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Currently, multivariate time series classification is widely used in various fields, including industrial process control, action recognition, and health monitoring. Due to their sequential modeling capabilities, Transformer networks with self-attention mechanisms have been successfully applied to multivariate time series classification tasks. However, the original transformer network can only calculate the relative dependence between two adjacent time steps, which makes it difficult to find local continuous dependence from scattered time steps. To address this issue, we propose an ensemble model called Ensemble Based Fully Convolutional Transformer Network (E-FCTN) that combines a gated transformer network (GTN) and a fully convolutional neural network (FCN). In the E-FCTN ensemble model, the GTN calculates the attention matrix between channels and time steps in a multivariate time series. Meanwhile, the FCN is also applied to extract local features to construct the basic belief assignment. Using the Proportional Conflict Redistribution rule no. 5 (PCR5) in the Dezert-Smarandache theory (DSmT), the output of the FCN and GTN are fused at the decision level, and the final decision is made according to the maximum plausibility. The information extracted by the FCN compensates for the deficiency of the GTN in local feature extraction. Finally, the proposed method is validated on eight publicly available datasets to demonstrate its effectiveness. [ABSTRACT FROM AUTHOR]

Background: Migraine research has highlighted the pivotal role of nitric oxide (NO) in migraine pathophysiology. Nitric oxide donors such as glyceryl trinitrate (GTN) induce migraine attacks in humans, whereas spontaneous migraine attacks can be aborted by inhibiting NO production. The present study aimed to investigate how GTN triggers migraine through its three nitric oxide synthase (NOS) isoforms (neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)) via a suspected feed-forward phenomenon. Methods: Migraine-relevant hypersensitivity was induced by repeated injection of GTN in an in vivo mouse model. Cutaneous tactile sensitivity was assessed using von Frey filaments. Signaling pathways involved in this model were dissected using non-selective and selective NOS inhibitors, knockout mice lacking eNOS or nNOS and their wild-type control mice. Also, we tested a soluble guanylate cyclase inhibitor and a peroxynitrite decomposition catalyst (Ntotal = 312). Results: Non-selective NOS inhibition blocked GTN-induced hypersensitivity. This response was partially associated with iNOS, and potentially nNOS and eNOS conjointly. Furthermore, we found that the GTN response was largely dependent on the generation of peroxynitrite and partly soluble guanylate cyclase. Conclusions: Migraine-relevant hypersensitivity induced by GTN is mediated by a possible feed-forward phenomenon of NO driven mainly by iNOS but with contributions from other isoforms. The involvement of peroxynitrite adds to the notion that oxidative stress reactions are also involved. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN). Method: Databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case--control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint. Result: Twenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m²), MTX (8 days), and MTX (30--50 mg/m²) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m²), MTX (8 days), and MTX (30--50 mg/m²) in RCT. Conclusion: Among the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies. [ABSTRACT FROM AUTHOR]

To identify the differentiating features in clinical presentation, management, and maternal/fetal outcome in complete hydatidiform mole and coexistent fetus compared with placental mesenchymal dysplasia. Between 1997 and 2015, five women with complete hydatidiform mole and coexistent fetus and four women with placental mesenchymal dysplasia were managed at the University of California San Francisco. Clinical features were analyzed and compared with previously published data. Of the five cases of complete hydatidiform mole and coexistent fetus, two had live births. β-hCG levels were > 200,000 IU/L in all cases. On imaging, a clear plane between the cystic component and the placenta favored a diagnosis of complete hydatidiform mole and coexistent fetus. None of the patients went on to develop gestational trophoblastic neoplasia (GTN), with a range of follow-up from 2 to 38 months. Combining this data with previously published work, the live birth rate in these cases was 38.8%, the rate of persistent GTN was 36.2%, and the rate of persistent GTN in patients with reported live births was 27%. Of the four cases of placental mesenchymal dysplasia, all four had live births. One patient developed HELLP syndrome and intrauterine growth restriction; the remaining three were asymptomatic. Maternal symptoms, fetal anomalies, β-hCG level, and placental growth pattern on imaging may help differentiate between complete hydatidiform mole and coexistent fetus and placental mesenchymal dysplasia. There was not an increased risk of gestational trophoblastic neoplasia in patients with complete hydatidiform mole and coexistent fetus who opted to continue with pregnancy.

Gestational trophoblastic neoplasia (GTN) arising in the placenta and presenting as a metastatic disease concurrently in the mother and the baby is extremely rare. GTN poses a diagnostic dilemma to the treating clinicians. In the current review, an electronic search of Scopus, PubMed, Embase and other databases was conducted for case reports and case series of GTN co-existing or metastatic to both the mother and the baby, published to date. Globally, a total of twenty-two cases of GTN with metastasis to both the mother and baby was found. The previous history of histopathology confirmed molar pregnancy was present in 4/22 cases. The median time to diagnose GTN in the mother was six weeks post-partum. In the majority of cases, diagnosis of maternal disease was made after the infant presented with clinical manifestation. Overall survival was reported in 17/22 mothers up to varying latest follow-up and in 6/22 infants. A knowledge of the varied clinical presentation, eliciting a history of previous pregnancy loss/term pregnancy and serum beta human chorionic gonadotrophin (p-hCG) estimations were helpful for early diagnosis. The concurrent presence of GTN in the mother and baby is a rare entity and poses a diagnostic dilemma. Diagnosis in the mother often follows diagnosis in the baby after an infant presents with clinical manifestations. GTN is a highly chemo-sensitive tumour, but the main prognostic factors determining survival are the time to diagnosis following previous pregnancy and serum p-hCG levels. [ABSTRACT FROM AUTHOR]

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor, first described by Shih and Kurman in 1998. ETT often present as abnormal vaginal bleeding in women of reproductive age, but unlike more common forms of GTN tend to produce much less human chorionic gonadotropin (hCG) for the volume of disease present. ETT can occur after any gestational event and can occur in both intrauterine and extrauterine sites. We present a case of a 46-year-old female patient incidentally diagnosed with ETT and hepatic metastasis. Therapy was multimodal and involved chemotherapy, operation, thermoablation of liver metastases and immunocheckpoint inhibitor. The patient remains disease free for almost four years now. ETT presents a diagnostic challenge due to their rarity and histologic resemblance to other pathologies. ETT can be relatively chemo resistant and are therefore often treated surgically. Misdiagnosis might delay effective treatment and affects survival.

Abstract Background Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50–60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan. Methods In vivo mouse models of PACAP38-, GTN-, and levcromakalim-induced migraine were applied using tactile sensitivity to von Frey filaments as measuring readout. Signaling pathways involved in the three models were dissected using PACAP-inhibiting antibodies (mAbs) and sumatriptan. Results We showed that PACAP mAbs block PACAP38 induced hypersensitivity, but not via signaling pathways involved in GTN and levcromakalim. Also, sumatriptan has no effect on PACAP38-induced hypersensitivity relevant to migraine. This is the first study testing the effect of a PACAP-inhibiting drug on GTN- and levcromakalim-induced hypersensitivity. Conclusions Based on the findings in our mouse model of migraine using migraine-inducing compounds and anti-migraine drugs, we suggest that PACAP acts via a distinct pathway. Using PACAP38 antagonism may be a novel therapeutic target of interest in a subgroup of migraine patients who do not respond to existing therapies.

Background: Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50–60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan. Methods: In vivo mouse models of PACAP38-, GTN-, and levcromakalim-induced migraine were applied using tactile sensitivity to von Frey filaments as measuring readout. Signaling pathways involved in the three models were dissected using PACAP-inhibiting antibodies (mAbs) and sumatriptan. Results: We showed that PACAP mAbs block PACAP38 induced hypersensitivity, but not via signaling pathways involved in GTN and levcromakalim. Also, sumatriptan has no effect on PACAP38-induced hypersensitivity relevant to migraine. This is the first study testing the effect of a PACAP-inhibiting drug on GTN- and levcromakalim-induced hypersensitivity. Conclusions: Based on the findings in our mouse model of migraine using migraine-inducing compounds and anti-migraine drugs, we suggest that PACAP acts via a distinct pathway. Using PACAP38 antagonism may be a novel therapeutic target of interest in a subgroup of migraine patients who do not respond to existing therapies. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic neoplasia (GTN) is a curable cancer with chemotherapy. However, some develop chemoresistance to standard chemotherapy and surgery can be a useful option in them. Our study aimed to assess the role of salvage surgery in GTN with chemoresistance. It is a retrospective hospital-based study from 2000 to 2021. Case sheets of women who underwent salvage surgery for chemoresistance were reviewed and clinical parameters like preoperative hCG, antecedent pregnancy, WHO risk score, multiple chemotherapy regimens prior surgery, presence of > 1 disease site, and presence of residual choriocarcinoma that predicted the effect of surgery on serological response were assessed using Fisher's exact test. A total of 19 patients with high-risk GTN developed chemoresistance and underwent salvage surgery. Eight underwent hysterectomy, 3 underwent hysterectomy plus adnexal tumour resection, six received fertility-sparing surgery, and two underwent segmental resection of the lung. Histopathological examination revealed viable tumour in 7/19 patients, but significant fall in median hCG level from 161.5 mIU/ml (preoperatively) to 15.5 mIU/ml (postoperatively) was noted. Preoperative hCG < 100 mIU/ml (p = 0.019) was the most important determinant of complete response to surgery. All the patients who had disease confined to the uterus and/or lungs at the time of surgery achieved remission after completion of treatment. Our study concludes that in the case of chemoresistant high-risk GTN, carefully selected cases with low hCG levels and disease confined to the uterus and/or lungs get the most benefit of surgery. The use of postoperative chemotherapy after complete response is essential to maintain remission and prevent relapse. [ABSTRACT FROM AUTHOR]

[Display omitted] • The original and shear-modified GTN ductile fracture criteria are utilized during the stretch bending process. • The original GTN model can be used only in processes where the stress state is the same as the calibration test stress state. • The evolution of damage, principal strains, and displacement of fractures under different forming conditions are investigated. In this paper, the original and shear-modified GTN ductile fracture criteria are utilized to investigate the fracture behavior of the AA6061-T6 aluminum alloy sheet during the stretch bending process. An appropriate calibration strategy is presented to find the unknown coefficients of the fracture models. In this way, different tension tests such as uniaxial tension, plane strain, notched tension, and shear tension specimens are utilized. Results show that the shear-modified GTN model calibrated by the mentioned tension tests is able to predict the onset of fracture of the stretch bending process with a 5% error, while the original GTN model, calibrated by the uniaxial tension is unable to predict the fracture properly. Since the accuracy of fracture prediction depends on the stress state, the effects of the calibration test on onset of fracture were investigated. It is shown that using the original GTN model with a proper calibration test (plane strain tension) can achieve a good accuracy with 3.5% error in the stretch bending process. In addition, results show that any change in the friction coefficient and bending radius in the stretch bending process can lead to different fracture behavior. Several investigations are carried out to examine the evolution of damage and displacement of fractures in the stretch bending process under different forming conditions. [ABSTRACT FROM AUTHOR]

Background: There is extensive literature on incorrect positioning of peripherally inserted central catheter (PICC) line tips, particularly concerning advancement into the right atrium causing cardiac tamponade. However, there is little literature concerning inadvertent arterial cannulation as a complication of PICC insertion and what steps could be taken to prevent it. Case presentation: An extreme preterm neonate had a PICC line inserted into the left arm to provide central venous access for parenteral nutrition. Following the insertion, an anteroposterior chest X-ray was used to confirm positioning and was deemed acceptable. It was reviewed by a consultant radiologist the next day. Fifteen hours after insertion, the nursing staff raised concerns that the fingertips on the neonate’s left hand appeared dusky and were getting progressively darker. Upon removal of the PICC line, an upper limb Doppler was performed, showing severe stenosis of the brachial artery with no flow distally in the radial or ulnar arteries. Conclusions: This case demonstrates that glyceryl trinitrate (GTN) patches can be used to reverse peripheral ischaemia in neonates with good effect. After reflecting on the case, we decided that monitoring distal limb colour and perfusion should be part of observations in neonates with central venous lines in situ and documentation should reflect this. Furthermore, when concerns are raised about distal perfusion in a limb with lines in situ, all lines should be removed immediately. We would like to emphasise that it is of vital importance to promote a culture of openness where all team members are empowered to raise concerns about patient safety.

Objective: Molar pregnancy coexistent with a live fetus can be a diagnostic and therapeutic challenge. With increasing incidence of multiple pregnancies, there has also been an increase in twin pregnancy with one mole in the recent years. The authors discuss the epidemiology, clinical presentation, and prenatal diagnosis and attempt to design a possible management strategy, to help guide the treating physician, in the management of partial mole with live pregnancy, thereby improving maternal and fetal prognosis. Material and Methods: Numerous case reports have been published in various journals regarding management of individual cases of partial molar pregnancy coexistent with live fetus (PMCF). Therefore, we conducted a systematic review of all the case reports and short case series in English concerning partial mole with live pregnancy from 1999 to 2019, that is in the last 20 years. Results: In total, 44 case reports of PMCF were analyzed. The mean gestational age at diagnosis was 20+6 (range: 10-40) weeks. Less than half (19/44; 43.2%) were asymptomatic at the time of detection and PMCF was detected on routine scan done for fetal well-being or 11-13-week scan. The majority (56.8%) resulted in the birth of a healthy live fetus. Gestational trophoblastic neoplasia developed in 3/44 (6.8%). Conclusion: PMCF involves a high risk of bleeding, preterm labour, intrauterine growth restriction and stillbirth. Successful management of such cases needs prenatal diagnosis, antepartum surveillance and post-natal follow-up. An obstetrician, maternal fetal medicine specialist, gynecology oncologist and neonatal intensivist should be involved in the care of such pregnancies. [ABSTRACT FROM AUTHOR]

Background: Transdermal glyceryl trinitrate (GTN) has potential beneficial properties in acute stroke including intracerebral hemorrhage (ICH) and possible clinical benefits suggested in ultra‐early stroke (≤6 h). Our meta‐analysis updated the evidence on its safety and benefits in acute stroke. Methods: We searched major electronic databases for randomized trials comparing transdermal GTN versus placebo/control in acute stroke. Primary outcomes were mortality, 90‐day modified Rankin Scale (mRS), and blood pressure (BP) effects. Secondary outcomes included early, late, resource utilization, and surrogate outcomes. Safety outcomes were adverse events. Reviewers identified studies, extracted data, and assessed risk of bias (RoB) using a modified Cochrane RoB instrument and quality of evidence (QoE) using GRADE. We also performed a priori subgroup and trial sequential analyses (TSA) on primary outcomes. These subgroup analyses were ICH versus ischemic stroke, minor (NIHSS ≤5) versus major (NIHSS >5) ischemic stroke, ischemic stroke with versus without thrombolysis, prehospital versus non prehospital settings, time from stroke to randomization ≤6 h versus >6 h, and high versus low overall RoB studies. Results: Seven eligible primary trials enrolled 5363 patients. GTN reduced BP (mean difference [MD] = –4.74 mm Hg, 95% confidence interval [CI] = –6.03 to –3.45 mm Hg] and diastolic BP (MD = –2.94 mm Hg, 95% CI = –3.74 to −2.13 mm Hg) 24 h posttreatment but did not affect 4‐ to 10‐day mortality (relative risk [RR] = 1.11, 95% CI = 0.82 to 1.49), 90‐day mortality (RR = 0.96, 95% CI = 0.77 to 1.19), and 90‐day mRS >2 (RR = 0.98, 95% CI = 0.93 to 1.03) compared to control/placebo. The QoE was high for primary outcomes with no subgroup effects detected. GTN did not affect secondary outcomes and increased risk of headache and hypotension. TSA generally supported our conclusions regarding primary outcomes. Conclusions: Transdermal GTN reduces BP in acute stroke but does not alter clinical outcomes even in ultra‐early stroke (≤6 h). [ABSTRACT FROM AUTHOR]

The single point incremental sheet forming (SPIF) is an advanced sheet metal forming technique, also known as dieless sheet forming. Formability in incremental sheet forming is defined by the maximum formable wall angle or the depth of forming. In this work, the formability in SPIF is predicted by the Gurson-Tvergaard-Needleman (GTN) model. The parameters of the GTN model was optimised by the response surface methodology (RSM). These parameters were determined by the tensile test experiment and simulation correlation. The optimised parameters were used in the numerical analysis of SPIF process to predict the failure. The results are in good agreement with experimental results and model predicts depth of forming with acceptable accuracy. Further, as the wall angle of the component increases the formability decreases in SPIF, which is well predicted by the numerical model with optimised parameters. In addition to this, the thickness reduction and damage evolution for varying wall angle has been reported with help of numerical analysis. [ABSTRACT FROM AUTHOR]

Choricocarcinoma is a highly malignant tumor. It metastasize commonly to the lungs. Metastasis to the kidney is uncommon, and bilateral metastasis is described rarely. Initial presentation with spontaneous bleeding of the renal metastatic tumor is scarce in the literatures. Here we present a case report of a choriocarcinoma patient with bilateral renal metastasis, presenting with spontaneous renal hemorrhage. A 22 years old female presented to our emergency department with sudden onset of left flank pain. She has history of spontaneous abortion 02 years back with biopsy from the manual vacuum aspiration (MVA) showing molar pregnancy. Up on evaluation, patient was anemic. CT scan showed left renal bleeding tumor. Exploratory laparotomy and radical nephrectomy was done with the impression of bleeding renal cell carcinoma. The biopsy revealed choriocarcinoma. On her follow up, CT scan showed right renal and brain metastasis. She was given multi agent chemotherapy and her serum beta-hCG became undetectable after 01 year. Choriocarcinoma can be gestational or nongestational. The commonest route of metastasis is hematogenous. Presenting symptoms of renal metastasis can be hematuria, pain or more commonly incidental finding during work up. Choriocarcinoma is highly chemo sensitive. Bilateral renal metastatic choriocarcinoma is uncommon. Spontaneous renal hemorrhage as an initial presentation is even rare, and it can mimic a bleeding renal cell carcinoma. High index of suspicion is needed in a young women with recent history of spontaneous abortion. • Choriocarcinoma is a highly malignant tumor. • Choriocarcinoma metastasis to the kidneys is uncommon. • Initial presentation of choriocarcinoma patients with spontaneous renal hemorrhage is rare. • Choriocarcinoma is highly chemo sensitive. Radical nephrectomy has a place in emergency settings. [ABSTRACT FROM AUTHOR]

Background: Anal fissure is a common condition that can be treated medically or surgically. Chemical sphincterotomy is often used before surgical intervention. This study aims to evaluate the effectiveness of topical agents for chemical sphincterotomy on healing of anal fissures and side-effects. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant systematic review was performed using MEDLINE, EMBASE, Scopus, and CENTRAL databases. Eligible studies included randomized controlled trials which compared topical sphincterotomy agents with topical placebo agents or each other. Studies that included surgical treatments were excluded. Overall evidence was synthesized according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: Thirty-seven studies met the study selection criteria. Seventeen studies show that glyceryl trinitrate (GTN) was significantly more likely to heal anal fissure than placebo (relative risk (RR) = 1.96, 95% confidence interval (95%CI) = 1.35–2.84, I2 = 80%). Eleven studies showed a marginally significant difference between healing rates for diltiazem vs GTN, RR = 1.16, (1.01–1.33) I2 = 48%. There was no significant difference in healing between diltiazem and placebo, RR = 1.65, (0.64–4.23), I2 = 92%. GTN significantly reduced pain on the visual analog scale compared to the placebo group, MD–0.97 (–1.64 to –0.29) I2 = 92%. There was high certainty of evidence that GTN was significantly more likely to cause headache than placebo (RR = 2.73 (1.82–4.10) I2 = 58%) and diltiazem RR = 6.88 (2.19–21.63) I2 = 17%. Conclusion: There is low certainty evidence topical nitrates are an effective treatment for anal fissure healing and pain reduction compared to placebo. Despite widespread use of topical diltiazem, more evidence is required to establish the effectiveness of calcium channel blockers compared to placebo. [ABSTRACT FROM AUTHOR]

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion. Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN. Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p < 0.001), left ventricular (LV) stroke work (7,708 ± 2,782 vs. 6,071 ± 2,660 ml mmHg, p < 0.001), and rate pressure product (7,214 ± 1,051 vs. 6,929 ± 976 mmHg bpm, p = 0.06) all fell. LV ejection fraction increased (61 ± 3 vs. 66 ± 4%, p < 0.001), with cardiac output remaining constant (6.2 ± 1.5 vs. 6.5 ± 1.4 l/min, p = 0.37). Myocardial PCr/ATP fell during GTN infusion (2.17 ± 0.2 vs. 1.99 ± 0.22, p = 0.03) with an increase in both CK kf (0.16 ± 0.07 vs. 0.25 ± 0.1 s−1, p = 0.006) and CK flux (1.8 ± 0.8 vs. 2.6 ± 1.1 μmol/g/s, p = 0.03). Conclusion: During GTN infusion, despite reduced LV stroke work and maintained cardiac output, there was a 44% increase in myocardial ATP delivery through CK. As PCr/ATP fell, this increase in ATP demand coincided with GTN-induced impairment of mitochondrial oxidative phosphorylation. Overall, this suggests that while GTN reduces cardiac work, it does so at the expense of increasing ATP demand beyond the capacity to increase ATP production. [ABSTRACT FROM AUTHOR]

Initiation and propagation of ductile fractures are major consideration during the design of high-pressure pipelines. Consequences of a pipeline failure can be catastrophic thus structural integrity must be ensured over several decades. Traditional lab-scale experiments such as the Charpy V-Notch (CVN) and Drop Weight Tear Test (DWTT), impact experiments on a notched three-point bending sample, are widely used to measure the fracture toughness of a material. However, with increasing wall thickness and the transition to high-grade steels in the pipeline industry, the size-effect of the specimen and inverse fracture became prominent issues. A new testing methodology called the Dynamic Tensile Tear Test (DT3) is currently investigated as to address the issues presented by the current state of the art. In this study, a numerical investigation is conducted on the CVN, DWTT and DT3 experiments to compare the modelling of dynamic ductile fracture propagation in three different testing scales using the Gurson-Tvergaard-Needleman (GTN) damage model. X70 and X100 pipeline steel grades are used to model material behaviour. For each considered lab-scale experiment, the dynamic ductile fracture behaviour was successfully reproduced using the GTN damage model.

Uterine surgery is a common predisposing factor for uterine rupture, while an invasive mole that leads to uterine rupture is a rare clinical occurrence. Here, we report a case of a 31-year-old childless woman who underwent abortion after 53 days of pregnancy. She still experienced abdominal pain and scanty vaginal bleeding after the abortion. Her levels of human chorionic gonadotropin (HCG) were high, while ultrasound and MRI results revealed an enlarged uterus and a mass in the myometrium. During preparation for treatment, the gynecologist ruptured the uterus of the patient, leaving her shocked. Eventually the patient's uterus was removed the uterus and pathologically diagnosed as result is the an invasive mole.

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p

To identify the differentiating features in clinical presentation, management, and maternal/fetal outcome in complete hydatidiform mole and coexistent fetus compared with placental mesenchymal dysplasia.Between 1997 and 2015, five women with complete hydatidiform mole and coexistent fetus and four women with placental mesenchymal dysplasia were managed at the University of California San Francisco. Clinical features were analyzed and compared with previously published data.Of the five cases of complete hydatidiform mole and coexistent fetus, two had live births. β-hCG levels were > 200,000 IU/L in all cases. On imaging, a clear plane between the cystic component and the placenta favored a diagnosis of complete hydatidiform mole and coexistent fetus. None of the patients went on to develop gestational trophoblastic neoplasia (GTN), with a range of follow-up from 2 to 38 months. Combining this data with previously published work, the live birth rate in these cases was 38.8%, the rate of persistent GTN was 36.2%, and the rate of persistent GTN in patients with reported live births was 27%. Of the four cases of placental mesenchymal dysplasia, all four had live births. One patient developed HELLP syndrome and intrauterine growth restriction; the remaining three were asymptomatic.Maternal symptoms, fetal anomalies, β-hCG level, and placental growth pattern on imaging may help differentiate between complete hydatidiform mole and coexistent fetus and placental mesenchymal dysplasia. There was not an increased risk of gestational trophoblastic neoplasia in patients with complete hydatidiform mole and coexistent fetus who opted to continue with pregnancy.

Abstract Background Some studies have suggested that transdermal administration of glyceryl trinitrate (GTN; nitroglycerin) in the first few hours after symptom onset increases the chance of a favourable outcome after ischaemic stroke or intracerebral haemorrhage, possibly through an increase in intracranial collateral blood flow and a reduction in blood pressure. The Multicentre Randomised trial of Acute Stroke treatment in the Ambulance with a nitroglycerin Patch (MR ASAP) aims to assess the effect of transdermal GTN, started within 3 h after stroke onset in the prehospital setting, on functional outcome at 90 days in patients with acute ischaemic stroke or intracerebral haemorrhage. Methods MR ASAP is a phase III, multicentre, randomised, open-label clinical trial with a blinded outcome assessment. A total of 1400 adult patients with suspected stroke and a systolic blood pressure ≥ 140 mmHg will be randomised to transdermal GTN (5 mg/day), administered as a transdermal patch by paramedics in the prehospital setting within 3 h of stroke onset and continued for 24 h or to standard care. The primary outcome is the score on the modified Rankin Scale (mRS) at 90 days, analysed with ordinal logistic regression. Secondary outcomes include blood pressure and collateral circulation at hospital admission, neurological deficit measured with the National Institutes of Health Stroke Scale at 24 h, and mortality and poor outcome (mRS score 3 to 6) at 90 days. This trial will be conducted in the Netherlands and will use a deferred consent procedure. The trial is part of the Collaboration for New Treatments of Acute Stroke (CONTRAST) programme. Discussion MR ASAP will assess whether very early administration of GTN improves outcome after stroke in a setting where rates of intravenous thrombolysis and endovascular treatment for acute ischaemic stroke are high. The deferred consent procedure facilitates prompt GTN treatment and will prevent delay to revascularisation therapies. If early transdermal GTN treatment proves to be effective, this low-cost treatment can be readily implemented into daily clinical practice. Trial registration ISRCTN Registry, ISRCTN99503308. Registered on 2 January 2018.

The Gurson–Tvergaard–Needleman (GTN) damage model is widely used to predict ductile failure initiation and propagation. However, the material-dependent parameters can show a significant spread when determined for the same steel grade material. Different calibration procedures and optimisation processes cause a significant variation in the obtained parameter values. Furthermore, there is no clear consensus on which parameters require calibration. In this study, the influence of the material-dependent parameters used to model the dynamic ductile fracture behaviour of X70 grade pipeline steel is investigated. A sensitivity analysis is performed on a finite element model of a Charpy V-Notch (CVN) specimen. Seven GTN model parameters are considered in a total of 70 simulations. A feedforward back-propagating artificial neural network (ANN) is constructed and trained using data obtained through the numerical simulations. A connected weights (CW) algorithm allows to determine the relative influence of each parameter on the fracture energy. It was observed that the void growth acceleration factor plays an important role with respect to the parameter influences. Remarkably, the mean nucleation strain, ε N has the highest relative importance whilst the critical void volume fraction, f c —which is considered as a crucial damage parameter—showed the smallest influence when the acceleration factor is low. On the contrary, when considering a high acceleration factor, f c becomes the most influential parameter. Based on the obtained importance for each parameter, it is suggested that parameters f 0 , f c , f F , and f N should be selected for calibration in each individual application. Finally, the applied machine learning approach is used to predict the fracture energy for a given set of damage parameters for X70 grade steel. It is observed that the trained neural network is able to provide a satisfactory approximation of the CVN fracture energy. [ABSTRACT FROM AUTHOR]

Initiation and propagation of ductile fractures are a major consideration during the design of high-pressure pipelines. Consequences of a pipeline failure can be catastrophic thus structural integrity must be ensured over several decades. Traditional lab-scale experiments such as the Charpy V-Notch (CVN) and Drop Weight Tear Test (DWTT), impact experiments on a notched three-point bending sample, are widely used to measure the fracture toughness of a material. However, with increasing wall thickness and the transition to high-grade steels in the pipeline industry, the size-effect of the specimen and inverse fracture became prominent issues. A new testing methodology called the Dynamic Tensile Tear Test (DT3) is currently investigated as to address the issues presented by the current state of the art. In this study, a numerical investigation is conducted on the CVN, DWTT and DT3 experiments to compare the modelling of dynamic ductile fracture propagation in three different testing scales using the Gurson-Tvergaard-Needleman (GTN) damage model. X70 and X100 pipeline steel grades are used to model material behaviour. For each considered lab-scale experiment, the dynamic ductile fracture behaviour was successfully reproduced using the GTN damage model.

In the present paper, we propose a numerical modeling of fracture behavior of High Density Polyethylene (HDPE) using different fracture mechanics approaches as well as a simulation of the static behavior by calibrating the static traction curves in order to highlight the feasibility of the model in reproducing the results of the EWF. The numerical determination of the fracture parameters by the global approach which will be validated by a simulation by means of DENT specimens and results obtained are compared to those of experimental results. [ABSTRACT FROM AUTHOR]

Initiation and propagation of ductile fractures are major consideration during the design of high-pressure pipelines. Consequences of a pipeline failure can be catastrophic thus structural integrity must be ensured over several decades. Traditional lab-scale experiments such as the Charpy VNotch (CVN) and Drop Weight Tear Test (DWTT), impact experiments on a notched three-point bending sample, are widely used to measure the fracture toughness of a material. However, with increasing wall thickness and the transition to high-grade steels in the pipeline industry, the size-effect of the specimen and inverse fracture became prominent issues. A new testing methodology called the Dynamic Tensile Tear Test (DT3) is currently investigated as to address the issues presented by the current state of the art. In this study, a numerical investigation is conducted on the CVN, DWTT and DT3 experiments to compare the modelling of dynamic ductile fracture propagation in three different testing scales using the Gurson-Tvergaard-Needleman (GTN) damage model. X70 and X100 pipeline steel grades are used to model material behaviour. For each considered lab-scale experiment, the dynamic ductile fracture behaviour was successfully reproduced using the GTN damage model. [ABSTRACT FROM AUTHOR]

Tumour lysis syndrome is rare in solid malignancies. Here, we report a case of tumour lysis syndrome and acute kidney injury in a 23-year-old female with gestational trophoblastic neoplasia. Hydration and early dialysis therapy were started with good recovery. On follow up she progressed to chronic kidney disease. After 6 years of follow up, the patient conceived and delivered successfully. [ABSTRACT FROM AUTHOR]

The two-pore potassium channel, TRESK has been implicated in nociception and pain disorders. We have for the first time investigated TRESK function in human nociceptive neurons using induced pluripotent stem cell-based models. Nociceptors from migraine patients with the F139WfsX2 mutation show loss of functional TRESK at the membrane, with a corresponding significant increase in neuronal excitability. Furthermore, using CRISPR-Cas9 engineering to correct the F139WfsX2 mutation, we show a reversal of the heightened neuronal excitability, linking the phenotype to the mutation. In contrast we find no change in excitability in induced pluripotent stem cell derived nociceptors with the C110R mutation and preserved TRESK current; thereby confirming that only the frameshift mutation is associated with loss of function and a migraine relevant cellular phenotype. We then demonstrate the importance of TRESK to pain states by showing that the TRESK activator, cloxyquin, can reduce the spontaneous firing of nociceptors in an in vitro human pain model. Using the chronic nitroglycerine rodent migraine model, we demonstrate that mice lacking TRESK develop exaggerated nitroglycerine-induced mechanical and thermal hyperalgesia, and furthermore, show that cloxyquin conversely is able to prevent sensitization. Collectively, our findings provide evidence for a role of TRESK in migraine pathogenesis and its suitability as a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective: The efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN)., Method: Databases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case-control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint., Result: Twenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m 2 ), MTX (8 days), and MTX (30-50 mg/m 2 ) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m 2 ), MTX (8 days), and MTX (30-50 mg/m 2 ) in RCT., Conclusion: Among the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou and Kemin.)

The formability of high strength AA7075 aluminum alloy under elevated temperatures is vital in guiding the fabrication of automobile structural parts. The ductile fracture forming limit of AA7075 at elevated temperatures is essentially governed by thermal damage evolution. In this paper, the hot tensile test (300ºC-450 °C, strain rate 0.1s−1-0.001s−1) for AA7075 was conducted and the corresponding flow behavior was fitted by Hensiel-Spittel (HS) constitutive equation. The GTN mesoscopic damage model was implemented to take account of the damage evolution phenomenon of AA7075 at elevated temperatures. The temperature-dependent damage void volume fractions (VVF) were identified accurately based on a novel inverse identification procedure, named the CCD parameters design-FEM inverse simulation-genetic algorithm (CCD-FEIS-GA) optimization method. Subsequently, the thermal forming limit diagram (TFLD) was calculated based on the GTN damage parameters and further validated by hot Nakajima-type bulging experiment. The corresponding damage evolution behaviors and effects of critical forming parameters were discussed in detail. The comparison of experimental and numerical results showed that the formability of AA7075 firstly increases and then decreases with the increasing forming temperature, the TFLD 0 reaches its maximum value when the temperature is 400 °C, and the formability also increases with the increasing strain rate and the decreasing surface coefficient of friction. The proposed simulated strategy coupled with mesoscopic GTN approach conduces to the accurate prediction of TFLD and damage fracture behavior of AA7075 in the hot forming process. Image 1 • Thermal mechanical behavior and damage characteristics of AA7075 were discussed. • The GTN damage fractions were identified by a novel inverse optimization procedure. • The TFLD of AA7075 was predicted by the GTN model and validated. • The effects of hot forming parameters of AA7075 were analyzed and discussed. [ABSTRACT FROM AUTHOR]

This work aims to study material nonlinearity related to a dual‐phase Steel (DP600) specimen loaded under a tension. Experiment is performed, and then captured data are processed by 3D digital image correlation (DIC). It deals with two analyses; firstly, elastoplastic response of material due to tension up to material plastification. Then, the problem is modelled using FEM, considering an isotropic von Mises criterion/hardening behaviour. To obtain comparable numerical results, model is solved using meshless methods. Besides strain fields, load/displacement response is evaluated, and numerical formulations are validated with experimental solution. Second, failure phenomenon due to plasticity is studied since material undergoes its failure. The empirical results rely on DIC, and then, damage model is resolved using Gurson‐Tvergaard‐Needleman (GTN) criterion. As a result, the engineering stress/strain curves are reported. Comparisons are made between DIC and GTN damage model. Promising computational results are verified by DIC results implying that supportive strategy is proficient. [ABSTRACT FROM AUTHOR]

Background and Objectives: GTN is a general term for an extensive range of malignant trophoblastic diseases including invasive mole, choriocarcinoma, epithelioid trophoblastic tumors and placental site trophoblastic tumors. The aim of this study was to predict the risk of GTN in patients with molar pregnancy in Tehran. Methods: All cases with partial and complete mole with a record of at least 4 titers of β-hCG were included in this study. Before and after fitting the appropriate model for calculating the area under the curve of each predictor variable, the type of the relationship (linear or non-linear) was first determined using locally weighted scatter plot smoothing (Lowess Smoother) and fractional polynomial regression‏ (Fracpoly); then, a model tailored to data processing was used for drawing the ROC diagram. Results: Nonparametric chi-square analysis indicated no significant difference between the components of high-risk molar pregnancy and GTN (P=0.39). Generally, among 201 cases of molar pregnancy, 61 (30%) had one of the components of high-risk molar pregnancy. The ROC curve with an AUC of 0.86 showed that the regression slope of β-hCG with 73% sensitivity and 88% specificity could be used as a predictor. Conclusion: The serum β-hCG measurement after 21 days of molar pregnancy evacuation and the slope of the linear regression line of β-hCG were found be good tests to distinguish between patients who will benefit from spontaneous disease remission and patients developing GTN.

This paper discusses the influence of the Tvergaard parameters, qi, which are basic constants of the Gurson-Tvergaard-Needleman (GTN) material model, on the numerically simulated load-carrying capacity of tensile elements made of S235JR steel. The elements were considered to be under static tension at low initial stress triaxiality σm/σe = 1/3. Two sets of the Tvergaard parameters qi were analyzed: those typical of structural steels and those dependent on material strength properties. The results showed that the Tvergaard parameters, qi, had influence on the load-carrying capacity of tensile elements at low initial stress triaxiality. They affected the strength curves and the changes in the void volume fractions determined for S235JR steel elements

Objectives: To compare the post-operative mean pain scores after using 0.2% GTN ointment and Placebo in patients with openhemorrhoidectomy. Material and Methods: This randomized control study was conducted in Surgical A unit of Khyber Teaching Hospital Peshawar, Pakistan from January 2016 to December 2016. Using non probability sampling technique, 92 patients with grade III and grade IV hemorrhoids were randomly selected through OPD and divided into two groups. Group A received 0.2% topical GTN and Group B received placebo (liquid paraffin) post-operatively after hemorrhoidectomy. The patients were followed up for mean pain scores at 7 post-operative day and data was collected. Results: A total of 92 patientswere divided in two equal groups. Male to female ratio was 1.49:1. The average age of the patients was38.97 years +13.23SD. Pain-wise distribution showed that placebo group have an average pain of 6.75+1.395SD while in GTN group it was 5.58+2.45SD with p-value = 0.032. Conclusion: Topical 0.2% GTN ointment was more effective than placebo in post- hemorrhoidectomy pain management. [ABSTRACT FROM AUTHOR]

In this paper, the initial values of damage parameters in the Gurson−Tvergaard−Needleman (GTN) model are determined by a microscopic test combined with empirical formulas, and the final accurate values are determined by finite element reverse calibration. The original void volume fraction (f0), the volume fraction of potential nucleated voids (fN), the critical void volume fraction (fc), the void volume fraction at the final failure (fF) of material are assigned as 0.006, 0.001, 0.03, 0.06 according to the simulation results, respectively. The hemispherical punch stretching test of commercially pure titanium (TA1) sheet is simulated by a plastic constitutive formula derived from the GTN model. The stress and strain are obtained at the last loading step before crack. The forming limit diagram (FLD) and the forming limit stress diagram (FLSD) of the TA1 sheet under plastic forming conditions are plotted, which are in good agreement with the FLD obtained by the hemispherical punch stretching test and the FLSD obtained by the conversion between stress and strain during the sheet forming process. The results show that the GTN model determined by the finite element reverse calibration method can be used to predict the forming limit of the TA1 sheet metal.