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2.
Ann Oncol ; 35(8): 728-738, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38866180

RÉSUMÉ

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.


Sujet(s)
Protocoles de polychimiothérapie antinéoplasique , Carboplatine , Tumeurs de l'endomètre , Paclitaxel , Humains , Femelle , Carboplatine/administration et posologie , Tumeurs de l'endomètre/traitement médicamenteux , Tumeurs de l'endomètre/mortalité , Tumeurs de l'endomètre/anatomopathologie , Paclitaxel/administration et posologie , Paclitaxel/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Méthode en double aveugle , Adulte d'âge moyen , Sujet âgé , Adulte , Sujet âgé de 80 ans ou plus , Récidive tumorale locale/traitement médicamenteux , Récidive tumorale locale/anatomopathologie , Récidive tumorale locale/mortalité , Survie sans progression , Anticorps monoclonaux humanisés
3.
Sci Total Environ ; 942: 173403, 2024 Sep 10.
Article de Anglais | MEDLINE | ID: mdl-38844217

RÉSUMÉ

With 24 million inhabitants and 6.6 million vehicles on the roads, Karachi, Pakistan ranks among the world's most polluted cities due to high levels of fine particulate matter (PM2.5). This study aims to investigate PM2.5 mass, seasonal and temporal variability, chemical characterization, source apportionment, and health risk assessment at two urban sites in Karachi. Samples were analyzed using ion chromatography and dual-wavelength optical transmissometer for various inorganic components (anions, cations, and trace elements) and black carbon (BC). Several PM2.5 pollution episodes were frequently observed, with annual mean concentrations at Kemari (140 ± 179 µg/m3) and Malir (95 ± 40.9 µg/m3) being significantly above the World Health Organization's guidelines of 5 µg/m3. Chemical composition at both sites exhibited seasonal variability, with higher pollution levels in winter and fall and lower concentrations in summer. The annual average BC concentrations were 4.86 ± 5.29 µg/m3 and 4.52 ± 3.68 µg/m3, respectively. A Positive Matrix Factorization (PMF) analysis identified 5 factors, crustal, sea salt, vehicular exhaust, fossil-fuel combustion, and industrial emission. The health risk assessment indicated a higher number of deaths in colder seasons (fall and winter) at the Kemari (328,794 and 287,814) and Malir (228,406 and 165,737) sites and potential non-carcinogenic and carcinogenic risks to children from metals. The non-carcinogenic risk of PM2.5 bound Pb, Fe, Zn, Mn, Cr, Cu and Ni via inhalation exposure were within the acceptable level (<1) for adults. However, potential non-carcinogenic and carcinogenic health risk posed by Pb and Cr through inhalation were observed for children. The findings exhibit critical levels of air pollution that exceed the safe limits in Karachi, posing significant health risks to children and sensitive groups. Our study underscores the urgent need for effective emission control strategies and policy interventions to mitigate these air pollution risks.


Sujet(s)
Polluants atmosphériques , Pollution de l'air , Surveillance de l'environnement , Matière particulaire , Pollution de l'air/statistiques et données numériques , Humains , Polluants atmosphériques/analyse , Matière particulaire/analyse , Pakistan , Appréciation des risques , Villes , Exposition environnementale/statistiques et données numériques
4.
Gynecol Oncol ; 188: 103-110, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-38943691

RÉSUMÉ

OBJECTIVES: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. METHODS: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. RESULTS: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. CONCLUSIONS: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.


Sujet(s)
5'-Nucleotidase , Anticorps monoclonaux , Protocoles de polychimiothérapie antinéoplasique , Carcinome épithélial de l'ovaire , Protéines liées au GPI , Récidive tumorale locale , Tumeurs de l'ovaire , Humains , Femelle , Adulte d'âge moyen , 5'-Nucleotidase/antagonistes et inhibiteurs , 5'-Nucleotidase/immunologie , Sujet âgé , Anticorps monoclonaux/administration et posologie , Anticorps monoclonaux/usage thérapeutique , Anticorps monoclonaux/pharmacologie , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/immunologie , Tumeurs de l'ovaire/anatomopathologie , Carcinome épithélial de l'ovaire/traitement médicamenteux , Carcinome épithélial de l'ovaire/immunologie , Carcinome épithélial de l'ovaire/anatomopathologie , Récidive tumorale locale/traitement médicamenteux , Récidive tumorale locale/immunologie , Récidive tumorale locale/anatomopathologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/pharmacologie , Protéines liées au GPI/immunologie , Protéines liées au GPI/antagonistes et inhibiteurs , Adulte , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/administration et posologie , Anticorps monoclonaux humanisés/pharmacologie
5.
Phys Rev Lett ; 132(14): 146302, 2024 Apr 05.
Article de Anglais | MEDLINE | ID: mdl-38640364

RÉSUMÉ

Transport measurement of electron optics in monolayer graphene p-n junction devices has been traditionally studied with negative refraction and chiral transmission experiments in Hall bar magnetic focusing setups. We show direct signatures of Klein (monolayer) and anti-Klein (bilayer) tunneling with a circular "edgeless" Corbino geometry made out of gated graphene p-n junctions. Noticeable in particular is the appearance of angular sweet spots (Brewster angles) in the magnetoconductance data of bilayer graphene, which minimizes head-on transmission, contrary to conventional Fresnel optics or monolayer graphene which show instead a sharpened collimation of transmission paths. The local maxima on the bilayer magnetoconductance plots migrate to higher fields with increasing doping density. These experimental results are in good agreement with detailed numerical simulations and analytical predictions.

6.
J Pharm Bioallied Sci ; 16(Suppl 1): S380-S382, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-38595630

RÉSUMÉ

Objective: Using cone beam computed tomography (CBCT), this study compared three rotary file systems-XP Endoshaper, Hyflex CM, and K3 XF-for centering, canal transportation, and root canal area growth. Materials and Methods: The rotating file system randomly separated 60 removed human mandibular molars into three groups (n = 20). Manufacturer-recommended root canal instrumentation was done. Specialized software examined pre- and post-instrumentation CBCT scans. Centering ability was measured by canal transportation and root canal area expansion at different levels from the apex. Results: The Hyflex CM file system had the best centering and the least canal transit at all levels (P < 0.05). XP Endoshaper increased the root canal area the most (P < 0.05). The K3 XF file system had average centering and canal transfer results. Conclusion: The Hyflex CM system centered well, whereas the XP Endoshaper system increased the root canal area the most. The clinical context and therapeutic goals should determine the rotating file system.

7.
Biology (Basel) ; 13(3)2024 Feb 27.
Article de Anglais | MEDLINE | ID: mdl-38534418

RÉSUMÉ

Understanding how seed functional traits interact with environmental factors to determine seedling recruitment is critical to assess the impact of climate change on ecosystem restoration. This study focused on the effects of environmental factors on the mother plant during early plant life history stages and during seed development. Desmodium brachypodum A. Gray (large tick trefoil, Fabaceae) was used as a model species. Firstly, this study analyzed seed germination traits in response to temperature and moisture stress. Secondly, it investigated how seed burial depth interacts with temperature and soil moisture to influence seedling emergence traits. Finally, it determined if contrasting levels of post-anthesis soil moisture could result in changes in D. brachypodum reproductive biology and seed and seedling functional traits. The results showed that elevated temperature and moisture stress interacted to significantly reduce the seed germination and seedling emergence (each by >50%), while the seed burial improved the seedling emergence. Post-anthesis soil moisture stress negatively impacted the plant traits, reducing the duration of the reproductive phenology stage (by 9 days) and seed production (by almost 50%). Unexpectedly, soil moisture stress did not affect most seed or seedling traits. In conclusion, elevated temperatures combined with low soil moisture caused significant declines in seed germination and seedling emergence. On the other hand, the reproductive output of D. brachypodum had low seed variability under soil moisture stress, which might be useful when sourcing seeds from climates with high variability. Even so, a reduction in seed quantity under maternal moisture stress can impact the long-term survival of restored plant populations.

8.
Physiol Rep ; 12(5): e15963, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38439737

RÉSUMÉ

Hypoxia is mainly caused by cardiopulmonary disease or high-altitude exposure. We used a driving simulator to investigate whether breathing hypoxic gas influences driving behaviors in healthy subjects. Fifty-two healthy subjects were recruited in this study, approved by the Science and Engineering Ethical Committee. During simulated driving experiments, driving behaviors, breathing frequency, oxygen saturation (SpO2 ), and heart rate variability (HRV) were analyzed. Each subject had four driving sessions; a 10-min practice and three 20-min randomized interventions: normoxic room air (21% FIO2 ) and medical air (21% FIO2 ) and hypoxic air (equal to 15% FIO2 ), analyzed by repeated measures ANOVA. Driving behaviors and HRV frequency domains showed no significant change. Heart rate (HR; p < 0.0001), standard deviation of the RR interval (SDRR; p = 0.03), short-term HRV (SD1; p < 0.0001), breathing rate (p = 0.01), and SpO2 (p < 0.0001) were all significantly different over the three gas interventions. Pairwise comparisons showed HR increased during hypoxic gas exposure compared to both normoxic interventions, while SDRR, SD1, breathing rate, and SpO2 were lower. Breathing hypoxic gas (15% FiO2 , equivalent to 2710 m altitude) may not have a significant impact on driving behavior in healthy subjects. Furthermore, HRV was negatively affected by hypoxic gas exposure while driving suggesting further research to investigate the impact of breathing hypoxic gas on driving performance for patients with autonomic dysfunction.


Sujet(s)
Altitude , Maladies du système nerveux autonome , Syndactylie , Humains , Volontaires sains , Hypoxie
9.
Heliyon ; 10(6): e27795, 2024 Mar 30.
Article de Anglais | MEDLINE | ID: mdl-38496905

RÉSUMÉ

Bangladesh's subtropical climate with an abundance of sunlight throughout the greater portion of the year results in increased effectiveness of solar panels. Solar irradiance forecasting is an essential aspect of grid-connected photovoltaic systems to efficiently manage solar power's variation and uncertainty and to assist in balancing power supply and demand. This is why it is essential to forecast solar irradiation accurately. Many meteorological factors influence solar irradiation, which has a high degree of fluctuation and uncertainty. Predicting solar irradiance multiple steps ahead makes it difficult for forecasting models to capture long-term sequential relationships. Attention-based models are widely used in the field of Natural Language Processing for their ability to learn long-term dependencies within sequential data. In this paper, our aim is to present an attention-based model framework for multivariate time series forecasting. Using data from two different locations in Bangladesh with a resolution of 30 min, the Attention-based encoder-decoder, Transformer, and Temporal Fusion Transformer (TFT) models are trained and tested to predict over 24 steps ahead and compared with other forecasting models. According to our findings, adding the attention mechanism significantly increased prediction accuracy and TFT has shown to be more precise than the rest of the algorithms in terms of accuracy and robustness. The obtained mean square error (MSE), the mean absolute error (MAE), and the coefficient of determination (R2) values for TFT are 0.151, 0.212, and 0.815, respectively. In comparison to the benchmark and sequential models (including the Naive, MLP, and Encoder-Decoder models), TFT has a reduction in the MSE and MAE of 8.4-47.9% and 6.1-22.3%, respectively, while R2 is raised by 2.13-26.16%. The ability to incorporate long-distance dependency increases the predictive power of attention models.

10.
Ann Oncol ; 35(5): 414-428, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38431043

RÉSUMÉ

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.


Sujet(s)
Protocoles de polychimiothérapie antinéoplasique , Tumeurs de l'endomètre , Immunothérapie , Humains , Femelle , Tumeurs de l'endomètre/anatomopathologie , Tumeurs de l'endomètre/traitement médicamenteux , Tumeurs de l'endomètre/thérapie , Tumeurs de l'endomètre/immunologie , Immunothérapie/méthodes , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Essais cliniques de phase III comme sujet , Survie sans progression , Essais contrôlés randomisés comme sujet , Instabilité des microsatellites , Métastase tumorale
11.
bioRxiv ; 2024 Jan 15.
Article de Anglais | MEDLINE | ID: mdl-38293159

RÉSUMÉ

Analyses of biomedical images often rely on accurate segmentation of structures of interest. Traditional segmentation methods based on thresholding, watershed, fast marching, and level set perform well in high-contrast images containing structures of similar intensities. However, such methods can under-segment or miss entirely low-intensity objects on noisy backgrounds. Machine learning segmentation methods promise superior performance but require large training datasets of labeled images which are difficult to create, particularly in 3D. Here, we propose an algorithm based on the Local Binary Fitting (LBF) level set method, specifically designed to improve the segmentation of low-contrast structures.

12.
Transplantation ; 108(2): 556-566, 2024 Feb 01.
Article de Anglais | MEDLINE | ID: mdl-37650722

RÉSUMÉ

BACKGROUND: Evidence on the optimal maintenance of immunosuppressive regimen in kidney transplantation recipients is limited. METHODS: The Amsterdam, LEiden, GROningen trial is a randomized, multicenter, investigator-driven, noninferiority, open-label trial in de novo kidney transplant recipients, in which 2 immunosuppression minimization strategies were compared with standard immunosuppression with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid. In the minimization groups, either steroids were withdrawn from day 3, or tacrolimus exposure was reduced from 6 mo after transplantation. The primary endpoint was kidney transplant function at 24 mo. RESULTS: A total of 295 participants were included in the intention-to-treat analysis. Noninferiority was shown for the primary endpoint; estimated glomerular filtration rate at 24 mo was 45.3 mL/min/1.73 m 2 in the early steroid withdrawal group, 49.0 mL/min/1.73 m 2 in the standard immunosuppression group, and 44.7 mL/min/1.73 m 2 in the tacrolimus minimization group. Participants in the early steroid withdrawal group were significantly more often treated for rejection ( P = 0.04). However, in this group, the number of participants with diabetes mellitus during follow-up and total cholesterol at 24 mo were significantly lower. CONCLUSIONS: Tacrolimus minimization can be considered in kidney transplant recipients who do not have an increased immunological risk. Before withdrawing steroids the risk of rejection should be weighed against the potential metabolic advantages.


Sujet(s)
Carbazoles , Transplantation rénale , Tacrolimus , Tryptamines , Humains , Tacrolimus/effets indésirables , Transplantation rénale/effets indésirables , Immunosuppresseurs/effets indésirables , Immunosuppression thérapeutique , Acide mycophénolique/effets indésirables , Stéroïdes , Rejet du greffon/prévention et contrôle
14.
ACS Omega ; 8(45): 42102-42113, 2023 Nov 14.
Article de Anglais | MEDLINE | ID: mdl-38024758

RÉSUMÉ

In this study, we fabricated and evaluated luliconazole-loaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box-Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78° for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

15.
Trauma Surg Acute Care Open ; 8(1): e001188, 2023.
Article de Anglais | MEDLINE | ID: mdl-38020862

RÉSUMÉ

Background: Clavicle fracture (CF) is the tenth most prevalent fracture, accounting for an annual incidence of 37/10,000. This systematic review highlights the factors contributing to the nonunion union of the clavicular fracture. Method: A systematic search was conducted using three web-based databases up to August 12, 2022, for conducting qualitative analysis. Articles were screened for relevance, and only studies that met inclusion criteria based on PECOS; P (patients): participants diagnosed with clavicular fracture; E (exposure): nonunion, C (control): not applicable; O (outcomes): factors contributing to nonunion or delayed union; S (studies): trials and observational studies. The Newcastle-Ottawa Scale was used to assess the quality of the cohort studies. The Cochrane risk of bias tool was used to assess the bias in randomized control trials. Results: Ten studies were selected after the final literature search. Two thousand seven hundred and sixty-six adult participants who were radiologically and clinically diagnosed with nonunion clavicular fracture were included to pool the qualitative results. Fall was the most dominant cause of clavicular fracture, followed by road traffic collisions. Open reduction was widely used to treat nonunion correction. The qualitative results suggested a prominent correlation of nonunion with advancing age, female gender, high energy trauma, high Disabilities of the Arm, Shoulder, and Hand Score, smoking, fracture displacement, clavicular shortening, the callus on radiography, and fracture movement. The mid-shaft fracture was the most dominant type of fracture in the included studies; highly associated with nonunion in comparison to medial or lateral CF. The previous history of operation was an independent factor contributing to nonunion. Conclusion: The results of this systematic review suggested the predictors contributing to nonunion in the CF. Demographic factors such as advancing age with female gender are at higher risk of developing clavicular nonunion. Smoking was the most dominantly highlighted environmental factor contributing to nonunion. Diaphyseal or midshaft fracture was the most common site for nonunion. Therefore, we suggested that patients with the predictors mentioned above require special attention to prevent nonunion of the CFs. More studies should be conducted on this subject to assess the factors that pose a risk associated with the nonunion of the bone for better clinical management and outcomes of the fracture.

16.
Cell Metab ; 35(11): 1944-1960.e7, 2023 11 07.
Article de Anglais | MEDLINE | ID: mdl-37898119

RÉSUMÉ

Human pancreatic plasticity is implied from multiple single-cell RNA sequencing (scRNA-seq) studies. However, these have been invariably based on static datasets from which fate trajectories can only be inferred using pseudotemporal estimations. Furthermore, the analysis of isolated islets has resulted in a drastic underrepresentation of other cell types, hindering our ability to interrogate exocrine-endocrine interactions. The long-term culture of human pancreatic slices (HPSs) has presented the field with an opportunity to dynamically track tissue plasticity at the single-cell level. Combining datasets from same-donor HPSs at different time points, with or without a known regenerative stimulus (BMP signaling), led to integrated single-cell datasets storing true temporal or treatment-dependent information. This integration revealed population shifts consistent with ductal progenitor activation, blurring of ductal/acinar boundaries, formation of ducto-acinar-endocrine differentiation axes, and detection of transitional insulin-producing cells. This study provides the first longitudinal scRNA-seq analysis of whole human pancreatic tissue, confirming its plasticity in a dynamic fashion.


Sujet(s)
Cellules endocrines , Analyse de l'expression du gène de la cellule unique , Humains , Pancréas , Différenciation cellulaire
17.
Microbiol Res ; 275: 127451, 2023 Oct.
Article de Anglais | MEDLINE | ID: mdl-37478540

RÉSUMÉ

Symbiotic interaction among legume and rhizobia is a complex phenomenon which results in the formation of nitrogen-fixing nodules. Mung bean is promiscuous host however expression profile of this important legume plant in response to rhizobial infection was particularly lacking and urgently needed. We have demonstrated the pattern of gene expression of mung bean roots inoculated with two symbionts Bradyrhizobium yuanmingense Vr50 and Sinorhizobium (Ensifer) aridi Vr33 and non-inoculated control (CK). The RNA-Seq data analyzed at two growth stages i.e., 1-3 h and 10-16 days post inoculation revealed significantly higher number of differentially expressed genes (DEGs) at nodulation stage. The DEGs encoding receptor kinases identified at early stage might be involved in perception of Nod factors produced by different rhizobia. At nodulation stage important genes involved in plant hormone signal transduction, nitrogen and sulfur metabolism were identified. KEGG pathway enrichment analysis showed that metabolic pathways were most prominent in both groups (Group 1: Vr33 vs CK; Group 2: Vr50 vs CK), followed by biosynthesis of secondary metabolites, plant hormone signal transduction and biosynthesis of amino acids. Furthermore, DEGs involved in cell communication and plant hormone signal transduction were found to be different among two symbiotic systems while DEGs involved in carbon, nitrogen and sulfur metabolism were similar but their expression varied in response to two rhizobial strains. This study provides the first insight into the mechanisms underlying interactions of mung bean host with two taxonomically different symbionts (Bradyrhizobium and Sinorhizobium) and the candidate genes for better understanding the mechanisms of symbiotic host-specificity.


Sujet(s)
Bradyrhizobium , Fabaceae , Rhizobium , Sinorhizobium , Vigna , Vigna/génétique , Rhizobium/génétique , Facteur de croissance végétal/métabolisme , RNA-Seq , Racines de plante , Symbiose/génétique , Sinorhizobium/génétique , Azote/métabolisme , Expression des gènes , Soufre/métabolisme , Bradyrhizobium/génétique
19.
Ann Med Surg (Lond) ; 85(3): 567-568, 2023 Mar.
Article de Anglais | MEDLINE | ID: mdl-36923761

RÉSUMÉ

Conversion disorder is a somatoform condition in which patients present with a range of neurologic deficits and sensorimotor loss with no obvious pathology. There has been a rising trend in the incidence of conversion disease in countries with low socioeconomic backgrounds, accounting to be one-third of ambulatory visits in middle and low-income countries (MLIC). However, even with such a high prevalence health-seeking practice for conversion disorder is low in MLIC. One possible reason for such behavior could be the high prevalence of mystical beliefs and traditional healing in MLIC. Existing economic distress with limited healthcare resources convinces people to opt for traditional and local healers who make use of mystical and superstition beliefs prevalent in those regions to offer prospering and cheaper methods of treatment. In this scenario, addressing and counseling mythological fallacies and the use of an economically friendly 'holistic model' of treatment should be adopted in these countries.

20.
Br Poult Sci ; 64(4): 491-496, 2023 Aug.
Article de Anglais | MEDLINE | ID: mdl-36930955

RÉSUMÉ

1. This study examined the feeding value of ten UK grown field bean (Vicia faba L. var. minor) cultivar samples from the same harvest year on nitrogen corrected apparent metabolisable energy (AMEn) and nutrient retention coefficients when fed to young female turkeys.2. A balancer feed (BF) was formulated to contain 12.39 MJ/kg ME and 269 g/kg crude protein. Ten nutritionally complete, mash diets were prepared by mixing 200 g/kg of each ground field bean cultivar with 800 g/kg of the BF, totalling eleven diets. Diets were fed to female BUT Premium turkeys from 40 to 50 d of age. Each diet was fed to eight raised floor pens, housing two birds, following randomisation. The AMEn was determined by the total collection technique over the last 4 d of the study. Relationships were examined between AMEn, chemical composition and quality variables of the field bean samples.3. The overall determined AMEn value of the beans ranged from 7.72 MJ/kg DM to 9.87 MJ/kg DM, giving an average AMEn of 8.80 MJ/kg DM (P < 0.05). The soluble non-starch polysaccharide (NSP) content of the beans negatively correlated with their determined AMEn (r = -0.730; P < 0.05). Bean flour lightness-darkness degree (L*) correlated positively with the AMEn (r = -0.643; P < 0.05)4. A positive correlation was observed between the degree of yellowness-blueness of bean flour and condensed tannins content (r = 0.696; P < 0.05). Step-wise regression indicated that soluble NSP + L* of field beans provided explanatory variables suitable for estimating the AMEn value for turkeys (r2 = 0.737; P < 0.05).


Sujet(s)
Dindons , Vicia faba , Animaux , Femelle , Aliment pour animaux/analyse , Phénomènes physiologiques nutritionnels chez l'animal , Poulets/métabolisme , Régime alimentaire/médecine vétérinaire , Digestion , Métabolisme énergétique , Vicia faba/composition chimique
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