bluuebunny/crossref_metadata_2025_split huggingface dataset:
HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast
Authors: Bièche Ivan , Coussy Florence , El-Botty Rania , Vacher Sophie , Château-Joubert Sophie , Dahmani Ahmed , Montaudon Elodie , Reyes Cécile , Gentien David , Reyal Fabien , Ricci Francesco , Nicolas André , Marchio Caterina , Vincent-Salomon Anne , Laé Marick , Marangoni Elisabetta 
Published: September 2021

AbstractMalignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.
Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus
Authors: Giandalia A. , Alibrandi A. , Giorgianni L. , Lo Piano F. , Consolo F. , Longo Elia G. , Asztalos B. , Cucinotta D. , Squadrito G. , Russo G. T. 
Published: September 2021

Abstract
Background
Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk.

Aims
To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women.

Methods
Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women.

Results
Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis.
Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986–1.344 95% CI), together with age, tHcy, LDL-C and hypertension.

Conclusions
Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.
Pharmaceutical workers’ perceptions of physical activity and healthy eating: a qualitative study
Authors: Gradidge Philippe Jean-Luc , Draper Catherine E. , Casteleijn Daleen , Palmeira António 
Published: September 2021

Abstract
Objective
The public health message ‘move for health’ is relevant given the high prevalence of insufficient physical activity, particularly in African countries. The call for behaviour modification including limiting unhealthy dietary patterns in these settings is therefore critical; however, there is limited knowledge on the adoption of health promotion strategies in the workplace. This study aimed to investigate workers’ perceptions of physical activity and healthy eating.

Results
Five focus groups were conducted with 28 participants employed in a South African pharmaceutical manufacturing company to explore perceptions of physical activity and healthy eating. Results showed that two categories emerged: physical activity and unhealthy behaviours. Participants recognised the importance of obtaining sufficient physical activity in various domains, however believed that contemporary lifestyle limited opportunities for movement. Likewise, participants viewed healthy eating as unrealistic due to financial constraints. There was however agreement that total physical activity time could be increased during recreational pursuits outside of vocational time and may include intermittent walking for travel. These findings are important for workplace interventions and provide a more robust understanding of workers’ perceptions of physical activity and healthy eating.
Ratio between Lactobacillus plantarum and Acetobacter pomorum on the surface of Drosophila melanogaster adult flies depends on cuticle melanisation
Authors: Mokeev Vladislav , Flaven-Pouchon Justin , Wang Yiwen , Gehring Nicole , Moussian Bernard 
Published: September 2021

Abstract
Objectives
As in most organisms, the surface of the fruit fly Drosophila melanogaster is associated with bacteria. To examine whether this association depends on cuticle quality, we isolated and quantified surface bacteria in normal and melanized flies applying a new and simple protocol.

Results
On wild flies maintained in the laboratory, we identified two persistently culturable species as Lactobacillus plantarum and Acetobacter pomorum by 16S rDNA sequencing. For quantification, we showered single flies for DNA extraction avoiding the rectum to prevent contamination from the gut. In quantitative PCR analyses, we determined the relative abundance of these two species in surface wash samples. On average, we found 17-times more A. pomorum than L. plantarum. To tentatively study the importance of the cuticle for the interaction of the surface with these bacteria, applying Crispr/Cas9 gene editing in the initial wild flies, we generated flies mutant for the ebony gene needed for cuticle melanisation and determined the L. plantarum to A. pomorum ratio on these flies. We found that the ratio between the two bacterial species reversed on ebony flies. We hypothesize that the cuticle chemistry is crucial for surface bacteria composition. This finding may inspire future studies on cuticle-microbiome interactions.
Exercise-induced anaphylaxis unrelated to food ingestion and with hyperleukotrieneuria during challenge testing
Authors: Motomura Chikako , Ide Koji , Shimoda Terufumi , Odajima Hiroshi 
Published: September 2021

Abstract
Background
Exercise-induced anaphylaxis (EIA) is a rare and potentially life-threatening disorder that can develop independently without food ingestion. Cold drinks can also trigger symptoms in some patients with cold-induced anaphylaxis. We present a case of a patient with EIA that was diagnosed on the basis of positive exercise loading test with hyperleukotrieneuria.

Case presentation
A 12-year-old girl presented with acute flushing, cyanosis, swollen eyelids, and dyspnea after an endurance run in winter or swimming in a cold-water pool. She also developed dyspnea after having a cold drink. She had no history of food allergies, atopy, or asthma. No association was noted between anaphylaxis and food intake in her history. On the first day, she ingested 200 mL of 5 °C cold water in 30 s, which did not trigger symptomatic responses, but her urinary leukotriene E4 (LTE4) level increased (pre-challenge test: 295 pg/mg-creatinine (cr), post-challenge test: 400 pg/mg-cr). On the second day, she underwent the exercise loading test according to the Bruce protocol by using an ergometer to increase the power of exercise every 2 min. She had been fasting for > 15 h and did not have breakfast. Just after the exercise loading test, the plasma adrenaline and noradrenaline increased. At 15 min after the exercise loading test, her plasma adrenaline and histamine (pre-challenge test: 0.7 ng/mL, 15 min post-challenge test: 81 ng/mL) rose sharply with anaphylaxis symptoms accompanied by increasing urinary LTE4 (pre-challenge test: 579 pg/mg-cr, post-challenge test: 846 pg/mg-cr). After she was discharged, she was restricted from strenuous exercise especially in cold environments and prescribed an adrenaline autoinjector.

Conclusion
Cold stimulation can become a co-effector of EIA. Measurements of urinary LTE4 levels during challenge testing are useful for diagnosing EIA and capture the pre-anaphylaxis stage.
Interstitial lung disease occurring shortly after tocilizumab infusion in a patient with polyarticular juvenile idiopathic arthritis: a case report
Authors: Sugihara Koichi , Wakiya Risa , Shimada Hiromi , Kato Mikiya , Kameda Tomohiro , Nakashima Shusaku , Mansour Mai Mahmoud Fahmy , Ushio Yusuke , Kadowaki Norimitsu , Dobashi Hiroaki 
Published: September 2021

Abstract
Background
Tocilizumab has been shown to be effective for treatment of juvenile idiopathic arthritis (JIA). To our knowledge, this is the first reported case of interstitial lung disease occurring shortly after tocilizumab infusion in a patient with JIA.

Case presentation
A 14-year-old female patient with polyarticular JIA developed interstitial lung disease after intravenous and subcutaneous administration of tocilizumab. Her condition improved with glucocorticoid therapy.

Conclusion
Our results suggest that increased interleukin-6 levels in the blood following tocilizumab treatment may be linked to development of interstitial lung disease.
Radial solutions for fully nonlinear elliptic equations of Monge–Ampère type
Authors: Dai Limei , Cheng Huihui , Li Hongfei 
Published: September 2021

AbstractFirst, the symmetry of classical solutions to the Monge–Ampère-type equations is obtained by the moving plane method. Then, the existence and nonexistence of radial solutions in a ball are got from the symmetry results. Finally, the existence and nonexistence of classical solutions to Hessian equations in bounded domains are considered.
Temperament-based treatment for young adults with eating disorders: acceptability and initial efficacy of an intensive, multi-family, parent-involved treatment
Authors: Knatz Peck Stephanie , Towne Terra , Wierenga Christina E. , Hill Laura , Eisler Ivan , Brown Tiffany , Han Emily , Miller McKenzie , Perry Taylor , Kaye Walter 
Published: September 2021

Abstract
Background
Adult eating disorder treatments are hampered by lack of access and limited efficacy. This open-trial study evaluated the acceptability and preliminary efficacy of a novel intervention for adults with eating disorders delivered to young adults and parent-supports in an intensive, multi-family format (Young Adult Temperament-Based Treatment with Supports; YA-TBT-S).

Methods
38 YA-TBT-S participants (m age = 19.58; SD 2.13) with anorexia nervosa (AN)-spectrum disorders, bulimia nervosa (BN)-spectrum disorders, and avoidant/restrictive food intake disorder (ARFID) completed self-report assessments at admission, discharge, and 12-month follow-up. Assessments measured program satisfaction, eating disorder psychopathology and impairment, body mass index (BMI), and trait anxiety. Outcomes were analyzed using linear mixed effects models to examine changes in outcome variables over time.

Results
Treatment was rated as highly satisfactory. 53.33% were in partial or full remission at 12-month follow-up. 56% of participants received other treatment within the 12-month follow-up period, suggesting that YA-TBT-S may be an adjunctive treatment. Participants reported reductions in ED symptomatology (AN and BN), increases in BMI (AN and ARFID), and reductions in clinical impairment (AN and ARFID) at 12-month follow-up.

Conclusions
YA-TBT-S is a feasible and acceptable adjunctive treatment for young adults with a broad range of ED diagnoses and may be a method for involving parents in ED treatment in ways that are acceptable to both parents and YA. Further evaluation of efficacy is needed in larger samples, and to compare YA-TBT-S to other ED treatment approaches.
Plain English summary Eating disorders are costly and dangerous psychiatric disorders that affect millions of individuals each year. Despite their risks and societal costs, currently available treatments are limited. This study examined the acceptability and efficacy of Young Adult, Temperament-Based Treatment with Supports (YA-TBT-S), a new treatment program for adults with eating disorders. YA-TBT-S was rated highly, and a significant portion of participants improved based on ratings collected 12 months after program participation. Those with anorexia nervosa (AN) and bulimia nervosa (BN) showed significant reductions in eating disorder pathology, and those with AN and avoidant/restrictive food intake disorder (ARFID) showed increases in BMI over time.
Remote patient monitoring and classifying using the internet of things platform combined with cloud computing
Authors: Iranpak Somayeh , Shahbahrami Asadollah , Shakeri Hassan 
Published: September 2021

AbstractMany researchers have recently considered patients’ health and provided an optimal and appropriate solution. With the advent of technologies such as cloud computing, Internet of Things and 5G, information can be exchanged faster and more securely. The Internet of things (IoT) offers many opportunities in the field of e-health. This technology can improve health services and lead to various innovations in this regard. Using cloud computing and IoT in this process can significantly improve the monitoring of patients. Therefore, it is important to provide a useful method in the medical industry and computer science to monitor the status of patients using connected sensors. Thus, due to its optimal efficiency, speed, and accuracy of data processing and classification, the use of cloud computing to process the data collected from remote patient sensors and IoT platform has been suggested. In this paper, a prioritization system is used to prioritize sensitive information in IoT, and in cloud computing, LSTM deep neural network is applied to classify and monitor patients’ condition remotely, which can be considered as an important innovative aspect of this paper. Sensor data in the IoT platform is sent to the cloud with the help of the 5th generation Internet. The core of cloud computing uses the LSTM (long short-term memory) deep neural network algorithm. By simulating the proposed method and comparing the obtained results with other methods, it is observed that the accuracy of the proposed method is 97.13%, which has been improved by 10.41% in average over the other methods.
Engineering practices as a framework for STEM education: a proposal based on epistemic nuances
Authors: Simarro Cristina , Couso Digna 
Published: September 2021

AbstractThe role of engineering education has gained prominence within the context of STEM education. New educational perspectives such as the National Research Council’s Framework for K-12 Science Education consider engineering practices one of the central pillars of a sound STEM education. While this idea of developing a set of practices analogous to those of professional engineering resonates with recent views of STEM education research, current approaches such as the NRC’s Framework seem too dependent on and interlinked with the list for scientific practices and adheres to this list too strictly. This paper draws on the NRC’s Framework proposing a new set of engineering practices that seek to incorporate the epistemic nuances that differentiate engineering from science. The nine engineering practices proposed contain epistemological nuances that are missing in other proposals, including essential aspects such as problem scoping, identifying multiple solutions, selecting, testing and improving solutions and materializing solutions. This epistemic approach may facilitate students’ content learning and thinking development, offering a more comprehensive and realistic view of the STEM fields.
A novel mice model of acute flares in osteoarthritis elicited by intra-articular injection of cultured mast cells
Authors: Dan Junpei , Izumi Masashi , Habuchi Hiroko , Habuchi Osami , Takaya Shogo , Kasai Yusuke , Hayashi Ryuzo , Aso Koji , Ushida Takahiro , Ikeuchi Masahiko 
Published: September 2021

Abstract
Purpose
Mast cells are multifunctional in osteoarthritis (OA), and infiltration of activated mast cells likely contributes to disease severity and progression. However, the detailed mechanisms of action are unclear. The purpose of this study was to elucidate the role of mast cell infiltration in OA at histological level using a new mice model and to investigate pharmacological inhibitory effects of existing mast cell stabilizers in this model.

Methods
Mice were injected intra-articularly with monosodium iodoacetate (MIA 0.5 mg) or PBS on day 0, and PBS, with or without mast cells (MC: 1 × 106 cells) on day 14. They were divided into four groups: OA flare (MIA + MC), OA (MIA + PBS), MC non-OA (PBS + MC), and PBS non-OA (PBS + PBS). In OA flare, the MC stabilizer drug (tranilast: 400 mg/kg/day) or PBS was administered intraperitoneally from days 15 to 21.

Results
Histologically, modified Mankin score of the OA flare was significantly higher than that of OA (7.0 [1.8] vs. 3.3 [1.3], P < 0.05), and a larger number of mast cells was observed in OA flare than in OA (34.5 [6.3]/mm2 vs. 27.2 [2.3]/mm2, P < 0.05) on day 22. OA flare also showed acute exacerbation of pain and increased gene expression of pro-inflammatory cytokines and aggrecanase compared with OA. Administration of tranilast to OA flare-up provoked significant improvements in term of histological changes, pain, and gene expression at day 22.

Conclusion
Our novel model possibly mimics OA flare conditions, which may open a new strategy of disease-modifying treatment for OA, focused on controlling the multiple functions of mast cells.
Spontaneous common bile duct perforation due to choledocolithiasis accompanied with pancreaticobiliary maljunction in an adult: a case report
Authors: Sakamoto Risa , Kai Kengo , Hiyoshi Masahide , Imamura Naoya , Yano Koichi , Hamada Takeomi , Nishida Takahiro , Kawano Fumiaki , Sakurahara Daichi , Uchise Yukako , Yamamoto Koji , Kataoka Hiroaki , Nanashima Atsushi 
Published: September 2021

Abstract
Background
Spontaneous common bile duct (CBD) perforation is an extremely rare disease in adults. We report an adult case of CBD perforation due to choledocolithiasis accompanied with pancreaticobiliary maljunction, which is, to our knowledge, the first such case report based on a search using PubMed.

Case presentation
A 71-year-old woman with consciousness disorder was transported to the emergency department of another hospital. She was diagnosed as having severe peritonitis with septic shock and transferred to our hospital for emergency surgery. Enhanced computed tomography (CT) revealed supraduodenal CBD dilation similar to a diverticulum and a defect of bile duct wall continuity. Furthermore, CT showed a long common channel of the pancreaticobiliary duct, so she was diagnosed as having spontaneous CBD perforation with pancreaticobiliary maljunction. Emergency surgery was performed that revealed a necrotic diverticulum-like change on the supraduodenal part, and a 2.5 × 1 cm perforation was found on the anterolateral wall of the CBD. Peritoneal lavage was performed, and CBD perforation was resolved with a T-tube. The patient suffered refractory intra-abdominal and retroperitoneal abscess formation and bleeding from the abdominal wall, which required a long period of postoperative management. The T-tube was removed on day 136, and the patient was transferred on day 153.

Conclusion
The cause of CBD perforation is commonly considered to be increased intraductal pressure or weakness of the bile duct wall. In this case, pancreaticobiliary maljunction may have significantly influenced onset and the postoperative course. This case suggests that early surgical intervention and appropriate drainage are important to ensure survival.
MOrgAna: accessible quantitative analysis of organoids with machine learning
Authors: Gritti Nicola , Lim Jia Le , Anlaş Kerim , Pandya Mallica , Aalderink Germaine , Martínez-Ara Guillermo , Trivedi Vikas 
Published: September 2021

ABSTRACT
Recent years have seen a dramatic increase in the application of organoids to developmental biology, biomedical and translational studies. Organoids are large structures with high phenotypic complexity and are imaged on a wide range of platforms, from simple benchtop stereoscopes to high-content confocal-based imaging systems. The large volumes of images, resulting from hundreds of organoids cultured at once, are becoming increasingly difficult to inspect and interpret. Hence, there is a pressing demand for a coding-free, intuitive and scalable solution that analyses such image data in an automated yet rapid manner. Here, we present MOrgAna, a Python-based software that implements machine learning to segment images, quantify and visualize morphological and fluorescence information of organoids across hundreds of images, each with one object, within minutes. Although the MOrgAna interface is developed for users with little to no programming experience, its modular structure makes it a customizable package for advanced users. We showcase the versatility of MOrgAna on several in vitro systems, each imaged with a different microscope, thus demonstrating the wide applicability of the software to diverse organoid types and biomedical studies.
Integrative transcriptomic profiling of a mouse model of hypertension-accelerated diabetic kidney disease
Authors: Sembach Frederikke E. , Ægidius Helene M. , Fink Lisbeth N. , Secher Thomas , Aarup Annemarie , Jelsing Jacob , Vrang Niels , Feldt-Rasmussen Bo , Rigbolt Kristoffer T. G. , Nielsen Jens C. , Østergaard Mette V. 
Published: September 2021

ABSTRACT
The current understanding of molecular mechanisms driving diabetic kidney disease (DKD) is limited, partly due to the complex structure of the kidney. To identify genes and signalling pathways involved in the progression of DKD, we compared kidney cortical versus glomerular transcriptome profiles in uninephrectomized (UNx) db/db mouse models of early-stage (UNx only) and advanced [UNxplus adeno-associated virus-mediated renin-1 overexpression (UNx-Renin)] DKD using RNAseq. Compared to normoglycemic db/m mice, db/db UNx and db/db UNx-Renin mice showed marked changes in their kidney cortical and glomerular gene expression profiles. UNx-Renin mice displayed more marked perturbations in gene components associated with the activation of the immune system and enhanced extracellular matrix remodelling, supporting histological hallmarks of progressive DKD in this model. Single-nucleus RNAseq enabled the linking of transcriptome profiles to specific kidney cell types. In conclusion, integration of RNAseq at the cortical, glomerular and single-nucleus level provides an enhanced resolution of molecular signalling pathways associated with disease progression in preclinical models of DKD, and may thus be advantageous for identifying novel therapeutic targets in DKD.