bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Menopausal Transition Health Promotion Intervention With Indigenous, Integrative, and Biomedical Health Education: A Community-Based Approach With Urban American Indian/Alaska Native Women
Authors: Taylor-Swanson Lisa , Kent-Marvick Jacqueline , Austin Sharon Déezbaaˈ , Ellis Jessica , Charles Claudia , Ward Ryan , Crandall Leslie , Macias Saraí Negrete , Moreno Camille , Simonsen Sara E
Published: August 2024

Background

Few studies have examined the menopausal transition in American Indian and Alaska Native (AI/AN) women; these reports indicate they are the most likely group to report bothersome vasomotor symptoms (VMS). Evidence demonstrates VMS may be a biomarker for chronic diseases. Thus, evidence-based interventions to improve VMS and other symptoms and health-screening rates for urban midlife AI/AN women are needed.

Objective

The objectives of this community-based project were to form a Community Advisory Board (CAB) with whom to: 1) conduct CAB meetings (similar to a focus group) with midlife AI/AN women to understand their lived health care experiences and needs during the menopausal transition; and 2) obtain guidance in creating a tailored intervention.

Methods

Eligible participants indicated they were registered members of American Indian Tribes, self-identified as a woman, aged 35 or older, and were recruited through the Urban Indian Center of Salt Lake and community outreach. Three CAB meetings were conducted via Zoom. A qualitative-descriptive approach was used for analysis, with the aim of staying close to the data to understand AI/AN women’s experiences and needs. Transcripts were iteratively coded using content/thematic analysis.

Results

Four themes emerged: 1) lack of and desire for information about the menopause transition; 2) barriers to accessing care; 3) matriarchal priorities impacting personal health outcomes; and 4) preferences for Indigenous and integrative medicine as first-line interventions, followed by conventional medicine.

Conclusions

Among this sample of urban AI/AN women, there was a great need for and interest in information about menopause, both for themselves and for their daughters and family. Integrative and Indigenous approaches were preferred. Proposed next steps include developing and pilot-testing a nurse-delivered health-education intervention with Indigenous, integrative, and conventional medical content.
Effects of Sample Handling on Visible and Near-Infrared Soil Reflectance
Authors: McGuirk Savannah L. , Cairns Iver H. , Evans Bradley J.
Published: August 2024

Soil reflectance is a cumulative attribute determined by interactions between light (photons) and the physical, chemical, and biological properties of soil. Soil properties such as organic matter, moisture, mineral oxide contents, soil texture, and surface roughness all influence soil reflectance at unique wavelengths. Many standard sample preparation techniques are designed to alter soil properties, so as to homogenize samples to improve the consistency of reflectance data collected. This study aims to quantify the effects of one standard sample preparation activity, drying, and repeated wetting–drying cycles on visible–near-infrared soil reflectance, by collecting reflectance data from nine samples which were dried then wetted for a total of three times. This study demonstrates the major, permanent effects of a drying and wetting cycle on soil reflectance, and then presents a model which can be used to correct for these effects. These results have direct implications for remote sensing activities, soil libraries, and soil spectral libraries. These results show that without correction, data from soil spectral libraries, spectral data collected from stored samples, and spectral data transferred between studies, have limited utility for characterizing soils as they exist in the field. Soil spectral data collected in the lab requires correction before it may be used to predict soil properties in the field, as standard sample handling procedures change intrinsic soil properties and introduce systematic error into these data.
Gepirone: A New Extended-Release Oral Selective Serotonin Receptor Agonist for Major Depressive Disorder
Authors: Phillips Bradley , O’Connor Colin , St. Onge Erin
Published: August 2024

Objective: To evaluate the safety, efficacy, and tolerability of gepirone (Exxua) in the treatment of adult patients with major depressive disorder. Data Sources: A literature search was performed through PubMed, Embase, and PsycINFO using the following terms: Exxua, gepirone, depression, major depressive disorder, anxiety, and anxiety disorders. Study Selection and Data Extraction: Articles that were selected included English-language dominant studies, or studies that could be translated into English by the authors, with terms associated with the safety, efficacy, and/or tolerability of gepirone. Data Synthesis: Gepirone exhibits its antidepressant activity through agonism of 5HT1A serotonin receptors. Phase 3 clinical trials showed that gepirone at a dose of 20 to 80 mg was proven to be effective in the treatment of major depressive disorder in adult patients. Common adverse effects reported in clinical trials included dizziness, nausea, headache, fatigue, and insomnia. Conclusion: This review evaluates the pharmacokinetic, pharmacologic, efficacy, and safety profile of gepirone and includes a discussion on its place in therapy for the treatment of major depressive disorder. Most clinical guidelines recommend second-generation antidepressants consisting of selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors as first-line therapy options. Gepirone is expected to receive greater clinical relevance and recommendations when compared to other azapirone medications (buspirone) within practice guidelines. Gepirone could be considered as either an alternative option for patients failing first-line therapies or for initial use to avoid unwanted side effects of other therapy options in the treatment of adult patients with major depressive disorder.
Polyethylene liner dissociation in total hip arthroplasty: a retrospective case–control study on a single implant design
Authors: Pagano S. , Plate J. F. , Kappenschneider T. , Reinhard J. , Scharf M. , Maderbacher G.
Published: August 2024

Background

Modular acetabular components for total hip arthroplasty (THA) provide intraoperative flexibility; however, polyethylene liner dissociation may occur. This study aimed to examine the incidence and causes of liner dissociation associated with a specific acetabular component design at a single centre.

Materials and methods

A retrospective analysis of 7027 patients who underwent primary THA was performed to identify isolated liner dislocations. Patient demographics, clinical presentations, surgical and implant details, and both radiographic and computed tomography (CT) findings were analysed. Patients with liner dislocation were matched to a control group via 2:1 propensity score matching, and a logistic regression analysis was employed to identify associated risk factors.

Results

A total of 32 patients (0.45%) experienced liner dislocation at a mean 71.47 ± 60.10 months post surgery. Significant factors contributing to dislocations included the use of a conventional compared with a highly crosslinked polyethylene component (p = 0.049) and screw fixation (p = 0.028). Radiographic and CT analysis highlighted the importance of proper component orientation, revealing that patients experiencing dislocations demonstrated significantly lower acetabular cup anteversion angles (p = 0.001) compared with the control group. Impingement and malposition, identified in 41% and 47% of the cases, respectively, further underscored the multifactorial nature of dislocation risks.

Conclusions

While the overall rate of polyethylene liner dislocation was low, the findings of this study highlight the importance of appropriate cup placement to decrease the risk of dissociation. It further substantiates the influence of impingement and malposition in liner displacement, with increased mechanical stress exerted on the locking mechanism under adverse conditions and the potential risk increase due to screw placement.
METTL3-mediated m6A modification of circGLIS3 promotes prostate cancer progression and represents a potential target for ARSI therapy
Authors: Cheng Xiaofeng , Yang Heng , Chen Yujun , Zeng Zhenhao , Liu Yifu , Zhou Xiaochen , Zhang Cheng , Xie An , Wang Gongxian
Published: August 2024

Background

Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported.

Methods

Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3.

Results

CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide.

Conclusions

METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.
Genome sequencing reveals novel causative structural and single nucleotide variants in Pakistani families with congenital hypogonadotropic hypogonadism
Authors: Zouaghi Yassine , Choudhary Anbreen Mazhar , Irshad Saba , Adamo Michela , Rehman Khaleeq ur , Fatima Ambrin , Shahid Mariam , Najmi Nida , De Azevedo Correa Fernanda , Habibi Imen , Boizot Alexia , Niederländer Nicolas J. , Ansar Muhammad , Santoni Federico , Acierno James , Pitteloud Nelly
Published: August 2024

Background/Objectives

This study aims to elucidate the genetic causes of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder resulting in GnRH deficiency, in six families from Pakistan.

Methods

Eighteen DNA samples from six families underwent genome sequencing followed by standard evaluation for pathogenic single nucleotide variants (SNVs) and small indels. All families were subsequently analyzed for pathogenic copy number variants (CNVs) using CoverageMaster.

Results

Novel pathogenic homozygous SNVs in known CHH genes were identified in four families: two families with variants in GNRHR, and two others harboring KISS1R variants. Subsequent investigation of CNVs in the remaining two families identified novel unique large deletions in ANOS1.

Conclusion

A combined, systematic analysis of single nucleotide and CNVs helps to improve the diagnostic yield for variants in patients with CHH.
Combination of transcriptome and Mendelian inheritance reveals novel prognostic biomarker of CTLA-4-related lncRNAs and protective role of nitrogen metabolism pathway in lung adenocarcinoma development
Authors: Shan Huisi , Wang Xiaocong , Yin Fei , Zhou Yiting , Mao Liuhan , Zhu Xiao , Liu Caixin
Published: August 2024

Objective

Since in the cancer setting, tumor cells may use cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to evade the immune system. This study aimed to identify CTLA-4-related long non-coding RNAs (lncRNAs) and assess their roles in lung adenocarcinoma (LUAD) development.

Methods

Clinical and genomic data were obtained from The Cancer Genome Atlas (TCGA), MSigDB and Gene Weaver. CTLA-4-related lncRNA-based gene signatures (CTLA4LncSigs) were identified using Cox regression, establishing a risk score model and an independent prognostic model. Enrichment analysis (GO/KEGG) was performed. Mendelian randomization (MR) analysis investigated the nitrogen metabolism and lung cancer relationship, with Bayesian weighted MR (BWMR) addressing uncertainties. Correlations with tumor microenvironment and drug sensitivity were explored.

Results

Nineteen CTLA4LncSigs significantly influenced LUAD prognosis. The risk score demonstrated independence as a prognostic factor. Functional analysis revealed lncRNAs' impact on nitrogen metabolism. MR and BWMR confirmed the protective role of the nitrogen metabolism pathway in lung cancer.

Conclusion

Our study identifies CTLA-4-related lncRNAs associated with LUAD prognosis and uncovers a previously undiscovered protective role of the nitrogen metabolism pathway in combating LUAD development, providing new insights into potential therapeutic targets and prognostic biomarkers for this aggressive cancer subtype.
Patient and provider perceptions of the relationship between alcohol use and TB and readiness for treatment: a qualitative study in South Africa
Authors: Kulkarni Suchitra , Weber Sarah E. , Buys Chané , Lambrechts Tersius , Myers Bronwyn , Drainoni Mari-Lynn , Jacobson Karen R. , Theron Danie , Carney Tara
Published: August 2024

Background

Unhealthy alcohol use is widespread in South Africa and has been linked to tuberculosis (TB) disease and poor treatment outcomes. This study used qualitative methods to explore the relationship between TB and alcohol use during TB treatment.

Methods

Focus group discussions (FGDs) were conducted with 34 participants who had previous or current drug-susceptible TB and self-reported current alcohol use. Eight interviews were conducted with healthcare workers who provide TB services in Worcester, South Africa.

Results

In this rural setting, heavy episodic drinking is normalized and perceived to be related to TB transmission and decreased adherence to TB medication. Both healthcare workers and FGD participants recommended the introduction of universal screening, brief interventions, and referral to specialized care for unhealthy alcohol use. However, participants also discussed barriers to the provision of these services, such as limited awareness of the link between alcohol and TB. Healthcare workers also specified resource constraints, while FGD participants or patients mentioned widespread stigma towards people with alcohol concerns. Both FGD participants and health providers would benefit from education on the relationship between TB and unhealthy alcohol use and had specific recommendations about interventions for alcohol use reduction. Healthcare workers also suggested that community health worker-delivered interventions could support access to and engagement in both TB and alcohol-related services.

Conclusion

Findings support strengthening accessible, specialized services for the identification and provision of interventions and psychosocial services for unhealthy alcohol use among those with TB.
Characterization of probiotics isolated from dietary supplements and evaluation of metabiotic-antibiotic combinations as promising therapeutic options against antibiotic-resistant pathogens using time-kill assay
Authors: El Far Mona S. , Zakaria Azza S. , Kassem Mervat A. , Edward Eva A.
Published: August 2024

Background

The global probiotics dietary supplements market size is continuously growing. To overcome probiotics’ health concerns, metabiotics are recognized as a safer alternative. Aiming to deal with the escalating antimicrobial resistance, the current work demonstrates synergistic metabiotic-antibiotic combinations against antibiotic-resistant pathogens.

Methods

The probiotic properties of lactic acid bacteria (LAB) strains isolated from 3 commercial dietary supplements were characterized in vitro. The combinations of the cell-free supernatants (CFS) of selected probiotic strains and conventional antibiotics against Staphylococcus aureus and Escherichia coli clinical isolates were evaluated using the time-kill assay. To our knowledge, the current literature lacks sufficient time-kill assay studies revealing the kinetics of such metabiotic-antibiotic combinations against S. aureus and E. coli.

Results

Four LAB strains isolated from dietary supplements as well as two reference strains were included in this study. The isolated LAB strains were identified by MALDI-TOF mass spectrometry as follows: P2: Lactobacillus acidophilus, P3: Lactiplantibacillus plantarum, P4: Lacticaseibacillus rhamnosus, and P5: Pediococcus acidilactici. The identification matched with that annotated by the manufacturers, except for P3. The tested strains could resist the acidic environment at pH 3. Excluding P2, the examined strains showed less than 1 log reduction in survivors upon the addition of reconstituted skimmed milk to pepsin at pH 2 and displayed an acceptable tolerance to 0.3% ox-bile. All the strains tolerated pancreatin. The hydrophobicity and autoaggregation capacities ranged between 7–92% and 36–66%, respectively. P2 was excluded owing to its inferior probiotic potential. Although the remaining strains showed excellent growth at 0.2% phenol, their growth was reduced at higher concentrations. L. plantarum and P. acidilactici strains possessed bile salt hydrolysis activity. The time-kill assay revealed promising synergistic activities of the combinations of CFS of L. rhamnosus P4 with either ceftazidime or gentamicin against E. coli and with only ceftazidime against S. aureus, as well as CFS of P. acidilactici P5 and ceftazidime against S. aureus.

Conclusions

Strict identification and evaluation of the probiotic strains incorporated in dietary supplements is crucial to ensure their safety and efficacy. The CFS of probiotics could be utilized to formulate novel biotherapeutics targeting problematic pathogens. However, future in vivo studies are required to evaluate the appropriate treatment regimen.
Developing a roadmap to reach and sustain 90% full immunization coverage through a cross-sectoral system strengthening strategy in Bihar, India
Authors: Ratna Manish , Singh Sanjay Kumar , Sinha Narendra Kumar , Kannure Mandar , Bhatia Mehak , Aggarwal Mahesh Kumar , Dalpath Suresh Kumar , Sharma Saurabh , Shah Vama
Published: August 2024

Introduction

Reducing childhood mortality by curtailing the incidence of vaccine preventable diseases is contingent upon a robust and high-performing routine immunization system. According to the available data, the full immunization coverage (FIC) in the state of Bihar (India) has reached ~ 71%. While the government aspires to reach 90% FIC, a systematic evidence-based investigation of the reasons behind underimmunization as well as the identification of drivers and enablers to reach and sustain 90% FIC is critical. This study aimed to review the factors leading to underimmunized children in the state of Bihar and develop a forward-looking roadmap to reach and sustain 90% FIC by adopting a system strengthening approach.

Method

We conducted a desk review, followed by extensive stakeholder interviews and field visits to document and analyze the data and evidence relevant to routine immunization system performance in the state of Bihar. The stakeholders included the State Immunization Officer, District Immunization Officers, Block-level health officials, representatives from development agencies, healthcare workers, and caregivers. A total of eighty-six structured interviews were conducted, which included qualitative and quantitative parameters.

Result

While positive results were observed from the assessment of Bihar’s immunization system, the implementation of targeted strategies for supply, service delivery and demand can provide a means to achieve FIC of 90%. The roadmap developed by the Government of Bihar enlists 40 + interventions across key thematic areas and has been prioritized over a 5-year time horizon as short, medium, and long-term milestones to achieve 90% FIC. These interventions include strengthening the data availability and quality, improving the governance and review mechanism, augmenting the capacity of health workers involve with immunization programme, and initiatives to increase demand for immunization services.

Conclusion

The Bihar’s Immunization Roadmap development project work follows a methodical approach to assess and identify intervention to improve immunization coverage and can provide information and reference to other states and countries that are aiming to formulate similar action plans.
PARK2 as a susceptibility factor for nontuberculous mycobacterial pulmonary disease
Authors: Park Youngmok , Hong Ji Won , Ahn Eunsol , Gee Heon Yung , Kang Young Ae
Published: August 2024

Background

The genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.

Methods

Peripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls). Differentially expressed genes (DEGs) were identified by RNA sequencing and subjected to functional enrichment and immune cell deconvolution analyses.

Results

We enrolled 48 participants, including 26 patients with NTM-PD (median age, 58.0 years; 84.6% female), and 22 healthy controls (median age, 58.5 years; 90.9% female). We identified 21 upregulated and 44 downregulated DEGs in the NTM-PD group compared to those in the control group. NTM infection did not have a significant impact on gene expression in the NTM-PD group compared to the control group, and there were no differences in the proportion of immune cells. However, through gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, we discovered that PARK2 is a key factor associated with NTM-PD. The PARK2 gene, which is linked to the ubiquitination pathway, was downregulated in the NTM-PD group (fold change, − 1.314, P = 0.047). The expression levels of PARK2 remained unaltered after favorable treatment outcomes, suggesting that the gene is associated with host susceptibility rather than with the outcomes of infection or inflammation. The area under the receiver operating characteristic curve for the PARK2 gene diagnosing NTM-PD was 0.813 (95% confidence interval, 0.694–0.932).

Conclusion

We identified the genetic signatures associated with NTM-PD in a cohort of Korean patients. The PARK2 gene presents as a potential susceptibility factor in NTM-PD .
SFRP4 promotes autophagy and blunts FSH responsiveness through inhibition of AKT signaling in ovarian granulosa cells
Authors: Bérubé Michael , Abedini Atefeh , Lapointe Evelyne , Gusscott Samuel , Brind’Amour Julie , Zamberlam Gustavo , Boerboom Derek
Published: August 2024

Background

Secreted frizzled-related proteins (SFRPs) comprise a family of WNT signaling antagonists whose roles in the ovary are poorly understood. Sfrp4-null mice were previously found to be hyperfertile due to an enhanced granulosa cell response to gonadotropins, leading to decreased antral follicle atresia and enhanced ovulation rates. The present study aimed to elucidate the mechanisms whereby SFRP4 antagonizes FSH action.

Methods

Primary cultures of granulosa cells from wild-type mice were treated with FSH and/or SFRP4, and effects of treatment on gene expression were evaluated by RT-qPCR and RNAseq. Bioinformatic analyses were conducted to analyse the effects of SFRP4 on the transcriptome, and compare them to those of FSH or a constitutively active mutant of FOXO1. Additional granulosa cell cultures from wild-type or Sfrp4-null mice, some pretreated with pharmacologic inhibitors of specific signaling effectors, were used to examine the effects of FSH and/or SFRP4 on signaling pathways, autophagy and apoptosis by western blotting and TUNEL.

Results

Treatment of cultured granulosa cells with recombinant SFRP4 was found to decrease basal and FSH-stimulated mRNA levels of FSH target genes. Unexpectedly, this effect was found to occur neither via a canonical (CTNNB1-dependent) nor non-canonical WNT signaling mechanism, but was found to be GSK3β-dependent. Rather, SFRP4 was found to antognize AKT activity via a mechanism involving AMPK. This lead to the hypophosphorylation of FOXO1 and a decrease in the expression of a portion of the FSH and FOXO1 transcriptomes. Conversely, FSH-stimulated AMPK, AKT and FOXO1 phosphorylation levels were found to be increased in the granulosa cells of Sfrp4-null mice relative to wild-type controls. SFRP4 treatement of granulosa cells also induced autophagy by signaling via AKT-mTORC1-ULK1, as well as apoptosis.

Conclusions

This study identifies a novel GSK3β-AMPK-AKT signaling mechanism through which SFPR4 antagonizes FSH action, and further identifies SFRP4 as a novel regulator of granulosa cell autophagy. These findings provide a mechanistic basis for the phenotypic changes previously observed in Sfrp4-null mice, and broaden our understanding of the physiological roles of WNT signaling processes in the ovary.
Sciatic nerve stimulation alleviates neuropathic pain and associated neuroinflammation in the dorsal root ganglia in a rodent model
Authors: Wong Chia-En , Liu Wentai , Huang Chi-Chen , Lee Po-Hsuan , Huang Han-Wei , Chang Yu , Lo Hsin-Tien , Chen Hui-Fang , Kuo Li-Chieh , Lee Jung-Shun
Published: August 2024

Background

Satellite glial cells (SGCs) in the dorsal root ganglia (DRG) play a pivotal role in the formation of neuropathic pain (NP). Sciatic nerve stimulation (SNS) neuromodulation was reported to alleviate NP and reduce neuroinflammation. However, the mechanisms underlying SNS in the DRG remain unclear. This study aimed to elucidate the mechanism of electric stimulation in reducing NP, focusing on the DRG.

Methods

L5 nerve root ligation (NRL) NP rat model was studied. Ipsilateral SNS performed 1 day after NRL. Behavioral tests were performed to assess pain phenotypes. NanoString Ncounter technology was used to explore the differentially expressed genes and cellular pathways. Activated SGCs were characterized in vivo and in vitro. The histochemical alterations of SGCs, macrophages, and neurons in DRG were examined in vivo on post-injury day 8.

Results

NRL induced NP behaviors including decreased pain threshold and latency on von Frey and Hargreaves tests. We found that following nerve injury, SGCs were hyperactivated, neurotoxic and had increased expression of NP-related ion channels including TRPA1, Cx43, and SGC-neuron gap junctions. Mechanistically, nerve injury induced reciprocal activation of SGCs and M1 macrophages via cytokines including IL-6, CCL3, and TNF-α mediated by the HIF-1α-NF-κB pathways. SNS suppressed SGC hyperactivation, reduced the expression of NP-related ion channels, and induced M2 macrophage polarization, thereby alleviating NP and associated neuroinflammation in the DRG.

Conclusions

NRL induced hyperactivation of SGCs, which had increased expression of NP-related ion channels. Reciprocal activation of SGCs and M1 macrophages surrounding the primary sensory neurons was mediated by the HIF-1α and NF-κB pathways. SNS suppressed SGC hyperactivation and skewed M1 macrophage towards M2. Our findings establish SGC activation as a crucial pathomechanism in the gliopathic alterations in NP, which can be modulated by SNS neuromodulation.
Urine-derived podocytes from steroid resistant nephrotic syndrome patients as a model for renal-progenitor derived extracellular vesicles effect and drug screening
Authors: Tanzi Adele , Buono Lola , Grange Cristina , Iampietro Corinne , Brossa Alessia , Arcolino Fanny Oliveira , Arigoni Maddalena , Calogero Raffaele , Perin Laura , Deaglio Silvia , Levtchenko Elena , Peruzzi Licia , Bussolati Benedetta
Published: August 2024

Background

Personalized disease models are crucial for evaluating how diseased cells respond to treatments, especially in case of innovative biological therapeutics. Extracellular vesicles (EVs), nanosized vesicles released by cells for intercellular communication, have gained therapeutic interest due to their ability to reprogram target cells. We here utilized urinary podocytes obtained from children affected by steroid-resistant nephrotic syndrome with characterized genetic mutations as a model to test the therapeutic potential of EVs derived from kidney progenitor cells (nKPCs).

Methods

EVs were isolated from nKPCs derived from the urine of a preterm neonate. Three lines of urinary podocytes obtained from nephrotic patients’ urine and a line of Alport syndrome patient podocytes were characterized and used to assess albumin permeability in response to nKPC-EVs or various drugs. RNA sequencing was conducted to identify commonly modulated pathways after nKPC-EV treatment. siRNA transfection was used to demonstrate the involvement of SUMO1 and SENP2 in the modulation of permeability.

Results

Treatment with the nKPC-EVs significantly reduced permeability across all the steroid-resistant patients-derived and Alport syndrome-derived podocytes. At variance, podocytes appeared unresponsive to standard pharmacological treatments, with the exception of one line, in alignment with the patient’s clinical response at 48 months. By RNA sequencing, only two genes were commonly upregulated in nKPC-EV-treated genetically altered podocytes: small ubiquitin-related modifier 1 (SUMO1) and Sentrin-specific protease 2 (SENP2). SUMO1 and SENP2 downregulation increased podocyte permeability confirming the role of the SUMOylation pathway.

Conclusions

nKPCs emerge as a promising non-invasive source of EVs with potential therapeutic effects on podocytes with genetic dysfunction, through modulation of SUMOylation, an important pathway for the stability of podocyte slit diaphragm proteins. Our findings also suggest the feasibility of developing a non-invasive in vitro model for screening regenerative compounds on patient-derived podocytes.
Segmentation and characterization of macerated fibers and vessels using deep learning
Authors: Qamar Saqib , Baba Abu Imran , Verger Stéphane , Andersson Magnus
Published: August 2024

Purpose

Wood comprises different cell types, such as fibers, tracheids and vessels, defining its properties. Studying cells’ shape, size, and arrangement in microscopy images is crucial for understanding wood characteristics. Typically, this involves macerating (soaking) samples in a solution to separate cells, then spreading them on slides for imaging with a microscope that covers a wide area, capturing thousands of cells. However, these cells often cluster and overlap in images, making the segmentation difficult and time-consuming using standard image-processing methods.

Results

In this work, we developed an automatic deep learning segmentation approach that utilizes the one-stage YOLOv8 model for fast and accurate segmentation and characterization of macerated fiber and vessel form aspen trees in microscopy images. The model can analyze 32,640 x 25,920 pixels images and demonstrate effective cell detection and segmentation, achieving a $$\hbox {mAP}_{0.5-0.95}$$

mAP

0.5
-
0.95

of 78 %. To assess the model’s robustness, we examined fibers from a genetically modified tree line known for longer fibers. The outcomes were comparable to previous manual measurements. Additionally, we created a user-friendly web application for image analysis and provided the code for use on Google Colab.

Conclusion

By leveraging YOLOv8’s advances, this work provides a deep learning solution to enable efficient quantification and analysis of wood cells suitable for practical applications.
Doege-Potter syndrome due to a solitary fibrous tumor of the pleura: a case report
Authors: Estrada-Maya Juan , Montejo Juan Sebastián , Báez López Katerin Dayana , Garzón Juan Carlos
Published: August 2024

Background

Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon.

Case presentation

A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence.

Conclusion

Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring.
An approach based on P-wave velocity for grouting effectiveness evaluation in earthen sites
Authors: Li Weihao , Zhang Jingke , Wang Nan , Zhang Yichen , Qi Bojia , Chen Jiayi , Yin Xingduo
Published: August 2024

Grouting technology is the primary method for repairing cracks in earthen sites. However, there has been a long-standing lack of effective methods for evaluating grouting effectiveness. This paper proposes a field evaluation method based on P-wave velocity. This method explicitly discusses two scenarios where the P-wave velocity of the grout is either higher or lower than that of the soil, using the depth ℎ of the “hypothetical crack” as the evaluation indicator. The experimental results indicate that specimens with 20% and 40% defects show increases in ℎ values of 0.0113 m and 0.0166 m, respectively. Laboratory tests have demonstrated that this method can accurately evaluate grouting effectiveness and is not affected by the P-wave velocity of the soil. The application of this evaluation method to three typical earthen sites resulted in more reliable and easily quantifiable evaluation outcomes. By considering the width of grout, the method provides a more intuitive comparison of reparation effectiveness. The study demonstrates the feasibility of the proposed method, thereby facilitating effective crack reparation in earthen sites.
Uncovering waterlogging-responsive genes in cucumber through machine learning and differential gene correlation analysis
Authors: Zinati Zahra , Nazari Leyla , Niazi Ali
Published: August 2024

As climate change intensifies, the frequency and severity of waterlogging are expected to increase, necessitating a deeper understanding of the cucumber response to this stress. In this study, three public RNA-seq datasets (PRJNA799460, PRJNA844418, and PRJNA678740) comprising 36 samples were analyzed. Various feature selection algorithms including Uncertainty, Relief, SVM (Support Vector Machine), Correlation, and logistic least absolute shrinkage, and selection operator (LASSO) were performed to identify the most significant genes related to the waterlogging stress response. These feature selection techniques, which have different characteristics, were used to reduce the complexity of the data and thereby identify the most significant genes related to the waterlogging stress response. Uncertainty, Relief, SVM, Correlation, and LASSO identified 4, 4, 10, 21, and 13 genes, respectively. Differential gene correlation analysis (DGCA) focusing on the 36 selected genes identified changes in correlation patterns between the selected genes under waterlogged versus control conditions, providing deeper insights into the regulatory networks and interactions among the selected genes. DGCA revealed significant changes in the correlation of 13 genes between control and waterlogging conditions. Finally, we validated 13 genes using the Random Forest (RF) classifier, which achieved 100% accuracy and a 1.0 Area Under the Curve (AUC) score. The SHapley Additive exPlanations (SHAP) values clearly showed the significant impact of LOC101209599, LOC101217277, and LOC101216320 on the model’s predictive power. In addition, we employed the Boruta as a wrapper feature selection method to further validate our gene selection strategy. Eight of the 13 genes were common across the four feature weighting algorithms, LASSO, DGCA, and Boruta, underscoring the robustness and reliability of our gene selection strategy. Notably, the genes LOC101209599, LOC101217277, and LOC101216320 were among genes identified by multiple feature selection methods from different categories (filtering, wrapper, and embedded). Pathways associated with these specific genes play a pivotal role in regulating stress tolerance, root development, nutrient absorption, sugar metabolism, gene expression, protein degradation, and calcium signaling. These intricate regulatory mechanisms are crucial for cucumbers to adapt effectively to waterlogging conditions. These findings provide valuable insights for uncovering targets in breeding new cucumber varieties with enhanced stress tolerance.
Conveyor CVD to high-quality and productivity of large-area graphene and its potentiality
Authors: Lee Dong Yun , Nam Jungtae , Lee Gil Yong , Lee Imbok , Jang A-Rang , Kim Keun Soo
Published: August 2024

The mass production of high-quality graphene is required for industrial application as a future electronic material. However, the chemical vapor deposition (CVD) systems previously studied for graphene production face bottlenecks in terms of quality, speed, and reproducibility. Herein, we report a novel conveyor CVD system that enables rapid graphene synthesis using liquid precursors. Pristine and nitrogen-doped graphene samples of a size comparable to a smartphone (15 cm × 5 cm) are successfully synthesized at temperatures of 900, 950, and 1000 °C using butane and pyridine, respectively. Raman spectroscopy allows optimization of the rapid-synthesis conditions to achieve uniformity and high quality. By conducting compositional analysis via X-ray photoelectron spectroscopy as well as electrical characterization, it is confirmed that graphene synthesis and nitrogen doping degree can be adjusted by varying the synthesis conditions. Testing the corresponding graphene samples as gas-sensor channels for NH3 and NO2 and evaluating their response characteristics show that the gas sensors exhibit polar characteristics in terms of gas adsorption and desorption depending on the type of gas, with contrasting characteristics depending on the presence or absence of nitrogen doping; nitrogen-doped graphene exhibits superior gas-sensing sensitivity and response speed compared with pristine graphene.
Enhancing marl soil stability: nanosilica’s role in mitigating ettringite formation
Authors: Amiri Mohammad , Asakereh Adel , Farokhdel Aminhosein , Atash poosh Hosein
Published: August 2024

Marl soil is highly prone to erosion when exposed to water flow, posing a potential threat to structural stability. The common practice of stabilizing soil involves the addition of cement and lime. However, persistent reports of severe ruptures in many stabilized soils, even after extended periods, have raised concerns. In stabilized marls, unexpected ruptures primarily result from the formation of ettringite, which gradually damages the soil structure. This article aims to assess the impact of nanosilica on the formation of ettringite and the nanostructure of calcium silicate hydrate (C-S-H) during the marl soil stabilization process with lime. To achieve this, marl soil was stabilized with varying percentages of lime and nanosilica. X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) images were collected to observe changes in mineralogy and microstructural properties. Various geotechnical parameters, including granularity, Atterberg limits, compressive strength, and pH, were measured. The results indicate that the uniform distribution of nanosilica in marl-lime soils enhances pozzolanic activities, calcium aluminate hydrate growth (C-A-H), and the nanostructure of calcium silicate hydrate (C-S-H). According to XRD and SEM experiments, the presence of nanosilica reduces the formation of ettringite. Moreover, the compressive strength of modified samples exhibited an upward trend. In the experimental sample manipulated with 1% nanosilica combined with 6% lime, the compressive strength increased by 1.84 MPa during the initial 7 days, representing an approximately 18-fold improvement compared to the control sample.
Barriers to and enablers of the use of the Otology Questionnaire Amsterdam in clinical practice—a qualitative post-implementation study
Authors: Kraak J.T. , Verhoef K. , Kramer S.E. , Merkus P.
Published: August 2024

Background

The Otology Questionnaire Amsterdam (OQUA) is developed to evaluate multiple ear complaints and their impact on patients’ daily lives. The current clinical use of this questionnaire is below the potential utilization.

Aim

To identify the barriers and enablers of using the OQUA as perceived by ENT surgeons and patients and provide recommendations for an implementation strategy.

Methods

Prospective and qualitative analysis was performed using focus groups and interviews with ENT professionals (n = 15) and patients (n = 25) with ear complaints of one tertiary referral hospital and two regional hospitals. Barriers and enablers were identified and classified by using the Capability-Opportunity-Motivation-Behavior model and the Theoretical Domains Framework. Suggestions for an implementation strategy will be made accordingly.

Results

ENT professionals’ barriers included lack of knowledge and skills to use the OQUA, inadequate technological support and perceived time constraints during consultation, uncertainty about the clinical relevance and lack of feedback on the outcomes of the OQUA. Enablers included beneficial consequences of the OQUA for the professional, organization and science. Patients’ barriers included lack of knowledge about the objective and usefulness of the OQUA, perceived burden, difficulties in completing the questionnaire and insufficient feedback during consultation. Patient enablers included beliefs about beneficial consequences of the OQUA for the patient, health care and society. Suggested interventions involved education, training, environmental restructuring and incentivisation.

Conclusion

Based on the findings, we propose an implementation strategy should focus on education and training about the objective, outcomes and relevance of the OQUA, environmental restructuring regarding the optimal use of the OQUA, and incentivisation with feedback on the valuable outcomes of the OQUA for the patient, professional and healthcare. Future research is needed to determine the feasibility of the implementation strategy.
Reproducibility of a single-volume dynamic CT myocardial blood flow measurement technique: validation in a swine model
Authors: Hadjiabdolhamid Negin , Zhao Yixiao , Hubbard Logan , Molloi Sabee
Published: August 2024

Background

We prospectively assessed the reproducibility of a novel low-dose single-volume dynamic computed tomography (CT) myocardial blood flow measurement technique.

Methods

Thirty-four pairs of measurements were made under rest and stress conditions in 13 swine (54.3 ± 12.3 kg). One or two acquisition pairs were acquired in each animal with a 10-min delay between each pair. Contrast (370 mgI/mL; 0.5 mL/kg) and a diluted contrast/saline chaser (0.5 mL/kg; 30:70 contrast/saline) were injected peripherally at 5 mL/s, followed by bolus tracking and acquisition of a single volume scan (100 kVp; 200 mA) with a 320-slice CT scanner. Bolus tracking and single volume scan data were used to derive perfusion in mL/min/g using a first-pass analysis model; the coronary perfusion territories of the left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA) were automatically assigned using a previously validated minimum-cost path technique. The reproducibility of CT myocardial perfusion measurement within the LAD, LCx, RCA, and the whole myocardium was assessed via regression analysis. The average CT dose index (CTDI) of perfusion measurement was recorded.

Results

The repeated first (Pmyo1) and second (Pmyo2) single-volume CT perfusion measurements were related by Pmyo2 = 1.01Pmyo1 − 0.03(ρ = 0.96; RMSE = 0.08 mL/min/g; RMSE = 0.07 mL/min/g) for the whole myocardium, and by Preg2 = 0.86Preg1 + 0.13(ρ = 0.87; RMSE = 0.31 mL/min/g; RMSE = 0.29 mL/min/g) for the LAD, LCx, and RCA perfusion territories. The average CTDI of the single-volume CT perfusion measurement was 10.5 mGy.

Conclusion

The single-volume CT blood flow measurement technique provides reproducible low-dose myocardial perfusion measurement using only bolus tracking data and a single whole-heart volume scan.

Relevance statement

The single-volume CT blood flow measurement technique is a noninvasive tool that reproducibly measures myocardial perfusion and provides coronary CT angiograms, allowing for simultaneous anatomic-physiologic assessment of myocardial ischemia.

Key Points

A low-dose single-volume dynamic CT myocardial blood flow measurement technique is reproducible.

Motion misregistration artifacts are eliminated using a single-volume CT perfusion technique.

This technique enables combined anatomic-physiologic assessment of coronary artery disease.

Graphical Abstract
Predictive biomarkers in thyroid cancer in the current molecular-morphology paradigm
Authors: Carneiro Humberto Carvalho , de Andrade Natal Rodrigo , Farias Evelin Cavalcante , Bastos Aline Almeida , Guastapaglia Leila , Bezerra Alanna Mara Pinheiro Sobreira , de Oliveira Hoff Ana Amélia Fialho
Published: August 2024

Thyroid cancer is one of the most common types of cancer worldwide. It is a spectrum of different diseases, ranging from very indolent to lethal tumors. Differentiated Thyroid Carcinoma (DTC), the most common thyroid malignancy, has often an excellent prognosis, but some patients develop metastatic Radioiodine-Refractory disease (RAIR) that cannot be controlled locally. In this setting, and for patients with metastatic Medullary Thyroid Carcinoma (MTC) and Anaplastic Thyroid Carcinoma (ATC), systemic treatment with non-selective Multikinase Inhibitors (MKIs) is often employed to improve survival rates and quality of life. The molecular characterization of thyroid cancer showed that the main drivers of thyroid carcinogenesis not only correlate with morphological and clinical features but can be targeted by some modern and highly selective Kinase Inhibitors: vemurafenib and dabrafenib for carcinomas with BRAF V600E mutation, including Papillary Thyroid Carcinoma (PTC) and its subtypes; dabrafenib in association with the MEK1/2 inhibitor trametinib for BRAF V600E-mutant ATC; larotrectinib and entrectinib for thyroid carcinomas with NTRK fusions and selpercatinib and pralsetinib for MTC with RET point mutations and DTC with RET-fusions. Apart of those markers, Microsatellite Instability status (MSI), Tumor Mutation Burden (TMB) and PD1/PD-L1 assessment have been explored in thyroid tumors, although immunotherapy for ATC has shown only modest results. Herein, we present a comprehensive review of the most relevant molecular markers with predictive value in thyroid pathology.