bluuebunny/crossref_metadata_2025 huggingface dataset:
An unlabelled probe-based real time PCR and modified semi-nested PCR as molecular tools for analysis of chloroquine resistant Plasmodium vivax isolates from Afghanistan
Authors: Mosawi Sayed Hussain , Dalimi Abdolhossein , Safi Najibullah , Fotouhi-Ardakani Reza , Ghaffarifar Fatemeh , Sadraei Javid
Published: July 2020

Background

Plasmodium vivax resistance to chloroquine (CQ) has been reported from many endemic regions in the world. Plasmodium vivax is responsible for 95% of malaria cases in Afghanistan and CQ is the first-line treatment given for vivax malaria. The pvmdr-1 and pvcrt-o (K10 insertion) genes are possible markers for CQ-resistance in P. vivax isolates. There have been no studies done on the presence or absence of molecular markers for CQ-resistance P. vivax in Afghanistan. The present work aimed to evaluate the frequency of mutations in the pvmdr-1 and K10 insertion in the pvcrt-o genes of P. vivax.

Methods

Plasmodium vivax isolates were collected from Laghman, Baghlan and Khost provinces. For investigation of polymorphisms of desired regions in pvmdr-1 and pvcrt-o genes, sequencing was applied on the PCR products. A new asymmetric qPCR and melting analysis assay based on unlabelled probe developed for scanning of K10 insertion in pvcrt-o gene.

Results

The analysis of sequencing data of the pvmdr-1 gene showed wild type Y976 and K997 and mutant M958 and L1076 in 33 isolates from three provinces. Of the 36 samples evaluated for K10 insertion in pvcrt-o, 2/18(11%), 0/10(0%) and 0/8(0%) isolates from Laghman, Baghlan and Khost province, respectively, possessed K10 insertion, confirmed by either sequencing and unlabelled probes.

Conclusion

Two samples with K10 insertion and 33 samples with pvmdr1 polymorphism, indicating on the possibility of CQ resistance in P. vivax populations in Afghanistan. Furthermore, unlabelled probes are simple and inexpensive alternative tools for screening of P. vivax mutations.
The skeletal muscles of mice infected with Plasmodium berghei and Plasmodium chabaudi reveal a crosstalk between lipid mediators and gene expression
Authors: Marrelli Mauro Toledo , Wang Zhiying , Huang Jian , Brotto Marco
Published: July 2020

Background

Malaria is one of the most prevalent infectious disease in the world with 3.2 billion humans at risk. Malaria causes splenomegaly and damage in other organs including skeletal muscles. Skeletal muscles comprise nearly 50% of the human body and are largely responsible for the regulation and modulation of overall metabolism. It is essential to understand how malaria damages muscles in order to develop effective preventive measures and/or treatments. Using a pre-clinical animal model, the potential molecular mechanisms of Plasmodium infection affecting skeletal muscles of mice were investigated.

Methods

Mouse Signal Transduction Pathway Finder PCR Array was used to monitor gene expression changes of 10 essential signalling pathways in skeletal muscles from mice infected with Plasmodium berghei and Plasmodium chabaudi. Then, a new targeted-lipidomic approach using liquid chromatography with tandem mass spectrometry (LC–MS/MS) to profile 158 lipid signalling mediators (LMs), mostly eicosanoids derived from arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was applied. Finally, 16 key LMs directly associated with inflammation, oxidative stress, and tissue healing in skeletal muscles, were quantified.

Results

The results showed that the expression of key genes altered by Plasmodium infection is associated with inflammation, oxidative stress, and atrophy. In support to gene profiling results, lipidomics revealed higher concentrations of LMs in skeletal muscles directly related to inflammatory responses, while on the levels of LMs crucial in resolving inflammation and tissue repair reduced significantly.

Conclusion

The results provide new insights into the molecular mechanisms of malaria-induced muscle damage and revealed a potential mechanism modulating inflammation in malarial muscles. These pre-clinical studies should help with future clinical studies in humans aimed at monitoring of disease progression and development of specific interventions for the prevention and mitigation of long-term chronic effects on skeletal muscle function.
Down regulating PHGDH affects the lactate production of sertoli cells in varicocele
Authors: Guo Wen-bin , Huang Zhen-hui , Yang Cheng , Lv Xian-yuan , Xia Hui , Tian Hu , Yang Jian-kun , Zhou Qi-zhao , Chen Ming-kun , Xue Kang-yi , Liu Cun-dong
Published: July 2020

Background

Although varicocele is considered to be one of the leading causes of male infertility, the precise mechanism underlying how varicocele leads to male infertility is not completely understood. We found the lactate concentration on the varicocele side of the patients was decreased compare with peripheral venous blood. In the testicles, the lactate produced by the sertoli cells through the glycolysis pathway provides most of the energy needed for spermatogenesis, the reduction of lactate will affect spermatogenesis. The objective of this study was to investigate the mechanism of this abnormal energy metabolism phenomenon in varicocele.

Methods

In this study, we collected the testicular tissue from patients with varicocele, the glycolysis related proteins PHGDH was identified by iTRAQ proteomics technology. Experimental rat varicocele model was constructed according to our new clip technique, the mRNA and protein expression levels of PHGDH were examined with qRT-PCR and Western blotting. We constructed a sertoli cell of PHGDH down-regulation model, and then detected the glucose consumption, LDH activities and lactate production in the sertoli cells. Western blot was conducted to investigate the effects of PHGDH on the expression of phosphoserine phosphatase (PSPH) and Pyruvate kinase M2 (PKM2). Flow cytometry was used to detect the cell apoptosis and cell cycle in sertoli cells.

Results

The results showed that testicular protein PHGDH was down-regulated in patients with varicocele and in experimental rat varicocele model. Down-regulation of PHGDH in sertoli cells significantly decreased the glucose consumption, LDH activities and lactate production in the sertoli cells, indicating that the low expression of PHGDH ultimately led to a decrease in lactate production by affecting the glycolysis. The Western blot results showed that the down-regulation of PHGDH significantly reduced the expression of pathway protein PSPH and PKM2, leading to the reduction of lactate production. Moreover, PHGDH knockdown can promote apoptosis and inhibit cell cycle to affect cell growth.

Conclusions

Overall, we conformed that varicocele lead to the decreasing of testis lactate production. Down-regulation of PHGDH in sertoli cells may mediate the process of abnormal glucose metabolism. Our study provide new insight into the mechanisms underlying metabolism-associated male infertility and suggests a novel therapeutic target for male infertility.
The deubiquitinase USP22 regulates PD-L1 degradation in human cancer cells
Authors: Wang Yu , Sun Qingguo , Mu Ning , Sun Xiaoyang , Wang Yingying , Fan Songqing , Su Ling , Liu Xiangguo
Published: July 2020

Background

Many cancers evade immune surveillance by overexpressing PD-L1. PD-L1 interacted with its receptor PD-1, resulting in reduction of T cell proliferation and activation and thereafter cancer cell death mediated by T-lymphocyte. Understanding the mechanisms that regulate PD-L1 was of vital importance for immune checkpoint blockade therapy (ICBT).

Methods

Human non-small cell lung cancer cells and 293FT cells were used to investigate the function of USP22 upon PD-L1 and CSN5 by WB, Immunoprecipitation, Immunofluorescence and Flow cytometry analysis. B16-F10 cells were used to explore the role of USP22 on tumorigenesis and T cell cytotoxicity. The relationship between USP22 and PD-L1 expression was investigated by Immunohistochemistry analysis in human non-small cell lung cancer samples.

Results

Our data showed that USP22 interacted with PD-L1 and promoted its stability. USP22 deubiquitinated PD-L1 and inhibited its proteasome degradation. Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination. Either USP22 or CSN5 could facilitate the interaction of PD-L1 with the other one. Furthermore, USP22 removed K6, K11, K27, K29, K33 and K63-linked ubiquitin chain of both CSN5 and PD-L1. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples.

Conclusions

Here, we suggested that USP22 is a new regulator for PD-L1. On the one hand, USP22 could directly regulate PD-L1 stability through deubiquitination. On the other hand, USP22 regulated PD-L1 protein level through USP22-CSN5-PD-L1 axis. In addition, USP22 depletion inhibited tumorigenesis and promoted T cell cytotoxicity. Besides, USP22 expression positively correlated with PD-L1 expression in human non-small cell lung cancer samples. Together, we identified a new regulator of PD-L1 and characterized the important role of USP22 in PD-L1 mediated immune evasion. Targeting USP22 might be a new solution to ICBT.

Graphical abstract
Radiotherapy for lentigo maligna and lentigo maligna melanoma – a systematic review
Authors: Hendrickx Alexandra , Cozzio Antonio , Plasswilm Ludwig , Panje Cédric M.
Published: July 2020

Lentigo maligna (LM) is the most common subtype of in situ melanoma und occurs frequently in the sun-exposed head and neck region in elderly patients. The therapeutic “gold standard” is surgical excision, as there is the risk of progression to invasive (lentigo maligna) melanoma (LMM). However, surgery is not feasible in certain patients due to age, comorbidities or patient preference. Radiotherapy using Grenz rays or superficial X-rays has been established as non-invasive alternative for the treatment of LM and LMM. We performed a systematic literature search of MEDLINE and Embase databases in September 2019 and identified 14 patient series using radiotherapy for LM or LMM. No prospective trials were found. The 14 studies reported a total of 1243 lesions (1075 LM and 168 LMM) treated with radiotherapy. Local recurrence rates ranged from 0 to 31% and were comparable to surgical series in most of the reports on radiotherapy. Superficial radiotherapy was prescribed in 5–23 fractions with a total dose of 35–57 Gy. Grenz ray therapy was prescribed in 42–160 Gy in 3–13 fractions with single doses up to 20 Gy. Cosmetic results were reported as “good” to “excellent” for the majority of patients.

In conclusion, the available low-level evidence suggests that radiotherapy may be a safe and effective treatment for LM and LMM. Data from prospective trials such as the phase 3 RADICAL trial are needed to confirm these promising findings and to compare radiotherapy to other non-surgical therapies and to surgery.
Neurofibromatosis I and multiple sclerosis
Authors: Bergqvist Christina , Hemery François , Ferkal Salah , Wolkenstein Pierre
Published: July 2020

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant genetic disorders with a birth incidence as high as 1:2000. It is caused by mutations in the NF1 gene on chromosome 17 which encodes neurofibromin, a regulator of neuronal differentiation. While NF1 individuals are predisposed to develop benign and malignant nervous system tumors, various non-tumoral neurological conditions including multiple sclerosis (MS) have also been reported to occur more frequently in NF1. The number of epidemiologic studies on MS in NF1 individuals is very limited. The aim of this study was to determine the estimated population proportion of MS in NF1 patients followed in our Referral Centre for Neurofibromatosis using the Informatics for Integrated Biology and the Bedside (i2b2) platform to extract information from the hospital’s electronic health records. We found a total 1507 patients with confirmed NF1, aged 18 years (y) and above (mean age 39.2y, range 18-88y; 57% women). Five NF1 individuals were found to have MS, yielding an estimated population proportion of 3.3 per 1000 (0.0033, 95% Confidence Interval 0.0014–0.0077). The median age at diagnosis was 45 y (range 28–49 y). Three patients had relapsing-remitting MS and two patients had secondary progressive MS. Patients with NF1 were found to be twice more likely to develop MS than the general population in France (odds ratio 2.2), however this result was not statistically significant (95% Confidence Interval 0.91–5.29). Our results show that patients with NF1 might have a slight increased tendency to develop MS; however, due to the small sample size of our study, the results may not be sufficiently powered to detect this rare association. Large-scale epidemiological studies based on nationwide datasets are needed to confirm our findings. These findings further emphasize the need for a focused follow-up of patients with NF1, as early detection and management of MS can prevent further neurological disability.
Multiplex HPV RNA in situ hybridization/p16 immunohistochemistry: a novel approach to detect papillomavirus in HPV-related cancers. A novel multiplex ISH/IHC assay to detect HPV
Authors: Zito Marino Federica , Ronchi Andrea , Stilo Marianna , Cozzolino Immacolata , La Mantia Elvira , Colacurci Nicola , Colella Giuseppe , Franco Renato
Published: July 2020

Background

High-risk human papillomavirus (HR-HPV) is notoriously associated with tumor progression in a broad spectrum of malignancies. Detection of HR-HPV is clinically important in the management of HPV-related carcinomas, particularly in cervical cancer and oropharyngeal squamous cell carcinoma (OPSCC). Several methods for HPV detection are currently available including Polymerase chain reaction (PCR)-based techniques, DNA in situ hybridization (ISH), RNA ISH, and p16 immunohistochemistry (IHC). Currently, the guidelines for HPV detection in cervical carcinoma are available, while no clear consensus has not yet been reached on the gold standard for HPV testing in OPSCC. Multimodality testing could help to reliably identify patients with transcriptionally active high-risk HPV-positive.

Methods

We propose a multiplex approach carrying out HPV RNA ISH and p16 IHC on the same slide to detect simultaneously HPV E6/E7 transcripts and p16INK4a overexpression. We tested this assay in two different series one of the cervical cancers with p16-positive, as control, and the other of oropharyngeal squamous cell carcinomas with blind p16 status.

Results

The multiplex HPV RNA ISH /p16 IHC results in the series both of the cervical cancers and the oral-oropharyngeal cancers were fully concordant with the previous results achieved through the classic p16 IHC and HPV RNA scope carried out on two different slides.

Conclusions

Our results suggesting several advantages of this technical approach, namely an easy interpretation fully in the light field, the feasibility in formalin-fixed paraffin-embedded tissue sections, complete automation and a potential wide spreadable for routine testing in several clinical laboratories.
The association of partial pressures of oxygen and carbon dioxide with neurological outcome after out-of-hospital cardiac arrest: an explorative International Cardiac Arrest Registry 2.0 study
Authors: Ebner Florian , Riker Richard R. , Haxhija Zana , Seder David B. , May Teresa L. , Ullén Susann , Stammet Pascal , Hirsch Karen , Forsberg Sune , Dupont Allison , Friberg Hans , McPherson John A. , Søreide Eldar , Dankiewicz Josef , Cronberg Tobias , Nielsen Niklas
Published: July 2020

Background

Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting.

Methods

Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 < 8.0 kPa), hypercapnemia (PaCO2 > 6.7 kPa) and hypocapnemia (PaCO2 < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2 > 40 kPa with PaCO2 < 4.0 kPa and PaO2 8.0–40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5) was used as outcome measure.

Results

Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P = 0.13–0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P = 0.11–0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates.

Conclusions

Exposure to extreme PaO2 or PaCO2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.
Abscess of the clivus in an adolescent with complicated acute rhinosinusitis: a case report
Authors: Solimeno Lorenzo , Torretta Sara , Marchisio Paola , Iofrida Elisabetta , Bosis Samantha , Tagliabue Claudia , Di Pietro Giada Maria , Pignataro Lorenzo , Guastella Claudio
Published: July 2020

Background

Complications of acute sinusitis affecting multiple sites are very uncommon, and generally develop for a delayed diagnosis of the primary infection, with possible severe and life-threatening evolution. Patients can have variable presentations according to the site and extent of the infection. Multiple forms generally include the coexistence of orbital manifestations and intracranial infections. We here present a case with unusual multiple sites locations (i.e.: intraorbital intraconic abscess, sigmoid sinus thrombosis, preclival abscess, multiple splanchnocranium osteomyelitic processes).

Case presentation

A 13-year-old male presented at our hospital with right progressive orbital oedema with eyesight worsening and signs of meningitis. Computed tomography and magnetic resonance (MRI) demonstrated right intraorbital intraconic abscess, left sphenoidal sinusitis, transverse and sigmoid sinus thrombosis. Ophthalmologic evaluation documented a right optic nerve sufferance. Endoscopic and superior right trans-palpebral surgical decompression was performed, and the abscess was drained. Microbiological analysis revealed the presence of multi-sensitive Streptococcus Intermedius. Subsequent prolonged antibiotic and anti-thrombotic treatments were started. In the following two-weeks the sinusal and ophthalmologic clinical conditions improved, whereas the patients complained of mild to moderate cervical pain and suffered from intermittent pyrexia. Control MRI documented clival abscess extending up to preclival soft tissues posterior to the nasopharynx, associated with mandible osteomyelitis, occipital condyles and anterior part of the temporal bone hyper intensity. Endoscopic trans-nasal surgical approach to the clival compartment with neurosurgery navigation-guided achieved preclival abscess drainage. Complete clinical and radiological recovery was achieved after 45 days of medical treatment.

Conclusions

Multiple sites complicated rhinosinusitis is uncommon, and its management is challenging. A proper history and thorough clinical examination along with a radiological evaluation are key factors in the final diagnosis of patients with complicated multiple sites acute rhinosinusitis. A quick multidisciplinary approach is always necessary to avoid unwanted life-threatening complications.
Somalier: rapid relatedness estimation for cancer and germline studies using efficient genome sketches
Authors: Pedersen Brent S. , Bhetariya Preetida J. , Brown Joe , Kravitz Stephanie N. , Marth Gabor , Jensen Randy L. , Bronner Mary P. , Underhill Hunter R. , Quinlan Aaron R.
Published: July 2020

Background

When interpreting sequencing data from multiple spatial or longitudinal biopsies, detecting sample mix-ups is essential, yet more difficult than in studies of germline variation. In most genomic studies of tumors, genetic variation is detected through pairwise comparisons of the tumor and a matched normal tissue from the sample donor. In many cases, only somatic variants are reported, which hinders the use of existing tools that detect sample swaps solely based on genotypes of inherited variants. To address this problem, we have developed Somalier, a tool that operates directly on alignments and does not require jointly called germline variants. Instead, Somalier extracts a small sketch of informative genetic variation for each sample. Sketches from hundreds of germline or somatic samples can then be compared in under a second, making Somalier a useful tool for measuring relatedness in large cohorts. Somalier produces both text output and an interactive visual report that facilitates the detection and correction of sample swaps using multiple relatedness metrics.

Results

We introduce the tool and demonstrate its utility on a cohort of five glioma samples each with a normal, tumor, and cell-free DNA sample. Applying Somalier to high-coverage sequence data from the 1000 Genomes Project also identifies several related samples. We also demonstrate that it can distinguish pairs of whole-genome and RNA-seq samples from the same individuals in the Genotype-Tissue Expression (GTEx) project.

Conclusions

Somalier is a tool that can rapidly evaluate relatedness from sequencing data. It can be applied to diverse sequencing data types and genome builds and is available under an MIT license atgithub.com/brentp/somalier.
Lower serum chromogranin B level is associated with type 1 diabetes and with type 2 diabetes patients with intensive conservative insulin treatment
Authors: Herold Zoltan , Herold Magdolna , Rosta Klara , Doleschall Marton , Somogyi Aniko
Published: July 2020

Background

Chromogranin B (CgB) plays an important role in the physiological insulin secretion of pancreatic beta cells. Serum CgB levels were investigated in type 1 and type 2 diabetes patients in a cross-sectional study.

Methods

An observational cross-sectional study was performed with the inclusion of 94 control subjects, 100 type 1 and 100 type 2 diabetes patients, at the Metabolic Outpatient Clinic of the Department of Internal Medicine and Hematology, Semmelweis University. Serum CgB levels were measured with enzyme-linked immunosorbent assay.

Results

Serum CgB level was lower in type 1 diabetes patients than in matched control subjects (p = 0.0241), while they were equal in type 2 diabetes patients and controls (p = 0.1698). The subgroup of type 2 diabetes patients who received intensive conservative insulin treatment had significantly lower CgB levels compared to those with other regimens of antidiabetic therapies (p = 0.0283).

Conclusion

The lower serum CgB levels in the patients with type 1 diabetes and the type 2 diabetes patients with progressed disease stage suggested that the CgB production might be decreased due to the beta cell destruction and depletion.
On-line virtual patient learning: a pilot study of a new modality in antimicrobial stewardship education for pediatric residents
Authors: Alshengeti Amer , Slayter Kathryn , Black Emily , Top Karina
Published: July 2020

Objectives

Our objective was to develop and validate a virtual patient (VP) learning module to educate pediatric residents about antimicrobial stewardship (AMS) principles. A VP module on complicated pneumonia was developed by experts in AMS and pediatric infectious diseases using the online platform DecisionSim™. Decision points were based on AMS principles (diagnosis, antimicrobial selection, dosing, de-escalation, route, duration). Pediatric residents in all training levels at a tertiary pediatric hospital were recruited to test the VP module. Knowledge was assessed via a multiple choice questionnaire. Mean knowledge scores were compared before, after, and 4 months after completing the module using Generalized Linear Mixed Repeated Measures (RM) Analysis. Resident satisfaction was assessed using a validated questionnaire.

Results

Seven of 24 pediatric residents (Years 1–4) completed the VP module and pre- and post-module questionnaires. Mean knowledge scores before, immediately after and 4 months after the module were 58.2%, 66.6%, and 71.6%, respectively. The change in knowledge across time was significant (p < 0.001). Residents were satisfied with the module as an AMS learning strategy.
Defeating data hiding in social networks using generative adversarial network
Authors: Wang Huaqi , Qian Zhenxing , Feng Guorui , Zhang Xinpeng
Published: July 2020

As a large number of images are transmitted through social networks every moment, terrorists may hide data into images to convey secret data. Various types of images are mixed up in the social networks, and it is difficult for the servers of social networks to detect whether the images are clean. To prevent the illegal communication, this paper proposes a method of defeating data hiding by removing the secret data without impacting the original media content. The method separates the clean images from illegal images using the generative adversarial network (GAN), in which a deep residual network is used as a generator. Therefore, hidden data can be removed and the quality of the processed images can be well maintained. Experimental results show that the proposed method can prevent secret transmission effectively and preserve the processed images with high quality.
Context-aware auction solution of cooperative fish market monitoring system for intelligent user
Authors: Seo Yeong-Seok , Huh Jun-Ho
Published: July 2020

This study proposes a context-aware auction solution suitable for the intelligent user. The solution informs the most reasonable prices for brokers after considering the size of each species of the catch along with other information and their effects on the fish price. This solution is expected to improve the safety of the catch and increase the competitiveness of auction sites by introducing a digitalized auction system to replace the traditional analog system which could be unsanitary sometimes. The solution’s Unified Modeling Language has been developed with Java Android and the data obtained from the proposed solution is useful in simplifying the bidding process, avoiding over-heated bidding, or stabilizing the fish prices for consumers in the distribution process starting from a broker, distributor and then to consumers. Such a simplified procedure will be able to maintain the freshness of the catch and strengthen the food safety as well as the competitiveness of auction sites, assisting brokers who often experience some difficulties in making a decision on the bidding price due to many variables. This study has focused on the new paradigms, software, middleware and systems for intelligent user. Thus, cost reduction was considered mainly in terms of software engineering. The proposed system is to be supplied with a price 30% less than the existing systems.
Evaluation of antihypertensive polyphenols of barley (Hordeum vulgare L.) seedlings via their effects on angiotensin-converting enzyme (ACE) inhibition
Authors: Ra Ji-Eun , Woo So-Yeun , Jin Hui , Lee Mi Ja , Kim Hyun Young , Ham Hyeonmi , Chung Ill-Min , Seo Woo Duck
Published: July 2020

Angiotensin-converting enzyme (ACE) is an important therapeutic target in the regulation of high blood pressure. This study was conducted to investigate the alterations in blood pressure associated with ACE inhibition activity of the polyphenols (1–10), including 3-O-feruloylquinic acid (1), lutonarin (2), saponarin (3), isoorientin (4), orientin (5), isovitexin (6), isoorientin-7-O-[6-sinapoyl]-glucoside (7), isoorientin-7-O-[6-feruloyl]-glucoside (8), isovitexin-7-O-[6-sinapoyl]-glucoside (9), and isovitexin-7-O-[6-feruloyl]-glucoside (10), isolated from barley seedlings (BS). All the isolated polyphenols exhibited comparable IC50 values of ACE inhibition activity (7.3–43.8 µM) with quercetin (25.2 ± 0.2 µM) as a positive control, and their inhibition kinetic models were identified as noncompetitive inhibition. Especially, compound 4 was revealed to be an outstanding ACE inhibitor (IC50 = 7.3 ± 0.1 µM, Ki = 6.6 ± 0.1 µM). Based on the compound structure–activity relationships, the free hydroxyl groups of flavone-moieties and glucose connections at the A ring of the flavone moieties were important factors for inhibition of ACE. The alcohol extract of BS also demonstrated potent ACE inhibition activity (66.5% ± 2.2% at 5000 µg mL−1). The polyphenols from BS had strong inhibitory activity on ACE and this study results suggest that BS can be used as an effective blood pressure regulator through ACE inhibition.
Morphological variation in two sigmodontine rodents along the mainland and the Fuegian archipelago in Chilean southern Patagonia
Authors: Valladares-Gómez Alejandro , Huenumilla-Linares Marcela , Rodríguez-Serrano Enrique , Hernández Cristián E. , Palma R. Eduardo
Published: July 2020

Background

Analysis of morphological variation in archipelagos has been essential to understand the evolution of terrestrial vertebrates. In particular, these natural scenarios allow to assess morphological changes experienced by insular fauna compared to their mainland counterparts. In mammals, morphological changes of insular forms have been observed in size and shape of body and cranial traits. The southern Patagonia of Chile represents a unique scenario to analyze morphological variation in two of the most widely distributed small rodents along western southern South America: Abrothrix olivacea and Oligoryzomys longicaudatus.

Methods

We applied linear and three-dimensional geometric morphometric tools to analyze the variation in cranial morphology of A. olivacea (N = 80) and O. longicaudatus (N = 49). Sampled localities were distributed in the mainland and islands of the Fuegian archipelago in Chilean Patagonia. Standard multivariate methods, as Principal Components Analysis, and Logistic Regression models were carried out to evaluate differences in size and shape of crania.

Results

We detected higher levels of morphological variation in the crania of A. olivacea if compared to O. longicaudatus. The variation was associated to cranial size instead of shape.

We observed significant differences between insular and mainland individuals in A. olivacea, being the cranium size of this species significantly bigger on islands. Indeed, specimens of A. olivacea from “Isla Wellington”, exhibited the higher increment in cranium size compared to any other mainland and insular site sampled for this species. In contrast, insular and mainland forms of O. longicaudatus did not show significant differences in cranial morphology.

Conclusions

We suggest that the patterns of morphological variation observed in these two small rodents along Patagonia, could be explained in terms of the historical biogeography of the region, and the different ecological features of the studied species.
Does solar irradiation drive community assembly of vulture plumage microbiotas?
Authors: Graves Gary R. , Matterson Kenan O. , Milensky Christopher M. , Schmidt Brian K. , O’Mahoney Michael J. V. , Drovetski Sergei V.
Published: July 2020

Background

Stereotyped sunning behaviour in birds has been hypothesized to inhibit keratin-degrading bacteria but there is little evidence that solar irradiation affects community assembly and abundance of plumage microbiota. The monophyletic New World vultures (Cathartiformes) are renowned for scavenging vertebrate carrion, spread-wing sunning at roosts, and thermal soaring. Few avian species experience greater exposure to solar irradiation. We used 16S rRNA sequencing to investigate the plumage microbiota of wild individuals of five sympatric species of vultures in Guyana.

Results

The exceptionally diverse plumage microbiotas (631 genera of Bacteria and Archaea) were numerically dominated by bacterial genera resistant to ultraviolet (UV) light, desiccation, and high ambient temperatures, and genera known for forming desiccation-resistant endospores (phylum Firmicutes, order Clostridiales). The extremophile genera Deinococcus (phylum Deinococcus-Thermus) and Hymenobacter (phylum, Bacteroidetes), rare in vertebrate gut microbiotas, accounted for 9.1% of 2.7 million sequences (CSS normalized and log2 transformed). Five bacterial genera known to exhibit strong keratinolytic capacities in vitro (Bacillus, Enterococcus, Pseudomonas, Staphylococcus, and Streptomyces) were less abundant (totaling 4%) in vulture plumage.

Conclusions

Bacterial rank-abundance profiles from melanized vulture plumage have no known analog in the integumentary systems of terrestrial vertebrates. The prominence of UV-resistant extremophiles suggests that solar irradiation may play a significant role in the assembly of vulture plumage microbiotas. Our results highlight the need for controlled in vivo experiments to test the effects of UV on microbial communities of avian plumage.
Fourteen Recommendations to Create a More Inclusive Environment for LGBTQ+ Individuals in Academic Biology
Authors: Cooper Katelyn M. , Auerbach Anna Jo J. , Bader Jordan D. , Beadles-Bohling Amy S. , Brashears Jacqueline A. , Cline Erica , Eddy Sarah L. , Elliott Deanna B. , Farley Elijah , Fuselier Linda , Heinz Heather M. , Irving Madison , Josek Tanya , Lane A. Kelly , Lo Stanley M. , Maloy Jeffrey , Nugent Michelle , Offerdahl Erika , Palacios-Moreno Juan , Ramos Jorge , Reid Joshua W. , Sparks Rachel A. , Waring Ashley L. , Wilton Mike , Gormally Cara , Brownell Sara E.
Published: July 2020

This essay highlights recommendations to make academic biology more inclusive of LGBTQ+ individuals. These recommendations are drawn from the literature and the collective experience of the 26-member author team.
BMP signaling is essential for sustaining proximo-distal progression in regenerating axolotl limbs
Authors: Vincent Etienne , Villiard Eric , Sader Fadi , Dhakal Sabin , Kwok Benjamin H. , Roy Stéphane
Published: July 2020

Amputation of a salamander limb triggers a regeneration process that is perfect. A limited number of genes have been studied in this context and even fewer have been analyzed functionally. In this work, we use the BMP signaling inhibitor LDN193189 on Ambystoma mexicanum to explore the role of BMPs in regeneration. We find that BMP signaling is required for proper expression of various patterning genes and that its inhibition causes major defects in the regenerated limbs. Fgf8 is downregulated when BMP signaling is blocked, but ectopic injection of either human or axolotl protein did not rescue the defects. By administering LDN193189 treatments at different time points during regeneration, we show clearly that limb regeneration progresses in a proximal to distal fashion. This demonstrates that BMPs play a major role in patterning of regenerated limbs and that regeneration is a progressive process like development.
O risco de informação assimétrica sobre a liquidez dos contratos futuros de commodities agrícolas
Authors: Ribeiro João Eduardo , Souza Antônio Artur de , Moraes Eduardo de Abreu
Published: July 2020

O objetivo deste estudo é analisar o efeito do risco de assimetria informacional na liquidez dos contratos futuros de commodities agrícolas negociados pela B3. Para tanto, escolheu-se como amostra as negociações intradiárias das commodities Boi Gordo, Café Arábica, Milho e Soja, no período de 01 de dezembro de 2018 a 30 de novembro de 2019. A analise foi realizada por meio de um modelo de dados em painel, utilizando-se como proxy para liquidez, o spread, para a probabilidade de presença de assimetria informacional nas negociações a VPIN e, como variáveis de controle, o número de negócios, o volume negociado e a volatilidade. Pelo modelo estimado, demostrou-se que as variáveis consideradas são capazes de explicar 43,08% da variação do spread. Além disso, os resultados mostraram uma relação inversa entre o risco de se negociar com assimetria informacional e a liquidez de mercado,  divergindo dos resultados encontrados na literatura nacional e internacional.
Recent advances in understanding and management of bronchopulmonary dysplasia
Authors: Sahni Mitali , Bhandari Vineet
Published: July 2020

In the current era, the survival of extremely low-birth-weight infants has increased considerably because of new advances in technology; however, these infants often develop chronic dysfunction of the lung, which is called bronchopulmonary dysplasia (BPD). BPD remains an important cause of neonatal mortality and morbidity despite newer and gentler modes of ventilation. BPD results from the exposure of immature lungs to various antenatal and postnatal factors that lead to an impairment in lung development and aberrant growth of lung parenchyma and vasculature. However, we still struggle with a uniform definition for BPD that can help predict various short- and long-term pulmonary outcomes. With new research, our understanding of the pathobiology of this disease has evolved, and many new mechanisms of lung injury and repair are now known. By utilizing the novel ‘omic’ approaches in BPD, we have now identified various factors in the disease process that may act as novel therapeutic targets in the future. New investigational agents being explored for the management and prevention of BPD include mesenchymal stem cell therapy and insulin-like growth factor 1. Despite this, many questions remain unanswered and require further research to improve the outcomes of premature infants with BPD.
Somnological findings based on the Körmend Growth Study (2008) data (Hungary)
Authors: Buda Botond L. , Marksz Lilla , Tóth Gábor A.
Published: July 2020

In 1958, a series of tests repeated every ten years, which is unique worldwide, was launched in Körmend, with the primary goal of assessing more than 20 different body size characteristics, constitution, and development of healthy children aged 3–18. The secular trend phenomenon was proved for the first time in Hungary in this study. A clear correlation between physiological sleeping and sleeping disorders compared to changes in body composition has been shown, which led to the inclusion of a sleep questionnaire study in 2008. The present study aims to analyze a part of the sleep questionnaires received in 2008. The aim of this study was to investigate the presence and frequency of growth pain, restless leg syndrome (RLS) and anaemia, and the associations between these parameters. According to the results, the incidence of growth pains was found to be higher than in international data. In many aspects this difference was confirmed by the present study, however, there were also contradictory, significantly detectable differences, the causes of which require further investigation. Due to the limitations of the questionnaire, many errors may occur. Other studies have shown strong genetic determinations for RLS; however, our results do not seem to confirm this. This may be due to the high latency of RLS and the inaccurate filling of the questionnaires as well. The results of our study showed that, in iron-deficient children, the incidence of RLS is an order of magnitude higher than in the general population.
Evaluation of innervation in cleft affected oral mucosa
Authors: Rimdenoka Olga , Pilmane Māra
Published: July 2020

Orofacial clefts are one of the most common pathologies present at birth. The aim of the study was to evaluate the presence of PGP 9.5, substance P, VIP, CGRP, myelin and NFG in cleft affected mucosa of alveolar process, soft and hard palate, vomer and lip.

Methods. Orofacial cleft affected mucosa tissue samples were obtained during surgical cleft correction from 21 children aged from 2 months to 9 years and 10 months. Prepared tissue sections were stained by immunohistochemistry for PGP 9.5, substance P, VIP, CGRP, myelin and NGF. The intensity of staining was graded semiquantitatively.

Results. Mostly moderate number and numerous PGP 9.5, substance P, VIP, CGRP, myelin and NGF-containing nerve fibres and nerve fibre bundles and CGRP and NGF positive keratinocytes were detected. The most immunoreactive for PGP 9.5, myelin and NGF were nerve fibres, nerve fibre bundles and keratinocytes in lip mucosa tissue samples. Typically, PGP 9.5-containing nerve fibres were detected in subepithelium close to basal lamina, near blood vessels; thin PGP 9.5 positive nerve fibres were also observed between keratinocytes. Immunoreactivity of CGRP was higher than of substance P in nerve fibres and nerve fibre bundles. Statistically significant positive correlation was observed between all markers in subepithelium of all tissue samples.

Conclusions. The proved statistically significant strong inter-correlation and the number of general neuropeptide-containing innervation (PGP 9.5), sensory nerves (CGRP and substance P), and parasympathetic nerves (VIP) is similar in orofacial cleft affected oral mucosa to such described in scientific literature healthy oral mucosa, except the alveolar process covering mucosa where the above innervation varies.

Very strong and strong statistically significant positive correlations between the number of PGP 9.5, substance P, CGRP and VIP positive structures on the one hand, and NGF and myelin, on the other hand, indicate a connection between quality markers and common neuropeptide-containing, sensory and parasympathetic innervation in cleft affected oral tissue.

The number of PGP 9.5, NGF and myelin immunoreactive neuronal structures in lip mucosa is higher than in the alveolar process, soft and hard palate and vomer mucosa, suggesting the significance of qualitative common innervation in this organ even in the cleft affected case.
Age-related variability of anthropometric indicators in urban school students – Belarusians and descendants of interethnic marriages
Authors: Salivon Inessa , Polina Natalya
Published: July 2020

In the 1990s – early 2000s, anthropometric indicators of school students of three age groups (8, 13 and 17 years) were studied in several cities of Belarus. In total 2088 students were examined. The material was distributed into sex and age cohorts taking into account the ethnic structure – Belarusians (both parents are Belarusians) and genetically more heterogeneous descendants of interethnic marriages (DIM) where one of the parents is Belarusian, and the other is Russian, Ukrainian or Polish (Slav).

In all sex and age samples, the number of students in Belarusians cohorts was almost twice higher than the number of DIM, which corresponds to their real proportion in the urban population of Belarus.

The sex and age dynamics of average values of body height and weight, body mass index (BMI) and chest circumference, as well as the distribution of body types (somatotypes) in groups of urban school students in Belarus were observed.

The differences between Belarusians and DIM in the studied anthropometric characteristics in all sex and age groups were insignificant. The phenomena of heterosis in the first generation of DIM were more clearly manifested only by the age of 17 among young men, who were 1.7 cm taller than their Belarusian peers, with correspondingly slightly higher values of body weight and chest circumference. In comparison with Belarusians, DIM girls of this age had a weak shift in all indicators of physical development towards lower average values.

The average values of the BMI, which increase during puberty, reflect the tendency of weakly expressed gracilization of the physique of the male and especially female body in DIM compared to their Belarusian peers.

The tendency to leptosomization (skeletal gracialization) and body asthenization was shown by the intragroup distribution of somatotypes among descendants of uninational marriages – Belarusians – and even more among DIM.

Intersex differences in morphogenesis during puberty were manifested in greater asthenization of the physique against the background of gracilization of the skeleton of the female body compared to the male.
Secular changes in anthropometric measurements of schoolchildren in Ankara, Turkey (1950–2017)
Authors: Özer Başak Koca , Özdemir Ayşegül
Published: July 2020

This study aimed to examine the physical growth of Turkish children and determine secular changes in their height and other anthropometric measurements since 1950. For this purpose, three cross-sectional surveys of a total of 4,902 healthy schoolchildren from Ankara (2,490 boys and 2,412 girls) between the ages of 6 and 17 years conducted in 1950, 2005 and 2017 were studied. Body height and sitting height were measured, centile curves were constructed using the LMS method, and sitting height/height ratio was calculated. The results of this study demonstrated positive secular changes in height and sitting height. The increasing rate of height for boys was approximately 2.5 cm/decade for their respective pubertal ages, whereas for girls, the rate was approximately 1.9 cm/decade at ages 9, 10 and 12; however, at the age of 11, the increment in girls was over 2 cm/decade. Data sets presented sexual differences at most ages, arising due to a difference in response to environmental and socio-economic conditions. However, due to the socio-economic fluctuations in Turkey, secular increase was not comparable to the increase experienced within developed countries; therefore a continuation of this secular increase can be expected in the near future.
The Effects of Search Advertising on Competitors: An Experiment Before a Merger
Authors: Golden Joseph , Horton John Joseph
Published: July 2020

We report the results of an experiment in which a company, Firm Vary, temporarily suspended its sponsored search advertising campaign on Google in randomly selected advertising markets in the United States. By shutting off its ads, Firm Vary lost customers, but only 63% as many as a nonexperimental estimate would have suggested. Following the experiment, Firm Vary merged with its closest competitor, Firm Fixed. Using combined data from both companies, the experiment revealed that spillover effects of Firm Vary’s search advertising on Firm Fixed’s business and its marketing campaigns were surprisingly small, even in the market for Firm Vary’s brand name as a keyword search term, where the two firms were effectively duopsonists.

This paper was accepted by Eric Anderson, marketing.
Quality and inequality in the NHS
Authors: Morris Jessica , Scobie Sarah
Published: July 2020

The NHS was founded on the principle that care should be based on need, not the ability to pay, and the Long Term Plan aims to reduce health inequalities. This article explores how inequalities in the quality of care between the most and least deprived groups have changed over the last decade, and what implications this has on the endeavour to reduce unwarranted variation in care.
Community rehabilitation teams and COVID-19: rehabilitation demand and innovation in delivery
Authors: Lavin Nicole , Farrar Elizabeth
Published: July 2020

The impact of the coronavirus on the NHS has been well publicised and the country has locked down to protect it. Acute hospital services needed additional resources and support leading up to the peak of the virus but, as the number of hospital admissions reduces, demand for community rehabilitation services will increase.
Outpatient services post-COVID-19: a paradigm drift or shift?
Authors: Edwards Lisa , Millington Paul , Gill Peter , Millington Jacqueline
Published: July 2020

This commentary describes how the coronavirus crisis has altered working practices in NHS outpatient services in the UK, and examines the opportunities and challenges presented by this pandemic.