Pancreatic ductal adenocarcinoma (PDAC) is characterized by a high degree of inflammation and profound immune suppression. Here we identify Yes-associated protein (Yap) as a critical regulator of the ...immunosuppressive microenvironment in both mouse and human PDAC. Within Kras:p53 mutant pancreatic ductal cells, Yap drives the expression and secretion of multiple cytokines/chemokines, which in turn promote the differentiation and accumulation of myeloid-derived suppressor cells (MDSCs) both in vitro and in vivo. Pancreas-specific knockout of Yap or antibody-mediated depletion of MDSCs promoted macrophage reprogramming, reactivation of T cells, apoptosis of Kras mutant neoplastic ductal cells and pancreatic regeneration after acute pancreatitis. In primary human PDAC, YAP expression levels strongly correlate with an MDSC gene signature, and high expression of YAP or MDSC-related genes predicts decreased survival in PDAC patients. These results reveal multifaceted roles of YAP in PDAC pathogenesis and underscore its promise as a therapeutic target for this deadly disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Resistance to therapies targeting the estrogen pathway remains a challenge in the treatment of estrogen receptor-positive breast cancer. To address this challenge, a systems biology approach was ...used. A library of small interfering RNAs targeting an estrogen receptor (ER)- and aromatase-centered network identified 46 genes that are dispensable in estrogen-dependent MCF7 cells, but are selectively required for the survival of estrogen-independent MCF7-derived cells and multiple additional estrogen-independent breast cancer cell lines. Integration of this information identified a tumor suppressor gene TOB1 as a critical determinant of estrogen-independent ER-positive breast cell survival. Depletion of TOB1 selectively promoted G1 phase arrest and sensitivity to AKT and mammalian target of rapmycin (mTOR) inhibitors in estrogen-independent cells but not in estrogen-dependent cells. Phosphoproteomic profiles from reverse-phase protein array analysis supported by mRNA profiling identified a significant signaling network reprogramming by TOB1 that differed in estrogen-sensitive and estrogen-resistant cell lines. These data support a novel function for TOB1 in mediating survival of estrogen-independent breast cancers. These studies also provide evidence for combining TOB1 inhibition and AKT/mTOR inhibition as a therapeutic strategy, with potential translational significance for the management of patients with ER-positive breast cancers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A BSTRACT Context: New pterygium surgery methods have been developed over the years because recurrence is high (30–70%) after simple excision. Aims: To compare the surgical time, ocular discomfort ...score, and recurrence rate in conventional pterygium surgery, where excision of pterygium and Tenon’s capsule is performed and the area is covered using conjunctival–limbal autograft (CLAU) with supra-Tenon excision of pterygium (STEP) along with small limbal autograft in patients with primary pterygium. Settings and Design: A Prospective comparative study was conducted at a rural medical college–hospital from November 1, 2017, to October 31, 2019, among 110 participants after ethical approval from Institutional Ethics Committee. Materials and Methods: All participants had primary pterygium of grades I and II depending on corneal encroachment and Tan’s stages T1 and T2 morphologically. Fifty-five underwent conventional surgery with CLAU (group A), and STEP with small limbal autograft (group B) was performed in the remaining fifty-five. The follow-up period was one year. The ocular problem, comfort of subject, recurrence, or other complications were documented, and statistical analysis was carried out with Statistical Package for the Social Sciences (SPSS) software version 21. Results: The mean surgical time was significantly less in group B (38.79 vs. 42.04 minutes) ( Z = 11.38, P = 0.001 with confidence interval 10.81–13.38) and ocular discomfort score (ODS) was lower in group B as compared with group A ( P < 0.05). Group B had two eyes with recurrence, though not statistically significant ( P = 0.49). Conclusion: STEP with small limbal autograft is worth consideration for primary pterygium management.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head‐to‐head studies comparing the clinical profile, ...constipation severity, impact on quality of life (QOL) and economic impact are lacking.
Methods
We conducted a cross‐sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease‐specific QOL, somatization, and psychiatric comorbidities. We used multivariable linear regression to determine the predictors of QOL and number of healthcare visits.
Key Results
Sixty‐six and 98 patients with CC were enrolled in the USA and India, respectively. Indian patients with CC had significantly more frequent bowel movements/week compared to their USA counterparts (Median 5 vs 3, P < .0001). The proportion of patients with Bristol stool form scale type 1 and 2 was significantly higher in the USA compared to India (65.5% vs 48%, P = .04). Higher depression score (P = .001), more severe constipation symptoms (P = .001) and site of the study being USA (P = .008) independently predicted worse QOL. Indian patients (P < .001) and worse QOL (P = .02) were independent predictors of number of healthcare visits in the last 12 months.
Conclusions and Inferences
Indian patients with CC have more frequent and softer bowel movements compared to those in the USA suggesting significant differences in perception of CC in different geographic and cultural settings. QOL and economic impact related to constipation varies with geographic/cultural setting irrespective of other clinical and psychosomatic features.
Ours is the first study with head‐to‐head comparison of clinical profile, psychosomatic burden, constipation‐related symptoms severity, constipation specific quality of life and economic impact of chronic constipation between Indian and US patients presenting to tertiary care centres with chronic constipation. We found that Indian patients had significantly higher stool frequency and softer stool consistency (consistent with faster colonic transit) compared to US counterparts. We also showed that constipation‐related quality of life not only depends on symptom severity, psychiatric burden but also site of study (Site of study being USA was independent predictor of inferior quality of life). Nevertheless, after adjusting for other covariates, Indian patients had higher direct and indirect healthcare expenditures with increased work absenteeism due to constipation‐related symptoms and higher number of healthcare visits for constipation compared to their US counterparts.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The most commonly cultivated vine cactus in the Cactaceae family is normally Hylocereus undatus, which would be native to Mexico and America. It is commonly referred to as "dragon fruit" or "pitaya." ...Additionally, it goes by the name "buahnaga," which means "dragon fruit." In addition to their attractive color, Hylocereus undatus fruits are popular around the world due to their abundance of polyphenolic components and their antioxidant activity. Due to the characteristics, degree of production, and financial benefits of the pitahaya fruit, a member of the Hylocereus genus, more land has been planted in agriculture during the past two decades. Stalks, fruits, and flowers from the plant are used in food and film.
•Application of building derived materials in ground improvement is proposed.•The technique is evaluated on the basis of several laboratory experiments.•Depending on the soil, proposed technique can ...be adopted with suitable judgement.•Concrete-based building derived material performs better than brick-based ones.
Construction and demolition (C&D)1C&D – Construction and Demolition.1 wastes consist of debris generated during the construction and demolition of structural elements. Rapid urbanization renders it necessary to reduce the consumption of non-renewable natural resources drastically and also to limit the dumping of these materials after the expiration of their service life. The primary components of C&D wastes are building derived materials2BDM – Building Derived Materials.2 (BDM) composed of rejected concrete and brick from construction and demolition sites. This study investigates and compares the potential for two different kinds of BDM in their virgin state for the purpose of improving the compaction and shear properties of soft soil having low bearing capacity. BDM are collected separately from demolition of brick walls containing cement-mortar as binder and also from demolition of plain concrete blocks. In the first step, these two types of BDM are compared on the basis of their resistance to impact or crushing loads. Then, the BDM are immersed in separate solutions of seawater, sulfuric, hydrochloric, and nitric acid solutions individually and their responses are determined. Concrete based BDM3CBDM – Concrete based BDM.3 (CBDM) shows greater resistance to impact or crushing, compared to brick based BDM4BBDM – Brick based BDM.4 (BBDM). Moreover, in presence of chemicals, CBDM shows greater resistance to weathering. Hence, for the purpose of ground improvement, CBDM is considered. Soil is partially replaced with different percentages of CBDM and the optimum soil-CBDM combination is found, based on compaction characteristics. This approach intends to prevent the dumping of any kind of BDM as solid waste and also provide an economic option to enhance the properties of soil. In this study, the chemical and physical properties of CBDM, BBDM, and soil are investigated separately. Mineralogical analysis through X-ray diffraction (XRD), and microstructural analyses through scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS) are conducted for CBDM, BBDM, soil, and soil+CBDM mixes. Compaction studies show that the optimum replacement of soil by CBDM is in the range of 17–23% by mass. However, there is a possibility of the presence of aggressive chemicals in soils near the vicinity of water bodies or chemical treatment plants. In order to test the compatibility of the CBDM in such soils, the properties mentioned above are re-evaluated after exposing the CBDM to aggressive chemical environments. Results indicate that virgin CBDM has suitable load carrying capacity, but this capacity decreases after exposure to chemicals. This is associated with change in physical and chemical characteristics of the CBDM, as assessed through XRD, stereomicroscopic imaging, and determination of change in weight. Although the overall performance of CBDM is better than that of BBDM, proper judgement is necessary for their practical application of any kind of BDM for ground improvement depending on location or site conditions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Construction and associated demolition processes produce huge amount of solid waste, generally termed as construction and demolition waste (CDW). Management and proper disposal of these wastes is an ...area of prime concern for modern civil engineers. About 90% of all CDW is composed of building derived materials (BDM) obtained from concrete, bricks, and tiles from structural and non-structural elements of a building. The present study emphasizes on the use of virgin BDM, which conserves natural aggregate, reduces the impact on landfills, saves energy, and thus can provide significant cost benefit. Five types of BDM—crushed lightweight concrete (T1), crushed marble tiles (T2), crushed high strength concrete (T3), crushed normal portland cement concrete (T4), and crushed bricks (T5)—are characterised to assess their compatibility when used in conjunction with local soil. The soil, BDM and soil–BDM mixes are characterized from physical, mechanical, mineralogical, microstructural, and chemical aspects. These tests are then repeated for the aforementioned soil-BDM mixes after immersion in acids. Aggregate impact value (AIV) results on the five types of BDM indicate that T1 and T5 are poorly resistant to impact loads. However, T2, T3, and T4 show relatively better resistance to impact loads and satisfy the requirements for sub-base material standards. Shear strength studies show that the average optimum replacement of soil by BDM is in the range of 17–23% by mass. In order to test the compatibility of BDM in soils containing aggressive chemicals, the properties mentioned above are re-evaluated after exposing the BDM to aggressive chemical environments. The results indicate that the internal angle of friction (
ϕ
) of virgin BDM is found to vary significantly due to acid attack. The results of AIV after exposing the BDM to acids show that BDM are highly susceptible to chemically aggressive environment. The performance of all types BDM are affected by the presence of acids and appropriate measures must be adopted while using BDM in such chemically aggressive environment. These standards can be used as guidelines in the present study in the absence of specific standards for BDM applications.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
OBJECTIVE
To analyse the presenting features, signs and operative findings of children presenting with intermittent testicular pain, as testicular torsion is a relatively common and serious emergency ...in children that can lead to testicular loss in up to 80%, although half of these children have previous episodes of pain suggestive of intermittent torsion.
PATIENTS AND METHODS
Data were collected prospectively for all patients presenting with recurrent pain between December 2000 and June 2001. Variables assessed included presenting symptoms, age, size, lie and position of the testis when supine and erect, the operative findings and follow‐up.
RESULTS
Eight children had at least two previous episodes of testicular pain; four of these were admitted on six occasions. Two had undergone previous scrotal exploration. On clinical examination, six boys had a transverse testicle and two a discrepancy in testicular size. All children had their testes fixed. At operation in all patients there was abnormal attachment of the tunica vaginalis with a typical ‘bell clapper’ deformity. On follow‐up only one patient still complains of pain.
CONCLUSION
In view of high incidence of abnormalities we consider that to improve the testicular salvage rate and prevent testicular atrophy, bilateral testicular fixation is recommended for boys with intermittent testicular pain and positive clinical findings.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract
Esophageal cancer (EC) is the sixth most common cause of cancer-related deaths. Esophageal squamous cell carcinomas (ESCCs) have a higher incidence and worse prognosis in males, which may ...be dependent on the difference of environment of sex steroids. The influence of androgen receptor (AR) and HER 2/neu expression on hormone-related cancers are well known but their role in EC shows conflicting data. This warrants further investigation on their influence on tumor microenvironment of EC.
Methods
All the cases of biopsy proven primary ESCC which presented to the institute in the years 2016–2020 were included. Patients undergoing neoadjuvant therapy were excluded.
Epidemiological and pathological data were noted from the patient records. Paraffin embedded tissue samples of the patient were collected and immunohistochemical staining (IHC) for AR and HER 2/Neu was performed. The stained slides were then scored independently by three pathologists.
Scoring criteria:
AR nuclear staining of ≥5% of the lesional cells were considered positive. Cells showing weak to strong complete/basolateral/lateral membrane staining in ≥5 cell groups were scored positive for HER 2/neu.
Results
The study included 24 individuals, 16 males and 8 females with esophageal SCC. The tumor cells showed AR positivity in 12.5% and HER 2/neu positivity in 16.67% of the tissue samples by IHC. There was no significant gender difference in the expression of AR and HER 2/neu in this study. In addition AR expression was seen in 41.67% (N = 10) of adjacent stromal cells (in 66.67% (2 of 3) of the AR positive and 38.09% (8 of 21) of the AR negative specimens) with a p value of 0.028 (p < 0.05). There was no significant variation by gender.
Conclusion
There was a statistically significant expression of AR in the stromal cells of both AR positive and negative tumors. AR expression has been reported in the stroma of esophageal adenocarcinoma which was attributed to paracrine effects following androgen stimulation. To our knowledge, this is the first report of AR expression in the tumor microenvironment of esophageal SCCs. This study is limited by the small sample size and warrants further research.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To determine the effect of preparation method on the physical properties of amorphous trehalose.
Amorphous anhydrous trehalose was prepared by four different methods. viz., freeze-drying, ...spray-drying, dehydration, and melt quenching. The glass transition temperature (Tg), enthalpic relaxation behavior, and crystallization were studied by differential scanning calorimetry, whereas X-ray diffractometry was used for phase identification. The rate and extent of water uptake at different relative humidity values were also obtained.
Though the enthalpic relaxation and crystallization behaviors were influenced by the method of preparation of amorphous trehalose, the Tg and fragility were not. The phase prepared by dehydration showed the highest enthalpic recovery at Tg, indicating that aging may have occurred during preparation. Among the four methods used, trehalose prepared by dehydration had the highest tendency to crystallize, whereas there was no crystallization in melt-quenched amorphous trehalose. The method of preparation influenced not only the rate and extent of water sorption but also the phase crystallized. Water vapor sorption removed the effects of structural history in the amorphous phase formed by dehydration.
The method of preparation strongly influenced the pharmaceutically relevant properties of amorphous trehalose. The resistance to crystallization can be rank ordered as trehalose prepared by dehydration < freeze-dried approximately spray-dried < melt-quenched. The rate of water sorption can be rank ordered as trehalose prepared by dehydration < freeze-dried < spray-dried.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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