bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low ERCC1 expression is a good predictive marker in lung adenocarcinoma patients receiving chemotherapy based on platinum in all TNM stages - a single-center study
Authors: Piljić Burazer Marina , Mladinov Suzana , Matana Antonela , Kuret Sendi , Bezić Joško , Glavina Durdov Merica 
Published: September 2019

Abstract

Background
High ERCC1 expression is thought to be related with resistance to chemotherapy based on platinum. The aim of this study was to present our institutional observations regarding to the association of ERCC1 and overall survival (OS) of the lung adenocarcinoma patients who received chemotherapy based on platinum.

Material/methods
A total of 253 lung adenocarcinoma patients in all TNM stages were retrospectively investigated. The diagnosis was based on small biopsy samples obtained during bronchoscopy. Depending on the TNM stage of the disease and clinical condition, patients received only the chemotherapy based on platinum, or in combination with radiotherapy or surgery. Tissue sample for ERCC1 immunohistochemical analysis was sufficient in 129 patients. Low from high ERCC1 expression was separated by the semi-quantitative H-score median.

Results
High ERCC1 expression was found in 47.3% patients, and was correlated with higher TNM (p = 0.021), tumor enlargement (p = 0.002), positive lymph nodes (p = 0.001), positive distant metastasis (p = 0.005), and higher relative risk of death (p < 0.001). Furthermore, significance association was observed for low ERCC1 expression and better performance status (ECOG) (p = 0.023). Longer OS was strongly associated with a low ERCC1 expression, not only in the group of patients in TNM stage I-III, who were treated with combination of chemotherapy with surgery or radiotherapy (p = 0.002), but also in the group of patients in TNM stage IV who received only chemotherapy based on platinum (p < 0.001), compared with the patients in the same TNM stage and high ERCC1 expression.

Conclusions
ERCC1 expression in lung adenocarcinoma is a useful prognostic marker and moreover, a useful predictive marker in patients receiving chemotherapy based on platinum in all stages of the disease.
Strategies for the expansion of human induced pluripotent stem cells as aggregates in single-use Vertical-Wheel™ bioreactors
Authors: Nogueira Diogo E. S. , Rodrigues Carlos A. V. , Carvalho Marta S. , Miranda Cláudia C. , Hashimura Yas , Jung Sunghoon , Lee Brian , Cabral Joaquim M. S. 
Published: September 2019

Abstract

Background
Since their inception, human induced pluripotent stem cells (hiPSCs) have held much promise for pharmacological applications and cell-based therapies. However, their potential can only be realised if large numbers of cells can be produced reproducibly on-demand. While bioreactors are ideal systems for this task, due to providing agitation and control of the culture parameters, the common impeller geometries were not designed for the expansion of mammalian cells, potentially leading to sub-optimal results.

Results
This work reports for the first time the usage of the novel Vertical-Wheel single-use bioreactors for the expansion of hiPSCs as floating aggregates. Cultures were performed in the PBS MINI 0.1 bioreactor with 60 mL of working volume. Two different culture media were tested, mTeSR1 and mTeSR3D, in a repeated batch or fed-batch mode, respectively, as well as dextran sulfate (DS) supplementation. mTeSR3D was shown to sustain hiPSC expansion, although with lower maximum cell density than mTeSR1. Dextran sulfate supplementation led to an increase in 97 and 106% in maximum cell number when using mTeSR1 or mTeSR3D, respectively. For supplemented media, mTeSR1 + DS allowed for a higher cell density to be obtained with one less day of culture. A maximum cell density of (2.3 ± 0.2) × 106 cells∙mL− 1 and a volumetric productivity of (4.6 ± 0.3) × 105 cells∙mL− 1∙d− 1 were obtained after 5 days with mTeSR1 + DS, resulting in aggregates with an average diameter of 346 ± 11 μm. The generated hiPSCs were analysed by flow cytometry and qRT-PCR and their differentiation potential was assayed, revealing the maintenance of their pluripotency after expansion.

Conclusions
The results here described present the Vertical-Wheel bioreactor as a promising technology for hiPSC bioprocessing. The specific characteristics of this bioreactor, namely in terms of the innovative agitation mechanism, can make it an important system in the development of hiPSC-derived products under current Good Manufacturing Practices.
Prospects for combining immune checkpoint blockade with PARP inhibition
Authors: Li Anping , Yi Ming , Qin Shuang , Chu Qian , Luo Suxia , Wu Kongming 
Published: September 2019

Abstract
The immunogenicity of a cancer cell is derived from accumulated somatic mutations. However, on the contrary to increased immunogenicity, anti-cancer immune response tends to be feeble. This impaired anti-cancer immunity could be attributed to multiple factors including loss of immunodominant epitopes, downregulation of major histocompatibility complex, and immunosuppressive microenvironment, as well as aberrant negative co-stimulatory signals. Immune checkpoint inhibitors block negative co-stimulatory signals such as programmed cell death-1 and cytotoxic T-lymphocyte-associated protein 4, ultimately reactivating anti-cancer immunity. Immune checkpoint inhibitors elicit potent anti-cancer effect and have been approved for multiple cancers. Nevertheless, there still are significant potential improvements for the applications of checkpoint inhibitor, especially considering frequent resistance. Recent studies demonstrated that additional PARP inhibition could alleviate resistance and enhance efficacy of immune checkpoint blockade therapy via promoting cross-presentation and modifying immune microenvironment. We proposed that PARP inhibitors could enhance the priming and tumor-killing activities of T cell, boost the whole cancer-immunity cycle, and thereby improve the response to immune checkpoint blockade. In this review, we focused the latest understanding of the effect of PARP inhibitors on anti-cancer immunity and PARP inhibitors combining immune checkpoint blockade therapy. Moreover, we summarized the preclinical and clinical evidence and discussed the feasibility of this combination therapy in future clinical practice.
Designing, synthesis and characterization of 2-aminothiazole-4-carboxylate Schiff bases; antimicrobial evaluation against multidrug resistant strains and molecular docking
Authors: Ejaz Saima , Nadeem Humaira , Paracha Rehan Zafar , Sarwar Sadia , Ejaz Sadaf 
Published: September 2019

AbstractBackground2-Aminothiazoles are significant class of organic medicinal compounds utilized as starting material for the synthesis of diverse range of heterocyclic analogues with promising therapeutic roles as antibacterial, antifungal, anti-HIV, antioxidant, antitumor, anthelmintic, anti-inflammatory & analgesic agents.ExperimentalEight compounds 1a, 2a–2g were synthesized and characterized by FTIR and NMR (1H and13C). Evaluation of antibacterial potential against multi-drug resistant clinical isolates was performed and minimum inhibitory concentration (MIC) values were determined. Antifungal activity was also performed. Protein–ligand interactions of compounds with target enzyme were evaluated through docking studies.ResultsResistance profiling of bacterical clinical isolates (MDRs) depicted that some standard drugs used were not active against these MDRs while our synthesized compounds showed good MIC values. Among all the synthesized compounds, 2a and 2b showed significant antibacterial potential towards gram-positiveStaphylococcus epidermidisand gram-negativePseudomonas aeruginosaat MIC 250 µg/mL and 375 µg/mL respectively. Likewise, compound 2d and 2g exhibited inhibitory potential against gram-positiveStaphylococcus aureusand gram-negativeEscherichia coliat MIC values of 250 and 375 µg/mL respectively. Compound 2b showed maximum antifungal potential againstCandida glabrata(ATCC 62934) with a zone of inhibition 21.0 mm as compared to the reference drug nystatin which showed lesser antifungal potential with a zone of inhibition of 19.1 mm.Candida albicans(ATCC 60387) showed maximum sensitivity to compound 2a with a zone of inhibition 20.0 mm. Its antifungal activity is more in comparison to reference drug nystatin with exhibited the zone of inhibition of 19.3 mm. Designed compounds were docked with the target enzyme UDP-N-acetylmuramate/l-alanine ligase. The compound 2b showed highest binding affinity (− 7.6 kcal/mol).ConclusionsThe synthesized compounds showed moderate to significant antibacterial and antifungal potential. It is clear from the binding affinities that compounds having hydroxyl group substituted on benzene ring possess strong binding affinity as compared to other analogues. These designed compounds could be considered to act as antagonists against target UDP-N-acetylmuramate/l-alanine ligase.
Cost-effectiveness of two long-lasting insecticidal nets delivery models in mass campaign in rural Mozambique
Authors: Arroz Jorge A. H. , Candrinho Baltazar , Mendis Chandana , Lopez Melanie , Martins Maria do Rosário O. 
Published: September 2019

Abstract

Objective
The aim is to compare the cost-effectiveness of two long-lasting insecticidal nets (LLINs) delivery models (standard vs. new) in universal coverage (UC) campaigns in rural Mozambique.

Results
The total financial cost of delivering LLINs was US$ 231,237.30 and US$ 174,790.14 in the intervention (302,648 LLINs were delivered) and control districts (219,613 LLINs were delivered), respectively. The average cost-effectiveness ratio (ACER) per LLIN delivered and ACER per household (HH) achieving UC was lower in the intervention districts. The incremental cost-effectiveness ratio (ICER) per LLIN and ICER per HH reaching UC were US$ 0.68 and US$ 2.24, respectively. Both incremental net benefit (for delivered LLIN and for HHs reaching UC) were positive (intervention deemed cost-effective). Overall, the newer delivery model was the more cost-effective intervention. However, the long-term sustainability of either delivery models is far from guaranteed in Mozambique’s current economic context.
Deficiency in the double-stranded RNA binding protein HYPONASTIC LEAVES1 increases sensitivity to the endoplasmic reticulum stress inducer tunicamycin in Arabidopsis
Authors: Hirata Rikako , Mishiba Kei-ichiro , Koizumi Nozomu , Iwata Yuji 
Published: September 2019

Abstract

Objective
microRNA (miRNA) is a small non-coding RNA that regulates gene expression by sequence-dependent binding to protein-coding mRNA in eukaryotic cells. In plants, miRNA plays important roles in a plethora of physiological processes, including abiotic and biotic stress responses. The present study was conducted to investigate whether miRNA-mediated regulation is important for the endoplasmic reticulum (ER) stress response in Arabidopsis.

Results
We found that hyl1 mutant plants are more sensitive to tunicamycin, an inhibitor of N-linked glycosylation that causes ER stress than wild-type plants. Other miRNA-related mutants, se and ago1, exhibited similar sensitivity to the wild-type, indicating that the hypersensitive phenotype is attributable to the loss-of-function of HYL1, rather than deficiency in general miRNA biogenesis and function. However, the transcriptional response of select ER stress-responsive genes in hyl1 mutant plants was indistinguishable from that of wild-type plants, suggesting that the loss-of-function of HYL1 does not affect the ER stress signaling pathways.
RETRACTED ARTICLE: Childhood nosocomial viral acute respiratory tract infections in teaching hospital Anuradhapura, Sri Lanka
Authors: Sampath Jayaweera Jayaweera Arachchige Asela , Reyes Mohammed 
Published: September 2019

Abstract
Objectives
We have assessed the risk factors for the occurrence of hospital-acquired (HA) and community-acquired (CA) viral acute respiratory tract infections (ARTIs) in children. Children (1–60 months) who were having ARTI on admission (CA) and develops ARTI following 48 h after admission or 3 days of discharge (HA) were included. Indirect immunofluorescence assay (IFA) was performed and multivariable analyses were done to determine the risk factors for the development of viral CA and HA-ARTI.

Results
Total of 818 with ARTIs, 226 (27.6%) RSV cases were detected. Out of 226, 86 (38.0%) HA-RSV cases were detected. CA-viral-ARTI was significantly high (p < 0.05). Compared to CA-RSV-ARTI immunodeficiency, seizures, trisomy-21 and congenital heart disease (CHD) were having 2.3, 3.2, 1.8- and 2.2-times risk for acquiring HA-RSV respectively. The number of deaths was significantly high following HA-RSV. The associated burden was significant following HA-RSV and it was 429.77 disability-adjusted life years. Children who are having immunodeficiency, CHD, seizure episodes and trisomy 21 would lead to the acquisition of nosocomial RSV infections in great. Adherence to meticulous infection control practices will be helpful to minimize the HA-viral ARTIs in great.
Endo-lysosomal proteins and ubiquitin CSF concentrations in Alzheimer’s and Parkinson’s disease
Authors: Sjödin Simon , Brinkmalm Gunnar , Öhrfelt Annika , Parnetti Lucilla , Paciotti Silvia , Hansson Oskar , Hardy John , Blennow Kaj , Zetterberg Henrik , Brinkmalm Ann 
Published: September 2019

Abstract

Background
Increasing evidence implicates dysfunctional proteostasis and the involvement of the autophagic and endo-lysosomal system and the ubiquitin-proteasome system in neurodegenerative diseases. In Alzheimer’s disease (AD), there is an accumulation of autophagic vacuoles within the neurons. In Parkinson’s disease (PD), susceptibility has been linked to genes encoding proteins involved in autophagy and lysosomal function, as well as mutations causing lysosomal disorders. Furthermore, both diseases are characterized by the accumulation of protein aggregates.

Methods
Proteins associated with endocytosis, lysosomal function, and the ubiquitin-proteasome system were identified in the cerebrospinal fluid (CSF) and targeted by combining solid-phase extraction and parallel reaction monitoring mass spectrometry. In total, 50 peptides from 18 proteins were quantified in three cross-sectional cohorts including AD (N = 61), PD (N = 21), prodromal AD (N = 10), stable mild cognitive impairment (N = 15), and controls (N = 68).

Results
A pilot study, including subjects selected based on their AD CSF core biomarker concentrations, showed increased concentrations of several targeted proteins in subjects with core biomarker levels indicating AD pathology compared to controls. Next, in a clinically characterized cohort, lower concentrations in CSF of proteins in PD were found compared to subjects with prodromal AD. Further investigation in an additional clinical study again revealed lower concentrations in CSF of proteins in PD compared to controls and AD.

Conclusion
In summary, significantly different peptide CSF concentrations were identified from proteins AP2B1, C9, CTSB, CTSF, GM2A, LAMP1, LAMP2, TCN2, and ubiquitin. Proteins found to have altered concentrations in more than one study were AP2B1, CTSB, CTSF, GM2A, LAMP2, and ubiquitin. Interestingly, given the genetic implication of lysosomal function in PD, we did identify the CSF concentrations of CTSB, CTSF, GM2A, and LAMP2 to be altered. However, we also found differences in proteins associated with endocytosis (AP2B1) and the ubiquitin-proteasome system (ubiquitin). No difference in any peptide CSF concentration was found in clinically characterized subjects with AD compared to controls. In conclusion, CSF analyses of subjects with PD suggest a general lysosomal dysfunction, which resonates well with recent genetic findings, while such changes are minor or absent in AD.
CSF evidence of pericyte damage in Alzheimer’s disease is associated with markers of blood-brain barrier dysfunction and disease pathology
Authors: Miners J. S. , Kehoe P. G. , Love S. , Zetterberg H. , Blennow K. 
Published: September 2019

Abstract

Background
We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF albumin and CSF/serum albumin ratio) and disease pathology (reduced CSF Aβ42 and elevated CSF total and phosphorylated tau) in Alzheimer’s disease (AD).

Methods
sPDGFRβ and albumin were measured by sandwich ELISA in ante-mortem CSF from 39 AD and 39 age-matched controls that were grouped according to their biomarker profile (i.e. AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL). sPDGFRβ was also measured in matched serum and CSF samples (n = 23) in a separate neurologically normal group for which the CSF/serum albumin ratio had been determined.

Results
CSF sPDGFRβ level was significantly increased in AD (p = 0.0038) and correlated positively with albumin (r = 0.45, p = 0.007), total tau (r = 0.50, p = 0.0017) and phosphorylated tau (r = 0.41, p = 0.013) in AD but not in controls. CSF sPDGFRβ did not correlate with Aβ42. Serum and CSF sPDGFRβ were positively correlated (r = 0.547, p = 0.0085) in the independent neurologically normal CSF/serum matched samples.

Conclusions
We provide further evidence of an association between pericyte injury and BBB breakdown in AD and novel evidence that a CSF marker of pericyte injury is related to the severity of AD pathology.
Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia
Authors: Suvakov Sonja , Cubro Hajrunisa , White Wendy M. , Butler Tobah Yvonne S. , Weissgerber Tracey L. , Jordan Kyra L. , Zhu Xiang Y. , Woollard John R. , Chebib Fouad T. , Milic Natasa M. , Grande Joseph P. , Xu Ming , Tchkonia Tamara , Kirkland James L. , Lerman Lilach O. , Garovic Vesna D. 
Published: September 2019

Abstract

Background
Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia.

Methods
MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n = 10) and those with normotensive pregnancies (NP-MSC, n = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis were assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP.

Results
After in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adipose tissue sections revealed a greater inflammatory response in preeclampsia, based on the higher levels of both TNF-alpha and MCP-1 compared to normotensive pregnancies (p < 0.001 and 0.024, respectively). MSC isolated from PE demonstrated a lower percentage of live MSC cells (p = 0.012), lower proliferation (p = 0.005), and higher migration (p = 0.023). At baseline, PE-MSC demonstrated a senescent phenotype, reflected by more abundant staining for SABG (p < 0.001), upregulation of senescence markers and SASP components, as well as lower angiogenic potential (p < 0.001), compared to NP-MSC. Treatment with dasatinib increased significantly the number of apoptotic PE-MSC compared to NP-MSC (0.011 vs. 0.093) and decreased the gene expression of p16 and six SASP components. The mechanistic link between senescence and impaired angiogenesis in PE was confirmed by improved angiogenic potential of PE-MSC (p < 0.001) after dasatinib treatment.

Conclusions
Our data suggest that MSC senescence exerts inhibitory effects on angiogenesis in preeclampsia. Senolytic agents may offer the opportunity for mechanism-based therapies.
Immunohistochemical phenotyping of T cells, granulocytes, and phagocytes in the muscle of cancer patients: association with radiologically defined muscle mass and gene expression
Authors: Anoveros-Barrera Ana , Bhullar Amritpal S. , Stretch Cynthia , Dunichand-Hoedl Abha R. , Martins Karen J. B. , Rieger Aja , Bigam David , McMullen Todd , Bathe Oliver F. , Putman Charles T. , Field Catherine J. , Baracos Vickie E. , Mazurak Vera C. 
Published: September 2019

Abstract

Background
Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients.

Methods
Intraoperative muscle biopsies were collected from cancer patients (n = 30, 91% gastrointestinal malignancies). Muscle mass was assessed histologically (muscle fiber cross-sectional area, CSA; μm2) and radiologically (lumbar skeletal muscle index, SMI; cm2/m2 by computed tomography, CT). T cells (CD4 and CD8) and granulocytes/phagocytes (CD11b, CD14, and CD15) were assessed by immunohistochemistry. Microarray analysis was conducted in the muscle of a second cancer patient cohort.

Results
T cells (CD3+), granulocytes/phagocytes (CD11b+), and CD3−CD4+ cells were identified. Muscle fiber CSA (μm2) was positively correlated (Spearman’s r = > 0.45; p = < 0.05) with the total number of T cells, CD4, and CD8 T cells and granulocytes/phagocytes. In addition, patients with the smallest SMI exhibited fewer CD8 T cells within their muscle. Consistent with this, further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively associated (Pearson’s r = ≥ 0.5; p = <0.0001) with key genes within muscle catabolic pathways for signaling (ACVR2B), ubiquitin proteasome (FOXO4, TRIM63, FBXO32, MUL1, UBC, UBB, UBE2L3), and apoptosis/autophagy (CASP8, BECN1, ATG13, SIVA1).

Conclusion
The skeletal muscle immune environment of cancer patients is comprised of immune cell populations from the adaptive and innate immunity. Correlations of T cells, granulocyte/phagocytes, and CD3−CD4+ cells with muscle mass measurements indicate a positive relationship between immune cell numbers and muscle mass status in cancer patients. Further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively correlated with components of muscle catabolism.