Size Extension Research Articles

ExpressGesture: Expressive gesture generation from speech through database matching

AbstractCo‐speech gestures are a vital ingredient in making virtual agents more human‐like and engaging. Automatically generated gestures based on speech‐input often lack realistic and defined gesture form. We present a database‐driven approach guaranteeing defined gesture form. We built a large corpus of over 23,000 motion‐captured co‐speech gestures and select individual gestures based on expressive gesture characteristics that can be estimated from speech audio. The expressive parameters are gesture velocity and acceleration, gesture size, arm swivel, and finger extension. Individual, parameter‐matched gestures are then combined into animated sequences. We evaluate our gesture generation system in two perceptual studies. The first study compares our method to the ground truth gestures as well as mismatched gestures. The second study compares our method to five current generative machine learning models. Our method outperformed mismatched gesture selection in the first study and showed competitive performance in the second.

Functionalized TiO2 mediated organic-inorganic composite membranes based on quaternized poly(arylene ether ketone) with enhanced ionic conductivity and alkaline stability for alkaline fuel cells

In this work, quaternized poly(arylene ether ketone) (QPAEK)/functionalized TiO2 (f-TiO2) composite membranes were fabricated with different f-TiO2 contents (1, 3, 5, 7, and 9 wt%), and the structure of the materials was characterized by 1H NMR, ATR-FT-IR, XRD, XPS, and FE-SEM. The addition of f-TiO2 enlarges the ion cluster in the membrane due to enhancing the interaction between the functional groups, and SAXS analysis revealed an extension of the ion domain size with an increase in the filler content (up to 5 wt%). In particular, the composite membrane with 5 wt% f-TiO2 displayed the highest ion conductivity (74.6 mS cm−1); such a result was attributed to the formation of water traps by the deliquescence of TiO2 and enhanced interfacial interactions between the pure organic polymers and inorganic nanomaterials. This work proves that a composite membrane with an appropriate f-TiO2 concentration is a promising candidate for application to anion exchange membranes.

Prediction of Hearing Preservation in Vestibular Schwannoma Surgery According to Tumor Size and Anatomic Extension.

Vestibular schwannoma (VS) surgery is feasible for various tumor sizes that are inappropriate for wait and scan or radiosurgery. The predictive value of 2 grading systems was investigated for postoperative hearing preservation (HP) in a large series. Retrospective analysis. Neurosurgical patient database of the University of Erlangen was queried between 2014 and 2017. Retrospective single-center analysis on 138 VSs operated on via a retrosigmoidal approach. The mean tumor size was 20.4 mm (SD, 7.6 mm) with fundal infiltration in 67.4%. The overall resection rate was 93.5%. Tumors were classified preoperatively by the 3-tier Erlangen grading system depending on size or the anatomically based 4-tier Koos grading system. Preoperative hearing preservation was found in 70.3% of patients and was significantly correlated to tumor size (P = .001). For Erlangen grading, a mean postoperative serviceable hearing preservation rate of 32% was achieved: 83.3% for tumors <12 mm, 30.3% for tumors between 12 and 25 mm, and 5.3% for tumors >25 mm. In contrast, according to Koos grading, postoperative serviceable hearing preservation was 100% for grade 1 tumors (meatal), 35.6% for grade 2 (cisternal), 23.1% for grade 3 (brainstem contact), and 21.7% for grade 4 (brainstem compression). Of the total cohort, 86% had normal or nearly normal postoperative facial function (House-Brackmann grades 1 and 2). Surgery on small VSs can achieve excellent hearing preservation. Different grading has a significant influence on and correlates with postoperative hearing preservation. Tumor size seems more important than anatomic relationship.

Mineralogical and geochemical characteristics of graphite-bearing rocks at Chenjere Area, south-eastern Tanzania: Implications for the nature and quality of graphite mineralization

This study focused on the mineralogical and geochemical characteristics of graphite-bearing rocks at Chenjere area by conducting surface geological mapping, geochemical and petrographical analyses with the intention of characterizing the nature of graphite occurrence in these lithological units. This paper presents results of the flake size, grade and mineralization extension of graphite in the graphitic gneiss. Field observations, petrographic investigation and comparison with other studies indicate that graphite occurrence at the Chenjere area is of sedimentary origin which fall under syngenetic type. The petrographic study revealed that nature of metamorphism of rocks in the Chenjere area is of high grade (amphibolite facies). Both field observations and petrographic studies indicate that minerals in the rock associated with graphite include quartz, feldspar (mostly K-feldspar) and biotite. Further, the mineralized zones are concordant to the rest of the lithologies of the area and biotite gneiss is forming the hangingwall and footwall. The rocks’ foliation is generally NE striking and dipping SE with the dip amount ranging from 30 to 60 degrees. The graphite mineralization at the study area occurs as medium to coarse grained crystalline, flake type graphite with long axis of up to 1000 micrometres in size. Graphite flakes are disseminated and oriented in the host rock that represents a normal metamorphic fabric. Geochemical results indicate that graphite contents in the host graphitic gneiss range from 3.03 wt.% to 16.00 wt.%. Mineralogy and texture of the graphite at Chenjere area meet the standards required for industrial applications in various advanced technologies.&#x0D; Keywords: Graphite Mineralization, Flake Graphite, Chenjere Area

Prior Sample Size Extensions for Assessing Prior Impact and Prior-Likelihood Discordance

AbstractThis paper outlines a framework for quantifying the prior’s contribution to posterior inference in the presence of prior-likelihood discordance, a broader concept than the usual notion of prior-likelihood conflict. We achieve this dual purpose by extending the classic notion of prior sample size, M, in three directions: (I) estimating M beyond conjugate families; (II) formulating M as a relative notion that is as a function of the likelihood sample size k, M(k), which also leads naturally to a graphical diagnosis; and (III) permitting negative M, as a measure of prior-likelihood conflict, that is, harmful discordance. Our asymptotic regime permits the prior sample size to grow with the likelihood data size, hence making asymptotic arguments meaningful for investigating the impact of the prior relative to that of likelihood. It leads to a simple asymptotic formula for quantifying the impact of a proper prior that only involves computing a centrality and a spread measure of the prior and the posterior. We use simulated and real data to illustrate the potential of the proposed framework, including quantifying how weak is a ‘weakly informative’ prior adopted in a study of lupus nephritis. Whereas we take a pragmatic perspective in assessing the impact of a prior on a given inference problem under a specific evaluative metric, we also touch upon conceptual and theoretical issues such as using improper priors and permitting priors with asymptotically non-vanishing influence.

Histology is more ιmportant than persistent anti-Tg antibodies for progression of differentiated thyroid cancer.

Anti-thyroglobulin antibodies (anti-Tg), present in 20%-25% of differentiated thyroid cancer (DTC) patients, interfere with thyroglobulin measurements posing a challenge in the follow-up. The aim of this study was to identify clinical-histological factors that may affect anti-Tg persistence and disease outcome in DTC with positive anti-Tg. We retrospectively studied 234 DTC patients, with positive anti-Tg at diagnosis (females: 82.1%, age at diagnosis: 46.0±14.4 yrs, median follow-up: 5 yrs (1.5-32yrs). 221/234 (94.4%) received radioiodine (RAI) ablation. Patients were divided into two subgroups: those whose anti-Tg became undetectable (anti-Tg-NEG) and those whose anti-Tg remained positive (anti-Tg-POS) at the end of the follow-up period. Anti-Tg-POS patients (n=80, 34.2%) compared to anti-Tg-NEG (n=154, 65.8%) had more frequently lymph node infiltration (36.3% vs 20.1%, P=.01), extrathyroidal extension (ETE, 35.0% vs 22.1%, P=.04), poorly differentiated DTC and increased tumour size (P≤.004). They received higher total RAI dose (P<.001). In most cases, additional RAI administration and/or additional surgeries did not lead to anti-Tg elimination. These had more frequently structural disease persistence/progression compared to anti-Tg-NEG (remission: 78.8% vs 95.5%, persistence: 13.8% vs 3.9%, progression: 7.5% vs 0.6%, P<.001). In Kaplan-Meier analysis, the probability of disease progression was higher in anti-Tg-POS. In Cox proportional hazard analysis, the predictors of disease progression were size (P=.002) and ETE (P=.006). Worse histological features are more frequent in patients with anti-Tg persistence during follow-up. Further additional RAI administration and/or surgeries do not affect anti-Tg elimination in most cases. Anti-Tg persistence correlates with structural persistence although tumour size and extrathyroidal extension are the main predictors of disease progression.

The appropriateness of thyroid lobectomy as an initial surgery for preoperatively detected unilateral multifocal papillary carcinoma

Whether multifocal papillary thyroid carcinoma (PTC) is more associated with recurrence than unifocal PTC is controversial. This study investigates the appropriateness of lobectomy for patients with preoperatively detected unilateral multifocal PTC. This study retrospectively analyzed 198 patients with unilateral multifocal PTC at the Asan Medical Center between 2000 and 2005. Clinicopathological features and locoregional recurrence rates were compared according to operation type (lobectomy, n=62; total thyroidectomy (TT), n=136). The lateral neck lymph node area was the most frequent recurrence site. Univariate analyses showed that gross extrathyroidal extension (ETE), bilateral multifocal malignancy diagnosed after operation (bilaterality), lymph node (LN) metastasis, lymphovascular invasion, tumor size (≥2 vs<2cm), and extranodal extension (ENE) were associated with locoregional recurrence (P<0.05). Multivariate analyses showed that ENE (hazard ratio (HR), 5.7; p=0.007; 95% confidence interval (CI)=1.1-9.8), LN metastasis (HR, 8.6; p=0.046; 95% CI=1.1-70.7), and lymphovascular invasion (HR, 11.1; p=0.001; 95% CI=2.7-46.1) were significantly associated with locoregional recurrence. The occult contralateral malignancy (rate, 15.4% of TT patients) and gross ETE were not risk factors for locoregional recurrence in the multivariate analysis of this study. Lobectomy may be considered as an alternative treatment to TT for patients with preoperatively detected unilateral multifocal PTC with diameters less than 2cm, eveninthepres-enceofriskfac-tors,suchasgrossETE,andthepos-si-bil-ityofoc-cultma-lig-nancyofthecon-tralat-erallobe. Although recurrence in the contralateral lobe after lobectomy could be diagnosed in unilateral multifocal PTC, it would not increase the rates of locoregional recurrence and death.

Appraisal of the American Joint Committee on Cancer Staging Parameters in Patients Undergoing Resection after Neoadjuvant Treatment for Pancreatic Ductal Adenocarcinoma

Purpose: The AJCC staging system has been modeled following upfront pancreatectomy, while its prognostic performance in patients receiving neoadjuvant treatment (NAT) is unknown. Our aim was to appraise the AJCC staging parameters in patients undergoing pancreatectomy after NAT for pancreatic ductal adenocarcinoma. Methods: All pancreatectomies after NAT at two academic institutions (2013-2017) were reviewed (n=389). Metrics of prognostic performance were compared between the AJCC-7th and -8th editions. A modified T-status definition, encompassing both size and extrapancreatic extension, was assessed. Results: The AJCC-7th T-status significantly predicted survival, although survival curves of ypT2 and ypT3 overlapped. The AJCC-8th T-status improved prognostic stratification, yet the significance remained driven by the favorable prognosis of ypT1. N-status was strongly associated with survival in both editions (Figure). The overall prognostic performance was improved in the 8th edition as confirmed by: C-index, Uno’s AUC over three years, and time-dependent ROC curves at 1-2-3 years postoperatively. The 3-year net reclassification index was 23.8%. The modified T-status further improved these metrics. At multivariable Cox regression, a significant interaction was detected between adjuvant treatment and T- and N- status, suggesting a potential survival benefit in tumors >2cm, those with extrapancreatic extension and/or lymph node metastases. Conclusion: In patients receiving pancreatectomy after NAT, the AJCC-8th edition shows a greater prognostic accuracy. While the performance of the new N-status appears solid, T-status classification might be further optimized. In particular, incorporating extrapancreatic extension in the current size-based definition seems valuable. Adjuvant therapy displays a heterogeneous effect on survival in the different T- and N-status classes, with possible clinical implications.

Clinical outcomes of management of posterior capsule rupture with air bubble techniques.

To introduce a new surgical technique, air-bubble technique for the management of posterior capsule rupture (PCR) and to evaluate the safety and efficacy of the technique. A retrospective case series analysis of 24 eyes of 24 patients, in which the air bubble technique was used for the management of PCR, was performed. Once PCR occurred, a dispersive ophthalmic viscosurgical device (OVD) was injected into the tear. And small volumes (0.2-0.3 mL) of air bubbles were injected beneath the OVD. The air bubble served as a physical barrier and supported the posterior capsule. After surgery, none of the patients had serious complications during the follow-up period of 1y. Extension of the PCR size occurred in only 2 cases, and additional OVD injection was required only in 3 cases. Air bubbles imparted great stability to the nuclear pieces and the posterior capsule. The air-bubble technique may be considered a safe and effective procedure for managing a PCR. It may be of value to the inexperienced cataract surgeon.

Multispecialty surgical management of carotid body tumors in the modern era

ObjectiveThe objective of this study was to assess the perioperative and long-term outcomes of carotid body tumor (CBT) resection with a multispecialty (head and neck surgery/vascular surgery) approach. MethodsOur institutional data registry was queried for Current Procedural Terminology codes (60600, 60605) pertaining to CBT excision. These patient records and operative reports were individually reviewed to determine laterality, preoperative tumor embolization, operative time, estimated blood loss, need for intraoperative transfusion, intraoperative electroencephalogram changes, intraoperative division of the external carotid artery, carotid artery repair, resection of the carotid bifurcation, tumor volume, final pathology, cranial nerve injury, stroke, death, and clinical or radiographic evidence of recurrence. ResultsFrom 1996 to 2018, 74 CBT resections were identified in 68 patients (41 [60%] females; mean age, 50.83 years). The mean tumor volume was 9.92 ± 14.26 cm3 (range, 0.0250-71.0627 cm3). Embolization was performed by a neurointerventional specialist in 27 CBT resections (36%) based on size (embolization 14.27 ± 16.84 cm3 vs 7.17 ± 11.86 cm3; P = .063) and superior extension. This practice resulted in one asymptomatic vertebral dissection, which postponed the surgery. There was a trend toward greater blood loss in the embolization group (embolization 437 ± 545 mL vs 262 ± 222 mL; P = .17); however, no transfusions were required in any patient. The mean operative time was also significantly longer in the embolization group (198.33 ± 61.13 minutes vs 161.5 ± 55.56 minutes; P = .03). Three resections had reversible intraoperative electroencephalogram changes, one of which occurred during carotid clamping. These changes resolved with shunting. Eight external carotid resections (11%) and 6 carotid reconstructions (8.1%; two primary, two patch, and two primary anastomosis) were required. Malignancy was identified in four tumors (5.4%), accounting for four of the six carotid reconstructions. There were no postoperative cranial nerve injuries, no strokes, no reexplorations, and no deaths. One patient developed transient dysphagia from pharyngeal tumor infiltration. Long-term follow-up (mean, 43 ± 54 months), available in 61 of the 68 patients (89.7%), revealed three (4.4%) recurrences. ConclusionsThis large, single-institution series demonstrates that a multispecialty team combining two surgical skill sets for the treatment of this rare, challenging condition yields unparalleled low complication rates with short operative times. This approach, including long-term surveillance for recurrent disease, should be considered to optimize outcomes of CBT resection.

Bartonella hanselae retinitis patient evaluated with multimodal retinal exams

BackgroundCat scratch disease is a systemic infectious illness caused by the bacterium Bartonella henselae. The most common ophthalmological involvement due to infection by Bartonella is Parinaud oculoglandular syndrome, whereas the most common posterior segment findings are neuroretinitis and subsequent late macular star. Moreover, other findings, such as retinal or subretinal lesions, intermediate uveitis and angiomatous lesions, may be present.Case presentationA 37-year-old female patient with retinal findings and serological confirmation of Bartonella infection was evaluated via multimodal retinal exams. The patient received treatment with doxycycline 100 mg twice daily for 2 weeks. One month after treatment, complete improvement of her visual scotoma symptoms was confirmed. A swept-source optical coherence tomography exam also showed decreases in the size and intraretinal extension of the lesion. Improvement of light perception at the affected area was confirmed by microperimetry.ConclusionsBartonella henselae infection, particularly retinitis, can present a variable spectrum of clinical and ophthalmological findings. Multimodal retinal exams can clearly identify lesion characteristics, thus providing important information for diagnosis and the evaluation of lesion improvement after antibiotic treatment.

EXTH-57. INVESTIGATION OF THE TUMORICIDAL EFFECTS OF SONODYNAMIC THERAPY IN MALIGNANT GLIOBLASTOMA BRAIN TUMORS

Abstract OBJECTIVE Glioblastoma is the most common primary brain tumor; survival is typically 12–18 months after diagnosis. We sought to study the effects of sonodynamic therapy (SDT) using 5-Aminolevulinic acid hydrochloride (5-ALA) and high frequency focused ultrasound (FUS) on 2 glioblastoma cell lines. PROCEDURE Rat C6 and human U87 glioblastoma cells were studied under the following conditions: 1mM 5-ALA (5-ALA); Focused ultrasound (FUS); 5-ALA and focused ultrasound (SDT); control. Studied responses included cell viability using an MTT assay, microscopic changes using phase contract microscopy, apoptotic induction through a caspase-3 assay, and apoptosis staining to quantify cell death. RESULTS SDT led to a marked decrease in cell extension and reduction in cell size. For C6, the MTT assay showed reductions in cell viability for 5-ALA, FUS, and SDT groups of 5%, 16%, and 47%, respectively compared to control (p&amp;lt; 0.05). Caspase 3 induction in C6 cells relative to control showed increases of 109%, 110%, and 278% for 5-ALA, FUS, and SDT groups, respectively (p&amp;lt; 0.05). For the C6 cells, caspase 3 staining positivity was 2.1%, 6.7%, 11.2%, and 39.8% for control, 5-ALA, FUS, and SDT groups, respectively. C6 Parp-1 staining positivity was 1.9%, 6.5%, 9.0%, and 37.8% for control, 5-ALA, FUS, and SDT groups, respectively. U87 cells showed similar responses to the treatments. CONCLUSIONS Sonodynamic therapy resulted in appreciable glioblastoma cell death as compared to 5-ALA or FUS alone. The approach couples two already FDA approved techniques in a novel way to treat the most aggressive and malignant of brain tumors. Further study of this promising technique is planned using glioma and also brain metastasis models.

Size and extranodal extension of metastatic lymph nodes in lung adenocarcinoma.

BackgroundThis study assessed the prognostic significance of metastatic lymph node size (MLNS) and extranodal extension (EN) in patients with node-positive lung adenocarcinoma (ADC).MethodsPrognostic factors influencing survival were analyzed, including age, sex, extent of operation, T- and N-stage, size of tumor, postoperative chemotherapy, presence of EN, and MLNS (>7.0 vs. ≤7.0 mm).ResultsThree hundred seventy-five patients met the inclusion criteria were enrolled (mean age: 59.8±10.5 years). Increasing MLNS was significantly correlated with large tumor size (P=0.015), advanced N status (P<0.001), and presence of EN (P<0.001). In multivariable analysis, large tumor size [hazard ratio (HR) 1.135, 95% confidence interval (CI): 1.050 to 1.228, P<0.001], adjuvant chemotherapy (HR 0.582, 95% CI: 0.430 to 0.787, P<0.001), EN (HR 1.454, 95% CI: 1.029 to 2.055, P=0.034), and MLNS greater than 7 mm (HR 1.741, 95% CI: 1.238 to 2.447, P<0.001) were significant prognostic factors for survival. Patients were classified into 3 groups: Group A, MLNS ≤7.0 mm/EN (−); Group B, MLNS ≤7.0 mm/EN (+) or MLNS >7.0 mm/EN (−); and Group C, MLNS >7.0 mm/EN (+). The 5-year overall survival (OS) was 72.2%, 59.0%, and 38.5% in Groups A, B and C, respectively (P<0.001).ConclusionsThe MLNS and presence of EN could provide an important prognostic implication for patients with node-positive lung ADC.

A new species of Lecithostaphylus Odhner, 1911 (Trematoda: Zoogonidae) from the Pacific needlefish, Tylosurus pacificus, off the Pacific coast of Mexico, with a molecular assessment of the phylogenetic position of this genus within the family

A new species of Lecithostaphylus Odhner, 1911 (Zoogonidae) is described from the Pacific agujon needlefish, Tylosurus pacificus (Steindachner) (Belonidae), from two localities off the Pacific coast of Mexico. Morphologically, the new species agrees with the diagnosis of the genus Lecithostaphylus. Lecithostaphylus brayi sp. nov. differs from other congeneric species by a combination of morphological traits, including the overall body size, anterior and posterior extension of the vitelline follicles in the hindbody, and the presence/absence of papilla-like denticles on internal surface of ventral sucker. Lecithostaphylus brayi sp. nov. most closely resembles L. retroflexus (Molin, 1859), Odhner, 1911 and Lecithostaphylus tylosuri Châari, Derbel & Neifar, 2013 from Mediterranean needlefishes and Lecithostaphylus nitens (Linton, 1898) Linton, 1940 from needlefishes in multiple marine ecoregions; however, it can be distinguished by subtle morphological differences, host association, and geographical distribution. The new species will require further verification through a more detailed morphological study of L. nitens and, ideally, molecular data for L. nitens, L. retorflexus, and L. tylosuri. Newly generated 28S rDNA sequences allowed a phylogenetic assessment of the genus and show that Lecithostaphylus clades within the Zoogonidae, sister to the genera Deretrema Linton, 1910 + Proctophantastes Odhner, 1911, although the family Zoogonidae is not resolved as monophyletic. The inclusion of more representative genera in the molecular phylogenetic analysis will be needed to generate a more robust classification scheme for the Zoogonidae, and to discuss host specificity patterns for members of the family.

Predictors and Outcomes of Neurological Deterioration in Intracerebral Hemorrhage: Results from the TICH-2 Randomized Controlled Trial

Neurological deterioration is common after intracerebral hemorrhage (ICH). We aimed to identify the predictors and effects of neurological deterioration and whether tranexamic acid reduced the risk of neurological deterioration. Data from the Tranexamic acid in IntraCerebral Hemorrhage-2 (TICH-2) randomized controlled trial were analyzed. Neurological deterioration was defined as an increase in National Institutes of Health Stroke Scale (NIHSS) of ≥ 4 or a decline in Glasgow Coma Scale of ≥ 2. Neurological deterioration was considered to be early if it started ≤ 48 h and late if commenced between 48 h and 7 days after onset. Logistic regression was used to identify predictors and effects of neurological deterioration and the effect of tranexamic acid on neurological deterioration. Of 2325 patients, 735 (31.7%) had neurological deterioration: 590 (80.3%) occurred early and 145 (19.7%) late. Predictors of early neurological deterioration included recruitment from the UK, previous ICH, higher admission systolic blood pressure, higher NIHSS, shorter onset-to-CT time, larger baseline hematoma, intraventricular hemorrhage, subarachnoid extension and antiplatelet therapy. Older age, male sex, higher NIHSS, previous ICH and larger baseline hematoma predicted late neurological deterioration. Neurological deterioration was independently associated with a modified Rankin Scale of > 3 (aOR 4.98, 3.70–6.70; p < 0.001). Tranexamic acid reduced the risk of early (aOR 0.79, 0.63–0.99; p = 0.041) but not late neurological deterioration (aOR 0.76, 0.52–1.11; p = 0.15). Larger hematoma size, intraventricular and subarachnoid extension increased the risk of neurological deterioration. Neurological deterioration increased the risk of death and dependency at day 90. Tranexamic acid reduced the risk of early neurological deterioration and warrants further investigation in ICH. URL:https://www.isrctn.com Unique identifier: ISRCTN93732214

Development and Validation of a Prognostic Nomogram to Predict Cancer-Specific Survival in Adult Patients With Pineoblastoma.

Pineoblastoma (PB) is a rare neoplasm of the central nervous system. This analysis aimed to identify factors and establish a predictive model for the prognosis of adult patients with PB. Data for 213 adult patients with PB (Surveillance, Epidemiology, and End Results database) were randomly divided into primary and validation cohorts. A predictive model was established and optimized based on the Akaike Information Criterion and visualized by a nomogram. Its predictive performance (concordance index and receiver operating characteristic curve) and clinical utility (decision curve analyses) were evaluated. We internally and externally validated the model using calibration curves. Multivariate Cox regression analysis identified age, year of diagnosis, therapy, tumor size, and tumor extension as independent predictors of PB. The model exhibited great discriminative ability (concordance index of the nomogram: 0.802; 95% confidence interval: 0.78–0.83; area under the receiver operating characteristic curve: ranging from 0.7 to 0.8). Calibration plots (probability of survival) showed good consistency between the actual observation and the nomogram prediction in both cohorts, and the decision curve analyses demonstrated great clinical utility of the nomogram. The nomogram is a useful and practical tool for evaluating prognosis and determining appropriate therapy strategies.

Lymphovascular invasion of papillary thyroid carcinoma revisited in the era of active surveillance

IntroductionLymphovascular invasion (LVI) is associated with disease recurrence and compromised survival in patients with thyroid cancer. Nonetheless, LVI is not identifiable on preoperative ultrasound or cytologic assessment. We aimed to explore the clinicopathological features associated with LVI. Patients and methodsWe conducted a retrospective review of our prospectively maintained database from 2009 to 2018. Multivariate analyses were performed to determine the associations between clinicopathological parameters and LVI. Generalized additive models were used to examine the nonlinear relationship between continuous variables and LVI. ResultsA total of 795 patients were included in the analysis, and 174 (22%) had LVI. Patients’ age (odds ratio [OR] = 0.982), tumor size (OR = 1.466), clinical lymphadenopathy (OR = 6.975), and advanced extrathyroidal extension (OR = 2.938) were independently associated with LVI. In the subset analysis of 198 patients with available genetic information, tumor size (OR = 1.599), clinical lymph node metastasis (OR = 3.657), and TERT promoter mutation (OR = 4.726) were predictive of LVI. Among 573 patients who had no clinical lymphadenopathy or advanced extrathyroidal extension, tumor size was the only predictor of LVI. Tumor size >1.5 cm had an increased risk of LVI based on the generalized additive model plot and receiver operating characteristic curve analysis. ConclusionTumor size is positively associated with the risk of LVI in papillary thyroid cancer. To avoid delayed treatment in patients with LVI, a tumor size of 1.5 cm may be considered as the safe upper limit for active surveillance.

Potential energy surfaces of charge transfer states

ABSTRACT In this paper the potential energy curves of charge transfer (CT) electronic states and their interaction with local ones have been investigated. Besides the global view of these curves, special attention has been paid to the region of the crossing and the infinite separation limit. It was found that triple excitations are needed to accurately describe potential energy surfaces of CT states. Among the cheaper variants, both STEOM-CCSD and CCSD(T)(a)* methods are promising in this respect. The somewhat larger error of CCSD for CT states can be explained by its size extensivity error and the overestimation of the asymptotic excitation energy. Second order approximations are not advantageous for the error cancellation, in fact CC2 is much worse for CT states than any other method investigated here. The results also show that the location of the (avoided) crossings of local and CT states depend very much on the accurate description of the CT states. Failure to describe this topology might affect dynamics, and a warning, in particular in case of CC2, should be issued if CT states play a role in the physics of the problem.

Effect of Nortriptyline on Spreading Depolarization

Background: Spreading depolarization is associated with the extension of lesion size and complications in some important neurological diseases such as stroke, epilepsy, migraine, and traumatic brain injury. Objectives: This study aimed to reveal some molecular aspects of spreading depolarization and suggesting new therapeutic targets for its control by changing the function of different astrocytic and neuronal ion channels. Methods: The effects of nortriptyline on spreading depolarization in cortical and hippocampal tissues and on the electrophysiological properties of CA1 hippocampal pyramidal neurons were assessed by extra- and intracellular recording, following washing rat brain slices by the drug. Results: Nortriptyline made a significant increase in the amplitude of spreading depolarization in cortical and hippocampal tissues relative to control but did not change the duration significantly in each of the tissues. No significant difference was found in the effects of spreading depolarization on the electrophysiological properties of the CA1 pyramidal neurons between nortriptyline and control groups. Conclusions: The stimulating effect of nortriptyline on spreading depolarization is probably related to the augmentation of extracellular potassium collection in the cortex and hippocampus due to inhibition of astrocytic potassium scavenging function. This change can make more neurons prone to depolarization and increase the overall amplitude of spreading depolarization waves. Further studies should assess the effect of enhancing the clearance function of astrocyte-specific inwardly rectifying potassium channels, Kir4.1, or preventing other factors contributing to spreading depolarization on control of the process.

Shedding light on dark genes: enhanced targeted resequencing by optimizing the combination of enrichment technology and DNA fragment length

The exome contains many obscure regions difficult to explore with current short-read sequencing methods. Repetitious genomic regions prevent the unique alignment of reads, which is essential for the identification of clinically-relevant genetic variants. Long-read technologies attempt to resolve multiple-mapping regions, but they still produce many sequencing errors. Thus, a new approach is required to enlighten the obscure regions of the genome and rescue variants that would be otherwise neglected. This work aims to improve the alignment of multiple-mapping reads through the extension of the standard DNA fragment size. As Illumina can sequence fragments up to 550 bp, we tested different DNA fragment lengths using four major commercial WES platforms and found that longer DNA fragments achieved a higher genotypability. This metric, which indicates base calling calculated by combining depth of coverage with the confidence of read alignment, increased from hundreds to thousands of genes, including several associated with clinical phenotypes. While depth of coverage has been considered crucial for the assessment of WES performance, we demonstrated that genotypability has a greater impact in revealing obscure regions, with ~1% increase in variant calling in respect to shorter DNA fragments. Results confirmed that this approach enlightened many regions previously not explored.