bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterior nutcracker syndrome: a case report
Authors: Gozzo Cecilia , Farina Renato , Foti Pietro Valerio , Iannace Francesco Aldo , Conti Andrea , Pennisi Isabella , Santonocito Serafino , Palmucci Stefano , Basile Antonio 
Published: February 2021

Abstract
Background
Posterior nutcracker syndrome is defined by the compression of the left renal vein between the abdominal aorta and a lumbar vertebral body. It can be clinically manifest with intermittent hematuria, gonadal or spermatic reflux resulting in varicocele. Ultrasound is the first-line imaging which require more accurate study with contrast-enhanced computed tomography. Management can be conservative in younger patients with mild hematuria due to the high spontaneous remission rate and invasive with open surgical and endovascular interventions. We describe a very rare case with compression of the left renal vein due to an osteophyte of the spine.

Case presentation
A 62-year-old Caucasic male came to our radiology department for chronic hepatitis B virus (HBV)-related liver disease follow-up and mild scrotal pain. The ultrasound examination revealed a compression of the left retro-aortic renal vein in the aorto-vertebral space caused by an osteophyte. Duplex Doppler ultrasound revealed flow congestion in the left renal vein and renal failure; power Doppler ultrasound showed left varicocele.

Conclusions
Doppler ultrasound is the first-line imaging and allows the detection of all the typical signs of posterior nutcracker: left renal vein stenosis, flow congestion and renal failure. Nutcracker syndrome should be suspected in older patients with left varicocele associated with hematuria. Failure to diagnose and treat these patients could have serious consequences for their health.
Analysis of reaction–diffusion systems where a parameter influences both the reaction terms as well as the boundary
Authors: Acharya A. , Fonseka N. , Shivaji R. 
Published: February 2021

AbstractWe study positive solutions to steady-state reaction–diffusion models of the form $$ \textstyle\begin{cases} -\Delta u=\lambda f(v);\quad\Omega, \\ -\Delta v=\lambda g(u);\quad\Omega, \\ \frac{\partial u}{\partial \eta }+\sqrt{\lambda } u=0;\quad \partial \Omega, \\ \frac{\partial v}{\partial \eta }+\sqrt{\lambda }v=0; \quad\partial \Omega, \end{cases} $$

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. In particular, we extend the results for the single equation case discussed in (Fonseka et al. in J. Math. Anal. Appl. 476(2):480-494, 2019) to the above system.
Prevalence of Schistosoma mansoni infection in Ethiopia: a systematic review and meta-analysis
Authors: Hussen Siraj , Assegu Demissie , Tadesse Birkneh Tilahun , Shimelis Techalew 
Published: February 2021

AbstractBackgroundSchistosomiasis is a common helminthic infection in the tropics and subtropics, particularly in sub-Saharan African countries including Ethiopia. In these counties,Schistosoma mansoniinfection is a significant public health problem due to the risk of reinfection and recurrent disease despite implementing several rounds preventive chemotherapy. This systematic review and meta-analysis aimed at assessing the pooled prevalence of schistosomiasis in Ethiopia.MethodsThe PRISMA guidelines were followed to perform the systematic review and meta-analysis. Published studies from January 1999 to June 2020 were searched in Medline, PubMed, Google Scholar, EMBASE, HINARI, and Cochrane Library using key words including: “prevalence”, “incidence”, “schistosomiasis” “Bilharziasis”, “Bilharzia”, “S. mansoni“, “Ethiopia”. Heterogeneity of included studies was assessed using Cochran’s Q test andI2test statistics while publication bias was assessed using Egger’s test.ResultsNinety-four studies were included in the systematic review and meta-analysis. The pooled prevalence ofS. mansoniin Ethiopia was 18.0% (95%CI: 14.0–23.0). The southern region of Ethiopia had a higherS. mansoniprevalence of 25.9% (995% CI, 14.9–41.1) than the national prevalence. The burden ofS. mansoniinfection was also higher than the national average in rural areas and among men with pooled prevalence of 20.2% (95% CI, 13.2–28.5) and 28.5% (95%CI, 22.7,35.1), respectively. The trend analysis showed that the prevalence ofS. mansoniinfection in Ethiopia decreased over the past 15 years, potentially because of the repeated preventive chemotherapy.ConclusionThe review unveiled a moderate prevalence ofS. mansoniinfection in Ethiopia. Targeted treatment of at-risk population groups ad high burden areas coupled with implementation of integrated vector control strategies are critical to address the burden of Schistosomiasis.
The Progestin Revolution: progestins are arising as the dominant players in the tight interlink between contraceptives and bleeding control
Authors: Shoupe Donna 
Published: February 2021

AbstractSince the introduction of the first modern contraceptive methods, the interlink between bleeding control and contraceptive development has been a dominant and critical factor. This interplay has led to the development of safer and better contraceptive methods that are often used to control bleeding in both women with normal bleeding patterns as well as in those suffering from heavy menstrual bleeding (HMB). The success of progestin-only methods, such as hormonal IUDs or progestin dominant oral contraceptives in substantially decreasing and controlling menstrual bleeding, has led to development of multiple progestin-only protocols for the sole purpose of bleeding control. These include protocols designed to stop acute heavy bleeding as well as manage long-term bleeding. Recent publications describe a variety of protocols using high dose oral progestin pills with or without a medroxyprogesterone acetate (MPA) injection that demonstrate high effectiveness and good tolerability. Comparted to many other progestins, MPA is not converted in part into ethinyl estradiol and appears to have a progestin-only advantage. Norethindrone acetate (NET acetate) is converted in part to ethinyl estradiol and therefore is an especially good option for bleeding control in patients with low estrogen levels that would benefit from estrogen replacement (such as in premenopausal women with premature menopause or hypothalamic hypogonadism).
Metabolism of human pluripotent stem cells and differentiated cells for regenerative therapy: a focus on cardiomyocytes
Authors: Tanosaki Sho , Tohyama Shugo , Kishino Yoshikazu , Fujita Jun , Fukuda Keiichi 
Published: February 2021

AbstractPluripotent stem cells (PSCs) exhibit promising application in regenerative therapy, drug discovery, and disease modeling. While several protocols for differentiating somatic cells from PSCs exist, their use is limited by contamination of residual undifferentiated PSCs and immaturity of differentiated somatic cells.The metabolism of PSCs differs greatly from that of somatic cells, and a distinct feature is required to sustain the distinct properties of PSCs. To date, several studies have reported on the importance of metabolism in PSCs and their derivative cells. Here, we detail advancements in the field, with a focus on cardiac regenerative therapy.
Predictors of the functional outcome after thrombolysis in an Egyptian patients’ sample
Authors: Eldeeb H. M. , Elsalamawy D. H. , Elabd A. M. , Abdelraheem H. S. 
Published: February 2021

AbstractBackgroundAbout 6.2 million individuals worldwide and approximately 200 Egyptians/100,000 citizens have cerebrovascular stroke annually, and only less than 1% of stroke patients received intravenous (IV) thrombolysis in 2014. Outcome of the ischemic stroke after IV thrombolysis varies, and there is lack of data about the predicting factors that contributes to the outcome of ischemic strokes after IV thrombolysis in Egypt.ObjectiveThe aim of this work is to study the predictors of the functional outcome of ischemic cerebrovascular stroke after IV thrombolysis in Egyptian patients.Patients and methodsThis is a prospective study that includes acute ischemic stroke patients who received IV thrombolysis at the Alexandria University Hospital during the year from February 2017 to February 2018, and they were evaluated initially by Rapid Arterial Occlusion Evaluation (RACE) scale and followed-up serially for 6 months after thrombolysis using the National Institutes of Health Stroke Scale (NIHSS) and modified ranking score (mRS).ResultsForty-five patients are included; 56% had favorable functional outcome (mRS 0–2) after 6 months, 68% had ≥ 4 points improvement in NIHSS after 6 months, and 13% had hemorrhagic conversion with 18% mortality rate. High initial RACE scale and long hospital stay are associated with poor functional outcome 6 months after thrombolysis.ConclusionStroke severity demonstrated by high initial RACE and the duration of hospital stay are the two most significant predictors with an impact on the functional outcome of ischemic cerebrovascular stroke after thrombolysis.
The association between C-reactive protein, mood disorder, and cognitive function in UK Biobank
Authors: Milton David C. , Ward Joey , Ward Emilia , Lyall Donald M. , Strawbridge Rona J. , Smith Daniel J. , Cullen Breda 
Published: February 2021

Abstract

Background
Systemic inflammation has been linked with mood disorder and cognitive impairment. The extent of this relationship remains uncertain, with the effects of serum inflammatory biomarkers compared to genetic predisposition toward inflammation yet to be clearly established.

Methods
We investigated the magnitude of associations between C-reactive protein (CRP) measures, lifetime history of bipolar disorder or major depression, and cognitive function (reaction time and visuospatial memory) in 84,268 UK Biobank participants. CRP was measured in serum and a polygenic risk score for CRP was calculated, based on a published genome-wide association study. Multiple regression models adjusted for sociodemographic and clinical confounders.

Results
Increased serum CRP was significantly associated with mood disorder history (Kruskal–Wallis H = 196.06, p < 0.001, η2 = 0.002) but increased polygenic risk for CRP was not (F = 0.668, p = 0.648, η2 < 0.001). Compared to the lowest quintile, the highest serum CRP quintile was significantly associated with both negative and positive differences in cognitive performance (fully adjusted models: reaction time B = −0.030, 95% CI = −0.052, −0.008; visuospatial memory B = 0.066, 95% CI = 0.042, 0.089). More severe mood disorder categories were significantly associated with worse cognitive performance and this was not moderated by serum or genetic CRP level.

Conclusions
In this large cohort study, we found that measured inflammation was associated with mood disorder history, but genetic predisposition to inflammation was not. The association between mood disorder and worse cognitive performance was very small and did not vary by CRP level. The inconsistent relationship between CRP measures and cognitive performance warrants further study.
Randomized Phase II Study of 3 Months or 2 Years of Adjuvant Afatinib in Patients With Surgically Resected Stage I-III EGFR-Mutant Non–Small-Cell Lung Cancer
Authors: Neal Joel W. , Costa Daniel B. , Muzikansky Alona , Shrager Joseph B. , Lanuti Michael , Huang James , Ramachandran Kavitha J. , Rangachari Deepa , Huberman Mark S. , Piotrowska Zofia , Kris Mark G. , Azzoli Christopher G. , Sequist Lecia V. , Chaft Jamie E. 
Published: February 2021

PURPOSE For patients with surgically resected disease, multiple studies suggest a benefit of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in delaying cancer recurrence. The necessary duration of therapy for benefit is unknown. MATERIALS AND METHODS This randomized phase II study enrolled patients with completely resected stage IA-IIIB EGFR-mutant non–small-cell lung cancer (American Joint Committee on Cancer 7th edition) after stage-appropriate standard-of-care adjuvant therapy. Patients were randomly assigned 1:1 to 3 months or 2 years of adjuvant afatinib starting at 30 mg by mouth daily. Computed tomography imaging was performed every 6 months for 3 years and then annually. The primary study end point for this planned 92-patient trial was recurrence rate at 2 years from randomization. A 20% improvement (from 70% with 3 months to 90% with 2 years) was targeted. RESULTS Forty-six patients enrolled and 45 were treated. The assigned course of afatinib treatment was completed by 96% (22/23) of patients in the 3-month group and only 41% (9/22) in the 2-year group. The 2-year recurrence-free survival (RFS) rates were 70% in the 3-month group and 81% in the 2-year group ( P = .55). The median RFS was 42.8 months in the 3-month group and 58.6 months in the 2-year group. Side effects were consistent with those previously described for afatinib. CONCLUSION Recurrences at 2 years were 11% less common with 2 years versus 3 months of adjuvant afatinib. This difference did not meet the 20% primary study target, likely because of underaccrual and early drug discontinuation on the 2-year group. With the availability of osimertinib with better efficacy and tolerability than earlier-generation agents, the optimal duration of adjuvant EGFR TKI therapy remains an important question.
Neurokinin 3 Receptor Antagonism Ameliorates Key Metabolic Features in a Hyperandrogenic PCOS Mouse Model
Authors: Sucquart Irene E , Nagarkar Ruchi , Edwards Melissa C , Rodriguez Paris Valentina , Aflatounian Ali , Bertoldo Michael J , Campbell Rebecca E , Gilchrist Robert B , Begg Denovan P , Handelsman David J , Padmanabhan Vasantha , Anderson Richard A , Walters Kirsty A 
Published: February 2021

Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine condition characterized by a range of endocrine, reproductive, and metabolic abnormalities. At present, management of women with PCOS is suboptimal as treatment is only symptomatic. Clinical and experimental advances in our understanding of PCOS etiology support a pivotal role for androgen neuroendocrine actions in PCOS pathogenesis. Hyperandrogenism is a key PCOS trait and androgen actions play a role in regulating the kisspeptin-/neurokinin B-/dynorphin (KNDy) system. This study aimed to investigate if targeted antagonism of neurokinin B signaling through the neurokinin 3 receptor (NK3R) would reverse PCOS traits in a dihydrotestosterone (DHT)-induced mouse model of PCOS. After 3 months, DHT exposure induced key reproductive PCOS traits of cycle irregularity and ovulatory dysfunction, and PCOS-like metabolic traits including increased body weight; white and brown fat pad weights; fasting serum triglyceride and glucose levels, and blood glucose incremental area under the curve. Treatment with a NK3R antagonist (MLE4901) did not impact the observed reproductive defects. In contrast, following NK3R antagonist treatment, PCOS-like females displayed decreased total body weight, adiposity, and adipocyte hypertrophy, but increased respiratory exchange ratio, suggesting NK3R antagonism altered the metabolic status of the PCOS-like females. NK3R antagonism did not improve circulating serum triglyceride or fasted glucose levels. Collectively, these findings demonstrate that NK3R antagonism may be beneficial in the treatment of adverse metabolic features associated with PCOS and support neuroendocrine targeting in the development of novel therapeutic strategies for PCOS.
Macrophage Responses to Environmental Stimuli During Homeostasis and Disease
Authors: Rasheed Adil , Rayner Katey J 
Published: February 2021

AbstractWork over the last 40 years has described macrophages as a heterogeneous population that serve as the frontline surveyors of tissue immunity. As a class, macrophages are found in almost every tissue in the body and as distinct populations within discrete microenvironments in any given tissue. During homeostasis, macrophages protect these tissues by clearing invading foreign bodies and/or mounting immune responses. In addition to varying identities regulated by transcriptional programs shaped by their respective environments, macrophage metabolism serves as an additional regulator to temper responses to extracellular stimuli. The area of research known as “immunometabolism” has been established within the last decade, owing to an increase in studies focusing on the crosstalk between altered metabolism and the regulation of cellular immune processes. From this research, macrophages have emerged as a prime focus of immunometabolic studies, although macrophage metabolism and their immune responses have been studied for centuries. During disease, the metabolic profile of the tissue and/or systemic regulators, such as endocrine factors, become increasingly dysregulated. Owing to these changes, macrophage responses can become skewed to promote further pathophysiologic changes. For instance, during diabetes, obesity, and atherosclerosis, macrophages favor a proinflammatory phenotype; whereas in the tumor microenvironment, macrophages elicit an anti-inflammatory response to enhance tumor growth. Herein we have described how macrophages respond to extracellular cues including inflammatory stimuli, nutrient availability, and endocrine factors that occur during and further promote disease progression.
Aristotle, Buddhist scripture and embryology in ancient Mexico: building inclusion by re-thinking what counts as the history of developmental biology
Authors: Wallingford John B. 
Published: February 2021

ABSTRACTIt has not gone unnoticed in recent times that historical writing about science is heavily Eurocentric. A striking example can be found in the history of developmental biology: textbooks and popular science writing frequently trace an intellectual thread from the Greek philosopher Aristotle through 19th century embryology to 20th century genetics. Few in our field are aware of the depth and breadth of early embryological thinking outside of Europe. Here, I provide a series of vignettes highlighting the rich history of embryological thinking in Asia and Latin America. My goal is to provide an entertaining, even provocative, synopsis of this important but under-studied topic. It is my hope that this work will spur others to carry out more thorough investigations, with the ultimate goal of building a more inclusive discipline.
Golgi localization of the LIN-2/7/10 complex points to a role in basolateral secretion of LET-23 EGFR in the Caenorhabditis elegans vulval precursor cells
Authors: Gauthier Kimberley D. , Rocheleau Christian E. 
Published: February 2021

ABSTRACT
The evolutionarily conserved LIN-2 (CASK)/LIN-7 (Lin7A-C)/LIN-10 (APBA1) complex plays an important role in regulating spatial organization of membrane proteins and signaling components. In Caenorhabditis elegans, the complex is essential for the development of the vulva by promoting the localization of the sole Epidermal growth factor receptor (EGFR) ortholog LET-23 to the basolateral membrane of the vulva precursor cells where it can specify the vulval cell fate. To understand how the LIN-2/7/10 complex regulates receptor localization, we determined its expression and localization during vulva development. We found that LIN-7 colocalizes with LET-23 EGFR at the basolateral membrane, whereas the LIN-2/7/10 complex colocalizes with LET-23 EGFR at cytoplasmic punctae that mostly overlap with the Golgi. Furthermore, LIN-10 recruits LIN-2, which in turn recruits LIN-7. We demonstrate that the complex forms in vivo with a particularly strong interaction and colocalization between LIN-2 and LIN-7, consistent with them forming a subcomplex. Thus, the LIN-2/7/10 complex forms on the Golgi on which it likely targets LET-23 EGFR trafficking to the basolateral membrane rather than functioning as a tether.
Distinct epithelial-to-mesenchymal transitions induced by PIK3CAH1047R and PIK3CB
Authors: Gjelaj Ersa , Hamel Paul A. 
Published: February 2021

ABSTRACT
The most common PIK3CA mutation, producing the H1047R mutant of p110α, arises in myriad malignancies and is typically observed in low-grade breast tumours. In contrast, amplification is observed for wild-type PIK3CB, encoding p110β, and occurs at low frequency but in aggressive, high-grade metastatic tumours. We hypothesized that mutant p110αH1047R and wild-type p110β give rise to distinct transformed phenotypes. We show that p110αH1047R and wild-type p110β, but not wild-type p110α, transform MCF-10A cells and constitutively stimulate phosphoinositide 3-kinase (PI3K)-AKT pathway signalling. However, their resultant morphological transformed phenotypes are distinct. p110αH1047R induced an epithelial-to-mesenchymal transition (EMT) commensurate with SNAIL (also known as SNAI1) induction and loss of E-cadherin. Upon p110β expression, however, E-cadherin expression was maintained despite cells readily delaminating from epithelial sheets. Distinct from the prominent filopodia in p110αH1047R-expressing cells, p110β induced formation of lamellipodia, and these cells migrated with significantly greater velocity and decreased directionality. p110β-induced phenotypic alterations were accompanied by hyperactivation of RAC1; the dependency of transformation of p110β-binding to Rac1 revealed using a Rac1-binding mutant of p110β. Thus, PIK3CB amplification induces a transformed phenotype that is dependent upon a p110β-Rac1 signalling loop and is distinct from the transformed phenotype induced by p110αH1047R.
The role of icIL-1RA in keratinocyte senescence and development of the senescence-associated secretory phenotype
Authors: Niklander Sven E. , Crane Hannah L. , Darda Lav , Lambert Daniel W. , Hunter Keith D. 
Published: February 2021

ABSTRACTThere is compelling evidence that senescent cells, through the senescence-associated secretory phenotype (SASP), can promote malignant transformation and invasion. Interleukin-1 (IL-1) is a key mediator of this cytokine network, but the control of its activity in the senescence programme has not been elucidated. IL-1 signalling is regulated by IL-1RA, which has four variants. Here, we show that expression of intracellular IL-1RA type 1 (icIL-1RA1), which competitively inhibits binding of IL-1 to its receptor, is progressively lost during oral carcinogenesis ex vivo and that the pattern of expression is associated with keratinocyte replicative fate in vitro. We demonstrate that icIL-1RA1 is an important regulator of the SASP in mortal cells, as CRISPR/Cas9-mediated icIL-1RA1 knockdown in normal and mortal dysplastic oral keratinocytes is followed by increased IL-6 and IL-8 secretion, and rapid senescence following release from RhoA-activated kinase inhibition. Thus, we suggest that downregulation of icIL-1RA1 in early stages of the carcinogenesis process can enable the development of a premature and deregulated SASP, creating a pro-inflammatory state in which cancer is more likely to arise.