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1.
Int J Fertil Steril ; 18(3): 228-233, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38973275

ABSTRACT

BACKGROUND: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation. MATERIALS AND METHODS: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022. RESULTS: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality. CONCLUSION: The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.

2.
J Environ Health Sci Eng ; 22(1): 313-327, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38887776

ABSTRACT

This study applied an electro-Fenton process using chemically modified activated carbon derived from rubber seed shells loaded with α-FeOOH (RSCF) as catalyst to remove tetracycline residues from aquatic environment. Catalyst characteristics were evaluated using SEM, EDS, XRD, and XPS, showing successful insertion of iron onto the activated carbon. The effects of the parameters were investigated, and the highest treatment efficiency was achieved at pH of 3, Fe: H2O2 ratio (w/w) of 500:1, catalyst dose of 1 g/L, initial TCH concentration of 100 mg/L, and electric current of 150 mA, with more than 90% of TCH being eliminated within 30 min. Furthermore, even after five cycles of use, the treatment efficiency remains above 90%. The rate constant is calculated to be 0.218 min-1, with high regression coefficients (R 2 = 0.93). The activation energy (Ea) was found to be 32.2 kJ/mol, indicating that the degradation of TCH was a simple reaction with a low activation energy. These findings showed that the RSCF is a highly efficient and cost-effective catalyst for TCH degradation. Moreover, the use of e-Fenton process has the advantage of high efficiency, low cost thanks to the recyclability of the catalyst, and environmental friendliness thanks to less use of H2O2.

3.
Cancers (Basel) ; 16(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38893189

ABSTRACT

Cervical cancer (CC) was diagnosed in 3159 women in France in 2023, and 1117 died from it. Organized screening for cervical cancer is potentially very effective for participating women. However, reaching under-screened populations remains a major challenge. The present qualitative study explored women's opinions on what discourages or encourages them to participate in CC screening and assessed the acceptability of two experimental strategies (urinary or vaginal self-sampling kits) to increase the screening coverage in three rural French administrative departments with low medical density and/or low screening participation rates. Forty-eight semi-structured interviews and four focus groups were conducted by a team of psychologists. Results showed that the participants accepted at-home self-sampling to reach non-participating women in medically underserved areas. However, they suggested that the type of kit sent should be adapted to the patient's profile (embarrassment from earlier exams, cultural aspects, fear of invasiveness, etc.), and that kits should be simple to use (in understandable language taking sociocultural aspects into account). Women wished to be assured that testing on self-samples is accurate and needed information about further actions in case of a positive result.

4.
Chem Biodivers ; : e202401273, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828879

ABSTRACT

Eight furostanol glycosides including five undescribed compounds, named tribufurostanosides A-E (1-5), and three known ones (6-8) were isolated from the fruits of Tribulus terrestris L. Their chemical structures were determined by the IR, HR-ESI-MS, 1D-, and 2D-NMR spectra. Furostanols 1-8 significantly inhibited nitric oxide production in LPS activated RAW 264.7 cells with IC50 values ranging from 14.2 to 64.7 µM, compared to that of the positive control compound, dexamethazone (IC50 13.6 µM).

5.
Front Plant Sci ; 15: 1245545, 2024.
Article in English | MEDLINE | ID: mdl-38872892

ABSTRACT

The resistance of Arabidopsis thaliana to clubroot, a major disease of Brassicaceae caused by the obligate protist Plasmodiophora brassicae, is controlled in part by epigenetic factors. The detection of some of these epigenetic quantitative trait loci (QTLepi) has been shown to depend on experimental conditions. The aim of the present study was to assess whether and how temperature and/or soil water availability influenced both the detection and the extent of the effect of response QTLepi. The epigenetic recombinant inbred line (epiRIL) population, derived from the cross between ddm1-2 and Col-0 (partially resistant and susceptible to clubroot, respectively), was phenotyped for response to P. brassicae under four abiotic conditions including standard conditions, a 5°C temperature increase, drought, and flooding. The abiotic constraints tested had a significant impact on both the leaf growth of the epiRIL population and the outcome of the epiRIL-pathogen interaction. Linkage analysis led to the detection of a total of 31 QTLepi, 18 of which were specific to one abiotic condition and 13 common to at least two environments. EpiRIL showed significant plasticity under epigenetic control, which appeared to be specific to the traits evaluated and to the abiotic conditions. These results highlight that the environment can affect the epigenetic architecture of plant growth and immune responses and advance our understanding of the epigenetic factors underlying plasticity in response to climate change.

6.
J Infect Public Health ; 17(7): 102443, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838606

ABSTRACT

BACKGROUND: The burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases. METHODS: Data on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019. The Bayesian age-period-cohort model was used to analyze the temporal trend and predict the disease burden by 2030. RESULTS: The number of HCV-related CLD deaths surpassed that of CLD deaths caused by HBV in 2019 (536833 deaths versus 523003 deaths) and is expected to be maintained until 2030 (689124 deaths versus 628824 deaths). East Asia had the highest burden of chronic HBV and HCV infections during the study period. In 2019, the largest age-standardized death rates (ASDR) of CLD deaths caused by HBV and HCV were mainly observed in Western Sub-Saharan Africa (18.75%) and Eastern Sub-Saharan Africa (16.42%), respectively. South Asia and East Asia are predicted to have the highest number of CLD deaths related to HCV and HBV by 2030. Eastern Europe and South Asia show the largest expected increase in disease burden caused by HCV or HBV between 2019 and 2030. No GBD region is projected to achieve the WHO target of a 65% reduction in mortality from chronic HBV and HCV infections by 2030. CONCLUSIONS: Although the mortality of CLD caused by HBV and HCV decreased in the last three decades (from 1990 to 2019), the number of deaths will continue to increase until 2030. Therefore, governments and international organizations need to strengthen the effectiveness of vaccines, screening, and treatment, especially in potential emerging hotspot regions.


Subject(s)
Global Health , Hepatitis B, Chronic , Hepatitis C, Chronic , Humans , Global Health/statistics & numerical data , Hepatitis C, Chronic/mortality , Hepatitis C, Chronic/epidemiology , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/complications , Male , Female , Risk Factors , Middle Aged , Adult , Hepatitis B/mortality , Hepatitis B/epidemiology , Global Burden of Disease , Liver Diseases/mortality , Liver Diseases/epidemiology , Chronic Disease/epidemiology , Hepatitis C/mortality , Hepatitis C/epidemiology , Bayes Theorem , Aged
8.
BMC Bioinformatics ; 25(1): 193, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755527

ABSTRACT

We have developed AMRViz, a toolkit for analyzing, visualizing, and managing bacterial genomics samples. The toolkit is bundled with the current best practice analysis pipeline allowing researchers to perform comprehensive analysis of a collection of samples directly from raw sequencing data with a single command line. The analysis results in a report showing the genome structure, genome annotations, antibiotic resistance and virulence profile for each sample. The pan-genome of all samples of the collection is analyzed to identify core- and accessory-genes. Phylogenies of the whole genome as well as all gene clusters are also generated. The toolkit provides a web-based visualization dashboard allowing researchers to interactively examine various aspects of the analysis results. Availability: AMRViz is implemented in Python and NodeJS, and is publicly available under open source MIT license at https://github.com/amromics/amrviz .


Subject(s)
Genome, Bacterial , Genomics , Software , Genomics/methods , Drug Resistance, Bacterial/genetics , Phylogeny , Bacteria/genetics , Bacteria/drug effects , Anti-Bacterial Agents/pharmacology
9.
Article in English | MEDLINE | ID: mdl-38743534

ABSTRACT

Recent connections in the adaptive control literature to continuous-time analogs of Nesterov's accelerated gradient method have led to the development of new real-time adaptation laws based on accelerated gradient methods. However, previous results assume that the system's uncertainties are linear-in-the-parameters (LIP). To compensate for non-LIP uncertainties, our preliminary results developed a neural network (NN)-based accelerated gradient adaptive controller to achieve trajectory tracking for nonlinear systems; however, the development and analysis only considered single-hidden-layer NNs. In this article, a generalized deep NN (DNN) architecture with an arbitrary number of hidden layers is considered, and a new DNN-based accelerated gradient adaptation scheme is developed to generate estimates of all the DNN weights in real-time. A nonsmooth Lyapunov-based analysis is used to guarantee the developed accelerated gradient-based DNN adaptation design achieves global asymptotic tracking error convergence for general nonlinear control affine systems subject to unknown (non-LIP) drift dynamics and exogenous disturbances. A comprehensive set of simulation studies are conducted on a two-state nonlinear system, a robotic manipulator, and a complex 20-D nonlinear system to demonstrate the improved performance of the developed method. Our simulation studies demonstrate enhanced tracking and function approximation performance from both DNN architectures and accelerated gradient adaptation.

10.
JAMA Netw Open ; 7(5): e2411938, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38780943

ABSTRACT

Importance: The human papillomavirus (HPV) vaccine is safe and effective, yet vaccination coverage remains below public health objectives in many countries. Objective: To examine the effectiveness of a 3-component intervention on HPV vaccination coverage among adolescents aged 11 to 14 years 2 months after the intervention ended, each component being applied alone or in combination. Design, Setting, and Participants: A cluster randomized trial with incomplete factorial design (PrevHPV) was conducted between July 1, 2021, and April 30, 2022, in French municipalities receiving 0, 1, 2, or 3 components of the intervention. Randomization was stratified by school district and municipalities' socioeconomic level. Analyses were carried out on 11- to 14-year-old adolescents living in all participating municipalities, regardless of what had been implemented. Intervention: The PrevHPV intervention had 3 components: (1) educating and motivating 11- to 14-year-old adolescents in middle schools, along with their parents; (2) training general practitioners (GPs) on up-to-date HPV information and motivational interviewing techniques; and (3) free HPV vaccination at school. Main Outcomes and Measures: The primary outcome was HPV vaccination coverage (≥1 dose) 2 months after the intervention ended among 11- to 14-year-old adolescents living in participating municipalities, based on the French national reimbursement database and data collected during the trial in groups randomized to implement at-school vaccination. Results: A total of 91 municipalities comprising 30 739 adolescents aged 11 to 14 years (15 876 boys and 14 863 girls) were included and analyzed. Half the municipalities were in the 2 lowest socioeconomic quintiles and access to GPs was poor in more than two-thirds of the municipalities. Thirty-eight of 61 schools (62.3%) implemented actions and 26 of 45 municipalities (57.8%) had at least 1 trained GP. The median vaccination coverage increased by 4.0 percentage points (IQR, 2.0-7.3 percentage points) to 14.2 percentage points (IQR, 9.1-17.3 percentage points) at 2 months. At-school vaccination significantly increased vaccination coverage (5.50 percentage points [95% CI, 3.13-7.88 percentage points]) while no effect was observed for adolescents' education and motivation (-0.08 percentage points [95% CI, -2.54 to 2.39 percentage points]) and GPs' training (-1.46 percentage points [95% CI, -3.44 to 0.53 percentage points]). Subgroup analyses found a significant interaction between at-school vaccination and access to GPs, with a higher effect when access was poor (8.62 percentage points [95% CI, 5.37-11.86 percentage points] vs 2.13 percentage points [95% CI, -1.25 to 5.50 percentage points]; P = .007 for interaction). Conclusions and Relevance: In this cluster randomized trial, within the context of the late COVID-19 pandemic period and limited school and GP participation, at-school HPV vaccination significantly increased vaccination coverage. The trial did not show a significant effect for training GPs and education and motivation, although it may be observed after more time has elapsed after the intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT04945655.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Primary Health Care , Humans , Adolescent , Papillomavirus Vaccines/administration & dosage , Papillomavirus Vaccines/therapeutic use , Female , Male , Child , Papillomavirus Infections/prevention & control , France , School Health Services , Vaccination Coverage/statistics & numerical data , Vaccination/statistics & numerical data , Vaccination/methods , Schools
11.
J Chem Phys ; 160(20)2024 May 28.
Article in English | MEDLINE | ID: mdl-38804496

ABSTRACT

The control of movement and orientation of gas-phase molecules has become the focus of many research areas in molecular physics. Here, ND3 molecules are polarized in a segmented, curved electrostatic guide and adiabatically aligned inside a rotatable mass spectrometer (MS). Alignment is probed by photoionization using a linearly polarized laser. Rotation of the polarization at fixed MS orientation has the same effect as the rotation of the MS at fixed polarization, proving that the molecular alignment adiabatically follows the MS axis. Polarization-dependent ion signals reveal state-specific populations and allow for a quantification of the aligned sample in the space-fixed reference frame.

12.
Sci Rep ; 14(1): 11959, 2024 05 25.
Article in English | MEDLINE | ID: mdl-38796495

ABSTRACT

AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1-5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy.Clinical Trial Registration Number: NCT04899908.Clinical Trial Registration Date: 25/05/2021.


Subject(s)
Brain Neoplasms , Gadolinium , Magnetic Resonance Imaging , Humans , Brain Neoplasms/secondary , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Brain Neoplasms/drug therapy , Gadolinium/metabolism , Gadolinium/administration & dosage , Magnetic Resonance Imaging/methods , Female , Middle Aged , Male , Nanoparticles/chemistry , Contrast Media/pharmacokinetics , Phantoms, Imaging , Aged , Adult , Double-Blind Method
13.
Patient ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693318

ABSTRACT

BACKGROUND: With the aim to optimize communication during HPV vaccination campaigns in France, we elicited parental preferences around HPV vaccination. METHODS: We conducted a single-profile discrete choice experiment (DCE) among parents of 11- to 14-year-old middle-school pupils, who completed an anonymous, self-administered, internet-based questionnaire during 2020-2021. The DCE comprised five attributes (vaccine-preventable disease, justification of optimal age, information on safety, indirect protection and coverage) of vaccination against an unnamed disease that were presented to respondents in ten choice tasks, or scenarios. We use fixed effect logit models to estimate attribute weights on theoretical vaccine acceptance, and random effect linear regression to estimate attribute coefficients on vaccine eagerness (decision and decision certainty). We estimated marginal effects of attributes on expected vaccine acceptance. RESULTS: Vaccination scenarios were accepted by 55.6-89.2% of the 1291 participants. The largest marginal effects on expected vaccine acceptance in the full sample arose from prevention of cancer versus genital warts (+ 11.3 percentage points); from a "severe side effect suspicion that was not scientifically confirmed" versus a statement about "more benefits than risks" (+ 8.9 percentage points), and information on 80% vaccine coverage in neighbouring countries versus on "insufficient coverage" (+ 4.2 percentage points). Explaining the early age of vaccination by sexual debut had a strong negative impact among French monolingual parents with lower education level (vs age-independent, OR 0.48, 95% CI 0.27-0.86), but not other socio-economic groups. After removing low-quality responses (unvaried certainty and short questionnaire completion), among serial non-demanders with children not vaccinated against HPV, only disease elimination impacted vaccine eagerness positively (coefficient 0.54, 0.06-1.02). DISCUSSION: Using DCEs to elicit parents' preferences around communication messages, notably on cancer prevention, vaccine coverage and information about vaccine safety, could help to optimize HPV vaccination promotion efforts.

14.
Liver Int ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38702958

ABSTRACT

BACKGROUND AND AIMS: Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation. METHODS: The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers. RESULTS: We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score. CONCLUSION: Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD.

15.
Health Secur ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38717837
16.
J Neuroendocrinol ; : e13387, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565500

ABSTRACT

In humans, the first 1000 days of life are pivotal for brain and organism development. Shortly after birth, gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus are activated, a phenomenon known as minipuberty. This phenomenon, observed in all mammals studied, influences the postnatal development of the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. This review will put into perspective the results of recent studies showing that the impact of minipuberty extends beyond reproductive function, influencing sensory and cognitive maturation. Studies in mice have revealed the role of nitric oxide (NO) in regulating minipuberty amplitude, with NO deficiency linked to cognitive and olfactory deficits. Additionally, findings indicate that cognitive and sensory defects in adulthood in a mouse model of Down syndrome are associated with an age-dependent decline of GnRH production, whose origin can be traced back to minipuberty, and point to the potential therapeutic role of pulsatile GnRH administration in cognitive disorders. Furthermore, this review delves into the repercussions of COVID-19 on GnRH production, emphasizing potential consequences for neurodevelopment and cognitive function in infected individuals. Notably, GnRH neurons appear susceptible to SARS-CoV-2 infection, raising concerns about potential long-term effects on brain development and function. In conclusion, the intricate interplay between GnRH neurons, GnRH release, and the activity of various extrahypothalamic brain circuits reveals an unexpected role for these neuroendocrine neurons in the development and maintenance of sensory and cognitive functions, supplementing their established function in reproduction. Therapeutic interventions targeting the HPG axis, such as inhaled NO therapy in infancy and pulsatile GnRH administration in adults, emerge as promising approaches for addressing neurodevelopmental cognitive disorders and pathological aging.

17.
J Interpers Violence ; : 8862605241245375, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622887

ABSTRACT

Although socioeconomic inequality has been identified as a significant factor for violence against women, the connection between these two variables has not been widely recognized and addressed in many countries. This study aims to quantify the degree of socioeconomic inequalities in intimate partner violence (IPV) in Vietnam and investigate the contribution of each determinant factor that contributes to the observed inequality. We utilized the Vietnamese National Survey on Domestic Violence against Women (N = 4,019) for the analysis. Household wealth was used as a proxy for socioeconomic status. We used a concentration index to quantify the degree of socioeconomic inequality in emotional, physical, or sexual violence and a combination of these three types of violence. We further decomposed the concentration index to identify the contribution of each determinant to the observed inequality in IPV. We found that the prevalence of IPV was significantly concentrated among the worse-off across all types of IPV and that disparities in husband's occupation (48%), women's education (39%), husband's education (38%), and class (34%) were the primary factors contributing to increased inequalities in IPV. Our results indicated that higher education and engagement in skilled jobs were highly concentrated among the better-off, creating unequal distribution of these variables across wealth. Policy could mitigate the inequality in IPV by expanding women's access to education and economic opportunities. However, interventions should target both men and women and within couples because husband's characteristics also play an important role in explaining socioeconomic inequalities in IPV.

18.
Signal Transduct Target Ther ; 9(1): 103, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38664368

ABSTRACT

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance. They, for instance, regulate appetite and satiety in certain hypothalamic neurons, as well as glucose and lipid metabolism and hormone secretion from adipocytes. Mutations in some GPCRs, such as the melanocortin receptor type 4 (MC4R), have been associated with early-onset obesity. Here, we identified the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) as a member of the regulating network governing food intake and the maintenance of energy balance. Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity, accompanied by dysregulation of glucose homeostasis. Consistently, we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity. Therefore, we propose that LPHN1 dysfunction is a risk factor for obesity development.


Subject(s)
Obesity , Receptors, G-Protein-Coupled , Receptors, Peptide , Animals , Humans , Mice , Energy Metabolism/genetics , Glucose/metabolism , Glucose/genetics , Obesity/genetics , Obesity/metabolism , Obesity/pathology , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, Peptide/genetics , Receptors, Peptide/metabolism
19.
Sci Data ; 11(1): 321, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548727

ABSTRACT

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Artificial Intelligence , Lung Neoplasms/diagnostic imaging , Thorax/diagnostic imaging , Anatomic Landmarks/diagnostic imaging
20.
JBMR Plus ; 8(3): ziad016, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38505222

ABSTRACT

Bone development and remodeling are controlled by the phosphoinositide-3-kinase (Pi3k) signaling pathway. We investigated the effects of downregulation of phosphatase and tensin homolog (Pten), a negative regulator of Pi3k signaling, in a mouse model of Pten deficiency in preosteoblasts. We aimed to identify mechanisms that are involved in the regulation of bone turnover and are linked to bone disorders. Femora, tibiae, and bone marrow stromal cells (BMSCs) isolated from mice with a conditional deletion of Pten (Pten cKO) in Osterix/Sp7-expressing osteoprogenitor cells were compared to Cre-negative controls. Bone phenotyping was performed by µCT measurements, bone histomorphometry, quantification of bone turnover markers CTX and procollagen type 1 N propeptide (P1NP), and three-point bending test. Proliferation of BMSCs was measured by counting nuclei and Ki-67-stained cells. In vitro, osteogenic differentiation capacity was determined by ALP staining, as well as by detecting gene expression of osteogenic markers. BMSCs from Pten cKO mice were functionally different from control BMSCs. Osteogenic markers were increased in BMSCs derived from Pten cKO mice, while Pten protein expression was lower and Akt phosphorylation was increased. We detected a higher trabecular bone volume and an altered cortical bone morphology in Pten cKO bones with a progressive decrease in bone and tissue mineral density. Pten cKO bones displayed fewer osteoclasts and more osteoblasts (P = .00095) per trabecular bone surface and a higher trabecular bone formation rate. Biomechanical analysis revealed a significantly higher bone strength (P = .00012 for males) and elasticity of Pten cKO femora. On the cellular level, both proliferation and osteogenic differentiation capacity of Pten cKO BMSCs were significantly increased compared to controls. Our findings suggest that Pten knockout in osteoprogenitor cells increases bone stability and elasticity by increasing trabecular bone mass and leads to increased proliferation and osteogenic differentiation of BMSCs.

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