bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles from the apoplastic fungal wheat pathogen Zymoseptoria tritici
Authors: Hill Erin H. , Solomon Peter S. 
Published: September 2020

Abstract
Background
The fungal pathogen Zymoseptoria tritici is a significant constraint to wheat production in temperate cropping regions around the world. Despite its agronomic impacts, the mechanisms allowing the pathogen to asymptomatically invade and grow in the apoplast of wheat leaves before causing extensive host cell death remain elusive. Given recent evidence of extracellular vesicles (EVs)—secreted, membrane-bound nanoparticles containing molecular cargo—being implicated in extracellular communication between plants and fungal pathogen, we have initiated an in vitro investigation of EVs from this apoplastic fungal wheat pathogen. We aimed to isolate EVs from Z. tritici broth cultures and examine their protein composition in relation to the soluble protein in the culture filtrate and to existing fungal EV proteomes.

Results
Zymoseptoria tritici EVs were isolated from broth culture filtrates using differential ultracentrifugation (DUC) and examined with transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Z. tritici EVs were observed as a heterogeneous population of particles, with most between 50 and 250 nm. These particles were found in abundance in the culture filtrates of viable Z. tritici cultures, but not heat-killed cultures incubated for an equivalent time and of comparable biomass. Bottom-up proteomic analysis using LC–MS/MS, followed by stringent filtering revealed 240 Z. tritici EV proteins. These proteins were distinct from soluble proteins identified in Z. tritici culture filtrates, but were similar to proteins identified in EVs from other fungi, based on sequence similarity analyses. Notably, a putative marker protein recently identified in Candida albicans EVs was also consistently detected in Z. tritici EVs.

Conclusion
We have shown EVs can be isolated from the devastating fungal wheat pathogen Z. tritici and are similar to protein composition to previously characterised fungal EVs. EVs from human pathogenic fungi are implicated in virulence, but the role of EVs in the interaction of phytopathogenic fungi and their hosts is unknown. These in vitro analyses provide a basis for expanding investigations of Z. tritici EVs in planta, to examine their involvement in the infection process of this apoplastic wheat pathogen and more broadly, advance understanding of noncanonical secretion in filamentous plant pathogens.
Cardioprotective effect of garlic extract in isoproterenol-induced myocardial infarction in a rat model: assessment of pro-apoptotic caspase-3 gene expression
Authors: Islam Dipa , Banerjee Shanta Monisha , Akhter Samina , Lyzu Chadni , Hakim Mahmuda , Islam Md. Rezuanul , Mohanta Liton Chandra , Lipy Evena Parvin , Roy Dipankar Chandra 
Published: September 2020

Abstract
Background
Myocardial Infarction (MI), also known as heart attack, is one of the most common cardiovascular diseases. Although certain drugs or mechanical means are used, day by day natural products such as herbs and spices based MI treatment is getting much popularity over the drugs or mechanical means for their pharmacological effects and have low or no side effects. This study was designed to assess the cardio-protective effect of methanolic extract of Bangladeshi multi clove garlic (Allium sativum) cultivar, a highly believed spice having cardioprotective activity, against isoproterenol (ISO) induced MI through cardiac histopathology as well as cardiac apoptotic caspase-3 gene expression study in female Wistar albino rats. Four groups containing 35 rats treated with respective agents like distill water / garlic extract (200 mg/kg-body-weight/day) up to 28 days and normal saline / ISO (100 mg/kg-body-weight/day) on 29th and 30th day were sacrificed (two rats/group/sacrifice) on the day 31, 46 and 61 and collecting the heart, cardiac histology and gene expression analysis were performed.

Results
ISO induced MI rats pretreated with garlic extract revealed up regulated expression of the cardiac apoptotic caspase-3 gene at the initial stage but finally the expressions gradually getting down regulated along with gradual improving the cardiac damage caused by apoptosis. Furthermore, only garlic extract pretreated rats were found undamaged cardioarchitecture and normal expressions of this gene.

Conclusions
These findings suggested that garlic extract confers having significant cardioprotective effect and consuming this spice with regular diet may reduce the risk of MI.
Clinical significance of red blood cell distribution width in systemic lupus erythematosus patients
Authors: Mohamed Osama Sayed Daifallah , Azmy Gehan Joseph , Elfadl Esam Mohammed Abu 
Published: September 2020

Abstract
Background
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with wide variety of clinical presentations. Recently, red blood cell distribution width (RDW) has been used as an inflammatory marker, similar to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) where systemic inflammation has been linked to increased RDW. Many researches have assessed independently selective different hematological markers that may reflect disease activity.
Our study aims to examine a number of hematological parameters that could reflect disease activity and to assess if there is a relationship between different hematological parameter (RDW, neutrophils and lymphocytes) to reflect SLE activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Results
The study comprised 60 SLE patients (52 females and 8 males) with a mean age of 34.53 years and mean disease duration was 4.085 years. The RDW values were significantly higher (p < 0.001) when comparing active patients (16.64 ± 4.7) versus inactive patients (13.16 ± 2.67) and controls (12.7 ± 1.13). Otherwise, insignificant differences were reported when comparing inactive SLE patients versus the control group (p = 0.242). There were no significant correlations (p > 0.05) between neutrophil count and lymphocyte count with C3, C4, SLEDAI score, 24 h urinary proteins, platelets count but significant only with hemoglobin level (p = 0.001).

Conclusion
Increased RDW is connected with active disease status of SLE patients. RDW could be used as a surrogate marker of the inflammation rather than neutrophil and lymphocyte count. It is a simple and easy testing included in CBC thus RDW could be used as a possible indicator to assess disease activity.
Tunicamycin-Induced Endoplasmic Reticulum Stress Mediates Mitochondrial Dysfunction in Human Adipocytes
Authors: Jackisch Laura , Murphy Alice M , Kumar Sudhesh , Randeva Harpal , Tripathi Gyanendra , McTernan Philip G 
Published: September 2020

Abstract

Context
Dysfunctional endoplasmic reticulum (ER) and mitochondria are known to contribute to the pathology of metabolic disease. This damage may occur, in part, as a consequence of ER-mitochondria cross-talk in conditions of nutrient excess such as obesity. To date, insight into this dynamic relationship has not been characterized in adipose tissue. Therefore, this study investigated whether ER stress contributes to the development of mitochondrial inefficiency in human adipocytes from lean and obese participants.

Methods
Human differentiated adipocytes from Chub-S7 cell line and primary abdominal subcutaneous adipocytes from lean and obese participants were treated with tunicamycin to induce ER stress. Key parameters of mitochondrial function were assessed, including mitochondrial respiration, membrane potential (MMP), and dynamics.

Results
ER stress led to increased respiratory capacity in a model adipocyte system (Chub-S7 adipocytes) in a concentration and time dependent manner (24 h: 23%↑; 48 h: 68%↑, P &lt; 0.001; 72 h: 136%↑, P &lt; 0.001). This corresponded with mitochondrial inefficiency and diminished MMP, highlighting the formation of dysfunctional mitochondria. Morphological analysis revealed reorganization of mitochondrial network, specifically mitochondrial fragmentation. Furthermore, p-DRP1, a key protein in fission, significantly increased (P &lt; 0.001). Additionally, adipocytes from obese subjects displayed lower basal respiration (49%↓, P &lt; 0.01) and were unresponsive to tunicamycin in contrast to their lean counterparts, demonstrating inefficient mitochondrial oxidative capacity.

Conclusion
These human data suggest that adipocyte mitochondrial inefficiency is driven by ER stress and exacerbated in obesity. Nutrient excess–induced ER stress leads to mitochondrial dysfunction that may therefore shift lipid deposition ectopically and thus have further implications on the development of related metabolic disorders.
Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity
Authors: Deshmukh Harshal A , Madsen Anne Lundager , Viñuela Ana , Have Christian Theil , Grarup Niels , Tura Andrea , Mahajan Anubha , Heggie Alison J , Koivula Robert W , De Masi Federico , Tsirigos Konstantinos K , Linneberg Allan , Drivsholm Thomas , Pedersen Oluf , Sørensen Thorkild I A , Astrup Arne , Gjesing Anette A P , Pavo Imre , Wood Andrew R , Ruetten Hartmut , Jones Angus G , Koopman Anitra D M , Cederberg Henna , Rutters Femke , Ridderstrale Martin , Laakso Markku , McCarthy Mark I , Frayling Tim M , Ferrannini Ele , Franks Paul W , Pearson Ewan R , Mari Andrea , Hansen Torben , Walker Mark 
Published: September 2020

Abstract

Context
Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

Objective
To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

Design
We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models.

Results
Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10−9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10−9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity.

Conclusion
We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.
Effects of Thyroid Function on Phosphodiester Concentrations in Skeletal Muscle and Liver: An In Vivo NMRS Study
Authors: Beiglböck Hannes , Wolf Peter , Pfleger Lorenz , Caliskan Burak , Fellinger Paul , Zettinig Georg , Anderwald Christian Heinz , Kenner Lukas , Trattnig Siegfried , Kautzky-Willer Alexandra , Krššák Martin , Krebs Michael 
Published: September 2020

Abstract

Context
Thyroid function is clinically evaluated by determination of circulating concentrations of thyrotropin (thyroid-stimulating hormone; TSH) and free thyroxine (fT4). However, a tissue-specific effector substrate of thyroid function is lacking. Energy-rich phosphorus-containing metabolites (PM) and phospholipids (PL) might be affected by thyroid hormone action and can be noninvasively measured by 31P nuclear magnetic resonance spectroscopy (NMRS).

Objectives
To measure the actions of peripheral thyroid hormones on PM and PL tissue concentrations.

Design and Setting
A longitudinal, prospective pilot study was performed.

Participants
Nine patients with hyperthyroidism (HYPER) and 4 patients with hypothyroidism (HYPO) were studied at baseline and 3 months after treatment.

Main Outcome Measures
High-field 1H/31P NMRS was used to assess profiles of PM, PL, and flux through oxidative phosphorylase in liver and skeletal muscle, as well as ectopic tissue lipid content.

Results
The concentrations of total skeletal muscle (m-) and hepatic (h-) phosphodiesters (PDE) and one of the PDE constituents, glycerophosphocholine (GPC), were lower in HYPER compared with HYPO (m-PDE: 1.4 ± 0.4 mM vs 7.4 ± 3.5 mM, P = 0.003; m-GPC: 0.9 ± 0.3 mM vs 6.7 ± 3.5 mM, P = 0.003; h-PDE: 4.4 ± 1.4 mM vs 9.9 ± 3.9 mM, P = 0.012; h-GPC: 2.2 ± 1.0 mM vs 5.1 ± 2.4 mM, P = 0.024). Both h-GPC (rho = −0.692, P = 0.018) and h-GPE (rho = −0.633, P = 0.036) correlated negatively with fT4. In muscle tissue, a strong negative association between m-GPC and fT4 (rho = −0.754, P = 0.003) was observed.

Conclusions
Thyroxine is closely negatively associated with the PDE concentrations in liver and skeletal muscle. Normalization of thyroid dysfunction resulted in a decline of PDE in hypothyroidism and an increase in hyperthyroidism. Thus, PDE might be a sensitive tool to estimate tissue-specific peripheral thyroid hormone action.
Immunotherapy in the treatment of non-small cell lung cancer (NSCLC) - analysis of epidemiology and cure - review
Authors: Ruszel Kinga , Piecewicz-Szczęsna Halina 
Published: September 2020

Cancer is the second leading cause of death in Poland. Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Cancer incidence and mortality trends observed in the world and also Poland for many years, have been the resultants of changes associated with exposure to tobacco smoke carcino-gens (active smoking). Until recently, chemotherapy was the main treatment for NSCLC patients. Currently, thanks to the development of numerous research centers around the world, there are several methods of treating patients, which leads to the extension of cancer patients' lives and the improvement of their quality. The immune system plays an important role in controlling and eradicating cancer. Immune checkpoint inhibitors (ICPs) have shown clear persistent responses and represent the emergence of a new approach to treating patients with NSCLC. PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer. Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. Immunotherapy with monoclonal antibodies targeting with PD-1 and PD-L1 has become standard of care for an increasing number of indications. However, many patients with metastatic non-small cell lung cancer (mNSCLC) experience disease progression after first- and second- line treatment; therefore more treatment options are needed for these patients. Due to the specific characteristics of cancer immunotherapy and the rapid advances in this field, clinical guidelines for the use of these drugs are needed, including patient selection, response monitoring, careful observation of side effects, and biomarker testing.
Pregnancy-associated breast cancer - diagnosis, treatment and outcomes for women and their offspring
Authors: Zielińska Martyna Maria , Zarankiewicz Natalia , Kuchnicka Aleksandra , Kosz Katarzyna , Ciseł Bogumiła 
Published: September 2020

Introduction: Pregnancy-associated breast cancer (PABC) is the most common malignancy in pregnant women with an incidence of 1 in 3-10 thousand pregnancies. It is mostly defined as breast cancer diagnosed during pregnancy or within 1 year postpartum. The number of PABCs is going to raise due to the trend of delaying childbearing. Purpose: This review summarizes data on the occurrence and characteristics of PABC. The analysis comprises diagnosis and proper treatment of BC during pregnancy. Prognosis of women and their offspring are emphasized. Material and methods: The review is based on publications mainly from 2010 to 2019 and 5 articles from 1994-2008 collected on the PubMed. Results: The sensitivity of breast ultrasonography (USG) in pregnancy is 70-100% and it is considered as safe for the fetus. Staging evaluation in pregnant women consists of chest x-ray, liver USG and non-contrast bone MRI. 71-88% of PABCs are invasive ductal carcinomas. Treatment consists of breast surgery regardless of time and optionally, chemotherapy from the 2nd trimester. Radiotherapy, tamoxifen and trastuzumab are contraindicated in PABC. Therapeutic abortion does not improve oncological outcome. Overall prognosis is similar for both pregnant and non-pregnant patients with similar type and stage of BC. The rate of congenital malformations is 1,3% for both children of PABC patients treated with chemotherapy and born from women without chemotherapeutic treatment. The most frequent obstetrical complication of PABC treatment is preterm delivery. Conclusions: Pregnancy does not impact oncologic outcome, if the treatment is appropriate. PABC patients have survival rates consistent with the stage of disease. Proper treatment of PABC does not increase the risk of congenital malformations and is relatively safe for the fetus.
Congenital Abnormalities of the Temporomandibular Joint - single conditions
Authors: Stangret Anna , Mularczyk Agata , Szczęśniak Angelika , Topczewska Katarzyna , Rogulska Karolina 
Published: September 2020

Temporomandibular joint (TMJ), due to its morphological structure, is a bicondylar joint, coupled in every movement. Intensive development of TMJ occurs in the early fetal period. Diseases of the temporomandibular joints differ in etiology and symptoms. The dysfunction of temporomandibular joint may lead to many problems connected with disorders of masseter muscles and bones building this joint and tissues around it. The aim of these studies is to describe several congenital abnormalities of the temporomandibular joint. Congenital deformities of the temporomandibular joint complex can present as a growth of mandible disturbances. They can occur as single condition characterized by hyperplasia or hypoplasia of joint structures. In extreme cases it can occure as agenesis, which is lack of formation. Tempotomandibular joint may be also affected by fibrous dysplasia, form of hyperplasia. They can also occur as a complex symptom with congenital mandible deformity, what can cause the problems with correct diagnosis. Temporomandibular joint disorders constitute a significant percentage of the viscerocranium diseases. All disorders occurring within these structures are usually associated with severe pain and significant discomfort. In dental practice, it is important to know in detail the symptoms associated with diseases of temporomandibular joint and also differentiate single conditions and complex symptoms.
Acetazolamide in prevention of altitude disease
Authors: Choroszewicz Paweł , Dobosiewicz Anna Maria , Badiuk Nataliia 
Published: September 2020

Mountain climbing is associated with many risky, life-threatening situations. One of the most common attacking diseases at altitudes above 2500 m is altitude disease (HAI). This disease consists of: acute alpine disease, cerebral oedema and pulmonary oedema at altitude.
The best way to prevent altitude diseases is by means of alcomatisation and slow increase in altitude. Climbers should follow the principle "climb high, sleep low". Sometimes, however, time or inability to descend do not allow for acclimatization. In such conditions, it is necessary to use pharmaceuticals that prevent the occurrence of an illness of altitude.
The following article discusses research on the most commonly used drug in the prevention of acute mountain disease - acetazolamide. This drug was first used in the 60s of the XX century, demonstrating its effectiveness in the prevention of mountain disease. Since then, it has been the subject of many studies.
Treatment of primary obstructive megaureter in children using minimally invasive technologies
Authors: Svekatun V. , Dmitryakov V. 
Published: September 2020

Introduction. The final formation of the child's functional systems completed during postnatal ontogeny. To create optimal conditions for the functioning of the body is necessary either to decrease the level of functional requirements to the immature system, or the creation of new operating conditions under which the extended maturation time factor.
Relevance. Currently, the most common treatment for obstructive uropathies is surgical treatment. To create optimal conditions for the functioning of the body, it is necessary either to reduce the level of requirements for an immature functional system, or to create new functioning conditions under which the ripening time factor is extended.
Objective: Rationale and introduction of minimally invasive endoscopic draining techniques aimed at restoring urodynamics by using a PVC intraluminal drainage (stent).
Materials and methods. The possibility of stenting with determination of the size of the ureteric orifice was investigated. The study involved 32 children aged from birth to three years. A retrospective analysis of previously treated 41 patients with obstructive ureterohydronephrosis was performed.
Results. The study found that the optimal age for endoscopic correction of the intramural ureter is up to 3 months of life, when telescopic bougienage with dilation of the intramural compartment of the compromised ureter can be performed with calibration of the ureteric orifice and stent of the ureter with a corresponding stent.
Retrospective analysis of previously treated patients allowed us to determine the same dependence. Thus, out of 41 patients with obstructive ureterohydronephrosis positive result was achieved in 29 children (70.73%) up to 1 year and 6 (14.63%) over 1 year. The impossibility of performing endoscopic correction of the orifice and stenting of the ureters in the age group up to 1 year was noted only in 1 patient (2.43%), whereas in the group from 1 year to 3 years - in 5 patients (12.19%).
Conclusions. The proposed tactics of treatment of obstructive uropathy in children has advantages in terms of open surgical techniques in the technical simplicity, minimally invasive, maximum physiological, reducing the incidence of postoperative complications. It should be remembered that the effectiveness of endoscopic stenting of the lower parts of the ureter depends on the age of the child.