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1.
Neurosurg Focus Video ; 10(2): V10, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38616907

RESUMO

This presentation showcases an endoscopic minimally invasive spine surgery (MISS) technique for lumbar interbody fusion. Significantly expanding the scope of Destandau's system within MISS, it serves as a pivotal link to unilateral biportal endoscopy (UBE) for endofusion. The method involves minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) using a 4-mm rigid endoscope through Destandau's system. With the widespread familiarity with Destandau's system and the absence of specialized instrument requirements, this approach is easily adoptable, particularly in resource-limited centers. The favorable clinical and radiological outcomes underscore the effectiveness of this technique, propelling the role of endoscopy in MISS, particularly in endofusion. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23216.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38598697

RESUMO

OBJECTIVE: The objectives of this study were to characterize and identify correlates of healthy days at home (HDaH) before and after TBI requiring inpatient rehabilitation. Setting: Inpatient hospital, nursing home, and home health services. PARTICIPANTS: Average of n= 631 community-dwelling fee-for-service age 66+ Medicare beneficiaries across 30 replicate samples who were hospitalized for traumatic brain injury (TBI) between 2012 and 2014 and admitted to an inpatient rehabilitation facility (IRF) within 72 hours of hospital discharge. DESIGN: Retrospective study using data from Medicare claims supplemented with data from the National Trauma Databank. MAIN MEASURES: The primary outcome, HDaH, was calculated as time alive not using inpatient hospital, nursing home, and home health services in the year before TBI hospitalization and after IRF discharge. RESULTS: We found HDaH declined from 93.2% in the year before TBI hospitalization to 65.3% in the year after IRF discharge (73.6% among survivors only). Most variability in HDaH was: (1) in the first 3 months after discharge and (2) by discharge disposition, with persons discharged from IRF to another acute hospital having the worst prognosis for utilization and death. In negative binomial regression models, the strongest predictors of HDaH in the year after discharge were rehabilitation Functional Independence Measure mobility score (ß = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score (ß = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors (ß = - 0.37; 95% CI, -0.66 to -0.07). CONCLUSION: In this study, among community-dwelling older adults with TBI, we found a notable decrease in the proportion of time spent alive at home without higher-level care after IRF discharge compared to before TBI. The finding that physical disability and comorbidities were the biggest drivers of healthy days alive in this population suggests that a chronic disease management model is required for older adults with TBI to manage their complex health care needs.

3.
Heliyon ; 10(8): e28998, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644884

RESUMO

The primary issues in the Himalayan Rivers are sediment and cavitation degradation of the hydroelectric power turbine components. During the monsoon season, heavy material is transported by streams in hilly areas like the Himalayas through regular rainfalls, glacial and sub-glacial hydrological activity, and other factors. The severe erosion of hydraulic turbines caused by silt abrasion in these areas requires hydropower facilities to be regularly shut down for maintenance, affecting the plant's overall efficiency. This article provides an in-depth examination of the challenges that can lead to cavitation, silt erosion, and a decrease in the efficiency of various hydroelectric turbines, and it demands attention on the design, manufacture, operation, and maintenance of the turbines. This study's main objective is to critically evaluate earlier theoretical, experimental, and numerical evaluation-based studies (on cavitation and silt erosion) that are provided and addressed throughout the study. As a part of this study, various strategies for mitigating the effects of these problems and elongating the time that turbine may be utilized before they must be replaced have been provided.

4.
J Craniovertebr Junction Spine ; 15(1): 83-91, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38644916

RESUMO

Purpose: To assess the accuracy of freehand cervical C1 C2 screws placement by knock and drill (K and D) technique in craniovertebral anomalous bony anatomy. Materials and Methods: From January 2017 to December 2022, 682 consecutive C1 C2 screws in 215 patients with craniovertebral junction (CVJ) anomalies were enrolled. All patients underwent posterior fixation with K and D technique without any fluoroscopic guidance. The patient's demographic details, clinical details, radiological details, major intraoperative events, and postoperative complications were noted. The screws malposition grades and direction on CT images in the axial and sagittal plane were defined as new per proposed "SGPGI accuracy criteria." All patients had a clinical evaluation at 3-month follow-up. Results: Total 682 C1, C2 screws were placed in 215 patients for CVJ anomalies using K and D technique. The accuracy of screws placement by freehand technique was 84.46% (576/682). So with technique explained the rate of malplacement in simple (16.35%) and complex (15.19%) groups were almost comparable and comparison difference was not significant (P = 0.7005). Conclusion: The freehand technique, as described, is effective in cases of anomalous bony anatomy, and it is mandatory in complex CVJ anomalies. The accuracy of screw placement and VA injury is comparable with major studies. This technique is supposedly cost-effective and less hazardous to both health-care workers and patients.

5.
Curr Radiopharm ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38584548

RESUMO

BACKGROUND: The reproductive organ, housing spermatogonial stem cells (SSCs), undergoes ongoing division impacted by the irradiation dosage and exposure duration. Within the male reproductive organ, germ stem cells (spermatogonia) and somatic cells (Sertoli and Leydig cells) are present. Lower doses of ionizing (>4-6 Gy) and non-ionizing radiation (radiofrequency and microwave range 900 MHz - 2.45 GHz) may cause sperm-related issues, while higher doses (15 Gy) may affect Leydig cells and testosterone production. Response to radiation varies with age and pubescence. Spermatogonial stem cells, crucial for regenerating the spermatogenic lineage, express molecular markers like Estrogen receptor, FSH (Follicular Stimulating Hormone) receptor, TLR-4 (Toll-like Receptor-4), TLR-5 (Toll-like Receptor-5), FGF2 (Fibroblast Growth Factor-2), KIT (Receptor Tyrosine Kinase), AT-1 (Angiotensin II Type-1 Receptor), LXRs-γ (Liver X Receptor-γ), TNF-ß (Tumor Necrosis Factor-ß), and PCNA (Proliferating Cell Nuclear Antigen), influencing stem cell activity in testes. OBJECTIVE: This study aimed to review the various available radioprotective agents and their efficacy in targeting the male reproductive system from the available literature. RESULT: Various radioprotective herbal/synthetic/microbial/metallic extracts/formulations/ drugs [Septilin, Silymarin, Organic Turmeric, Oestrogen, Melatonin, Febuxostat, SQGD (Semiquinone glucoside derivative), Rapamycin, Entolimod, Zinc, Selenium, etc.] have been investigated up to exposure, but owing to effectiveness issues, they are unable to fulfil the aim to the fullest of restoring male fertility and normal testosterone levels during such eventuality. CONCLUSION: Further study is needed to optimize these tactics and fill knowledge gaps. Also, the effective components of herbal, synthetic drugs, etc., should be isolated and tested up to clinical levels, paving the way for successful radioprotection and radiomitigation strategies in the male reproductive system.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38483265

RESUMO

OBJECTIVE: This study aimed to characterize the types and timing of repetitive head impact (RHI) exposures in individuals with moderate to severe traumatic brain injury (TBI) and to examine the effects of RHI exposures on mental health outcomes. SETTING: TBI Model Systems National Database. PARTICIPANTS: 447 patients with moderate to severe TBI who reported RHI exposure between 2015 and 2022. DESIGN: Secondary data analysis. MAIN MEASURES: RHI exposures reported on the Ohio State University TBI Identification Method (OSU TBI-ID) were characterized by exposure category, duration, and timing relative to the index TBI. Mental health outcomes were evaluated at the 5-year follow-up assessment using the Patient Health Questionnaire-9 (PHQ-9) for depression symptoms and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. RESULTS: The majority of RHI exposures were sports-related (61.1%), followed by other causes (20.8%; including falls), repetitive violence/assault (18.8%), and military exposures (6.7%). Males predominantly reported sports and military exposures, while a larger proportion of females reported violence and falls. Sports exposures were most common before the index TBI, while exposures from falls and violence/abuse were most common after TBI. RHI exposures occurring after the index TBI were associated with higher levels of depression (ß = 5.05; 95% CI, 1.59-8.50) and anxiety (ß = 4.53; 95% CI, 1.02-8.05) symptoms than exposures before the index TBI. CONCLUSION: The findings emphasize the need to consider RHI exposures and their interaction with TBI when assessing mental health outcomes. Understanding the prevalence and challenges associated with RHI post-TBI can inform targeted interventions and improve the well-being of individuals with TBI. Preventive measures and ongoing care should be implemented to address the risks posed by RHI, particularly in individuals with prior TBI, especially surrounding fall and violence/abuse prevention.

8.
Heliyon ; 10(6): e26784, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496867

RESUMO

Micro-electrical discharge machining (µEDM) is severely affected by tool wear and its process variants, which can lead to compromised precision and dimensional disruptions in micro-part production. Several attempts have been made to address this problem by suggesting offline and online (real-time) tool wear compensation strategies. Research efforts in this area have intensified over the last 20 years. However, most methods proposed were applicable only for a few work-tool combinations and in limited input process parametric settings. Instead of tool wear compensation, several research articles have focused on strategies to reduce the negative impact of tool wear on the quality of fabricated parts. The present study systematically reviews various investigations conducted in this area and aims to add cutting-edge compensation for tool wear to future inquiries. The articles reviewed here are explored in detail. Critical findings/innovations are classified into four categories: tool wear in µEDM, tool wear compensation techniques, and offline and online compensation methods.

9.
J Neurosci Rural Pract ; 15(1): 95-102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476427

RESUMO

Objectives: Stereotactic biopsy (STB) is a potential diagnostic tool considering its minimal invasiveness, high diagnostic yield, and minimal associated complications. Over the years, various frame-based instrument systems and frameless stereotactic biopsy systems have emerged to be employed in clinical use. With this study, we intend to get more by doing less in the form of STB for the patients of doubtful intracranial lesions treated over the past 5 years. We also want to highlight the technique of performing the procedure under scalp block, which can be used as a versatile tool in many clinical scenarios. Stereotactic biopsies may be planned even in rural district-level health facilities. One-time investment to procure instruments and avail existing imaging can lead to establishing definitive diagnoses in many doubtful cases. This will result in lesser cost and early establishment of treatment. Independent risk factors determining the outcome, such as deep-seated lesions, associated edema, and intraoperative hypertension, were studied. Establishing the diagnosis helped in prognosticating the disease, explaining the natural progression of symptoms, and starting adjuvant therapy. This tissue biopsy would also help secure samples for research and molecular analysis. Materials and Methods: Twenty patients underwent STBs at our institution between January 2018 and December 2022. We retrospectively analyzed patient characteristics, tumor pathology, surgical procedures, and outcomes, including the diagnostic value and surgery-related complications. These patients were followed up, and their progression-free and overall survival were analyzed. The need for adjuvant treatment was noted and analyzed. All procedures were performed using Cosman Roberts Wells® stereotactic frame. Pre-procedure magnetic resonance scans were performed at the time of admission. Contrast-enhanced computerized tomography (CT) scan after frame application was performed to identify targets and calculate the coordinates. A post-procedure CT scan was done to confirm the accessibility of the targeted lesion. Results: The most common location of the tumor was a deep-seated thalamic lesion. A definitive diagnosis was established in 19 patients (95%) at the first STB. The diagnoses were glioma in 55% of cases, primary central nervous system lymphoma, tuberculosis, and demyelinating disorders in 10% of each, and a metastatic brain tumor in 1 (5%). The post-operative complications were all transient except in one patient with deterioration of motor weakness. The follow-up was noted, and modes of adjuvant treatment needed in these patients were recorded. Conclusion: Stereotactic biopsy is a useful and effective method for achieving a definitive diagnosis and aiding in treating multifocal or small deep-seated lesions in or around eloquent regions.

10.
J Biol Chem ; : 107224, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537695

RESUMO

Accumulation of lipids within the arterial wall is the key initiating event in the development of atherosclerosis. Impaired cholesterol efflux and/or uptake can influence arterial lipid accumulation. Here, we report that tripartite motif-containing protein 13 (TRIM13), a RING-type E3 ubiquitin ligase, plays a role in arterial lipid accumulation leading to atherosclerosis. Using molecular approaches and knockout mouse model, we found that TRIM13 expression was induced both in the aorta and peritoneal macrophages (pMφ) of ApoE-/- mice in response to western diet (WD) in vivo. Furthermore, proatherogenic cytokine IL-1ß also induced TRIM13 expression both in pMφ and vascular smooth muscle cells (VSMCs). Furthermore, we found that TRIM13 via ubiquitination and degradation of LXRα/ß downregulates the expression of their target genes ABCA1/G1 and thereby inhibits cholesterol efflux. In addition, TRIM13 by ubiquitinating and degrading SOCS1/3 mediates STAT1 activation, CD36 expression and foam cell formation. In line with these observations, genetic deletion of TRIM13 by rescuing cholesterol efflux and inhibiting foam cell formation protects against diet-induced atherosclerosis. We also found that while TRIM13 and CD36 levels were increased, LXRα/ß, ABCA1/G1 and SOCS3 levels were decreased both in Mφ and SMCs of stenotic human coronary arteries as compared to non-stenotic arteries. More intriguingly, the expression levels of TRIM13 and its downstream signaling molecules were correlated with the severity of stenotic lesions. Together, these observations reveal for the first time that TRIM13 plays a crucial role in diet-induced atherosclerosis, and that it could be a potential drug target against this vascular lesion.

11.
Thorac Res Pract ; 25(2): 51-56, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454199

RESUMO

OBJECTIVE: Hypersensitivity pneumonitis (HP) is an inflammatory and/or fibrotic lung disease. The restrictive lung function with low diffusing capacity of carbon monoxide (DLCO) is common in interstitial lung diseases (ILD). There are limited data on pulmonary function test (PFT) in HP and its role for diagnosis is questionable. We analyzed the data of 152 HP patients for type of defect, lung volume, and DLCO. MATERIAL AND METHODS: The present study is a retrospective analysis of 152 patients at one of the tertiary chest institutes in India. All diagnosed cases with at least spirometry were included. PFT findings were classified and graded as obstructive, restrictive, and mixed patterns. The correlation of PFT was calculated with disease duration and 6MWT distance. RESULTS: The majority were female [106 (70%)], with a mean age of 47.8 ± 12.3 years. Spirometry with lung volume data were available for 97% patients. PFT was abnormal in 118 (80%) cases. Among the patterns of abnormality, the most common type was restrictive (74%) followed by mixed (15%) and obstructive (11%) with the majority in the severe to very severe grade. The mean total lung capacity (TLC) and residual volume (RV) were reduced, with the grade more severe when the pattern of abnormality was restrictive while the RV/ TLC was higher suggestive of air tapping. DLCO data were available for 132 (87%) cases, with levels decreased in 67%. The severity of DLCO was highest when the pattern of abnormality was restrictive. One of the PFT parameters was abnormal in 137 (90%) cases, with isolated decreased DLCO levels seen in 16 (10%) cases. Forced vital capacity (FVC), TLC, and DLCO showed positive correlation with 6MWT distance (FVC r = .22, P = .02; TLC r = .28, P = .003; DLCO r = .30, P = .002). CONCLUSION: The PFT abnormality is seen in >80% of HP patients. All types of abnormality were seen, with the restrictive pattern being the most common. Isolated decreased DLCO levels were seen in 10% of cases. We advised to do full PFT for diagnosis and followup of HP.

12.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): A15-A24, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437419

RESUMO

Due to shrinkage in photopolymer materials, the angle of the reconstruction beam in holographic optical elements (HOEs) does not match with the Bragg condition, resulting in a decreased amount of light in the desired direction or loss of transmitted information to rematch the Bragg condition. Thus, to ensure final display features it is imperative to precompensate the shrinkage effect. We derived simplified expressions for precompensation in recording geometries of required HOEs in holographic waveguide-based Maxwellian near eye displays. An acceptable range of detuning from the Bragg angle is also analyzed. The experimentally measured 4.95% shrinkage in photopolymer film for 0° and 45° recording angles of beams was precompensated using -0.86∘ and 43.7° recording angles. Theoretical results are validated through simulation and experiments.

13.
Br J Cancer ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438589

RESUMO

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

14.
Clin Neurol Neurosurg ; 239: 108230, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490076

RESUMO

INTRODUCTION: Traditional large craniotomies have been the standard for aneurysm surgery. However, minimally invasive "keyhole" approaches have gained popularity for aneurysm clipping in recent years. This study focuses on Supra-Orbital Keyhole Approach (SOKHA),its use in clipping of aneurysms of the anterior Circle of Willis. Here we share the experiences of a tertiary care center regarding aneurysm clipping using SOKHA. MATERIALS AND METHODS: We retrospectively reviewed 166 cases involving aneurysm clipping, with 62 patients undergoing SOKHA and 104 patients undergoing the pterional approach. Factors evaluated included patient demographics, aneurysm characteristics, incidence of intraoperative complications, temporary-clipping usage, and postoperative clinical outcomes. Glasgow Outcome Scale scores were utilized to assess clinical outcomes. RESULTS: The study found that both the SOKHA and pterional approaches were similar in terms of age distribution, Hunt and Hess grades, and the incidence of hydrocephalus. The majority of aneurysms in both groups were anterior communicating artery aneurysms.Hydrocephalus was observed in 14.5 % of SOKHA cases and 13.5 % of pterional cases. Intraoperative aneurysm rupture occurred in 8.1 % of SOKHA cases and 7.7 % of pterional cases. There were no mortalities in the SOKHA group, while the pterional group had 1.92 % mortality rate. At the last follow-up, 77.4 % of SOKHA cases and 75.9 % of pterional cases had a favorable outcome (Glasgow Outcome Scale IV and V), with no significant difference. CONCLUSION: SOKHA offers the advantage of potential cosmetic benefit with neurological outcomes comparable to those of the traditional pterional approach, in properly selected patients.


Assuntos
Hidrocefalia , Aneurisma Intracraniano , Humanos , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Resultado do Tratamento , Craniotomia , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Hidrocefalia/cirurgia
15.
Sci Rep ; 14(1): 3140, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326386

RESUMO

Dissolved oxygen (DO) is an important parameter in assessing water quality. The reduction in DO concentration is the result of eutrophication, which degrades the quality of water. Aeration is the best way to enhance the DO concentration. In the current study, the aeration efficiency (E20) of various numbers of circular jets in an open channel was experimentally investigated for different channel angle of inclination (θ), discharge (Q), number of jets (Jn), Froude number (Fr), and hydraulic radius of each jet (HRJn). The statistical results show that jets from 8 to 64 significantly provide aeration in the open channel. The aeration efficiency and input parameters are modelled into a linear relationship. Additionally, utilizing WEKA software, three soft computing models for predicting aeration efficiency were created with Artificial Neural Network (ANN), M5P, and Random Forest (RF). Performance evaluation results and box plot have shown that ANN is the outperforming model with correlation coefficient (CC) = 0.9823, mean absolute error (MAE) = 0.0098, and root mean square error (RMSE) = 0.0123 during the testing stage. In order to assess the influence of different input factors on the E20 of jets, a sensitivity analysis was conducted using the most effective model, i.e., ANN. The sensitivity analysis results indicate that the angle of inclination is the most influential input variable in predicting E20, followed by discharge and the number of jets.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38417777

RESUMO

OBJECTIVE: To describe the characteristics and outcomes of older (65+) Medicare beneficiaries with traumatic brain injury (TBI) treated in inpatient rehabilitation facilities between 2013 and 2018. DESIGN: Descriptive study using IRF Patient Assessment Instrument (IRF-PAI) data reporting trends of the sociodemographic and clinical characteristics and outcomes of inpatient rehabilitation facilities Medicare patients with TBI. SETTING: Inpatient rehabilitation facilities in the United States. PARTICIPANTS: 99,804 older Medicare fee-for-service and Medicare Advantage patients with TBI (N=99,804). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Length of stay, self-care, and mobility functional outcomes, discharge destination. RESULTS: The number of older Medicare beneficiaries with TBI treated in inpatient rehabilitation facilities increased from 14,657 in 2013 to 18,791 in 2018, an increase of 28.2%. In addition to this overall increase in patients, we also found the percentage of men increased slightly (52.9% to 54.8%), there was a higher percentage of patients with tier 3 comorbidities, there was a decrease in the variability of length of stay, there was slightly more self-care and mobility improvement and a slightly higher percentage of patients discharged to the community (67.8% in 2013 and 71.6% in 2018). Newer standardized data showed that prior to the injury, more than one-third used a walker and more than three-quarters had a history of recent falls. CONCLUSIONS: Between 2013 and 2018, the number of Medicare beneficiaries with TBI treated in IRFs increased by approximately 28%. The characteristics of IRF older patients with TBI changed between 2013 and 2018 toward a slightly higher proportion of men, more comorbidities, and a higher percentage being discharged home after inpatient rehabilitation.

17.
Sensors (Basel) ; 24(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38339448

RESUMO

Digital holography (DH) is an important method for three-dimensional (3D) imaging since it allows for the recording and reconstruction of an object's amplitude and phase information. However, the field of view (FOV) of a DH system is typically restricted by the finite size of the pixel pitch of the digital image sensor. We proposed a new configuration of the DH system based on Fresnel's bi-mirror to achieve doubling the camera FOV of the existing off-axis DH system which leveraged single-shot acquisition and a common-path optical framework. The dual FOV was obtained by spatial frequency multiplexing corresponding to two different information-carrying beams from an object. Experimental evidence of the proposed dual FOV-DH system's viability was provided by imaging two different areas of the test object and an application to surface profilometry by measuring the step height of the resolution chart which showed excellent agreement with an optical profiler. Due to the simple configuration, the proposed system could find a wide range of applications, including in microscopy and optical metrology.

18.
J Ovarian Res ; 17(1): 41, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374055

RESUMO

BACKGROUND: Mucin 16 (MUC16) overexpression is linked with cancer progression, metastasis, and therapy resistance in high grade serous ovarian cancer and other malignancies. The cleavage of MUC16 forms independent bimodular fragments, the shed tandem repeat sequence which circulates as a protein bearing the ovarian cancer biomarker (CA125) and a proximal membrane-bound component which is critical in MUC16 oncogenic behavior. A humanized, high affinity antibody targeting the proximal ectodomain represents a potential therapeutic agent against MUC16 with lower antigenic potential and restricted human tissue expression. RESULTS: Here, we demonstrate the potential therapeutic versatility of the humanized antibody as a monoclonal antibody, antibody drug conjugate, and chimeric antigen receptor. We report the crystal structures of 4H11-scFv, derived from an antibody specifically targeting the MUC16 C-terminal region, alone and in complex with a 26-amino acid MUC16 segment resolved at 2.36 Å and 2.47 Å resolution, respectively. The scFv forms a robust interaction with an epitope consisting of two consecutive ß-turns and a ß-hairpin stabilized by 2 hydrogen bonds. The VH-VL interface within the 4H11-scFv is stabilized through an intricate network of 11 hydrogen bonds and a cation-π interaction. CONCLUSIONS: Together, our studies offer insight into antibody-MUC16 ectodomain interaction and advance our ability to design agents with potentially improved therapeutic properties over anti-CA125 moiety antibodies.


Assuntos
Reações Antígeno-Anticorpo , Antígeno Ca-125 , Proteínas de Membrana , Feminino , Humanos , Antígeno Ca-125/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias Ovarianas/patologia
19.
Sci Rep ; 14(1): 868, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195737

RESUMO

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020-2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.


Assuntos
Antioxidantes , Cucurbitaceae , Flavonoides , Variação Genética , Azia , Fenóis , Melhoramento Vegetal
20.
Antibiotics (Basel) ; 13(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38247619

RESUMO

Foodborne infections pose a substantial global threat, causing an estimated 600 million illnesses and resulting in approximately 420,000 deaths annually. Among the diverse array of pathogens implicated in these infections, Escherichia coli (E. coli), specifically the O157 strain (E. coli O157), emerges as a prominent pathogen associated with severe outbreaks. This study employs a comprehensive bibliometric analysis and scholarly review focused on E. coli O157 research. The bibliometric analysis highlights the significant role played by the United States in the E. coli O157 research domain. Further exploration underscores the noteworthy contributions of the researcher Doyle MP, whose body of work, consisting of 84 documents and an impressive H-Index of 49, reflects their substantial impact in the field. Recent research trends indicate a discernible shift towards innovative detection methods, exemplified by the adoption of CRISPR-CAS and Loop-Mediated Isothermal Amplification. Moreover, high-throughput whole-genome sequencing techniques are gaining prominence for the expeditious analysis of pathogenic E. coli strains. Scientists are increasingly exploring antimicrobial agents, including phage therapy, to address the challenges posed by antibiotic-resistant E. coli strains, thereby addressing critical concerns related to multi-drug resistance. This comprehensive analysis provides vital insights into the dynamic landscape of E. coli O157 research. It serves as a valuable resource for researchers, policymakers, and healthcare professionals dedicated to mitigating E. coli O157 outbreaks and advancing global public health strategies.

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