bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplays between Enterovirus A71 and the innate immune system
Authors: Chen Kuan-Ru , Ling Pin 
Published: December 2019

AbstractEnterovirus A71 (EV-A71) is a growing threat to public health, particularly in the Asia-Pacific region. EV-A71 infection is most prevalent in infants and children and causes a wide spectrum of clinical complications, including hand-foot-and-mouth disease (HFMD), pulmonary and neurological disorders. The pathogenesis of EV-A71 infection is poorly understood at present. It is likely that viral factors and host immunity, and their interplay, affect the pathogenesis and outcome of EV-A71 infection. The mammalian innate immune system forms the first layer of defense against viral infections and triggers activation of adaptive immunity leading to full protection. In this review, we discuss recent advances in our understanding of the interaction between EV-A71 and the innate immune system. We discuss the role of pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and inflammasomes, in the detection of EV-A71 infection and induction of antiviral immunity. As a counteraction, EV-A71 viral proteins target multiple innate immune pathways to facilitate viral replication in host cells. These novel insights at the virus-host interphase may support the future development of vaccines and therapeutics against EV-A71 infection.
Combined artificial high-silicate medium and LED illumination promote carotenoid accumulation in the marine diatom Phaeodactylum tricornutum
Authors: Yi Zhiqian , Su Yixi , Cherek Paulina , Nelson David R. , Lin Jianping , Rolfsson Ottar , Wu Hua , Salehi-Ashtiani Kourosh , Brynjolfsson Sigurdur , Fu Weiqi 
Published: December 2019

Abstract
Background
Diatoms, which can accumulate large amounts of carotenoids, are a major group of microalgae and the dominant primary producer in marine environments. Phaeodactylum tricornutum, a model diatom species, acquires little silicon for its growth although silicon is known to contribute to gene regulation and play an important role in diatom intracellular metabolism. In this study, we explored the effects of artificial high-silicate medium (i.e. 3.0 mM sodium metasilicate) and LED illumination conditions on the growth rate and pigment accumulation in P. tricornutum, which is the only known species so far that can grow without silicate. It’s well known that light-emitting diodes (LEDs) as novel illuminants are emerging to be superior monochromatic light sources for algal cultivation with defined and efficient red and blue lights.

Results
Firstly, we cultivated P. tricornutum in a synthetic medium supplemented with either 0.3 mM or 3.0 mM silicate. The morphology and size of diatom cells were examined: the proportion of the oval and triradiate cells decreased while the fusiform cells increased with more silicate addition in high-silicate medium; the average length of fusiform cells also slightly changed from 14.33 µm in 0.3 mM silicate medium to 12.20 µm in 3.0 mM silicate medium. Then we cultivated P. tricornutum under various intensities of red light in combination with the two different levels of silicate in the medium. Higher biomass productivity also achieved in 3.0 mM silicate medium than in 0.3 mM silicate medium under red LED light irradiation at 128 μmol/m2/s or higher light intensity. Increasing silicate reversed the down-regulation of fucoxanthin and chlorophyll a under high red-light illumination (i.e. 255 μmol/m2/s). When doubling the light intensity, fucoxanthin content decreased under red light but increased under combined red and blue (50:50) lights while chlorophyll a content reduced under both conditions. Fucoxanthin accumulation and biomass productivity increased with enhanced red and blue (50:50) lights.

Conclusion
High-silicate medium and blue light increased biomass and fucoxanthin production in P. tricornutum under high light conditions and this strategy may be beneficial for large-scale production of fucoxanthin in diatoms.
The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site
Authors: Machin Jonathan M. , Kantsadi Anastassia L. , Vakonakis Ioannis 
Published: December 2019

Abstract
Background
Malaria kills over 400,000 people each year and nearly half the world’s population live in at-risk areas. Progress against malaria has recently stalled, highlighting the need for developing novel therapeutics. The parasite haemoglobin degradation pathway, active in the blood stage of the disease where malaria symptoms and lethality manifest, is a well-established drug target. A key enzyme in this pathway is the papain-type protease falcipain-2.

Methods
The crystallographic structure of falcipain-2 at 3.45 Å resolution was resolved in complex with an (E)-chalcone small-molecule inhibitor. The falcipain-2–(E)-chalcone complex was analysed with reference to previous falcipain complexes and their similarity to human cathepsin proteases.

Results
The (E)-chalcone inhibitor binds falcipain-2 to the rear of the substrate-binding cleft. This is the first structure of a falcipain protease where the rear of the substrate cleft is bound by a small molecule. In this manner, the (E)-chalcone inhibitor mimics interactions observed in protein-based falcipain inhibitors, which can achieve high interaction specificity.

Conclusions
This work informs the search for novel anti-malaria therapeutics that target falcipain-2 by showing the binding site and interactions of the medically privileged (E)-chalcone molecule. Furthermore, this study highlights the possibility of chemically combining the (E)-chalcone molecule with an existing active-site inhibitor of falcipain, which may yield a potent and selective compound for blocking haemoglobin degradation by the malaria parasite.
Role of the microbiome in occurrence, development and treatment of pancreatic cancer
Authors: Wang Yicheng , Yang Gang , You Lei , Yang Jinshou , Feng Mengyu , Qiu Jiangdong , Zhao Fangyu , Liu Yueze , Cao Zhe , Zheng Lianfang , Zhang Taiping , Zhao Yupei 
Published: December 2019

AbstractPancreatic cancer is one of the most lethal malignancies. Recent studies indicated that development of pancreatic cancer may be intimately connected with the microbiome. In this review, we discuss the mechanisms through which microbiomes affect the development of pancreatic cancer, including inflammation and immunomodulation. Potential therapeutic and diagnostic applications of microbiomes are also discussed. For example, microbiomes may serve as diagnostic markers for pancreatic cancer, and may also play an important role in determining the efficacies of treatments such as chemo- and immunotherapies. Future studies will provide additional insights into the various roles of microbiomes in pancreatic cancer.
Kidney and uro-trauma: WSES-AAST guidelines
Authors:   WSES-AAST Expert Panel, Coccolini Federico , Moore Ernest E. , Kluger Yoram , Biffl Walter , Leppaniemi Ari , Matsumura Yosuke , Kim Fernando , Peitzman Andrew B. , Fraga Gustavo P. , Sartelli Massimo , Ansaloni Luca , Augustin Goran , Kirkpatrick Andrew , Abu-Zidan Fikri , Wani Imitiaz , Weber Dieter , Pikoulis Emmanouil , Larrea Martha , Arvieux Catherine , Manchev Vassil , Reva Viktor , Coimbra Raul , Khokha Vladimir , Mefire Alain Chichom , Ordonez Carlos , Chiarugi Massimo , Machado Fernando , Sakakushev Boris , Matsumoto Junichi , Maier Ron , di Carlo Isidoro , Catena Fausto 
Published: December 2019

AbstractRenal and urogenital injuries occur in approximately 10-20% of abdominal trauma in adults and children. Optimal management should take into consideration the anatomic injury, the hemodynamic status, and the associated injuries. The management of urogenital trauma aims to restore homeostasis and normal physiology especially in pediatric patients where non-operative management is considered the gold standard. As with all traumatic conditions, the management of urogenital trauma should be multidisciplinary including urologists, interventional radiologists, and trauma surgeons, as well as emergency and ICU physicians. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and the American Association for the Surgery of Trauma (AAST) kidney and urogenital trauma management guidelines.
eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5′UTR
Authors: Wilczynska Ania , Gillen Sarah L. , Schmidt Tobias , Meijer Hedda A. , Jukes-Jones Rebekah , Langlais Claudia , Kopra Kari , Lu Wei-Ting , Godfrey Jack D. , Hawley Benjamin R. , Hodge Kelly , Zanivan Sara , Cain Kelvin , Le Quesne John , Bushell Martin 
Published: December 2019

AbstractBackgroundRegulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood.ResultsHere, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex. We demonstrate that while DDX6 interacts with Ccr4-Not, its effects in the mechanism are not as pronounced. Through its interaction with the Ccr4-Not complex, eIF4A2 represses mRNAs at translation initiation. We show evidence that native eIF4A2 has similar RNA selectivity to chemically inhibited eIF4A1. eIF4A2 exerts its repressive effect by binding purine-rich motifs which are enriched in the 5′UTR of target mRNAs directly upstream of the AUG start codon.ConclusionsOur data support a model whereby purine motifs towards the 3′ end of the 5′UTR are associated with increased ribosome occupancy and possible uORF activation upon eIF4A2 binding.
The critical role of histology in distinguishing sarcoidosis from common variable immunodeficiency disorder (CVID) in a patient with hypogammaglobulinemia
Authors: Ameratunga Rohan , Ahn Yeri , Tse Dominic , Woon See-Tarn , Pereira Jennifer , McCarthy Sinead , Blacklock Hilary 
Published: December 2019

AbstractBackgroundCommon variable immunodeficiency disorders (CVID) are a rare group of primary immune defects, where the underlying cause is unknown. Approximately 10–20% of patients with typical CVID have a granulomatous variant, which has closely overlapping features with sarcoidosis.Case presentationHere we describe a young man who sequentially developed refractory Evans syndrome, cauda equina syndrome and most recently renal impairment. Following immunosuppression, he has made a recovery from all three life-threatening autoimmune disorders. As the patient was hypogammaglobulinemic for most of the time while on immunosuppression, vaccine challenges and other tests were not possible. Histological features were in keeping with sarcoidosis rather than the granulomatous variant of CVID. In the brief period when immunosuppression was lifted between the cauda equina syndrome and renal impairment, he normalised his immunoglobulins, confirming sarcoidosis rather than CVID was the underlying cause.ConclusionWe discuss diagnostic difficulties distinguishing the two conditions, and the value of histological features in our diagnostic criteria for CVID in identifying sarcoidosis, while the patient was hypogammaglobulinemic. The key message from this case report is that the characteristic histological features of CVID can be very helpful in making (or excluding) the diagnosis, particularly when other tests are not possible.
Soliton solutions to the time-dependent coupled KdV–Burgers’ equation
Authors: Alqahtani Aisha , Kumar Vikas 
Published: December 2019

AbstractIn this article, the authors apply the Lie symmetry approach and the modified $( G'/G )$(G′/G)-expansion method for seeking the solutions of time-dependent coupled KdV–Burgers equation. Using suitable similarity transformations, the time-dependent coupled KdV–Burgers equation is reduced to a system of nonlinear ordinary differential equations. Further, the reduced system of nonlinear ordinary differential equations for the coupled KdV equation is solved with the help of the modified $( G'/G )$(G′/G)-expansion method to obtain soliton solutions which are expressed by hyperbolic functions, trigonometric functions, and rational functions.
Do age-related macular degeneration genes show association with keratoconus?
Authors: Cao Ke , Sahebjada Srujana , Richardson Andrea J. , Baird Paul N. 
Published: December 2019

Abstract
Background
Keratoconus (KC) is a common corneal condition with an unknown gender predominance. Although numerous studies have investigated the genetic component of KC, no specific genes have yet been attributed to the condition. We recently reported posterior segment changes occurring in the eyes of KC patients. However, it is not clear whether these changes are part of KC pathogenesis or reflect changes in anatomical features of the eye manifested by changes at the cornea. Given retinal changes represent the main characteristics observed in age-related macular degeneration (AMD) and that pleiotropy has been demonstrated between different eye diseases, we wished to assess if known AMD associated genes were also associated with KC.

Methods
A total of 248 KC subjects and 366 non-KC (control) subjects were recruited from public and private clinics in Melbourne for this analysis. Nineteen single nucleotide polymorphisms (SNPs) previously associated with AMD, including rs10490924 (ARMS2/HTRA1), rs10737680 (CFH), rs13278062 (TNFRSF10A), rs1864163 (CETP), rs2230199 (C3), rs3130783 (IER3/DDR1), rs334353 (TGFBR1), rs3812111 (COL10A1), rs429608 (C2/CFB), rs4420638 (APOE), rs4698775 (CFI), rs5749482 (TIMP3), rs6795735 (ADAMTS9), rs8017304 (RAD51B), rs8135665 (SLC16A8), rs920915 (LIPC), rs943080 (VEGFA), rs9542236 (B3GALTL) and rs13081855 (COL8A1/FILIP1L), were genotyped in this cohort. Logistic regression was applied to evaluate the association between these SNPs and KC on both genders together, as well as each gender separately. Linear regression was also applied to assess the association between SNPs and corneal curvature. Bonferroni correction was applied to adjust for multiple testing.

Results
Genotyping data were available for 18 SNPs. The SNP, rs6795735 (ADAMTS9) was significantly associated with KC (p = 3.5 × 10− 4) when both genders were assessed, whereas rs5749482 (TIMP3) was only associated in males (p = 7.7 × 10− 4) following Bonferroni multiple correction. However, when the covariates of age and gender were included, the associations became non-significant. In addition, none of the SNPs appeared significant for corneal curvature.

Conclusions
Our study suggested a potential association of rs6795735 in the ADAMTS9 gene and rs5749482 in the TIMP3 gene in KC and that different associations may be gender specific. Overall, SNPs initially identified as associated with AMD following multiple correction may be further impacted by other factors such as age or gender and further studies are needed to resolve this issue.
Nutritional status and Cardiometabolic health among adolescents; findings from southwestern Nigeria
Authors: Adeomi Adeleye Abiodun , Adelusi Iyanuoluwa Odunayo , Adedeji Praise Oluwatooni , Awofeso Adedoyin Esther , Oroleye Olajumoke Omotoyosi , Gbadegesin Doyinfunmi Lydia 
Published: December 2019

Abstract
Background
Obesity has been associated with an increased risk for cardio-metabolic diseases. The prevalence of obesity among adolescents is increasing worldwide, including Nigeria, but only little data exist on the relationship of nutritional status with cardio-metabolic health among adolescents in Nigeria. This study therefore investigated the relationship of nutrition status, raised blood pressure, glucose intolerance and risk for metabolic diseases among adolescents in southwestern Nigeria.

Methods
This was a cross-sectional study conducted among 313 in-school adolescents in Ile-Ife, southwestern Nigeria. The respondents were selected using multi-stage sampling technique, and data were collected using pre-tested structured questionnaires. Anthropometric, blood pressure and random blood glucose measurements were done using standard protocols. Nutritional assessment was done using the World Health Organization (WHO) 2007 reference. Pre-hypertension and hypertension were measured using percentiles for gender, age and height. Analysis was done using IBM SPSS and the level of significance was set at p ≤ 0.05.

Results
The mean age of the respondents was 14.4 ± 2.0 years. The prevalence of overweight and obesity was 10.2%, and it was significantly higher among females (12.5%) than males (7.0%). The prevalence of systolic and diastolic pre-hypertension was 10.9 and 11.5% respectively, while the prevalence for systolic and diastolic hypertension were 14.4 and 8.6% respectively. Using WHtR to assess cardio-metabolic risk, 7.3% of the respondents were at risk. There were statistically significant relationships between BMI, WHtR and blood pressure levels (< 0.05).

Conclusions
The prevalence of overweight/obesity among the adolescents was relatively high, and this was significantly associated with elevated blood pressure and increased risk for cardio-metabolic diseases. There is need for more interest and intervention by stakeholders into the cardio-metabolic health of adolescents in Nigeria.
Efficacy of spinal extension exercise program versus muscle energy technique in treatment of chronic mechanical low back pain
Authors: Fahmy E. , Shaker H. , Ragab W. , Helmy H. , Gaber M. 
Published: December 2019

AbstractBackgroundMechanical low back pain (MLBP) is a major cause of illness and disability, especially in people of working age. People with chronic low back pain often experience anger, fear, anxiety, decrease in physical ability, and inadequacy of role fulfillment.ObjectiveThis study aimed to compare the efficacy of extension exercise program versus muscle energy technique in treating patients with chronic mechanical low back pain.Subjects and methodsForty patients complaining of chronic mechanical low back pain participated in the study. Patients were randomly allocated into two equal groups: group A which received spinal extension exercise program and group B which received muscle energy technique. Treatment sessions were given three times per week for four successive weeks. Patients were assessed before and after treatment using visual analogue scale (VAS), Oswestry Disability Index (ODI), and digital goniometer to assess pain intensity, functional disability, and range of motion (ROM) of lumbar spine respectively.ResultsThere was significant decrease in the scores of pain and functional disability in both groups post-treatment especially in group B. There was significant increase in lumbar range of motion in both groups post-treatment, especially in group A.ConclusionExtension exercise program had better effect on improving lumbar range of motion, whereas muscle energy technique was better in decreasing pain and functional disability in patients with chronic mechanical low back pain.
Insulin Signaling Via Progesterone-Regulated Insulin Receptor Substrate 2 is Critical for Human Uterine Decidualization
Authors: Neff Alison M , Yu Jie , Taylor Robert N , Bagchi Indrani C , Bagchi Milan K 
Published: December 2019

Abstract
Decidualization, the process by which fibroblastic human endometrial stromal cells (HESC) differentiate into secretory decidual cells, is a critical event during the establishment of pregnancy. It is dependent on the steroid hormone progesterone acting through the nuclear progesterone receptor (PR). Previously, we identified insulin receptor substrate 2 (IRS2) as a factor that is directly regulated by PR during decidualization. IRS2 is an adaptor protein that functionally links receptor tyrosine kinases, such as insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R), and their downstream effectors. IRS2 expression was induced in HESC during in vitro decidualization and siRNA-mediated downregulation of IRS2 transcripts resulted in attenuation of this process. Further use of siRNAs targeted to IR or IGF1R transcripts showed that downregulation of IR, but not IGF1R, led to impaired decidualization. Loss of IRS2 transcripts in HESC suppressed phosphorylation of both ERK1/2 and AKT, downstream effectors of insulin signaling, which mediate gene expression associated with decidualization and regulate glucose uptake. Indeed, downregulation of IRS2 resulted in reduced expression and membrane localization of the glucose transporters GLUT1 and GLUT4, resulting in lowered glucose uptake during stromal decidualization. Collectively, these data suggest that the PR-regulated expression of IRS2 is necessary for proper insulin signaling for controlling gene expression and glucose utilization, which critically support the decidualization process to facilitate pregnancy. This study provides new insight into the mechanisms by which steroid hormone signaling intersects with insulin signaling in the uterus during decidualization, which has important implications for pregnancy complications associated with insulin resistance and infertility.
The formation of perianchor fluid associated with various suture anchors used in rotator cuff repair
Authors: Kim Sae H. , Yang Seok H. , Rhee Sung-Min , Lee Kwang J. , Kim Hyong S. , Oh Joo H. 
Published: December 2019

Aims The aim of this study was to compare the osseous reactions elicited by all-suture, polyetheretherketone (PEEK), and two different biodegradable anchors used during rotator cuff repair. Patients and Methods Transosseous-equivalent rotator cuff repair was performed in 73 patients. The patients were divided into two groups, in both of which two different medial-row anchors were used. In group 1, anchor A comprised 30% β-tricalcium phosphate (TCP) + 70% fast-absorbing poly lactic-co-glycolic acid copolymer (85% polylactic acid enantiomers + 15% polyglycolic acid) and anchor B comprised all-sutures. In group 2, anchor C comprised 23% micro β-TCP + 77% polylactic acid enantiomers and anchor D comprised PEEK polymer. There were 37 patients in group 1 and 36 patients in group 2. The presence and severity of fluid collection around anchors and healing of the rotator cuff were assessed using MRI scans, approximately one year postoperatively. The severity of the collection was graded as 0 (no perianchor fluid signal), 1 (minimal perianchor fluid), 2 (local collection of fluid), 3 (fluid collection around the whole length of the anchor but of a diameter less than twice the anchor diameter), or 4 (fluid collection around the whole length of the anchor and of a diameter greater than twice the anchor diameter). Results A perianchor fluid signal was seen in three patients (8.1%) with anchor A, four (10.8%) with anchor B, 15 (41.7%) with anchor C, and 15 (41.7%) with anchor D. The severity of the collection around anchor was grade 2:1:0:0 for anchor A, grade 2:2:0:0 for anchor B, grade 12:2:0:1 for anchor C, and grade 11:3:0:1 for anchor D (grade 1:2:3:4, respectively). The prevalence and severity of fluid formation was not significantly different between anchors A and B, and anchors C and D. However, on intergroup analysis, there were significant differences for the prevalence and severity of fluid formation between anchors in group 1 and group 2. The prevalence of failure to heal was not significant in group 1 (seven, 18.9%) or group 2 (nine, 25.0%). There was no relationship between the presence of perianchor fluid and each type of anchor, and the integrity of the rotator cuff repair, in either group. Conclusion Despite the nonabsorbable nature of all-suture and PEEK anchors, all-suture anchors produced less osseous reaction after rotator cuff repair. In deciding which kind of anchor to use, consideration should be given not only to the strength of the initial fixation, but also to the postoperative biological reaction. Cite this article: Bone Joint J 2019;101-B:1506–1511