bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe varus knees result in a high rate of undercorrection of lower limb alignment after opening wedge high tibial osteotomy
Authors: Kamada Satoshi , Shiota Etsuji , Saeki Kazuhiko , Kiyama Takahiko , Maeyama Akira , Yamamoto Takuaki 
Published: May 2019

Purpose: The purpose of this study was to clarify the indication for opening wedge high tibial osteotomy (OWHTO) in terms of lower limb alignment to achieve satisfactory clinical results. Methods: Ninety-two patients (98 knees) with medial compartment knee osteoarthritis were investigated in this study. The average follow-up period was 34 months (range, 24–68 months). The average age of the patients at the time of surgery was 63 years (range, 41–77 years). Results: The patients were divided into the following two groups according to the preoperative femorotibial angle (FTA) on anteroposterior full-length radiographs of the lower limbs while weight bearing: 29 knees with a preoperative FTA of ≥185° were defined as those with severe varus (S group), and the remaining 69 knees with a preoperative FTA of <185° were defined as those with mild varus (M group). Knees with a postoperative FTA of >175° were defined as undercorrected. The Lysholm score was used to assess the clinical results. The average postoperative FTA was 175.7° ± 4.1° in the S group and 174.6° ± 3.1° in the M group ( p = 0.013). Significantly, more undercorrected knees were observed in the S than M group ( p = 0.00035). The postoperative Lysholm score was 85.6 ± 8.5 in the S group and 88.5 ± 5.7 in the M group at the last follow-up ( p = 0.0033). Conclusion: Based on these results, we recommend that a preoperative FTA of <185° should be included as a criterion for OWHTO alone.
The quality of informed consent obtained for orthopedic surgeries—elective versus trauma: A prospective interview-based study
Authors: Shemesh S , Sidon E , Heller S , Cohen N , Kosashvili Y , Dovrat R , Velkes S , Burg A 
Published: May 2019

Background: Orthopedic surgeons routinely obtain informed consent prior to surgery. Legally adequate informed consent necessitates a thorough discussion of treatment options and risks and proper documentation. However, the quality of informed consent in orthopedic trauma patients is an under-researched area. Purpose: To assess the quality of the informed consent process in trauma compared with elective orthopedic patients and to assess patients’ emotional state at the time of signing consent form. Methods: Sixty-two consecutive patients undergoing either elective total joint arthroplasty ( N = 32) or orthopedic trauma surgery ( N = 30) were included. The data were collected through personal interviews using a proposed informed consent score. The interviews were held after obtaining the informed consent and before the index procedure. Patients were asked to describe their diagnosis, the surgical procedure, its’ benefits, and risks as well as alternative treatments. Results: Mean age differed significantly between elective and trauma group patients (66.1 vs. 51.6, respectively, p < 0.01), while gender and education level were comparable ( p = 0.075, p = 0.55, respectively). The quality of consent was significantly better for patients with post-high-school education compared to elementary education level (consent score: 16.9 ± 4.1 vs. 12.2 ± 5.5, p = 0.021). Patients in the elective group showed an overall higher quality of consent, as reflected by a mean score of 17.03 ± 4.2 versus a mean score of only 13.73 ± 4.7 in the trauma group ( p = 0.005, 95% CI: 1.02–5.57). Specifically, trauma patients demonstrated a lower comprehension of the diagnosis, the benefits of surgical treatment, the possible complications, and the expected postoperative course. Conclusion: Patients undergoing trauma surgery are significantly more likely to have an inadequate understanding of the proposed treatment. These findings raise questions concerning the validity of consent from trauma patients.
Signaling mechanisms inducing hyporesponsiveness of phagocytes during systemic inflammation
Authors: Freise Nicole , Burghard Alina , Ortkras Theresa , Daber Niklas , Imam Chasan Achmet , Jauch Saskia-L. , Fehler Olesja , Hillebrand Julia , Schakaki Mosab , Rojas Jessica , Grimbacher Bodo , Vogl Thomas , Hoffmeier Andreas , Martens Sven , Roth Johannes , Austermann Judith 
Published: May 2019

Abstract
The inflammatory responsiveness of phagocytes to exogenous and endogenous stimuli is tightly regulated. This regulation plays an important role in systemic inflammatory response syndromes (SIRSs). In SIRSs, phagocytes initially develop a hyperinflammatory response, followed by a secondary state of hyporesponsiveness, a so-called “tolerance.” This hyporesponsiveness can be induced by endotoxin stimulation of Toll-like receptor 4 (TLR4), resulting in an ameliorated response after subsequent restimulation. This modification of inflammatory response patterns has been described as innate immune memory. Interestingly, tolerance can also be triggered by endogenous TLR4 ligands, such as the alarmins myeloid-related protein 8 (MRP8, S100A8) and MRP14 (S100A9), under sterile conditions. However, signaling pathways that trigger hyporesponsiveness of phagocytes in clinically relevant diseases are only barely understood. Through our work, we have now identified 2 main signaling cascades that are activated during MRP-induced tolerance of phagocytes. We demonstrate that the phosphatidylinositol 3-kinase/AKT/GSK-3β pathway interferes with NF-κB–driven gene expression and that inhibition of GSK-3β mimics tolerance in vivo. Moreover, we identified interleukin-10–triggered activation of transcription factors STAT3 and BCL-3 as master regulators of MRP-induced tolerance. Accordingly, patients with dominant-negative STAT3 mutations show no tolerance development. In a clinically relevant condition of systemic sterile stress, cardiopulmonary bypass surgery, we confirmed the initial induction of MRP expression and the tolerance induction of monocytes associated with nuclear translocation of STAT3 and BCL-3 as relevant mechanisms. Our data indicate that the use of pharmacological JAK-STAT inhibitors may be promising targets for future therapeutic approaches to prevent complications associated with secondary hyporesponsiveness during SIRS.
Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura
Authors: Sun Lova , Mack Johnathan , Li Ang , Ryu Justine , Upadhyay Vivek A. , Uhl Lynne , Kaufman Richard M. , Stowell Christopher P. , Dzik Walter S. , Makar Robert S. , Bendapudi Pavan K. 
Published: May 2019

AbstractPatients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not. Of 124 patients, 60 (48%) received RTX and 34 (27%) experienced relapse. Median time to relapse was 3.71 (interquartile range, 1.75-4.9) and 1.33 (interquartile range, 0.43-2.35) years for RTX-treated and untreated patients, respectively. RTX conferred protection from relapse at 1 year of follow-up (P = .01) but not at 5 years of follow-up. Extended Cox regression was then used to identify predictors of relapse and to estimate the protective effect of RTX. The following parameters were independently associated with increased risk for subsequent relapse: presenting in iTTP relapse (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.4-6.4), age younger than 25 years (HR, 2.94; 95% CI, 1.2-7.2), and non-O blood group (HR, 2.15; 95% CI, 1.06-4.39). RTX initially provided protection from relapse (HR, 0.16; 95% CI, 0.04-0.70), but this effect gradually diminished, returning to the baseline risk for untreated patients at approximately 2.6 years. Patients who are young, have non-O blood group, or present with relapsed iTTP are at increased risk for subsequent relapse. RTX appears to confer short-term protection from relapse.
Elimination of the fibrinogen integrin αMβ2-binding motif improves renal pathology in mice with sickle cell anemia
Authors: Nasimuzzaman Md , Arumugam Paritha I. , Mullins Eric S. , James Jeanne M. , VandenHeuvel Katherine , Narciso Marilou G. , Shaw Maureen A. , McGraw Sarah , Aronow Bruce J. , Malik Punam 
Published: May 2019

AbstractSickle cell anemia (SCA) is caused by a point mutation in the β-globin gene that leads to devastating downstream consequences including chronic hemolytic anemia, episodic vascular occlusion, and cumulative organ damage resulting in death. SCA patients show coagulation activation and inflammation even in the absence of vascular occlusion. The coagulation factor fibrinogen is not only central to hemostasis but also plays important roles in pathologic inflammatory processes, in part by engaging neutrophils/macrophages through the αMβ2 integrin receptor. To determine whether fibrin(ogen)-mediated inflammation is a driver of SCA-associated pathologies, hematopoietic stem cells from Berkeley sickle mice were transplanted into homozygous Fibγ390-396A mice that express normal levels of a mutant form of fibrin(ogen) that does not engage αMβ2. Fibγ390-396A mice with SCA displayed an impressive reduction of reactive oxygen species (ROS) in white blood cells (WBCs), decreased circulating inflammatory cytokines/chemokines, and significantly improved SCA-associated glomerular pathology highlighted by reduced glomerulosclerosis, inflammatory cell infiltration, ischemic lesions, mesangial thickening, mesangial hypercellularity, and glomerular enlargement. In addition, Fibγ390-396A mice with SCA had improved glomerular protective responses and podocyte/mesangial transcriptional signatures that resulted in reduced albuminuria. Interestingly, the fibrinogen γ390-396A mutation had a negligible effect on cardiac, lung, and liver functions and pathologies in the context of SCA over a year-long observation period. Taken together, our data support that fibrinogen significantly contributes to WBC-driven inflammation and ROS production, which is a key driver of SCA-associated glomerulopathy, and may represent a novel therapeutic target against irreversible kidney damage in SCA.
RETRACTED ARTICLE: Long non-coding RNA TPTEP1 inhibits hepatocellular carcinoma progression by suppressing STAT3 phosphorylation
Authors: Ding Hongda , Liu Junpeng , Zou Ruoyao , Cheng Pengrui , Su Yang 
Published: May 2019

Abstract
Background
Hepatocellular carcinoma (HCC) is still the most common cause of tumor-related death worldwide and accumulating studies report that long non-coding RNAs (LncRNAs) are closely related with HCC development, metastasis and prognosis. Cisplatinum, a well-known chemotherapeutic drug, has been widely used for treatment of numerous human cancers including HCC. This study aimed to investigate the differential expressions of LncRNAs in HCC cells treated with cisplatinum and its underlying mechanism.

Methods
The differential expressions of LncRNAs in HCC cells treated with cisplatinum were determined by RNA-seq. The roles of TPTEP1 in HCC development by applying gene function gain and loss analysis in MHCC97H and QYG-7703 cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell proliferation, colony formation, cell invasion and flow cytometry assays. The underlying mechanism of TPTEP1 sensitizing hepatocellular carcinoma cells to cisplatinum was examined by RNA-pull down, western blotting, subcellular fractionation, RNA immunoprecipitation and dual luciferase reporter assays. The effect of TPTEP1 on tumorigenesis in vivo was performed with a subcutaneous xenograft mouse model of HCC. In addition, TPTEP1 expression was detected in clinical tumor tissue samples by qRT-PCR.

Results
LncRNA TPTEP1 was highly expressed in cisplatinum-treated HCC cells, which sensitizes hepatocellular carcinoma cell to cisplatinum-induced apoptosis. TPTEP1 overexpression inhibited, while TPTEP1 knockdown promoted HCC cell proliferation, tumorigenicity and invasion. Furthermore, TPTEP1 exerted its tumor suppressing activities by interacting with signal transducer and activator of transcription 3 (STAT3) to inhibit its phosphorylation, homodimerization, nuclear translocation and down-stream genes transcription. Moreover, TPTEP1 overexpression obviously inhibits tumor masses in vivo in a subcutaneous xenograft mouse model of HCC and TPTEP1 is frequently downregulated in HCC tissues, compared to its corresponding pre-tumor tissues.

Conclusion
LncRNA TPTEP1 inhibits hepatocellular carcinoma cells progression by affecting IL-6/STAT3 signaling. Taken together, our findings suggest a tumor suppressing role of TPTEP1 in HCC progression and provide a novel understanding of TPTEP1 during the chemotherapy for HCC.
Correction to: One-step templated synthesis of chiral organometallic salicyloxazoline complexes
Authors: Luo Mei , Zhang Jing Cheng , Yin Hao , Wang Cheng Ming , Morris-Natschke Susan , Lee Kuo-Hsiung 
Published: May 2019

Following publication of the original article [1], the authors reported an error in Schemes 1 and 2 and repeated line in subsection “Bis(ligand) nickel(II) chelate (NiL12)”.
Symbol spotting for architectural drawings: state-of-the-art and new industry-driven developments
Authors: Rezvanifar Alireza , Cote Melissa , Branzan Albu Alexandra 
Published: May 2019

AbstractThis review paper offers a contemporary literature survey on symbol spotting in architectural drawing images. Research on isolated symbol recognition is quite mature; the same cannot be said for recognizing a symbol in context. One important challenge is the segmentation/recognition paradox: a system should segment symbols before recognizing them, but some kind of recognition may be necessary to obtain a correct segmentation. Research has thus been recently directed toward symbol spotting, a way of locating possible symbol instances without using full recognition methods. In this paper, we thoroughly review symbol spotting methods with a focus on architectural drawings, an application domain providing the document image analysis and graphic recognition communities with an interesting set of challenges linked to the sheer complexity and density of embedded information, that have yet to be resolved. While most existing methods perform well in terms of recall, their performance is rather poor in terms of precision and false positives. In light of the review, we also propose a simple yet effective symbol spotting method based on template matching and a novel clutter-tolerant cross-correlation function that achieves state-of-the-art results with high precision, high recall, and few false positives, able to cope with “real-life clutter” found in industry-standard architectural drawings.
Actions and Potential Therapeutic Applications of Growth Hormone–Releasing Hormone Agonists
Authors: Schally Andrew V , Zhang Xianyang , Cai Renzhi , Hare Joshua M , Granata Riccarda , Bartoli Manuela 
Published: May 2019

Abstract
In this article, we briefly review the identification of GHRH, provide an abridged overview of GHRH antagonists, and focus on studies with GHRH agonists. Potent GHRH agonists of JI and MR class were synthesized and evaluated biologically. Besides the induction of the release of pituitary GH, GHRH analogs promote cell proliferation and exert stimulatory effects on various tissues, which express GHRH receptors (GHRH-Rs). A large body of work shows that GHRH agonists, such as MR-409, improve pancreatic β-cell proliferation and metabolic functions and facilitate engraftment of islets after transplantation in rodents. Accordingly, GHRH agonists offer a new therapeutic approach to treating diabetes. Various studies demonstrate that GHRH agonists promote repair of cardiac tissue, producing improvement of ejection fraction and reduction of infarct size in rats, reduction of infarct scar in swine, and attenuation of cardiac hypertrophy in mice, suggesting clinical applications. The presence of GHRH-Rs in ocular tissues and neuroprotective effects of GHRH analogs in experimental diabetic retinopathy indicates their possible therapeutic applications for eye diseases. Other effects of GHRH agonists, include acceleration of wound healing, activation of immune cells, and action on the central nervous system. As GHRH might function as a growth factor, we examined effects of GHRH agonists on tumors. In vitro, GHRH agonists stimulate growth of human cancer cells and upregulate GHRH-Rs. However, in vivo, GHRH agonists inhibit growth of human cancers xenografted into nude mice and downregulate pituitary and tumoral GHRH-Rs. Therapeutic applications of GHRH analogs are discussed. The development of GHRH analogs should lead to their clinical use.
The Role of Sexual Hormones on the Enteroinsular Axis
Authors: Handgraaf Sandra , Philippe Jacques 
Published: May 2019

AbstractSex steroid estrogens, androgens, and progesterone, produced by the gonads, which have long been considered as endocrine glands, are implicated in sexual differentiation, puberty, and reproduction. However, the impact of sex hormones goes beyond these effects through their role on energy metabolism. Indeed, sex hormones are important physiological regulators of glucose homeostasis and, in particular, of the enteroinsular axis. In this review, we describe the roles of estrogens, androgens, and progesterone on glucose homeostasis through their effects on pancreatic α- and β-cells, as well as on enteroendocrine L-cells, and their implications in hormonal biosynthesis and secretion. The analysis of their mechanisms of action with the dissection of the receptors implicated in the several protective effects could provide some new aspects of the fine-tuning of hormonal secretion under the influence of the sex. This knowledge paves the way to the understanding of transgender physiology and new potential therapeutics in the field of type 2 diabetes.
Sacubitril/Valsartan Augments Postprandial Plasma Concentrations of Active GLP-1 When Combined With Sitagliptin in Men
Authors: Wewer Albrechtsen Nicolai J , Mark Peter D , Terzic Dijana , Hansen Lasse H , Andersen Ulrik Ø , Hartmann Bolette , Carr Richard D , Gustafsson Finn , Deacon Carolyn F , Holst Jens J , Goetze Jens P , Plomgaard Peter 
Published: May 2019

Abstract

Context
Combined inhibition of neprilysin and dipeptidyl peptidase 4 (DPP-4) has been shown to augment plasma concentrations of glucagon-like peptide-1(GLP-1) in animal models, but whether this occurs in humans is unknown.

Objective
To investigate the effects of inhibition of neprilysin by sacubitril/valsartan alone or in combination with a DPP-4 inhibitor (sitagliptin) on plasma concentrations of GLP-1 in healthy men.

Design
Two open-labeled crossover studies were performed in human subjects.

Setting
General community.

Participants
Nine and 10 healthy young men were included in study 1 and study 2, respectively.

Intervention
Study participants received a standardized meal (34% carbohydrates, 45% fat, 21% protein; total caloric content, 2106 kJ) combined with a prior dose of either sacubitril/valsartan (194/206 mg) or control in study 1 and in study 2, with a prior dose of sitagliptin (2 ×100 mg, given ∼10 hours apart) either alone or with sacubitril/valsartan (194/206 mg).

Main Outcome Measures
Plasma concentrations of total and intact GLP-1.

Results
Sacubitril/valsartan increased postprandial plasma concentrations of total GLP-1 by 67% [total area under the curve (tAUC)0–240min: 3929 ± 344 vs 2348 ± 181 minutes × pmol/L, P = 0.0023] and increased concentrations of intact GLP-1 plasma concentrations more than sitagliptin alone (tAUC0–240min: 1021 ± 114 vs 660 ± 80 minutes × pmol/L, P = 0.01). Plasma concentrations of glucose, insulin, and GIP were not significantly (P > 0.10) changed upon sacubitril/valsartan treatment.

Conclusions
Sacubitril/valsartan combined with a DPP-4 inhibitor led to markedly higher concentrations of intact GLP-1 than DPP-4 inhibition alone, supporting a role for both neprilysin and DPP-4 in the metabolism of GLP-1 in humans, a finding that may have therapeutic implications.
OR04-6 Predictors of Clinical Outcome after Adrenalectomy for Unilateral Primary Aldosteronism
Authors: Moises Caio , Alencar Natalia , Castanheira Thaís , Vilela Leticia , Rassi-Cruz Marcela , Guimarães Augusto , Pereira Maria Adelaide , Silva Giovanio , Abreu Andrea , Zerbini Maria Claudia , Cavalcante Aline , Carnevale Francisco , Pilan Bruna , Yamauchi Fernando , Srougi Vitor , Chambo José , Latronico Ana Claudia , Mendonca Berenice , Fragoso Maria , Bortolotto Luiz , Drager Luciano , Almeida Madson 
Published: May 2019

Abstract
Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT) with an estimated prevalence of 10% in referred populations and 15-20% in patients with resistant hypertension. The most common cause of unilateral PA is aldosterone-producing adenomas (APAs). HT and hypokalemia improve in nearly 100% of patients with unilateral PA after unilateral adrenalectomy. However, complete clinical success (defined as blood pressure ≤130x80 mmHg without anti-hypertensive drugs) has been reported in about 50% (range, 35-80%) of patients with unilateral PA after surgery. HT duration and severity have been associated with clinical outcome after adrenalectomy, but few reports with a limited number of cases evaluated the prognostic role of somatic KCNJ5 mutations. In this study, our aim was to determine clinical and molecular features associated with complete clinical success after unilateral adrenalectomy in unilateral PA patients. We retrospectively evaluated 103 PA patients (42 males; median age 49 yrs, 20-74) with a median follow-up of 25 months. Hypokalemia was present in 78% of the cases. Anatomopathological analysis revealed 94 APAs and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 mutations were identified in 27 out of 67 (40%) tumors: p.Gly151Arg (n= 13), p.Leu168Arg (n= 13) and p.Glu145Gln (n= 1). Complete clinical success was reported in 32 out of 103 (31%) patients. In univariate analysis, HT duration, body mass index (BMI kg/m2), female sex and somatic KCNJ5mutations were associated with HT resolution after adrenalectomy. Complete clinical success was reported in 50% of patients with HT duration ≤5 yrs (vs. 24% with HT duration &gt;5 yrs; p= 0.011), in 40% of patients with BMI &lt;25 (vs. 22% with BMI ≥25; p= 0.042), in 38% of women (vs. 21% of men; p= 0.079) and in 70% of the patients with tumors harboring KCNJ5 somatic mutations (vs. 30% with WT tumors; p= 0.003). According to a stepwise multivariate logistic regression analysis, only the presence of a somatic KCNJ5 mutation was an independent predictor of complete success after adrenalectomy (relative risk 4.8, 95% confidence interval 1.24 to 19.21; p= 0.023). In conclusion, the presence of a somatic KCNJ5 mutation was an independent predictor of complete clinical success after unilateral adrenalectomy in patients with unilateral PA.