Search

Abstract Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited availability of targeted therapies, TNBC is associated with higher mortality as compared to other forms of breast cancer. In order to develop new therapeutic options for TNBC, we characterized the factors involved in TNBC growth and progression. Here, we demonstrate that N-acylsphingosine amidohydrolase 1 (ASAH1) is overexpressed in TNBC cells and is regulated via p53 and PI3K-AKT signaling pathways. Genetic knockdown or pharmacological inhibition of ASAH1 suppresses TNBC growth and progression. Mechanistically, ASAH1 inhibition stimulates dual-specificity phosphatase 5 (DUSP5) expression, suppressing the mitogen-activated protein kinase (MAPK) pathway. Furthermore, pharmacological cotargeting of the ASAH1 and MAPK pathways inhibits TNBC growth. Collectively, we unmasked a novel role of ASAH1 in driving TNBC and identified dual targeting of the ASAH1 and MAPK pathways as a potential new therapeutic approach for TNBC treatment.

Purpose: This study aims to establish DROL (disruption of retinal outer layers), PROS (photoreceptor outer segment length), SND (subfoveal neuroretinal detachment), and hyperreflective walls of foveal cystoid spaces (HRW) as optical coherence tomography (OCT) biomarkers and predictors of central macular thickness (CMT) and visual acuity in diabetic macular edema (DME) treated with intravitreal ranibizumab (IVR). Methods: In this prospective, interventional study performed at a tertiary care center over a span of 1 year from December 2021 to December 2022, 50 eyes of 46 patients of DME were included. Visual acuity and spectral domain OCT imaging were performed at baseline. Using inbuilt calipers on SD-OCT, the horizontal extent of DROL and the vertical extent of PROS were measured manually. SND and HRW were assessed qualitatively. IVR was administered and patients were followed up at 4, 8, and 12 weeks. Results: The eyes without DROL had statistically significant (P < 0.05) lesser CMT and better BCVA (best-corrected visual acuity) (P < 0.05) after pro re nata injection of IVR. There was a positive correlation between the extent of baseline DROL with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05), whereas negative correlation with the extent of baseline PROS with final CMT (P < 0.05) and final logMAR BCVA (P > 0.05). The presence of HRW and SND predicted non-resolution of CMT and worse visual acuity after treatment with IVR in DME . Conclusion: DROL, PROS, SND, and hyperreflective walls of foveal cystoid spaces may be utilized as qualitative as well as quantitative biomarkers to predict the post-treatment CMT and visual acuity in DME.

Purpose: The present study was done to assess the use of optical coherence tomography angiography (OCTA) in detecting earlier stages of diabetic retinopathy and for the early management and effective blood glucose control in preclinical diabetic patients for preventing retinal nerve fiber layer (RNFL) thinning. Methods: A tertiary care center–based prospective observational study was conducted from the year 2021 to 2022 in the Department of Ophthalmology. The study included 50 cases and 50 controls. The parameters analyzed by using OCTA (Topcon 3D OCT-1 Maestro2) were RNFL thickness and peripapillary vessel density. Results: We found that the RNFL thickness in the temporal and superior disc in patients with preclinical diabetic retinopathy was significantly (0.041 and 0.044, respectively) decreased. The duration of diabetes and glycated hemoglobin (HbA1c) were the risk factors for peripapillary vessel density reduction in patients with preclinical diabetic retinopathy (P < 0.001). Conclusion: RNFL thinning is an early sign of retinal neurodegeneration and is associated with peripapillary vessel density reduction. Early management and effective blood glucose control in diabetes patients may be beneficial for preventing RNFL thinning in superior and temporal disc.

The high prevalence of childhood overweight and obesity demonstrates the need for effective intervention strategies. The Shaping Healthy Choices Program (SHCP) is a school-based intervention that promotes nutrition and physical education, develops family and community partnerships, and incorporates foods available on the school campus, with the goal of achieving sustainable student health outcomes. Partnerships developed through implementation of the SHCP were analyzed using the RE-AIM: Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework to assess the potential for adoption, scaling and sustainability of the program. The RE-AIM framework is a comprehensive approach to evaluating public health interventions through reach, effectiveness, adoption, implementation and maintenance. Partners of the SHCP include site staff (teachers, administration and health professionals), parents, peer teachers, and state and federal agencies, such as the Supplemental Nutrition Assistance Program Education (SNAP-Ed), which funds CalFresh Healthy Living, University of California (CFHL, UC), and UC Cooperative Extension. This analysis highlights how partnerships developed and sustained with the SHCP may serve as a model for other programs to expand, while also enabling programs to remain responsive to the diverse challenges and needs of local community partners.

Introduction: Reclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas. Methods: We reviewed all high-grade Mullerian cancers between 2016 and 2021, where HER2 by IHC and/or FISH tests were available. Additional clinical information was recorded, and statistical analysis was performed using SPSS (version 27). Results: Forty (49.4%) tumors were endometrial, 20 (24.7%) ovarian, 16 (19.8%) fallopian tubal, and 5 (6.2%) primarily peritoneal. Overall, 17 (21.0%) were HER2 positive (IHC 3+/IHC 2+/FISH amplified), 31 (38.3%) HER2 low (IHC 1+/2+/FISH non-amplified), and 30 (37.0%) were HER2 negative (IHC = 0). HER2 low expression was noted in 15% ovarian, 25% fallopian tubal, 53% endometrial, and 60% peritoneal tumors; 34% and 21% of serous carcinomas, 63% and 13% of carcinosarcomas, and 67% and 33% of endometrioid carcinomas were HER2 low and HER2 positive respectively. HER2 negative and HER2 low expression had a significant association with primary tumor location (p = 0.001); endometrium and peritoneal tumors were more likely to be HER2 low and HER2 negative. During a mean follow-up of 13.2 months (range: 1–34), 5% of the patients were deceased. Conclusions: Based on the current HER2-low recommendations in the breast, about one-third of patients with high-grade Mullerian carcinomas might qualify for anti-HER2 therapy with a potential for improved progression-free and overall survival.

Purpose: To record and evaluate the reliability parameters (fixation loss (FL) %, false positive (FP) %) and global indices (mean sensitivity (MS), mean deviation (MD), pattern standard deviation in dB) in three visual field test sessions within two weeks to assess the learning effect in normal healthy subjects and POAG patients and comparison of learning effect gender wise and age wise in primary open-angle glaucoma (POAG) patients. Methods: This study was a prospective observational study. An oculus visual field testing was done and analyzed in 30 eyes of POAG patients and 30 eyes of normal healthy subjects in three visits. Results: There were 16 (53.3%) males and 14 (46.6%) females in the POAG group and 16 (53.33%) males and 14 (46.66%) females in the normal healthy subject group. A significant difference in data change between each visit in FL, FP, MD, MS was found though the difference was more pronounced in the second visit than in the third visit. The pattern standard deviation does not change significantly in subsequent visits in both groups. Gender wise and age wise no significant difference was found in the POAG group. Conclusion: Significant improvement in reliability parameters and global indices with each subsequent visit in both the POAG group and normal patients signifies the importance of learning effect on these parameters and the need to perform at least three tests to get the baseline perimetry chart, especially in POAG patients, while in normal subjects, second perimetric result can be accepted. It was also concluded that the learning effect is not influenced by age and gender.

Purpose: To study the prevalence of dry eye disease (DED), further categorize using DEWS II protocol, grade squamous metaplasia in each group, and determine associated risk factors in a tertiary care hospital. Methods: This cross-sectional hospital-based study screened 897 patients ≥30 years via systematic random sampling. Patients with both symptoms and signs as defined by the Dry Eye Workshop II protocol were considered as DED, further categorized, and subjected to impression cytology. Categorical data were assessed using the Chi-square test. P value < 0.05 was considered statistically significant. Results: In total, 265 (of 897) patients were defined as DED based on the presence of symptoms (DEQ-5 ≥6) and at least one positive sign (fluorescein breakup time [FBUT]

Abstract Bimetals are widely used as a thermal tripping mechanism inside the miniature circuit breakers (MCBs) products when an overload current passes through the circuit for a certain period. Experimental, numerical, and, recently artificial intelligence methods are widely used in designing electric components. However, developing the bimetal for MCB products somewhat differs from developing other conductor items since they are strongly related to the electrical, mechanical, and thermal performance of the MCB. The conventional experimental and numerical approaches are time-consuming processes that cannot be easily utilized in optimizing the product's performance within the development lead time. In this study, a simple, fast, robust, and accurate novel methodology has been introduced to predict the temperature rise of the bimetal and other related performance characteristics. The numerical model has been built on the time-based finite difference method to frame the theoretical thermal model of the bimetal. Then, the numerical model has been consolidated by the machine learning (ML) model to take advantage of the experiments to provide an accurate, fast and reliable model finally. The novel model agrees well with the experimental tests, where the maximum error does not exceed 8%. The model has been used to redesign the bimetal of a 32 A MCB product and significantly reduce the maximum temperature by 24 °C. The novel model is promising since it considerably reduces the required design time, provides accurate predictions, and helps to optimize the performance of the circuit breaker products.

We report a facile synthesis of mesoporous TiO2 with a large specific surface area and rich oxygen vacancies using La-doped TiO2 through high-temperature annealing. Such integration of a unique mesoporous structure and oxygen vacancies provides effective carrier transport and increased surface active sites. The effects of lanthanum on mesoporous TiO2 were studied experimentally and theoretical calculations were performed. Thermal treatment was conducted at temperatures ranging from 350 to 900 °C. The x-ray diffraction analyses confirm that the formation of anatase TiO2 remains stable until 650 °C for pure TiO2 and 850 °C for the La doped sample. It was noted that there was a phase transformation from anatase to rutile with an increase in temperature. Morphological analysis confirmed a mesoporous structure with lanthanum covering the surface of the TiO2 mesospheres. Elemental analysis confirms the presence of La in the TiO2 composition and increased oxygen vacancies with increased lanthanum concentration. The density functional theory calculations reveal that the oxygen vacancy heavily alters the electronic structure of TiO2. The distance between the oxygen vacancy and lanthanum was shown to play an important role in altering the bandgap of TiO2. When lanthanum was near the oxygen vacancy, the bandgap was larger than that of all the models. Lanthanum, when away from the vacancy, leads to the lowest bandgap among all the models.

Background: Chronic obstructive pulmonary disease (COPD) has deleterious systemic impact due to spillage of inflammatory mediators in the circulation though its association with highly sensitive C-reactive protein (hs-CRP) considers as surrogate marker of inflammation is not much explored hitherto. Aims and Objectives: This study aims to study the impact of COPD on bone mineral density (BMD) and its association with hs-CRP in rural population of Haryana. Materials and Methods: Tertiary care hospital-based case–control multigroup study conducted in the Department of Respiratory Medicine, BPSGMCW, Khanpur Kalan, Sonepat, Haryana, India. A total of 150 female study subjects included and comprise in three groups, G1: Biomass exposed COPD patients; G2: Biomass smoke exposed non-COPD subjects; and G3: Non-biomass exposed healthy control. Bone density measured using dual-energy X-ray absorptiometry, hs-CRP considers as surrogate marker of inflammation. Statistical software SPSS Version 23 used to measure Chi-square/Fisher’s exact test, Student’s t-test, and Pearson/Spearman’s rank correlation as test of significance, P

Aims: Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that share common mutations. We report three MLAs and hypothesize that concurrent endometriosis and cystadenofibroma with focal borderline changes might also carry common mutations. Methods and results: We searched “mesonephric” in our database from 2015 to mid-2021 to retrieve MLA cases. Somatic mutation analysis was performed on tumors and on associated benign proliferative lesions. All MLAs (2 ovarian and 1 uterine) harbored KRAS G12D or G12 V mutations. A PIK3CA alteration (H1047Q) was detected in one MLA and in the associated cystadenofibroma with focal borderline changes. The molecular profile of MLA-associated Müllerian lesions (endometriosis and seromucinous cystadenofibroma with focal borderline changes) was similar to concurrent adenocarcinoma. However, tumor contamination could not be excluded in the endometriotic lesion. Patients presented at various stages, with no evidence of post-operative recurrence after 15 months (FIGO IC) and 33 months (FIGO IIA2). One patient (FIGO IIIA1) died of disease 32 months after surgery. Conclusions: KRAS mutations commonly characterize MLA. At least some MLA-associated Müllerian lesions show MLA-like genetic profiles, suggesting a precursor role. As far as we are aware, we describe for the first time in MLA the potentially actionable H1047Q variant of PIK3CA.

Marfan’s syndrome is an autosomal dominant genetic disorder related to a mutation in fibrillin gene type 1 involving mainly the cardiovascular, ocular, skeletal, and pulmonary systems. A 22-year-old female patient presented with cough, blood-stained sputum, and fever for 4 months. The patient was tall and on skeletal examination, high arched palate, arm-span longer than height, positive finger thumb sign, arachnodactyly, asymmetrical chest, and skin striae were present. Family history of Marfan’s syndrome was present. Echocardiography showed large ventricular septal defect with aortic override and severe pulmonary stenosis. CECT thorax showed bronchiectasis changes. Marfan’s syndrome with cardiovascular abnormalities usually has aortic dilatation, aortic regurgitation, aortic aneurysm, mitral valve prolapse, mitral regurgitation, etc. In this case, the patient has Marfan’s syndrome with tetralogy of Fallot (TPF) and bronchiectasis. The association of TOF with Marfan’s syndrome is one of the rarest findings.

Abstract The goal of this Phase I/II trial is to assess the safety and efficacy of administering durvalumab concurrent with weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide (ddAC) neoadjuvant therapy for stages I–III triple-negative breast cancer. The primary endpoint is pathologic complete response (pCR:ypT0/is, ypN0). The response was correlated with PDL1 expression and stromal tumor-infiltrating lymphocytes (sTILs). Two dose levels of durvalumab (3 and 10 mg/kg) were assessed. PD-L1 was assessed using the SP263 antibody; ≥1% immune and tumor cell staining was considered positive; sTILs were calculated as the area occupied by mononuclear inflammatory cells over the total intratumoral stromal area. 59 patients were evaluable for toxicity and 55 for efficacy in the Phase II study (10 mg/kg dose). No dose-limiting toxicities were observed in Phase I. In Phase II, pCR rate was 44% (95% CI: 30–57%); 18 patients (31%) experienced grade 3/4 treatment-related adverse events (AE), most frequently neutropenia (n = 4) and anemia (n = 4). Immune-related grade 3/4 AEs included Guillain–Barre syndrome (n = 1), colitis (n = 2), and hyperglycemia (n = 2). Of the 50 evaluable patients for PD-L1, 31 (62%) were PD-L1 positive. pCR rates were 55% (95% CI: 0.38–0.71) and 32% (95% CI: 0.12–0.56) in the PD-L1 positive and negative groups (p = 0.15), respectively. sTIL counts were available on 52 patients and were significantly higher in the pCR group (p = 0.0167). Concomitant administration of durvalumab with sequential weekly nab-paclitaxel and ddAC neoadjuvant chemotherapy resulted in a pCR rate of 44%; pCR rates were higher in sTIL-high cancers.

The main intent of the cloud computing to provide utilities to the demands of the users that are booming day by day. To meet the requirements, existing scheduling algorithms focus on the improving the performance and neglecting the energy consumed to fulfill those demands. Hence, we propose a new Hybrid Scheduling Algorithm (HS) which is based on the Genetic Algorithm (GA) and Flower Pollination based Algorithm (FPA) for cloud environments. The proposed scheduling algorithm has surpassed in terms of performance across various parameters, i.e. completion time, resource utilization, cost of computation, and energy consumption for both cloud environments than the existing scheduling algorithms (GA and FPA). The simulation results revealed that HS has demonstrated maximum resource utilization with minimum energy consumption in less completion time for the execution of the tasks as compared to the existing scheduling algorithms in both environments. The simulation results have shown that HS has utilization of the resources, 36% better than GA and 16% better than FPA in homogeneous environment whereas in heterogenous environment, HS has performed 12% better than GA and 3.8% better than FPA. The performance of HS has an improvement of 2.6% from FPA and 6.9% from the GA for completion time in homogeneous environment whereas the completion time of the HS is reduced by 17.8% from FPA and 33.7% from GA in heterogeneous environment. For energy consumption, HS has improved 22% than FPA and 11% from GA in the homogeneous environment and HS is 4% better than FPA and 14% from GA in heterogeneous environment.

Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been reported in only 3 previous cases of SCC of vagina. Herein, we present a unique case of vaginal small cell carcinoma with discordant HPV testing results between vaginal and cervical samples. We also review and discuss findings from previously reported cases of small cell carcinoma of vagina.

Background: Oncotype Dx (ODx) is a genomic assay which estimates the risk of distant recurrence and predicts adjuvant chemotherapy benefit in early stage breast cancer patients. Most ODx data is derived from excisional specimens. Aim: We assess the utility of ODx on core needle biopsies (CNB) and measure its impact on neoadjuvant treatment decisions, particularly in patients with clinically complicated situations. Methods: Consecutive ODx results on breast CNBs with invasive carcinoma from 2012-2020 at 3 tertiary care hospitals with dedicated Breast Health Centers were reviewed. Clinical indications to perform ODx on CNB were recorded through a review of patients’ electronic medical records. Clinicopathologic features, surgical or oncologic modalities and follow-up data were recorded. Results: Three distinct clinical indications for performing ODx on CNB in 85 ER+ invasive breast carcinomas were identified: 1) Excisions with insufficient tissue to perform ODx, 2) adjudicate neoadjuvant therapy versus primary surgical resection, and 3) select neoadjuvant chemotherapy (NAC) versus neoadjuvant endocrine therapy (NET). Primary surgery was selected in patients with low score RS (18). NET was preferred over NAC in patients with low RS (

Localized cutaneous amyloidosis was reported recently in association with vulvar squamous intraepithelial neoplasia (VIN). High-risk human papillomavirus (hrHPV) type 16 is the most commonly reported subtype found in usual-type VIN. However, it is unknown whether any hrHPV subtype(s) is/are prevalent in simultaneous squamous intraepithelial lesions and localized amyloidosis in the same individual - the subject matter of this report. To observe the potential clinical significance, study cases were followed and compared to usual-type VINs without amyloid deposition. Of 45 patients of usual-type VINs associated with amyloidosis, 33 had detectable hrHPV, and 12 were negative. HPV 16 alone or in combination with HPV 31 accounted for 72%, HPV 51 alone accounted for 2% of the cases, and 26% were negative for hrHPV. Lack of demonstrable hrHPV in a significant proportion of cases (26%) raises the possibility of a novel or presently undetected hrHPV subtype. Five of the total 22 (23%) patients with amyloid had either Squamous cell carcinoma or high-grade VIN on follow-up. In contrast, 14 of 18 (78%) patients exhibiting lesions without amyloid had disease on follow-up. These findings may indicate that amyloid deposition may represent a feature of regression or a potential favorable prognostic indicator.

Abstract Background The breast cancer microenvironment contributes to tumor progression and response to chemotherapy. Previously, we reported that increased stromal Type X collagen α1 (ColXα1) and low TILs correlated with poor pathologic response to neoadjuvant therapy in estrogen receptor and HER2-positive (ER+/HER2+) breast cancer. Here, we investigate the relationship of ColXα1 and long-term outcome of ER+/HER2+ breast cancer patients in an adjuvant setting. Methods A total of 164 cases with at least 5-year follow-up were included. Immunohistochemistry for ColXα1 was performed on whole tumor sections. Associations between ColXα1expression, clinical pathological features, and outcomes were analyzed. Results ColXα1 expression was directly proportional to the amount of tumor associated stroma (p = 0.024) and inversely proportional to TILs. Increased ColXα1 was significantly associated with shorter disease free survival and overall survival by univariate analysis. In multivariate analysis, OS was lower in ColXα1 expressing (HR = 2.1; 95% CI = 1.2–3.9) tumors of older patients (> = 58 years) (HR = 5.3; 95% CI = 1.7–17) with higher stage (HR = 2.6; 95% CI = 1.3–5.2). Similarly, DFS was lower in ColXα1 expressing (HR = 1.8; 95% CI = 1.6–5.7) tumors of older patients (HR = 3.2; 95% CI = 1.3–7.8) with higher stage (HR = 2.7; 95% CI = 1.6–5.7) and low TILs. In low PR+ tumors, higher ColXα1 expression was associated with poorer prognosis. Conclusion ColXα1 expression is associated with poor disease free survival and overall survival in ER+/HER2+ breast cancer. This study provides further support for the prognostic utility of ColXα1 as a breast cancer associated stromal factor that predicts response to chemotherapy.

The systematic evaluation of the link budget calculation for the satellite and terrestrial communication is presented in this article. Communication link between the satellite and earth station is dependent on various propagation and associated losses which are either constant or vary with weather conditions. Role of receiver noise, antenna pointing mechanism, atmospheric effects, slant height, interferences, bit error rate on the link margin are detailed in this article. Various equations for link budget calculation and a comparative table at various frequency bands are shown in this article which is useful for predicting link margin of LEO, GEO and Deep space missions. Tele-command, telemetry and ranging link margin at various frequencies are presented and budget analysis at Ka-band frequency performed.

Cataract surgery has undergone many changes with the size of incision progressively decreasing over time with an incision of 12.0 mm for intracapsular cataract extraction to 2.2–2.8 mm in phacoemulsification. However, phacoemulsification due to high cost and equipment maintenance cannot be employed widely in developing countries. Manual small-incision cataract surgery (MSICS) offers similar advantages with the merits of wider applicability, less time consuming, a shorter learning curve, and lower cost. MSICS can be performed in high-volume setups due to fast technique. Here, we review the various techniques, safety and efficacy of MSICS, and its progress and utility in developing and underdeveloped countries.

Pyomyositis is a primary bacterial infection of striated muscles nearly always caused by Staphylococcus aureus. Development of the intramuscular abscess involving the extra-ocular muscles (EOMs) remains an extremely rare process. We herein present a case of isolated EOM pyomyositis involving superior rectus muscle in a 2-year male child who was referred with complaints of swelling in left eye (LE) and inability to open LE since last 1-month. Orbital computed tomography (CT) scan showed a well-defined, hypo-dense, peripheral rim-enhancing lesion in relation to left superior rectus muscle suggestive of left superior rectus abscess. The abscess was drained through skin approach. We concluded that pyomyositis of EOM should be considered in any patient presenting with acute onset of orbital inflammation and characteristic CT or magnetic resonance imaging features. Management consists of incision and drainage coupled with antibiotic therapy.

Background: Diabetic Mellitus is a group of metabolic disease characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. Distal Sensorimotor Polyneuropathy is the most common complication of diabetes which mainly affects the lower limbs. Most of the studies aimed at individually increasing muscle strength or sensation but not on overall performance enhancements of the diabetic lower limbs. The evidence supporting the effectiveness of PNF in diabetic neuropathic patients is scarce. Methods: 30 patients, with age between 50 to 70 years, diagnosed with Diabetic Sensorimotor Polyneuropathy (DSP) were selected from the department of Medicine and department of Neurosurgery Guru Gobind Singh Medical College and Hospital. Patients were evaluated at the beginning and at the end of the intervention using Diabetic Neuropathy Examination scores. Patients received 3 sets of exercises one hour/day with 3 days/week for 3 months. Each set of exercises consists of 5 repetitions of PNF patterns (alternate day) and techniques. Results: D1 & D2 patterns of PNF are effective in improving both motor and sensory functions of diabetic patients with neuropathic symptoms. Improvement in muscle strength, reflex and sensations occurred to a greater extent after the treatment of three months in these subjects. This study shows that PNF patterns were effective at enhancing sensorimotor problems of lower limbs. Conclusion: This study concluded that PNF is found to be effective in improving sensorimotor functions of diabetic neuropathic patients affecting lower limbs.