bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of NADPH oxidase and its therapeutic intervention in TGF-β-mediated EMT progression: an in vitro analysis on HeLa cervical cancer cells
Authors: Muthuramalingam Karthika , Cho Moonjae , Kim Youngmee 
Published: January 2020

AbstractEpithelial to mesenchymal transition (EMT) is a complex biological event, wherein polarized epithelial cells lose their integrity resulting in a mesenchymal phenotype with enhanced motility, a phenomenon known as metastasis. However, the underlying mechanisms of EMT are still poorly understood in cervical carcinomas. In this study, we investigated the molecular signalling events responsible for the effect of TGF-β, a potent inducer of EMT, on HeLa cervical cancer cells. We observed that TGF-β treatment (5 ng/mL) upregulates the expression of EMT-associated transcription factors such as Snail and Slug and downregulates the expression of epithelial markers such as ZO-1 and E-cadherin. Furthermore, treatment with TGF-β activates both Smad-dependent and Smad-independent signaling pathways, which subsides upon addition of Diphenyleneiodonium (DPI), a potent ROS inhibitor that inhibits NADPH
oxidase (NOX). TGF-β treatment enhanced cellular migration and invasion ability was diminished in the presence of ROS inhibitors. In addition, we also observed that ROS-mediated, TGF-β-induced EMT progression was inhibited using therapeutic candidates that target the key signal transduction mediators, including PI3K/AKT, ERK, and P38/MAPK. Accordingly, we demonstrated the involvement of redox biology (NOX2 and NOX4 mediate migration and invasion) in TGF-β-mediated EMT advancement and explored suitable therapeutic interventions.
Severe intoxication caused by sodium-glucose cotransporter 2 inhibitor overdose: a case report
Authors: Nakamura Miho , Nakade Junya , Toyama Tadashi , Okajima Masaki , Taniguchi Takumi 
Published: January 2020

Abstract
Background
Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the urinary excretion of excess glucose. SGLT2 inhibitors have been reported to suppress the complications of diabetes and reduce overall mortality. However, little is known about the types of symptoms that may occur in response to an overdose of an SGLT2 inhibitor. Here, we describe a case of intoxication caused by an overdose of an SGLT2 inhibitor.

Case presentation
An otherwise physically healthy adult woman ingested an overdose of ipragliflozin, an SGLT2 inhibitor, and a polypill of olmesartan medoxomil, and azelnidipine in a suicide attempt. Although her blood ipragliflozin concentration was very high (9516.3 ng/mL) upon hospital arrival, her initial blood glucose level was normal, and she did not exhibit symptoms such as hypoglycemia or polyuria. Moderate renal dysfunction associated with an estimated glomerular filtration rate of 42.3 mL/min/1.73 m2 was observed. Thirty-six hours after ingestion, her blood ipragliflozin concentration decreased to a level equivalent to that observed after a therapeutic dose and her renal function improved almost simultaneously. After improvement in her renal function, the osmotic diuretic effect of the drug progressed. Her blood glucose level declined slightly but was in the normal range due to glucose administration. During the clinical course, fatal hypoglycemia was not observed.

Conclusions
Our case showed that an overdose of an SGLT2 inhibitor caused toxic effects on renal function, but severe hypoglycemia was not observed. Additional cases of intoxication from SGLT2 inhibitors alone would be helpful to clarify the mechanism of intoxication.
Novel immunomodulatory drugs and neo-substrates
Authors: Gao Shaobing , Wang Shichao , Song Yongping 
Published: January 2020

AbstractThalidomide, lenalidomide and pomalidomide are immunomodulatory drugs (IMiDs) effective in the treatment of multiple myeloma, myelodysplastic syndrome (MDS) with deletion of chromosome 5q and other hematological malignancies. Recent studies showed that IMiDs bind to CRBN, a substrate receptor of CRL4 E3 ligase, to induce the ubiquitination and degradation of IKZF1 and IKZF3 in multiple myeloma cells, contributing to their anti-myeloma activity. Similarly, lenalidomide exerts therapeutic efficacy via inducing ubiquitination and degradation of CK1α in MDS with deletion of chromosome 5q. Recently, novel thalidomide analogs have been designed for better clinical efficacy, including CC-122, CC-220 and CC-885. Moreover, a number of neo-substrates of IMiDs have been discovered. Proteolysis-targeting chimeras (PROTACs) as a class of bi-functional molecules are increasingly used as a strategy to target otherwise intractable cellular protein. PROTACs appear to have broad implications for novel therapeutics. In this review, we summarized new generation of immunomodulatory compounds, their potential neo-substrates, and new strategies for the design of novel PROTAC drugs.
Towards the restoration of the Mesoamerican Biological Corridor for large mammals in Panama: comparing multi-species occupancy to movement models
Authors: Meyer Ninon F. V. , Moreno Ricardo , Reyna-Hurtado Rafael , Signer Johannes , Balkenhol Niko 
Published: January 2020

Abstract
Background
Habitat fragmentation is a primary driver of wildlife loss, and the establishment of biological corridors is a conservation strategy to mitigate this problem. Identifying areas with high potential functional connectivity typically relies on the assessment of landscape resistance to movement. Many modeling approaches exist to estimate resistance surfaces but to date only a handful of studies compared the outputs resulting from different methods. Moreover, as many species are threatened by fragmentation, effective biodiversity conservation requires that corridors simultaneously meet the needs of multiple species. While many corridor planning initiatives focus on single species, we here used a combination of data types and analytical approaches to identify and compare corridors for several large mammal species within the Panama portion of the Mesoamerican Biological Corridor.

Methods
We divided a large mammal assemblage into two groups depending on the species sensitivity to habitat disturbance. We subsequently used cost-distance methods to produce multi-species corridors which were modeled on the basis of (i) occupancy of nine species derived from camera trapping data collected across Panama, and (ii) step selection functions based on GPS telemetry data from white-lipped peccary Tayassu pecari, puma Puma concolor, and ocelot Leopardus pardalis. In addition to different data sources and species groups, we also used different transformation curves to convert occupancy and step-selection results into landscape resistance values.

Results
Corridors modeled differed between sensitive and tolerant species, between the data sets, and between the transformation curves. There were more corridors identified for tolerant species than for sensitive species. For tolerant species, several corridors developed with occupancy data overlapped with corridors produced with step selection functions, but this was not the case for sensitive species.

Conclusion
Our study represents the first comparison of multispecies corridors parametrized with step selection functions versus occupancy models. Given the wide variability in output corridors, our findings underscore the need to consider the ecological requirements of several species. Our results also suggest that occupancy models can be used for estimating connectivity of generalist species. Finally, this effort allowed to identify important corridors within the MBC (i) at a country scale and (ii) for several species simultaneously to accurately inform the local authorities in conservation planning. The approach we present is reproducible in other sites and/or for other species.
Patients suffering from psychological impairments following critical illness are in need of information
Authors: Vlake Johan H. , van Genderen Michel E. , Schut Anna , Verkade Martijn , Wils Evert-Jan , Gommers Diederik , van Bommel Jasper 
Published: January 2020

Abstract
Background
Because critical illness survivors frequently experience several long-term psychological impairments altering quality of life after ICU, there is a trend towards increasing follow-up care, mainly via ICU follow-up clinics. Despite these and other initiatives, understanding of patient’s post-ICU needs to help them cope with their problems and subsequently improve quality of life is largely lacking. Our aim was therefore to assess the needs, expectations and wishes in ICU survivors to receive information with the purpose to help them better grasp ICU treatment. In addition, we assessed the perceived burden of psychological trauma after ICU treatment and the health-related quality of life (HRQoL) up to 2.5 years after ICU discharge.

Methods
In a multicentre, retrospective cross-sectional cohort study, the needs and preferred intervention methods were assessed using a self-composed inventory in adult mechanically ventilated ICU survivors (n = 43). Additionally, the Impact of Event Scale Revised, the Beck Depression Inventory, the EuroQol-5D-5L, and the Short-Form 12 were used to assess psychological burden and HRQoL.

Results
A substantial proportion of all ICU survivors (59%, 95% CI 44% to 74%) suffered from psychological impairments after ICU treatment. Seventy-five percent of these patients expressed a wish to receive information, but only 36% desired to receive this information using a commonly used information brochure. In contrast, 71% of these patients had a wish to receive information using a video film/VR. Furthermore, only 33% of these patients was satisfied with the information provided by their treating hospital. Patients with psychological PICS reported a worse HRQoL as compared to a normative Dutch sample (P < 0.001) and as compared to patients without psychological PICS (P < 0.01).

Conclusions
In a Dutch cohort of critical illness survivors, a substantial part of ICU survivors suffer from psychological impairments, such as PTSD and depression, which was associated with a worse HRQoL. These patients are in need of information, have no desire using an information brochure, but are willing to receive information using a video film/virtual reality module. These results support the exploration of such an intervention.
Carbon monoxide in intensive care medicine—time to start the therapeutic application?!
Authors: Goebel Ulrich , Wollborn Jakob 
Published: January 2020

AbstractCarbon monoxide (CO) is not only known as a toxic gas due to its characteristics as an odorless molecule and its rapid binding to haem-containing molecules, thus inhibiting the respiratory chain in cells resulting in hypoxia. For decades, scientists established evidence about its endogenously production in the breakdown of haem via haem-oxygenase (HO-1) and its physiological effects. Among these, the modulation of various systems inside the body are well described (e.g., anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-proliferative). Carbon monoxide is able to modulate several extra- and intra-cellular signaling molecules leading to differentiated response according to the specific stimulus. With our growing understanding in the way CO exerts its effects, especially in the mitochondria and its intracellular pathways, it is tempting to speculate about a clinical application of this substance. Since HO-1 is not easy to induce, research focused on the application of the gaseous molecule CO by itself or the implementation of carbon monoxide releasing molecules (CO-RM) to deliver the molecule at a time- and dose dependently safe way to any target organ. After years of research in cellular systems and animal models, summing up data about safety issues as well as possible target to treat in various diseases, the first feasibility trials in humans were established. Up-to-date, safety issues have been cleared for low-dose carbon monoxide inhalation (up to 500 ppm), while there is no clinical data regarding the injection or intake of any kind of CO-RM so far. Current models of human research include sepsis, acute lung injury, and acute respiratory distress syndrome as well as acute kidney injury. Carbon monoxide is a most promising candidate in terms of a therapeutic agent to improve outbalanced organ conditions. In this paper, we summarized the current understanding of carbon monoxide’s biology and its possible organ targets to treating the critically ill patients in tomorrow’s ICU.
A model of opinion and propagation structure polarization in social media
Authors: Prasetya Hafizh A. , Murata Tsuyoshi 
Published: January 2020

AbstractThe issue of polarization in online social media has been gaining attention in recent years amid the changing political landscapes of many parts of the world. Several studies empirically observed the existence of echo chambers in online social media, stimulating a slew of works that tries to model the phenomenon via opinion modeling. Here, we propose a model of opinion dynamics centered around the notion that opinion changes are invoked by news exposure. Our model comes with parameters for opinions and connection strength which are updated through news propagation. We simulate the propagation of multiple news under the model in synthetic networks and observe the evolution of the model’s parameters and the propagation structure induced. Unlike previous models, our model successfully exhibited not only polarization of opinion, but also segregated propagation structure. By analyzing the results of our simulations, we found that the formation probability of echo chambers is primarily connected to the news polarization. However, it is also affected by intolerance to dissimilar opinions and how quickly individuals update their opinions. Through simulations on Twitter networks, we found that the behavior of the model is reproducible across different network structure and sizes.
Analysis of river bed variation using SSARR and RMA-2 models
Authors: Hwang Ju Ha , Maeng Seung Jin , Kim Hyung San , Lee Seung Wook 
Published: January 2020

AbstractFuture changes in river bed were predicted under the assumption that flow velocity of past and changes in flow rate at upstream river due to construction of large-scale artificial structures downstream occur in the future. Therefore, the long-term runoff volume from the downstream part of Hosan Stream was estimated using the SSARR (Stream Synthesis and Reservoir Regulation Model). Changes in the river bed were simulated using RMA-2 and SED-2D, which are hydraulic models. As a result, it was found that the river bed variation is significantly affected by the inclusion of sediment in flood flow at upstream. A comprehensive evaluation of above results revealed that the river width has significantly affected flow rate, and the inclusion of sediment in flood flow from the upstream has a huge effect on changes in the riverbed. In this regard, there is a need to devise measures to mitigate future flood damage to artificial structures by reflecting sedimentation trends downstream before the construction of large-scale artificial structures at downstream of river.
A case of ileus surgery using the water pressure method against ileus caused by incarceration into the inverted bladder diverticulum
Authors: Morioka Hirotsugu , Aoki Jun , Fujino Kazuyoshi , Sugahara Yuki , Orihata Michihiro , Goto Michitoshi , Kobayashi Shigeru , Okazawa Yu 
Published: January 2020

Abstract
Background
Ileus is quite a common disease, but is associated with various causes. As far as we know, there have only been one case of ileus due to inverted bladder diverticulum, which is extremely rare.

Case presentation
The patient was a 53-year-old male. He made an emergency visit to our hospital with a chief complaint of left lower quadrant pain. He underwent right inguinal hernia surgery at 2 years of age with no history of laparotomy. An abdominal enhanced CT revealed inversion of the bladder left side wall where part of enlarged small intestine was found. Ascites were also found between the incarcerated small intestine and the bladder, leading to a diagnosis of strangulation ileus due to internal hernia and subsequent emergency surgery. A laparotomy revealed incarceration of the small intestine in the bladder left wall as a Richter type. The incarceration was rigid. We believed it would be difficult to pull out by extraction. Therefore, we inserted a Nelaton catheter between the incarcerated small intestine and the bladder and carried out the water pressure method to release the ileus. We did not perform an enterectomy since no manifest necrosis or perforation of the small intestine was found. The inverted bladder wall was a partial depression. We interpreted it to be a bladder diverticulum. We made a suture for occlusion with the bladder diverticulum inverted. Ileus arising from inverted bladder diverticulum is a very rare disease state. We hereinafter report on this case along with bibliographical considerations.

Conclusions
We experienced a case of small intestine ileus due to inverted bladder diverticulum, which is very rare. In terms of preservation of the bowel, we believed the water pressure method to release the ileus was useful.
Massive hiatal hernia involving prolapse of the entire stomach and pancreas resulting in pancreatitis and bile duct dilatation: a case report
Authors: Tomida Hidenori , Hayashi Masahiro , Hashimoto Shinichi 
Published: January 2020

Abstract
Background
Hiatal hernia is defined by the permanent or intermittent prolapse of any abdominal structure into the chest through the diaphragmatic esophageal hiatus. Prolapse of the stomach, intestine, transverse colon, and spleen is relatively common, but herniation of the pancreas is a rare condition. We describe a case of acute pancreatitis and bile duct dilatation secondary to a massive hiatal hernia of pancreatic body and tail.

Case presentation
An 86-year-old woman with hiatal hernia who complained of epigastric pain and vomiting was admitted to our hospital. Blood tests revealed a hyperamylasemia and abnormal liver function test. Computed tomography revealed prolapse of the massive hiatal hernia, containing the stomach and pancreatic body and tail, with peripancreatic fluid in the posterior mediastinal space as a sequel to pancreatitis. In addition, intrahepatic and extrahepatic bile ducts were seen to be dilated and deformed. After conservative treatment for pancreatitis, an elective operation was performed. There was a strong adhesion between the hernial sac and the right diaphragmatic crus. After the stomach and pancreas were pulled into the abdominal cavity, the hiatal orifice was closed by silk thread sutures (primary repair), and the mesh was fixed in front of the hernial orifice. Toupet fundoplication and intraoperative endoscopy were performed. The patient had an uneventful postoperative course post-procedure.

Conclusion
A rare massive hiatal hernia, involving the stomach and pancreatic body and tail, can cause acute pancreatitis with bile duct dilatation. The etiology can be flexure of the main pancreatic and extrahepatic bile ducts. Symptomatic herniation is best treated with surgery. Elective surgery is thought to be safer than emergent surgery in patients with serious complications.
A case of esophagojejunal varices rupture after proximal gastrectomy with double-tract reconstruction
Authors: Shinno Naoki , Kawabata Ryohei , Furukawa Haruna , Goda Seiichi , Sueda Toshinori , Matsumura Tae , Koga Chikato , Noura Shingo , Shimizu Junzo , Okada Atsuya , Hasegawa Junichi 
Published: January 2020

Abstract
Background
The varices after proximal or total gastrectomy are uncommon because the supplying vessels are all divided. Emergent upper gastrointestinal endoscopy is the cornerstone of first-line management for the diagnosis and treatment of esophageal varices. However, there is no widely accepted standard strategy for esophagojejunal varices. We report a patient with esophagojejunal varices rupture 3 months after proximal gastrectomy treated with percutaneous transhepatic obliteration.

Case presentation
A 50-year-old man who had undergone proximal gastrectomy with double-tract reconstruction for esophagogastric junctional cancer 3 months before was admitted to the hospital due to gastrointestinal perforation. We performed emergency surgery and abdominal symptoms and inflammatory response improved postoperative. However, on POD3, he had eruptive bleeding at the just anal side of esophagojejunal anastomosis. Endoscopic clipping was unsuccessful because the mucosa was fragile and easily lacerated. Contrast-enhanced CT scan revealed the dilatation of the jejunal vein flowing into the ascending jejunal limb. Therefore, he was diagnosed as esophagojejunal varices rupture and percutaneous transhepatic obliteration (PTO) was tried for hemostasis. The portal and superior mesenteric veins were catheterized with the percutaneous transhepatic approach. Contrast agent injection into the jejunal branch demonstrated retrograde flow to the azygos vein through esophagojejunal varices. The microcatheter was inserted into the variceal blood supply branch and 10 mL of 5% ethanolamine oleate with iopamidol was injected. After obliteration therapy, the superior mesenteric venogram showed complete occlusion of the variceal supply branch. The patient was discharged from the hospital without any complications after 14 days.

Conclusion
PTO can be effective for gastroesophageal varices rupture with a dilated jejunal vein of the ascending limb, few supplying vessels, and little ascites.
The performance of the World Rugby Head Injury Assessment Screening Tool: a diagnostic accuracy study
Authors: Fuller G. W. , Tucker R. , Starling L. , Falvey E. , Douglas M. , Raftery M. 
Published: January 2020

AbstractBackgroundOff-field screening tools, such as the Sports Concussion Assessment Tool (SCAT), have been recommended to identify possible concussion following a head impact where the consequences are unclear. However, real-life performance, and diagnostic accuracy of constituent sub-tests, have not been well characterized.MethodsA retrospective cohort study was performed in elite Rugby Union competitions between September 2015 and June 2018. The study population comprised consecutive players identified with a head impact event undergoing off-field assessments with the World Rugby Head Injury Assessment (HIA01) screening tool, an abridged version of the SCAT3. Off-field screening performance was investigated by evaluating real-life removal-from-play outcomes and determining the theoretical diagnostic accuracy of the HIA01 tool, and individual sub-tests, if player-specific baseline or normative sub-test thresholds were strictly applied. The reference standard was clinically diagnosed concussion determined by serial medical assessments.ResultsOne thousand one hundred eighteen head impacts events requiring off-field assessments were identified, resulting in 448 concussions. Real-life removal-from-play decisions demonstrated a sensitivity of 76.8% (95% CI 72.6–80.6) and a specificity of 86.6% (95% CI 83.7–89.1) for concussion (AUROC 0.82, 95% CI 0.79–0.84). Theoretical HIA01 tool performance worsened if pre-season baseline values (sensitivity 89.6%, specificity 33.9%, AUROC 0.62,p < 0.01) or normative thresholds (sensitivity 80.4%, specificity 69.0%, AUROC 0.75,p < 0.01) were strictly applied. Symptoms and clinical signs were the HIA01 screening tool sub-tests most predictive for concussion; with immediate memory and tandem gait providing little additional diagnostic value.ConclusionsThese findings support expert recommendations that clinical judgement should be used in the assessment of athletes following head impact events. Substitution of the tandem gait and 5-word immediate memory sub-tests with alternative modes could potentially improve screening tool performance.