bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlations between CD4+FoxP3+ Treg and expression of FoxM1 and Ki‐67 in gastric cancer patients
Authors: Ma Kai , Li Xiaoxiao , Lv Jing , Liu Zimin , Zhang Lijian , Cong Hui , Wang Huiyun , Shen Fangzhen , Yue Lu
Published: January 2020

Aims

In this study, we intended to analyze the clinical significance of CD4+FoxP3+ Tregs in gastric cancer patients and investigate the relationship between the proportion of CD4+FoxP3+ Tregs in the peripheral blood and the expression of FoxM1 and Ki‐67 in gastric cancer tissues.

Methods

Flow cytometry was used to measure the CD4+FoxP3+ Tregs level in peripheral blood from 70 gastric cancer patients one day before gastrectomy and D2 lymph node dissection. Immunohistochemistry staining was used to detect the expression of FoxM1 and Ki‐67 in gastric cancer tissues. Data on clinico‐pathological features and correlation between Tregs and the expression of FoxM1 and Ki‐67 were then analyzed.

Results

The average proportion of CD4+FoxP3+ Tregs in gastric cancer patients’ peripheral blood before surgery was 10.12 ± 2.85%, which was significantly higher in patients with late AJCC stage (P = 0.029) or lymph node metastasis (P = 0.003) compared to patients at earlier AJCC stage or without lymph node metastasis. The levels of CD4+FoxP3+ Treg cells was positively correlated with the protein expression of FoxM1 (P = 0.003) and Ki‐67 (P = 0.001), respectively.

Conclusion

These results suggest the level of CD4+FoxP3+ Treg cells in peripheral blood has clinical significance in gastric cancer patients. The overexpression of FoxM1 and Ki‐67 may relate to immunosuppression in gastric cancer.
Sestrin2 alleviates palmitate‐induced endoplasmic reticulum stress, apoptosis, and defective invasion of human trophoblast cells
Authors: Lee Solji , Shin Jiha , Hong Yeji , Shin Seong Min , Shin Hye Won , Shin Jongdae , Lee Sung Ki , Park Hwan‐Woo
Published: January 2020

Problem

Maternal obesity induces elevated saturated fatty acid palmitate levels in the blood and causes pregnancy complications such as gestational diabetes, preeclampsia, fetal growth abnormalities, and stillbirth. Sestrin2, a highly conserved stress‐inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation. However, the effects of Sestrin2 on trophoblast cells have not yet been investigated. Here, we investigated the role of Sestrin2 in palmitate‐induced lipotoxicity and its underlying mechanisms in human first‐trimester trophoblast cells (Sw.71).

Method of study

Mouse placental tissues were obtained from low‐fat diet‐fed mice (n = 14) and high‐fat diet‐fed mice (n = 14) at gestation day 17.5. Sw.71 cells were treated with palmitate or bovine serum albumin as vehicle controls. The role of Sestrin2 in palmitate‐induced lipotoxicity was examined by immunocytochemistry, immunoblot analysis, quantitative real‐time PCR, and invasion assay.

Results

Expression of placental Sestrin2 was elevated in high‐fat diet‐fed dams compared to that of low‐fat diet‐fed dams. Prolonged treatment of Sw.71 cells with palmitate‐induced endoplasmic reticulum (ER) stress‐dependent expressions of Sestrin2 protein and mRNA, and the treatment also triggered apoptosis. Knockdown of Sestrin2 increased palmitate‐mediated ER stress, inflammatory signaling, and apoptosis. Furthermore, Sestrin2 suppressed impaired trophoblast invasion caused by palmitate and attenuated palmitate‐induced ER stress and inflammation via AMPK/mTORC1 pathways.

Conclusion

Our study provides the relationship between Sestrin2, AMPK/mTORC1 pathway, and trophoblast function, suggesting that Sestrin2 may be a novel potential therapeutic target for the prevention of pregnancy complications.
Colonoscopy withdrawal time and polyp/adenoma detection rate: a single‐site retrospective study in regional Queensland
Authors: Wong Wen Jye , Arafat Yasser , Wang Serena , Hawes Susan , Hung Kevin
Published: January 2020

Backgrounds

Bowel cancer is the second most common non‐cutaneous cancer diagnosed in Australia among both genders. Colonoscopy withdrawal time of at least 6 min has been accepted as the standard to achieve the target polyp detection rate (PDR) and adenoma detection rate (ADR). A retrospective review was conducted in Bundaberg Hospital to evaluate the relationship between colonoscopy withdrawal time against polyp, adenoma and cancer detection rates.

Methods

A retrospective study was carried out in Bundaberg Hospital on patients who had colonoscopies performed between 1 October 2016 and 30 September 2017 by the general surgical team. Data collection was conducted by reviewing patient charts, general practitioner referral letters and endoscopy reports. Statistical analysis was performed with chi‐squared test using Prism 8.2.1.

Results

A total of 1579 colonoscopies were analysed. The median age of patients undergoing a colonoscopy was 64 years (95% confidence interval (CI) 60.55–61.93). Median total duration of colonoscopy was 19 min (95% CI 20.9–22.0), with median withdrawal time of 9 min (95% CI 10.06–10.95). PDR, ADR and sessile serrated adenoma (SSA) detection rates were 43.3%, 33.1% and 5.4%, respectively. Cancer detection rate was 2.8%. Longer withdrawal times were associated with higher PDR, ADR and SSA detection rates (P < 0.0001) and higher mean number of polyp/adenoma/SSA detected.

Conclusion

Colonoscopies with withdrawal times of less than 6 min did not achieve the target detection rates. It is clear that achieving the advocated withdrawal time for screening colonoscopy improves detection rates.
Outcomes of inguinal hernia repair in cirrhotics: a single tertiary centre experience
Authors: Sidhu Ankur , Cabalag Carlos , Lee Eunice , Liew Chon Hann , Young Alastair , Christophi Christopher
Published: January 2020

Background

Patients with liver cirrhosis are at a higher risk of perioperative anaesthetic and surgical complications. Surgical repair of abdominal wall hernias in these patients has been widely discouraged. The main objective of this study was to evaluate the post‐operative outcomes of patients with liver cirrhosis after inguinal hernia repair at a single institution.

Methods

A retrospective review of a prospectively maintained database of 31 patients with liver cirrhosis undergoing inguinal hernia repair between 2006 and 2016 was undertaken. Data in relation to patient demographics, clinicopathological characteristics, morbidity and mortality were collected.

Results

Thirty‐one patients with median Model for End‐stage Liver Disease score of 14 (7–36) underwent inguinal hernia repair within a 10‐year period of our study. There was one mortality in a patient with Model for End‐stage Liver Disease score of 36 who presented with a strangulated hernia. Only one patient required return to theatre for the evacuation of haematoma and one patient developed a recurrent hernia in 1‐year follow up.

Conclusion

Inguinal hernia repair in patients with cirrhosis is a safe procedure to perform in the elective setting. Nevertheless, significant consideration must be given in performing these operations in centres with liver transplant units due to their extensive experience in pre‐operative optimization to reduce the risk of hepatic decompensation.
We Need a Loud and Fractious Poor
Authors: Maskovsky Jeff , Piven Frances Fox
Published: January 2020

This article explores the political consequences of four decades of consistent humiliation of the poor by the most authoritative voices in the land, and offers insights into ways that new movements are creating spaces for poor people’s political voices to surface and become relevant again. Our specific concern is the challenge that the current humiliation regime poses to those who seek to revive radical, disruptive and fractious anti‐poverty activism and politics. By humiliation regime, we mean a form of political violence that maltreats those classified popularly and politically as “the poor” by treating them as undeserving of citizenship, rights, public goods or resources, and, importantly, that seeks to delegitimate them as political actors. Our article demonstrates the historical importance of authoritative voices in inspiring political unrest involving poor and working people, charts the depoliticising effects of poverty politics and governance since the 1980s, and highlights the new political possibilities that are surfacing now not just to defeat the very dangerous political forms of Trumpism and the new white nationalism but that seek as well to create something that looks like justice, freedom and equality. We insist on the importance of loud and fractious poor people’s politics and call on scholars to direct attention to the incipient political potentialities of poor people today.
Healthcare utilisation and measles, mumps and rubella vaccination rates among children with an extended postnatal home visiting programme in a disadvantaged area in Stockholm, Sweden—A 3‐year follow‐up
Authors: Burström Bo , Mellblom Johanna , Marttila Anneli , Kulane Asli , Martin Helena , Lindberg Lene , Burström Kristina
Published: January 2020

Aim

To follow up healthcare utilisation and measles, mumps and rubella (MMR) vaccination rates among children 0‐36 months, receiving an extended postnatal home visiting programme in a disadvantaged area with poorer child health, and in control groups, in Stockholm, Sweden.

Methods

We analysed electronic child health records regarding outpatient visits, inpatient episodes and MMR vaccination for children 0‐36 months receiving the home visiting programme (Intervention Group) and in control groups (Control Group and Rinkeby Comparison Group).

Results

Children in the Intervention Group had significantly higher MMR vaccination rate than children in the Rinkeby Comparison Group. Healthcare utilisation was similar in the Intervention Group and the control groups. In stratified analyses by number of home visits received, children receiving the recommended six home visits had significantly fewer inpatient episodes and somewhat fewer emergency visits than those receiving fewer home visits.

Conclusion

The extended home visiting programme had a positive impact on the MMR vaccination rate. Children receiving the recommended six home visits had lower use of inpatient care. In addition to being positively perceived by parents in an area with greater healthcare needs, the programme may have a positive impact on their children's healthcare utilisation.
Exploring health professionals' understanding of evidence‐based treatment for idiopathic toe walking
Authors: Williams Cylie M. , Gray Kelly , Davies Nina , Barkocy Marybeth , Fahey Michael , Simmonds Jane , Accardo Pasquale , Eastwood Deborah , Pacey Verity
Published: January 2020

Background

Idiopathic toe walking (ITW) is an exclusionary diagnosis resulting in a child walking on the balls of their feet. Preferred treatment options may be due to the severity of the toe or the health professional preference There are limited guidelines supporting consistent treatment recommendations for this condition. This research aimed to understand agreement between health professionals' knowledge of evidence for common treatment strategies for ITW and if health professionals supported these strategies being used in clinical practice.

Methods

An international online survey was opened to registered health professionals who treat children with ITW between July 2017 and March 2018. The survey had two components: (a) demographic variables and variables relating to knowledge of evidence about ITW treatments and (b) support for common treatment strategies. Additional data on strategy use, referrals, and preference were collected. Kappa statistics described intra‐rater agreement between evidence knowledge and support. Multivariable regression analyses identified factors associated with the 10 most commonly preferred treatments.

Results

There were 908 international responses. Kappa agreement for paired correct responses determined a fair agreement for evidence support knowledge for four strategies including watch and wait (Kappa = 0.24), stretching (Kappa = 0.30), sensory integration strategies (Kappa = 0.40), and motor control strategies (Kappa = 0.24) and moderate responses for 13 others. No strategies had greater than moderate agreement between correct knowledge of evidence and strategy support. Profession, location, number of children seen in practice, and not correctly identifying the evidence factored into many of the most commonly used strategies for ITW (p < .05).

Conclusions

The results from this study, which confirm a variety of interventions, are utilized in the management of ITW around the world. Furthermore, there remains a disconnection between paediatric health professionals' understanding of the evidence of common treatment strategies of ITW and a consensus for the treatment of this condition.
Genetic and epigenetic regulation of abdominal aortic aneurysms
Authors: Mangum Kevin D. , Farber Mark A.
Published: January 2020

Abdominal aortic aneurysms (AAAs) are focal dilations of the aorta that develop from degenerative changes in the media and adventitia of the vessel. Ruptured AAAs have a mortality of up to 85%, thus it is important to identify patients with AAA at increased risk for rupture who would benefit from increased surveillance and/or surgical repair. Although the exact genetic and epigenetic mechanisms regulating AAA formation are not completely understood, Mendelian cases of AAA, which result from pathologic variants in a single gene, have helped provide a basic understanding of AAA pathophysiology. More recently, genome wide associated studies (GWAS) have identified additional variants, termed single nucleotide polymorphisms, in humans that may be associated with AAAs. While some variants may be associated with AAAs and play causal roles in aneurysm pathogenesis, it should be emphasized that the majority of SNPs do not actually cause disease. In addition to GWAS, other studies have uncovered epigenetic causes of disease that regulate expression of genes known to be important in AAA pathogenesis. This review describes many of these genetic and epigenetic contributors of AAAs, which altogether provide a deeper insight into AAA pathogenesis.
Eosinophil‐to‐monocyte ratio is an excellent predictor of acute cellular rejection in pancreas transplant alone recipients
Authors: Ryu Je Ho , Ko Hyo Jung , Shim Jae Ryong , Lee Tae Beom , Yang Kwang Ho , Lee Jung Hee , Lee Hyun Ji , Kim Taeun , Choi Byung Hyun
Published: January 2020

Serum pancreatic enzymes (serum amylase and lipase) are sensitive markers for monitoring acute rejection in pancreatic transplant recipients. However, those enzymes are not specific, as their levels are elevated in other conditions. We evaluated the eosinophil‐to‐monocyte ratio (EMR) in peripheral blood as a biomarker of acute rejection in the clinical setting in recipients of pancreatic transplant alone. We performed 32 cases of pancreatic transplantation alone since 2015. Nine patients were diagnosed with rejection. Serum amylase and lipase levels and eosinophil and monocytes counts were analyzed and compared retrospectively between the non‐rejection and rejection groups. The serum eosinophil count, eosinophil fraction of the complete blood count, and serum amylase and lipase levels were significant predictors of rejection according to the receiver operation characteristic (ROC) curve. However, the EMR was the best indicator of rejection based on the ROC curve (area under the curve 0.918, sensitivity 100%, specificity 76.2% at the cutoff value 0.80, P < .001). The combination of EMR and the lipase level had 100% sensitivity and 90.5% specificity. The EMR is a simple and excellent predictor of acute rejection in recipients of pancreatic transplant alone.
Controlling Nutritional Status score does not predict patients' overall survival or hepatocellular carcinoma recurrence after deceased donor liver transplantation
Authors: Pravisani Riccardo , Mocchegiani Federico , Isola Miriam , Lorenzin Dario , Adani Gian Luigi , Cherchi Vittorio , Righi Elda , Terrosu Giovanni , Vivarelli Marco , Risaliti Andrea , Baccarani Umberto
Published: January 2020

Background

The Controlling Nutritional Status (CONUT) score is a newly developed laboratory‐derived immunonutritional score which has been validated as prognostic marker for survival and tumor recurrence in surgically treated patients with various tumor types, including hepatocellular carcinoma (HCC). The aim of the present study was to test the CONUT score performance in HCC patients treated with liver transplantation (LT).

Methods

A retrospective study on a bi‐centers cohort of 280 HCC patients submitted to LT between 2006 and 2017 was performed. Indication to LT was limited to Milan criteria or UCSF criteria, defined by preoperative imaging.

Results

Median pre‐LT CONUT score was 5 (interquartile range 3‐7). Overall patients' survival at 1, 3, and 5 years was 84%, 76.6%, and 68.3%, respectively. Multivariate analysis showed that HCC recurrence (hazard ratio [HR] = 1.987, P = .012] and pre‐LT neutrophil to lymphocyte ratio (NLR) (HR = 1.064, P = .003) were independent risk factors for reduced survival. Cumulative incidence of HCC recurrence at 1, 3, and 5 years was 5.1%, 11.5%, and 15.5%, respectively. Pre‐LT platelet‐to‐lymphocyte ratio (PLR) (subdistribution hazard ratio [SHR] = 1.086, P = .044], tumor max diameter (SHR = 1.695, P < .001), and bilobar tumor distribution (SHR = 6.892, P = .006) were independent risk factors for tumor recurrence. The CONUT score did not show any prognostic value.

Conclusions

The CONUT score did not predict poor survival or tumor recurrence in LT recipients.
Comparative effects of sulphonylureas, dipeptidyl peptidase‐4 inhibitors and sodium‐glucose co‐transporter‐2 inhibitors added to metformin monotherapy: a propensity‐score matched cohort study in UK primary care
Authors: Wilkinson Samantha , Williamson Elizabeth , Pokrajac Ana , Fogarty Damian , Stirnadel‐Farrant Heide , Smeeth Liam , Douglas Ian J. , Tomlinson Laurie A.
Published: January 2020

Aim

To assess the comparative effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase‐4 (DPP‐4) inhibitors on cardiometabolic risk factors in routine care.

Materials and methods

Using primary care data on 10 631 new users of SUs, SGLT2 inhibitors or DPP‐4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity‐score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96 weeks.

Results

HbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: −15.2 mmol/mol (95% confidence interval [CI] –16.9, −13.5); SUs: −14.3 mmol/mol (95% CI –15.5, −13.2); and DPP‐4 inhibitors: −11.9 mmol/mol (95% CI –13.1, −10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow‐up, but not for DPP‐4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: −2.3 mmHg (95% CI –3.8, −0.8); SUs: −0.8 mmHg (95% CI –1.9, +0.4); and DPP‐4 inhibitors: −0.9 mmHg (95% CI –2.1,+0.2).

BMI decreased for SGLT2 inhibitor and DPP‐4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: −0.7 kg/m2 (95% CI –0.9, −0.5); SUs: 0.0 kg/m2 (95% CI –0.3, +0.2); and DPP‐4 inhibitors: −0.3 kg/m2 (95% CI –0.5, −0.1). eGFR fell at 12 weeks for SGLT2 inhibitor and DPP‐4 inhibitor users. At 60 weeks, the fall in eGFR from baseline was similar for each drug class.

Conclusions

In routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials.
Pharmacokinetic and pharmacodynamic analysis of (2S,3S)‐sec‐butylpropylacetamide (SPD) in rats and pigs—A CNS‐active stereoisomer of SPD
Authors: Bibi David , Bialer Meir
Published: January 2020

Objectives

To advance the development of (2S,3S)‐sec‐butylpropylacetamide (SPD) as a new treatment for acute repetitive seizures (ARS), by studying its pharmacokinetics (PK) in pigs and its PK‐pharmacodynamic (PK‐PD) correlation in rats.

Methods

Two (2S,3S)‐SPD intramuscular formulations (FA and FB) were administered to pigs and rats and blood samples were withdrawn at different times after dosing. Major PK parameters were estimated in both species. PD analysis was conducted in rats utilizing the maximal‐electroshock seizure threshold (MEST) test. Because ARS treatment requires a rapid action, the MEST test allows comparative evaluation of (2S,3S)‐SPD intramuscular injection on rat susceptibility to electroconvulsive shock at various times after dosing.

Results

In rats, (2S,3S)‐SPD plasma exposure increased proportionally following intramuscular dosing (20, 25 and 40 mg/kg) of FA and FB. Peak plasma concentration (Cmax) was obtained at 1‐2 hours after dosing and ranged between 6.8 and 9.4 mg/L. (2S,3S)‐SPD plasma concentration at 10 minutes after dosing (C10) ranged between 2.1 and 3.5 mg/mL, and its half‐life ranged between 0.9 and 2.3 hours. The highest C10 value, which may indicate rapid activity onset, and the highest Cmax were observed following administration of FA (40 mg/kg): C10 = 3.5 mg/L and Cmax = 9.5 mg/L. In the MEST test, (2S,3S)‐SPD (20 and 60 mg/kg) significantly raised the tonic seizure threshold compared to vehicle at 4, 7, 10, and 20 minutes after dosing, with a 1.6‐fold increase at 20 minutes, which coincided with (2S,3S)‐SPD brain Cmax. Following intramuscular dosing of (2S,3S)‐SPD (12 mg/kg) to pigs of FA and FB, a Cmax value of 0.9 mg/L was obtained 0.42 and 0.75 hours after dosing, respectively. (2S,3S)‐SPD C10 was 0.27 mg/L (FA) and 0.49 mg/L (FB). (2S,3S)‐SPD clearance, volume of distribution, and half‐life were 2 L/h/kg, 18‐28 L/kg, and 6.1‐9.7 hours, respectively.

Significance

(2S,3S)‐SPD demonstrated a good PK‐PD correlation in the rat MEST test, with a rapid onset. (2S,3S)‐SPD first PK study in pigs showed that doses >12 mg/kg are required to achieve in pigs the plasma concentrations associated with activity at the rat MEST test.
Genotyping‐by‐sequencing illuminates high levels of divergence among sympatric forms of coregonines in the Laurentian Great Lakes
Authors: Ackiss Amanda S. , Larson Wesley A. , Stott Wendylee
Published: January 2020

Effective resource management depends on our ability to partition diversity into biologically meaningful units. Recent evolutionary divergence, however, can often lead to ambiguity in morphological and genetic differentiation, complicating the delineation of valid conservation units. Such is the case with the “coregonine problem,” where recent postglacial radiations of coregonines into lacustrine habitats resulted in the evolution of numerous species flocks, often with ambiguous taxonomy. The application of genomics methods is beginning to shed light on this problem and the evolutionary mechanisms underlying divergence in these ecologically and economically important fishes. Here, we used restriction site‐associated DNA (RAD) sequencing to examine genetic diversity and differentiation among sympatric forms in the Coregonus artedi complex in the Apostle Islands of Lake Superior, the largest lake in the Laurentian Great Lakes. Using 29,068 SNPs, we were able to clearly distinguish among the three most common forms for the first time, as well as identify putative hybrids and potentially misidentified specimens. Population assignment rates for these forms using our RAD data were 93%–100% with the only mis‐assignments arising from putative hybrids, an improvement from 62% to 77% using microsatellites. Estimates of pairwise differentiation (FST: 0.045–0.056) were large given the detection of hybrids, suggesting that reduced fitness of hybrid individuals may be a potential mechanism for the maintenance of differentiation. We also used a newly built C. artedi linkage map to look for islands of genetic divergence among forms and found widespread differentiation across the genome, a pattern indicative of long‐term drift, suggesting that these forms have been reproductively isolated for a substantial amount of time. The results of this study provide valuable information that can be applied to develop well‐informed management strategies and stress the importance of re‐evaluating conservation units with genomic tools to ensure they accurately reflect species diversity.
Rare and unique adaptations to cancer in domesticated species: An untapped resource?
Authors: Thomas Frédéric , Giraudeau Mathieu , Dheilly Nolwenn M. , Gouzerh Flora , Boutry Justine , Beckmann Christa , Biro Peter A. , Hamede Rodrigo , Abadie Jerome , Labrut Sophie , Bieuville Margaux , Misse Dorothée , Bramwell Georgina , Schultz Aaron , Le Loc'h Guillaume , Vincze Orsolya , Roche Benjamin , Renaud François , Russell Tracey , Ujvari Beata
Published: January 2020

Strong and ongoing artificial selection in domestic animals has resulted in amazing phenotypic responses that benefit humans, but often at a cost to an animal's health, and problems related to inbreeding depression, including a higher incidence of cancer. Despite high rates of cancer in domesticated species, little attention has been devoted to exploring the hypothesis that persistent artificial selection may also favour the evolution of compensatory anticancer defences. Indeed, there is evidence for effective anti‐cancer defences found in several domesticated species associated with different cancer types. We also suggest that artificial selection can favour the “domestication” of inherited oncogenic mutations in rare instances, retaining those associated to late and/or less aggressive cancers, and that by studying these seemingly rare anticancer adaptations, novel cancer treatments may be found.
Melanoma—Time to fast or time to feast? An interplay between PPARs, metabolism and immunity
Authors: Grabacka Maja , Plonka Przemyslaw M. , Reiss Krzysztof
Published: January 2020

Development and progression of melanoma can be accelerated by intensification of particular metabolic pathways, such as aerobic glycolysis and avid amino acid catabolism, and is accompanied by aberrant immune responses within the tumor microenvironment. Contrary to other cancer types, melanoma reveals some unique tissue‐specific features, such as melanogenesis, which is intertwined with metabolism. Nuclear peroxisome proliferator‐activated receptors (PPARs) take part in regulation of systemic and cellular metabolism, inflammation and melanogenesis. They appear as a focal regulatory point for these three distinct processes by occupying the intersection among AMP‐dependent protein kinase (AMPK), mammalian target of rapamycin (mTOR) and PPAR gamma coactivator 1‐alpha (PGC‐1α) signalling pathways. When deregulated, they may accelerate melanoma malignant growth. Presenting the contribution of PPARα and PPARγ in melanoma biology, we attempt to ask how two contrasting metabolic states: obesity and fasting, can change progression of the disease and possible outcome of the treatment. This short essay is aimed to provoke a discussion about some practical implications for melanoma prevention and treatment, especially: how metabolic manipulation may be exploited to overcome immunosuppression and support immune checkpoint blockade efficacy.
Disentangling the potential effects of land‐use and climate change on stream conditions
Authors: Maloney Kelly O. , Krause Kevin P. , Buchanan Claire , Hay Lauren E. , McCabe Gregory J. , Smith Zachary M. , Sohl Terry L. , Young John A.
Published: January 2020

Land‐use and climate change are significantly affecting stream ecosystems, yet understanding of their long‐term impacts is hindered by the few studies that have simultaneously investigated their interaction and high variability among future projections. We modeled possible effects of a suite of 2030, 2060, and 2090 land‐use and climate scenarios on the condition of 70,772 small streams in the Chesapeake Bay watershed, United States. The Chesapeake Basin‐wide Index of Biotic Integrity, a benthic macroinvertebrate multimetric index, was used to represent stream condition. Land‐use scenarios included four Special Report on Emissions Scenarios (A1B, A2, B1, and B2) representing a range of potential landscape futures. Future climate scenarios included quartiles of future climate changes from downscaled Coupled Model Intercomparison Project ‐ Phase 5 (CMIP5) and a watershed‐wide uniform scenario (Lynch2016). We employed random forests analysis to model individual and combined effects of land‐use and climate change on stream conditions. Individual scenarios suggest that by 2090, watershed‐wide conditions may exhibit anywhere from large degradations (e.g., scenarios A1B, A2, and the CMIP5 25th percentile) to small degradations (e.g., scenarios B1, B2, and Lynch2016). Combined land‐use and climate change scenarios highlighted their interaction and predicted, by 2090, watershed‐wide degradation in 16.2% (A2 CMIP5 25th percentile) to 1.0% (B2 Lynch2016) of stream kilometers. A goal for the Chesapeake Bay watershed is to restore 10% of stream kilometers over a 2008 baseline; our results suggest meeting and sustaining this goal until 2090 may require improvement in 11.0%–26.2% of stream kilometers, dependent on land‐use and climate scenario. These results highlight inherent variability among scenarios and the resultant uncertainty of predicted conditions, which reinforces the need to incorporate multiple scenarios of both land‐use (e.g., development, agriculture, etc.) and climate change in future studies to encapsulate the range of potential future conditions.
Modeling and empirical validation of long‐term carbon sequestration in forests (France, 1850–2015)
Authors: Le Noë Julia , Matej Sarah , Magerl Andreas , Bhan Manan , Erb Karl‐Heinz , Gingrich Simone
Published: January 2020

The development of appropriate tools to quantify long‐term carbon (C) budgets following forest transitions, that is, shifts from deforestation to afforestation, and to identify their drivers are key issues for forging sustainable land‐based climate‐change mitigation strategies. Here, we develop a new modeling approach, CRAFT (CaRbon Accumulation in ForesTs) based on widely available input data to study the C dynamics in French forests at the regional scale from 1850 to 2015. The model is composed of two interconnected modules which integrate biomass stocks and flows (Module 1) with litter and soil organic C (Module 2) and build upon previously established coupled climate‐vegetation models. Our model allows to develop a comprehensive understanding of forest C dynamics by systematically depicting the integrated impact of environmental changes and land use. Model outputs were compared to empirical data of C stocks in forest biomass and soils, available for recent decades from inventories, and to a long‐term simulation using a bookkeeping model. The CRAFT model reliably simulates the C dynamics during France's forest transition and reproduces C‐fluxes and stocks reported in the forest and soil inventories, in contrast to a widely used bookkeeping model which strictly only depicts C‐fluxes due to wood extraction. Model results show that like in several other industrialized countries, a sharp increase in forest biomass and SOC stocks resulted from forest area expansion and, especially after 1960, from tree growth resulting in vegetation thickening (on average 7.8 Mt C/year over the whole period). The difference between the bookkeeping model, 0.3 Mt C/year in 1850 and 21 Mt C/year in 2015, can be attributed to environmental and land management changes. The CRAFT model opens new grounds for better quantifying long‐term forest C dynamics and investigating the relative effects of land use, land management, and environmental change.
Modeled spatial assessment of biomass productivity and technical potential ofMiscanthus × giganteus,Panicum virgatumL., andJatrophaon marginal land in China
Authors: Zhang Bingquan , Hastings Astley , Clifton‐Brown John C. , Jiang Dong , Faaij André P. C.
Published: January 2020

This article identifies marginal land technically available for the production of energy crops in China, compares three models of yield prediction forMiscanthus × giganteus,Panicum virgatumL.(switchgrass), andJatropha, and estimates their spatially specific yields and technical potential for 2017. Geographic Information System (GIS) analysis of land use maps estimated that 185 Mha of marginal land was technically available for energy crops in China without using areas currently used for food production. Modeled yields were projected forMiscanthus × giganteus, a GIS‐based Environmental Policy Integrated Climate model for switchgrass and Global Agro‐Ecological Zone model forJatropha. GIS analysis and MiscanFor estimated more than 120 Mha marginal land was technically available forMiscanthuswith a total potential of 1,761 dry weight metric million tonne (DW Mt)/year. A total of 284 DW Mt/year of switchgrass could be obtained from 30 Mha marginal land, with an average yield of 9.5 DW t ha−1 year−1. More than 35 Mha marginal land was technically available forJatropha, delivering 9.7 Mt/year ofJatrophaseed. The total technical potential from available marginal land was calculated as 31.7 EJ/year forMiscanthus, 5.1 EJ/year for switchgrass, and 0.13 EJ/year forJatropha. A total technical bioenergy potential of 34.4 EJ/year was calculated by identifying best suited crop for each 1 km2grid cell based on the highest energy value among the three crops. The results indicate that the technical potential per hectare ofJatrophais unable to compete with that of the other two crops in each grid cell. This modeling study provides planners with spatial overviews that demonstrate the potential of these crops and where biomass production could be potentially distributed in China which needs field trials to test model assumptions and build experience necessary to translate into practicality.
Coining the Pablo Picasso Syndrome
Authors: Suri Ritika , Ali Ashhar
Published: January 2020

Background

The Alice in Wonderland Syndrome has been well described in the literature. Along with sensory disturbances, patients notably experience metamorphopsias, or distortions in size (micropsia/macropsia) and distance (teleopsia), particularly of body parts. Some migraineurs, however, report dislocation and disorientation of body parts, which are common features found in paintings of Pablo Picasso.

Methods

A 60‐year‐old female with a 20‐year history of chronic migraine presented for evaluation of frequent headaches and visual disturbances. In between her attacks of migraine, she would occasionally notice alterations which she describes as a “Picasso” painting. When looking at people, she would note their ear on top of their head, or their right arm would be short and attached to the face. This would occur 1‐2 times per week and would last 5 to 10 minutes. Inanimate objects, however, would not appear distorted.

Results

The available literature, including published works and biographies, suggests Picasso did not suffer from migraine. Nonetheless, careful descriptions taken from migraineurs with visual disturbances may uncover features that resemble his paintings, be it dislocation of limbs with hints of cubism, as reported above, or illusory splitting as has been previously reported.

Conclusion

Dislocation or disorientation of body parts as a migraine‐related visual phenomenon is rare and only sparsely reported in the medical literature. Coining of a “Pablo Picasso Syndrome” may better describe this occurrence.
SYSTEMATIC MONETARY POLICY AND THE MACROECONOMIC EFFECTS OF SHIFTS IN RESIDENTIAL LOAN‐TO‐VALUE RATIOS
Authors: Bachmann Rüdiger , Rüth Sebastian K.
Published: January 2020

What are the macroeconomic consequences of changing aggregate lending standards in residential mortgage markets, as measured by loan‐to‐value (LTV) ratios? Using a structural vector autoregression (VAR), we find that GDP and business investment increase following an expansionary LTV shock. Residential investment, by contrast, falls after a small initial uptick, a result that depends on the systematic reaction of monetary policy. We show that, historically, the Fed tended to respond to expansionary LTV shocks by raising the monetary policy instrument, and, as a result, mortgage rates increased and residential investment declined. House prices are affected in a similar manner.
Clinical performance of automated chemiluminescent methods for anticardiolipin and anti‐β2‐glycoprotein I antibodies detection in a large cohort of Chinese patients with antiphospholipid syndrome
Authors: Wan Li‐yan , Gu Jie‐yu , Liu Ting‐ting , Hu Qiong‐yi , Jia Jin‐chao , Teng Jia‐lin , Sun Yue , Liu Hong‐lei , Cheng Xiao‐bing , Ye Jun‐na , Su Yu‐tong , Wu Xin‐yao , Chi Hui‐hui , Zhou Zhuo‐chao , Wang Zhi‐hong , Zhou Jin‐feng , Norman Gary L. , Dai Jing , Yang Cheng‐de , Shi Hui
Published: January 2020

Introduction

To assess the clinical performance and correlations of automated chemiluminescence assay (CIA) and enzyme‐linked immunosorbent assay (ELISA) for detecting antiphospholipid (aPL) antibodies in the diagnosis of antiphospholipid syndrome (APS).

Methods

The study recruited 505 subjects, including 192 with APS, 193 with connective tissue diseases other than APS, and 120 healthy donors. We measured anticardiolipin (aCL) and anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies IgG, IgM, and IgA in all the samples using both CIA and ELISA.

Results

Total agreement between the two methods ranged from 83.50% for anti‐β2GPI IgG antibodies to 92.76% for anti‐β2GPI IgM antibodies in all the groups. Anti‐β2GPI and aCL IgG assays showed the highest Spearman's rho coefficients (anti‐β2GPI IgG = 0.742, aCL IgG = 0.715). Anti‐β2GPI IgG CIA showed the highest sensitivity for diagnosis of APS at 80.21%, which was significantly higher than the sensitivity of anti‐β2GPI IgG ELISA (52.08%). For diagnosis of APS, anti‐β2GPI IgG CIA had the best discrimination power with the area under the curves (AUC) of 0.922, followed by aCL IgG CIA (AUC of 0.905). While the CIA AUC was slightly higher in all cases, the difference was not statistically significant.

Conclusion

CIA measurements had a good agreement and correlation with comparative ELISA assays. The CIA anti‐β2GPI IgG however was significantly more sensitive for APS diagnosis. The two assay methodologies showed comparable predictive powers and support the value of the CIA method for improved diagnosis and management of patients with APS.
Corporate irresponsibility and stock price crash risk
Authors: Zaman Rashid , Bahadar Stephen , Mahmood Haroon
Published: January 2020

We investigate the impact of corporate irresponsibility on future stock price crash by employing a unique dataset of 1,529 penalties imposed on 411 United States (U.S.) firms, from 2003 to 2015. We provide robust evidence that the total amount of penalties (in U.S. dollars) imposed on firms are negatively associated with firm‐specific future stock price crash risk. Our findings are consistent with the following view that imposition of penalties remove uncertainty about a particular firm's future, investors please that the case is closed, the firm successfully manages the aftermath of misconduct and the firm's financial gains are often larger compared to the total cost of the penalty imposed. Moreover, we find corporate social responsibility (CSR) to be a channel through which penalties impact stock price crash risk. Our findings demonstrate that the negative association between monetary penalties and stock price crash risk is more pronounced in the postfinancial crisis and in environmentally sensitive firms.
Whether a retailer should enter an e‐commerce platform taking into account consumer returns
Authors: Cao Kaiying , Xu Yuqiu , Cao Jiajia , Xu Bing , Wang Jia
Published: January 2020

Considering consumers are increasingly shopping online nowadays and the online sales market is dominated by e‐commerce giants, traditional retailers need to choose whether to enter e‐commerce platforms. Moreover, traditional retailers need to determine whether to offer offline return services considering online return services are very popular. To address these challenges, we explore a retailer's optimal offline return strategy and channel choice of whether or not to enter a platform in the contexts of symmetric information and asymmetric information, respectively. We present conditions for the retailer to share information. Interestingly, we find that the retailer in some conditions has no motivation to improve customer satisfaction rate of offline store. Most important, we find that the retailer's channel choice depends on the magnitude of the annual service fee that is affected by offline return strategy and asymmetric information, and the offline return strategy depends on the magnitude of the average residual value of returned products.
Protective effect of Agrimonia pilosa polysaccharides on dexamethasone‐treated MC3T3‐E1 cells via Wnt/β‐Catenin pathway
Authors: Huang Wei , Jin Shengyang , Yang Wenbo , Tian Shuo , Meng Chunqing , Deng Huan , Wang Hong
Published: January 2020

A water‐soluble polysaccharide (APP‐AW) was isolated from Agrimonia pilosa and prepared to three sulphated derivatives (S1, S2 and S3). The results showed that pre‐treatment with APP‐AW, S1, S2 and S3 each at the concentration of 50 μg/mL for 48 hours was able to prevent cytotoxicity induced by 1 μmol/L dexamethasone (Dex) in MC3T3‐E1 cells via inhibition of apoptosis, which is in line with the findings in flow cytometry analysis. Meanwhile, the decreased ALP activity, collagen content, mineralization, BMP2, Runx2, OSX and OCN protein expression in DEX‐treated MC3T3‐E1 cells were reversed by the addition of APP‐AW, S1, S2 and S3. Moreover, APP‐AW, S1, S2 and S3 rescued DEX‐induced increase of Bax, cytochrome c and caspase‐3 and decrease of Bcl‐2, Wnt3, β‐catenin and c‐Myc protein expression in MC3T3‐E1 cells. Our findings suggest that pre‐treatment with APP‐AW, S1, S2 and S3 could significantly protect MC3T3‐E1 cells against Dex‐induced cell injury via inhibiting apoptosis and activating Wnt/β‐Catenin signalling pathway, thus application of these polysaccharides may be a promising alternative strategy for steroid‐induced avascular necrosis of the femoral head (SANFH) therapy.
Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA‐328‐3p‐mediated inhibition of COL1A1
Authors: Liu Ting , Ye Ping , Ye Yuanyuan , Lu Sen , Han Baosan
Published: January 2020

Circular RNAs (circRNAs) are a group of non‐coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain‐ and loss‐of‐function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_circRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR‐328‐3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR‐328‐3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability. Hsa_circRNA_002178 could competitively bind to miR‐328‐3p and down‐regulated its expression. Restoration of miR‐328‐3p eliminated the tumour‐promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR‐328‐3p, could be up‐regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up‐regulating miR‐328‐3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti‐tumour effects achieved by silencing hsa_circRNA_002178.
MicroRNA‐129‐1‐3p protects cardiomyocytes from pirarubicin‐induced apoptosis by down‐regulating the GRIN2D‐mediated Ca2+ signalling pathway
Authors: Li Qi , Qin Meng , Tan Qi , Li Tengteng , Gu Zehui , Huang Peng , Ren Liqun
Published: January 2020

Pirarubicin (THP), an anthracycline anticancer drug, is a first‐line therapy for various solid tumours and haematologic malignancies. However, THP can cause dose‐dependent cumulative cardiac damage, which limits its therapeutic window. The mechanisms underlying THP cardiotoxicity are not fully understood. We previously showed that MiR‐129‐1‐3p, a potential biomarker of cardiovascular disease, was down‐regulated in a rat model of THP‐induced cardiac injury. In this study, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses to determine the pathways affected by miR‐129‐1‐3p expression. The results linked miR‐129‐1‐3p to the Ca2+ signalling pathway. TargetScan database screening identified a tentative miR‐129‐1‐3p‐binding site at the 3′‐UTR of GRIN2D, a subunit of the N‐methyl‐D‐aspartate receptor calcium channel. A luciferase reporter assay confirmed that miR‐129‐1‐3p directly regulates GRIN2D. In H9C2 (rat) and HL‐1 (mouse) cardiomyocytes, THP caused oxidative stress, calcium overload and apoptotic cell death. These THP‐induced changes were ameliorated by miR‐129‐1‐3p overexpression, but exacerbated by miR‐129‐1‐3p knock‐down. In addition, miR‐129‐1‐3p overexpression in cardiomyocytes prevented THP‐induced changes in the expression of proteins that are either key components of Ca2+ signalling or important regulators of intracellular calcium trafficking/balance in cardiomyocytes including GRIN2D, CALM1, CaMKⅡδ, RyR2‐pS2814, SERCA2a and NCX1. Together, these bioinformatics and cell‐based experiments indicate that miR‐129‐1‐3p protects against THP‐induced cardiomyocyte apoptosis by down‐regulating the GRIN2D‐mediated Ca2+ pathway. Our results reveal a novel mechanism underlying the pathogenesis of THP‐induced cardiotoxicity. The miR‐129‐1‐3p/Ca2+ signalling pathway could serve as a target for the development of new cardioprotective agents to control THP‐induced cardiotoxicity.
Treatment of hypoxia‐dependent cardiovascular diseases by myo‐inositol trispyrophosphate (ITPP)‐enhancement of oxygen delivery by red blood cells
Authors: Oknińska Marta , El‐Hafny‐Rahbi Bouchra , Paterek Aleksandra , Mackiewicz Urszula , Crola‐Da Silva Claire , Brodaczewska Klaudia , Mączewski Michał , Kieda Claudine
Published: January 2020

Heart failure is a consequence of progression hypoxia‐dependent tissue damages. Therapeutic approaches to restore and/or protect the healthy cardiac tissue have largely failed and remain a major challenge of regenerative medicine. The myo‐inositol trispyrophosphate (ITPP) is a modifier of haemoglobin which enters the red blood cells and modifies the haemoglobin properties, allowing for easier and better delivery of oxygen by the blood. Here, we show that this treatment approach in an in vivo model of myocardial infarction (MI) results in an efficient protection from heart failure, and we demonstrate the recovery effect on post‐MI left ventricular remodelling in the rat model. Cultured cardiomyocytes used to study the molecular mechanism of action of ITPP in vitro displayed the fast stimulation of HIF‐1 upon hypoxic conditions. HIF‐1 overexpression was prevented by ITPP when incorporated into red blood cells applied in a model of blood‐perfused cardiomyocytes coupling the dynamic shear stress effect to the enhanced O2 supply by modification of haemoglobin ability to release O2 in hypoxia. ITPP treatment appears a breakthrough strategy for the efficient and safe treatment of hypoxia‐ or ischaemia‐induced injury of cardiac tissue.