide. We demonstrate the ability to control concentration-dependent crystallization as well as the induction of the preferred orientation of the polymer chains through the combination of extrusion-based robotic fabrication and directional toolpathing. Anisotropy is demonstrated and assessed through high-resolution micro-X-ray diffraction in conjunction with finite element simulations. Using this approach, we can leverage controlled and user-defined small-scale propagation of residual stresses to induce large-scale folding of the resulting structures.
Head trauma impairs HPA-axis functions by increased R-loop structure and shortens telomeres
Authors: Şükranlı Zeynep Yılmaz , Taheri Serpil , Mehmetbeyoğlu Ecmel , Gülcihan Önal Müge , Memiş Mehmet , Er Begüm , Karaca Züleyha , Tanrıverdi Fatih , Ünlühızarcı Kürsad , Rassoulzadegan Minoo , Keleştimur Fahrettin
Published: June 2024

Traumatic brain injury (TBI) causes inflammation, one of the main causes of cellular aging. Telomere repeat-containing RNA (TERRA) hybridizes to telomere regions, forming R-loop structures and ensuring genome stabilization. Deregulation of R-loop homeostasis leads to genomic instability linked to neurodegenerative diseases and cancer. The hypothalamus-pituitary-adrenal (HPA) axis response is critical to maintaining homeostasis after TBI. We showed that the local increase in the transcription levels of theCrhandPomcgenes, in particular, suggests a defensive response through transcriptional alteration against mild TBI despite the decreased rate in the serum in the chronic phase. Additionally, changes in the transcription levels of TERRA and correlations with hormonal deficits after repetitive mTBI head trauma were observed. Telomere shortening and increased hybridized TERRA levels, especially after repeated mTBI in the chronic phase, suggest a possible disorder of genome stabilization and loss of cellular function in tissues of the hypothalamus, pituitary, and adrenal glands.
Increased motility inCampylobacter jejuniand changes in its virulence, fitness and morphology following protein expression on ribosomes with altered RsmA methylation
Authors: Sałamaszyńska-Guz Agnieszka , Murawska Małgorzata , Bącal Paweł , Ostrowska Agnieszka , Kwiecień Ewelina , Stefańska Ilona , Douthwaite Stephen
Published: June 2024

Infection withCampylobacter jejuniis the major cause of human gastroenteritis in the United States and Europe, leading in many cases to debilitating autoimmune sequelae. While considerable progress has been made in detailing the infectious cycle ofC. jejuni, a full understanding of the molecular mechanisms responsible for virulence remains to be elucidated. Here, we apply a novel approach by modulating protein expression on the pathogen’s ribosomes by inactivating a highly conserved rRNA methyltransferase. Loss of the RsmA methyltransferase results in a more motile strain with greater adhesive and cell invasive properties. These phenotypical effects correlate with enhanced expression of specific proteins related to flagellar formation and function, together with enzymes involved in cell wall/membrane and amino acid synthesis. Despite the enhancement of certain virulent traits, the null-strain grows poorly on minimal media and is rapidly out-competed by the wild-type strain. Complementation with an active copy of thersmAgene rescues most of the traits changed in the mutant. However, the complemented strain overexpressesrsmAand displays new flaws including loss of the spiral cell shape that is distinctive forC. jejuni. Proteins linked with altered virulence and morphology are identified here by mass spectrometry proteomic analyses of the strains.

Author summary

Infections withCampylobacter, and particularly with the most prevalent species of this genus,Campylobacter jejuni, are the leading cause of human bacterial gastroenteritis. Sadly, illnesses caused byC. jejunioften do not end with the infection itself, but continue with serious post-infectious autoimmune sequelae including the peripheral neuropathies Guillain–Barré syndrome, Miller Fisher syndrome and irritable bowel syndrome. Despite decades of research into theC. jejuniinfection cycle, the molecular mechanisms by which pathogenicity progresses are not yet fully understood. Here, we described a novel approach whereby we modulate protein synthesis on the pathogen’s ribosomes to interfere with specific virulence traits. This is followed up with proteome analyses of the engineered strains using state-of-the-art mass spectrometry techniques, enabling us to link specific proteins with steps in the infection cycle. Specifically, we disabled the ribosomal RNA modification enzyme RsmA, and this causes unexpectedly large changes inC. jejunimotility and its ability to attach to and invade human epithelial cells. We then identified specific flagellar, transpeptidase and peptidoglycan peptidase proteins involved in these processes. We propose that this approach of modulating protein synthesis via changes in rRNA methylation can be applied to study the infection cycles of other bacterial pathogens.
Multi-step engineered adeno-associated virus enables whole-brain mRNA delivery
Authors: Bai Weiya , Yang Dong , Zhao Yaqing , Li Guoling , Liu Zhen , Xiong Panzhi , Quan Haifeng , Wu Xiaoqing , Chen Peng , Kong Xiangfeng , Wang Xuchen , Zhang Hainan , Zhou Yingsi , Li Tong , Yuan Yuan , Yao Xuan , Shi Linyu , Yang Hui
Published: June 2024

Adeno-associated viruses (AAVs) are commonly used vectors for DNA delivery in gene therapy. Here we developed a system that enables the AAV shell to package mRNAs by multi-step introduction of RNA-packaging components and modification of AAV Rep proteins. The resultant mRNA-carrying AAVs (RAAVs) retained most properties of conventional AAVs, including capsid composition, virus morphology, and tissue tropism. These RAAVs could mediate mRNA transfer into target cells and tissues, leading to transient expression of the functional protein. Importantly, intravenously injected RAAVs efficiently crossed the blood-brain barrier (BBB) and infected the whole mouse brain. Thus, the DNA viral vector could be modified for RNA delivery, and our RAAV represents the first highly efficient BBB-crossing mRNA delivery system that could be used for therapeutic purposes via whole-brain infection.
The Fem Cell-surface Signaling System is Regulated by ExsA inPseudomonas aeruginosaand Affects Pathogenicity
Authors: Li Yanqi , Badr Sara , Zhang Pansong , Chen Lin , Bhagirath Anjali Y. , Dadashi Maryam , Surette Michael G. , Duan Kangmin
Published: June 2024

Bacterial interspecies interactions shape the function and the structural dynamics of microbial communities and affect the progression of polymicrobial infections. The FemA-FemR-FemI (Fem) cell surface signaling system inPseudomonas aeruginosais known to be involved in the uptake of iron-chelating mycobactin produced by theMycobacteriumspecies. In this report, we present the data that indicates thefemA-PA1909 operon was positively regulated by ExsA, a master regulator for the type three secretion system (T3SS), connecting the Fem system with T3SS. Intriguingly, the Fem system also influenced virulence factors inP. aeruginosa,including the quorum sensing systems, pyocyanin production, biofilm formation and the type six secretion systems (T6SSs). Using aGalleria mellonellainfection model we observed that anfemAdeletion in PAO1 significantly increased the host survival rate whilefemIover-expression decreased it, suggesting a role for the Fem system in bacterial pathogenicityin vivo. Our data indicate the Fem system is a target of the T3SS master activator ExsA, and it affectsP. aeruginosapathogenicity.
Low determinism in pelagic fungal community assembly across climate zones in Scandinavian lakes
Authors: Eiler Alexander , Martin-Sanchez Pedro M , Wurzbacher Christian , Fontaine Laurent , Jimenez Lara Maria , Juottonen Heli , Valiente Nicolas , Werner Even , Nilsson Henrik
Published: June 2024

In lakes, fungi play pivotal roles in biogeochemical processes, particularly in the decomposition of organic matter. However, these organisms have been historically underrepresented and taxonomically unresolved in previous research. In this study, we employ high-resolution sequencing to delve into the fungal diversity within two distinct Scandinavian lake datasets spanning a vast latitudinal gradient, diverse climatic zones ranging from nemoral to arctic, and a wide spectrum of nutrient conditions. Utilizing eukaryotic primers, we reveal that fungi contribute, on average, 2.07% in the Norwegian and 5.4% in the Swedish sequencing dataset, with remarkable spikes of up to 55% in forested lakes. Fungal-specific sequencing identified the prevalence of several fungal phyla, including Ascomycota, Rozellomycota, Basidiomycota, Chytridiomycota, Aphelidiomycota, and Mortierellomycota. Notably, our research uncovers a striking degree of variability in fungal communities across the studied lakes, defying correlations with measured environmental factors or geographic distance. Null model analyses suggest that deterministic processes do not consistently override the influence of ecological drift in shaping these biogeographic patterns. However, signals for dispersal limitations and mass effects could be detected. These findings challenge conventional paradigms of eukaryotic communities being strongly guided by deterministic processes and underscore the complexity of fungal community assembly processes across climate zones.
The Dual Roles of the CXCL10-CXCR3 Axis and Its Therapeutic Potential in Osteosarcoma
Authors: Gyau Benjamin B. , Wang Junyan , Chen Xiang , Clement Margaret , Man Zoe D. , Major Angela , Weiser Mathew , Xu Jun , Hicks John , Man Tsz-Kwong
Published: June 2024

The CXCL10-CXCR3 axis is recognized for its dual role in tumor biology, promoting tumor growth and metastasis via autocrine signaling while also eliciting anti-tumor responses through paracrine signaling. However, its specific functions in osteosarcoma (OS), the most prevalent malignant bone tumor in children, remain poorly understood. Our previous research has demonstrated that elevated circulating CXCL10 levels correlate with poor prognosis in OS patients. Analysis of the TARGET OS RNAseq dataset revealed that high expression levels of CXCL10 or its receptor CXCR3 are associated with improved prognosis. Given the known role of CXCL10 in recruiting CXCR3+ immune cells to combat cancer, we further analyzed single-cell RNAseq data and found that CXCR3 is predominantly expressed in CD3+ T cell populations. These findings suggest that CXCL10 may also play a protective role in OS by recruiting anti-tumor immune cells. To elucidate the causal role of the CXCL10-CXCR3 axis in OS, we conductedin vitrophenotypic assays on three OS cell lines with and without CXCL10. The chemokine was found to enhance tumor cell migration and AKT phosphorylation. Utilizing a CRISPR-mediated CXCR3 deletion mutant, we demonstrated that the absence of CXCR3 significantly inhibited OS tumor growth and pulmonary metastasis in an orthotopic xenograft mouse model. Transfection with the CXCR3A isoform, but not the CXCR3B isoform, restored the migratory phenotype of the CXCR3 deletion mutant to levels comparable to the parental cell line. Additionally, pharmacological inhibition of CXCR3 with AMG487 markedly reduced OS cell migrationin vitroand metastasis development in the orthotopic xenograft mouse model. Our research highlights the complex interplay of the CXCL10-CXCR3 axis in both tumor and immune cells. We propose a working model for the roles of the CXCL10-CXCR3 axis in OS, suggesting that targeting CXCR3 may be an effective strategy to inhibit OS metastasis, particularly in immune-cold OS subtypes.
Evaluating the Diagnostic Performance of Large Language Models in Identifying Complex Multisystemic Syndromes: A Comparative Study with Radiology Residents
Authors: Olshaker Hagar , Brin Dana , Kalderon Elinor , Kraus Matan , Konen Eliahu , Klang Eyal
Published: June 2024

Aim

This study evaluates the diagnostic capabilities of large language models (LLMs) in interpreting imaging patterns, focusing on their utility as a resource for radiology residents. We compare the diagnostic performance of OpenAI’s GPT-3.5, GPT-4, and Google’s Gemini Pro against radiology residents in identifying complex, multisystemic syndromes with an increased risk of cancer.

Methods

We assessed diagnostic accuracy using textual descriptions of radiological findings from 60 diseases selected from The Familial Cancer Database. Participants included three LLMs and three radiology residents. Diagnostic responses were scored on accuracy and first choice correctness. Experiments with AI models were conducted using default API settings.

Results

GPT-4 achieved the highest diagnostic accuracy (63%) and first choice accuracy (40%), significantly outperforming the radiology residents whose accuracy ranged from 22% to 43%. The overall average accuracy for AI models was 49.3%, compared to 29.0% for residents. Error analysis revealed that while some diseases were universally recognized, others highlighted diagnostic challenges across both human and AI participants.

Conclusion

GPT-4 outperforms radiology residents in diagnosing complex, infrequent multisystemic diseases. These findings suggest potential benefits of integrating AI tools to improve diagnostic accuracy for rare conditions and imply a need for revisions in medical training to incorporate AI competencies, enhancing diagnostic processes and resident education in radiology.
Sympathetic structural and electrophysiological remodeling in a rabbit model of reperfused myocardial infarction
Authors: Guevara Amanda , Smith Charlotte E.R. , Wang Lianguo , Caldwell Jessica L. , Tapa Srinivas , Stuart Samantha D. Francis , Ma Betty W. , Ng G. Andre , Habecker Beth A. , Wang Zhen , Ripplinger Crystal M.
Published: June 2024

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post myocardial infarction (MI), causing regional hypo-innervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypo-innervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca2+-sensitive dyes. SNS was performed with electrical stimulation of the spinal cord and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct and border zone of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct vs. remote region. Action potential duration (APD) dispersion and susceptibility to ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI hearts but not in sham. SNS decreased APD80in MI but not sham hearts, while isoproterenol decreased APD80in both groups. Isoproterenol also shortened Ca2+transient duration (CaTD80) in both groups but to a greater extent in MI hearts. Our data suggest sympathetic remodeling post-MI is similar between species, with CSPGs associated with sympathetic hypo-innervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underly increased APD dispersion and susceptibility for VT/VF.

NEW & NOTEWORTHY

Here we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypo-innervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between species, with hypo-innervation likely associated with enhanced β-adrenergic sensitivity.
Replay of procedural experience is independent of the hippocampus
Authors: Thompson Emmett J. , Rollik Lars , Waked Benjamin , Mills Georgina , Kaur Jasvin , Geva Ben , Carrasco-Davis Rodrigo , George Tom , Domine Clementine , Dorrell William , Stephenson-Jones Marcus
Published: June 2024

Sleep is critical for consolidating all forms of memory1-3, from episodic experience to the development of motor skills4-6. A core feature of the consolidation process is offline replay of neuronal firing patterns that occur during experience7,8. This replay is thought to originate in the hippocampus and trigger the reactivation of ensembles of cortical and subcortical neurons1,3,9-18. However, non-declarative memories do not require the hippocampus for learning or for sleep-dependent consolidation19-26meaning what drives their consolidation is unknown. Here we show, using an unsupervised method, that replay occurs in the dorsal striatum of mice during offline consolidation of a non-declarative, procedural, memory and that this replay is generated independently of the hippocampus. Replay occurred at both real-world and time-compressed speeds and was also prioritised both at the level of the individual neurons and the type of neural sequence. Complete bilateral lesions of the hippocampus had no effect on any feature of this replay. Our results demonstrate that procedural replay during consolidation of a non-declarative memory is independent of the hippocampus. These results support the view that replay drives active consolidation of all types of memory during sleep but challenges the idea that the hippocampus is the source of this replay.
Data mining redefines the timeline and geographic spread of cotton leafroll dwarf virus
Authors: Olmedo-Velarde Alejandro , Shakhzadyan Hayk , Rethwisch Michael , West-Ortiz Michael , Waisen Philip , Heck Michelle
Published: June 2024

Cotton leafroll dwarf virus (CLRDV), a threat to the cotton industry, was first reported in the United States (US) as an emergent pathogen in 2017. Phylogenetic analysis supports the hypothesis that US CLRDV strains are genetically distinct from strains in South America and elsewhere, which is not consistent with the hypothesis that the virus is newly introduced into the country. Therefore, using database mining, we evaluated the timeline and geographic distribution of CLRDV in the country. We uncovered evidence that shows that CLRDV had been in the US for over a decade before its official first report. CLRDV sequences were detected in datasets derived from Mississippi in 2006, Louisiana in 2015, and California in 2018. Additionally, through field surveys of upland cotton in 2023, we confirmed that CLRDV is present in California, which had no prior reports of the virus. Viral sequences from these old and new datasets exhibited high nucleotide identities (>98%) with recently characterized US isolates, and phylogenetic analyses with their homologs placed these sequences within a US-specific clade, further supporting the earlier presence of CLRDV in the country. Moreover, potential new hosts, including another fiber crop, flax, were determined through data mining. Retrospective analysis suggests CLRDV presence in the US since at least 2006 (Mississippi). These findings necessitate a reevaluation of spread patterns, inoculum sources, symptomology variations, and control strategies. Our findings challenge the current understanding of the arrival and spread of CLRDV in the US, highlight the power of data mining for virus discovery, and underscore the need for further investigation into CLRDV’s impact on US cotton.
Characterizing the Relationship between Personality Dimensions and Psychosis-Specific Clinical Characteristics
Authors: Jang Youjin Jenny , Yassin Walid , Mesholam-Gately Raquelle , Gershon Elliot S. , Keedy Sarah , Pearlson Godfrey G. , Tamminga Carol A. , McDowell Jennifer , Parker David A. , Sauer Kodiak , Keshavan Matcheri S.
Published: June 2024

Background

Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality’s relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods

A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included. Three biomarker-derived biotypes were used to separately categorize the probands. Mean personality factors (openness, conscientiousness, extraversion, agreeableness, and neuroticism) were compared between HC and proband subgroups using independent sample t-tests. A robust linear regression was utilized to determine personality differences across biotypes and diagnostic subgroups. Associations between personality factors and cognition were determined through Pearson’s correlation. A canonical correlation was run between the personality factors and general functioning, positive symptoms, and negative symptoms to delineate the relationship between personality and clinical outcomes of psychosis.

Results

There were significant personality differences between the proband and HC groups across all five personality factors. Overall, the probands had higher neuroticism and lower extraversion, agreeableness, conscientiousness, and openness. Openness showed the greatest difference across the diagnostic subgroups and biotypes, and greatest correlation with cognition. Openness, agreeableness, and extraversion had the strongest associations with symptom severity.

Conclusions

Individuals with psychosis have different personality profiles compared to HC. In particular, openness may be relevant in distinguishing psychosis-specific phenotypes and experiences, and associated with biological underpinnings of psychosis, including cognition. Further studies should identify potential causal factors and mediators of this relationship.
Impact of Prior Dengue Infection on the Severity and Outcomes of Subsequent Infections: A Meta-Analysis of the Placebo Arm of Clinical Trials
Authors: Macchia Alejandro , Figar Silvana , Biscayart Cristián , González Bernaldo de Quirós Fernán
Published: June 2024

Importance

The increasing incidence and prevalence of dengue in Latin America is well-documented. Historical case-control series also highlight that secondary infections are a risk factor for severe dengue, hospitalization, and death. This has generated alarm among some sectors of the population and the scientific community. However, there has been no examination based on the results of randomized clinical trials that analyzes the risk of severe events in individuals with and without prior dengue infection.

Objective

To evaluate the association between serologically confirmed prior dengue infection (DVC) and the subsequent risk of DVC, severe dengue (DS), dengue hospitalization (DHOSP), dengue-related death, and all-cause mortality.

Methods

A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies were searched in PubMed, CINAHL, Medline, Cochrane Library, and Web of Science, including only phase III randomized clinical trials of vaccine efficacy with data on participants in the placebo groups and information on previous infections. Random-effects models were applied to calculate combined odds ratios (OR), and heterogeneity among studies was assessed.

Results

A total of four studies corresponding to three phase III clinical trials were included. Participants with prior infection had a lower likelihood of developing DVC during follow-up (OR: 0.85; 95% CI: [0.75; 0.98]; p=0.024) and the same risk of dengue hospitalization as those without prior dengue (OR: 1.18; 95% CI: [0.92; 1.53]; p=0.198). However, they had a higher rate of DS during follow-up (OR: 2.91; 95% CI: [1.23; 6.87]; p=0.015). No dengue-related deaths were observed in any of the clinical trials during follow-up.

Conclusions

Prior dengue infection significantly reduces the risk of DVC and increases the risk of DS, although it does not significantly affect the risk of dengue hospitalization or dengue-related death during follow-up. The findings of this study highlight the need to reconsider the value of prior infection as an independent risk factor.
Sleep Quality mediates the association between Tea Consumption and Duration of COVID-19-related Symptoms in the Elderly
Authors: Fan Yuxing , Wang Yunyu , Jiang Jun , Yang Shaopeng , Lu Jie , Ma Qinghua , Zhu Hong
Published: June 2024

The association between tea consumption and the duration of COVID-19-related symptoms remains inconclusive. This cross-sectional study aims to investigate the potential mediating role of sleep quality in this association.

Methods

We conducted a cross-sectional study using data from elderly individuals aged 50 and above in Weitang Town in 2023. Detailed information on tea consumption, duration of COVID-19-related symptoms, and sleep quality was collected using pre-designed questionnaires. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Spearman correlation analysis was employed to examine the relationships between variables. Mediation effect analysis utilized a mediation model with multi-category independent variables.

Results

The correlation analysis revealed negative associations between tea drinking frequency, type, years, concentration, and sleep quality. Additionally, sleep quality was significantly and positively associated with the duration of COVID-19-related symptoms, whereas various tea consumption variables were significantly and negatively associated with the duration of COVID-19-related symptoms. The mediation analysis confirmed that sleep quality partially mediated the relationship between daily tea drinking and the duration of COVID-19-related symptoms. Moreover, sleep quality fully mediated the associations between drinking green tea, consuming tea for less than 15 years or more than 30 years, the concentration of tea consumption, and the duration of COVID-19-related symptoms.

Conclusions

Tea consumption indirectly influences the duration of COVID-19-related symptoms through its impact on sleep quality. These findings highlight the importance of considering the effects of tea consumption on COVID-19 infection, as well as the potential to reduce the duration of COVID-19-related symptoms by improving sleep quality.
Serum BMP8B levels in women with polycystic ovary syndrome: a case-control study
Authors: Xue Hui-Ling , Hao Wan-Jiao , Song Jie , Li Ye , Liu Man , Wei Jun-XIU , Ren Xiao-Pang
Published: June 2024

Objectives

Bone morphogenetic protein-8B (BMP8B) is an adipokine that is synthesized in many tissues and has been shown to be associated with the development of obesity and metabolic disorders in animals and humans. The aim of this study is to investigate the relationship between serum BMP8B levels and various metabolic parameters in women with PCOS.

Material and methods

This cross-sectional study included 80 women with PCOS and 40 age- and BMI-matched controls without PCOS. BMP8B, total cholesterol, triglyceride,fasting blood glucose (FBG), insulin, total testosterone (T),follicle stimulating hormone (FSH), luteinizing hormone (LH),estradiol (E2) levels were measured in all the participants. HOMA-IR was used to calculate the insulin resistance.

Results

Serum BMP8B levels were lower in women with PCOS than in healthy women(43.11±13.09 [ng/mL]vs. 106.45±52.32 [ng/mL], p< 0.001). HOMA-IR, LH/FSH, total-testosterone, total cholesterol, and triglyceride levels were significantly higher in women with PCOS than controls. Circulating BMP8B levels were positively correlated with HOMA-IR,BMI in PCOS group; was positively correlated with triglyceride in Control group.

Conclusion

The low concentration of circulating BMP8B in PCOS may be associated with insulin resistance,Lipid metabolism and BMI,bat may be a new target for PCOS treatment.