bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthodontic Space Closure of a Missing Maxillary Lateral Incisor Followed by Canine Lateralization
Authors: Gupta Sanjay Prasad , Rauniyar Shristi
Published: November 2020

Maxillary lateral incisor agenesis is the most prevalent developmental dental anomaly. The management of missing lateral incisor was either closure using canine as substitution or creation of space orthodontically for prosthetic replacement. A careful diagnosis and treatment plan are deemed essential to address the patient’s needs as the spacing is present in the esthetic region. Such problem is very challenging for orthodontists, prosthodontists, and general practitioners. This case report describes the orthodontic management of a 22-year-old adult female patient with missing upper left lateral incisor tooth and upper anterior spacing by closing the space with canine lateralization and reshaping to simulate it with the lateral incisor. However, some modifications in the treatment mechanics are crucial to achieve the optimal esthetic and to improve the occlusion. Space closure with canine lateralization option seems less invasive, treatment can be completed relatively in a short period of time, and its adaptation with the facial changes throughout life without having artificial prosthesis provided other factors favoring for this option.
Experimental Behavior of the Curved Continuous Twin I‐Girder Composite Bridge with a Precast Concrete Slab Subjected to Bending, Shear, and Torsion
Authors: Shen Chuandong , Song Yifan , Yan Lei , Li Yuan , Wang Xueli , He Shuanhai
Published: November 2020

In order to investigate the mechanical behavior, ultimate load carrying capacity, and failure mode of the intact curved continuous twin I‐girder composite bridge (TGCB) with a precast concrete slab, one curved continuous composite bridge model with a scale ratio of 1 : 5 of a prototype bridge was designed and manufactured considering the influence of the construction sequence. Four symmetric point loads’ test was carried out. In this paper, load‐deflection relationship and strain development of steel girders, concrete slab, and reinforcement at key sections were tested and analyzed. Failure mode, crack development, and major crack width at the top surface of the concrete slab in the hogging moment region were also reported. The experimental results demonstrated that the load capacity under the initial cracking level, cracking level with the width of 0.2 mm, and steel girder yielding state is about 1.7, 5.0, and 6.3 times of the design load, respectively. Due to the influence of curvature, the stiffness of the external girder is less than that of the internal girder. However, the ultimate bearing capacity is basically the same, approximately 13.6 times of the design load. During the loading process, plastic hinge was first observed at the intermediate support section as a result of the hogging moment which should be emphasized in design. The local buckling took place after yielding, indicating a class 2 section according to Eurocode 4. In addition, the TGCB had good ductility since the displacement ductility coefficients of the external and internal girders were 4.40 and 4.06, respectively.
Internal Iliac Aneurysm Causing Hydroureteronephrosis
Authors: Sangey Tawfeeq , Moledina Sibtain
Published: November 2020

A 63-year-old presented with right lumbar pain and increased frequency of urination. Imaging revealed right internal iliac artery aneurysm causing hydroureteronephrosis and compressing the urinary bladder.
Evaluation of the Physical Performance and Working Mechanism of Asphalt Containing a Surfactant Warm Mix Additive
Authors: Shi Jingtao , Fan Weiyu , Wang Tihong , Zhao Pinhui , Che Fa
Published: November 2020

This paper analyzes the influence of a surfactant warm mix additive on unmodified asphalt’s conventional performance, viscosity‐temperature characteristics, surface energy, and spreading performance on aggregate surfaces. The effect of the additive on asphalt’s microstructure was explored by infrared (IR) spectral analysis. The results show the additive has little influence on the penetration, softening point, ductility, and viscosity‐temperature characteristics of asphalt; this suggests that the additive does not work by lowering viscosity. The additive can reduce the zero‐shear viscosity of asphalt, and adding too much can reduce antirutting performance. The additive also increases the asphalt’s surface energy and the asphalt‐water contact angle, while the polar component of surface energy decreases. The additive improves the spreading performance of asphalt on aggregate surfaces and reduces the asphalt‐aggregate contact angle; the lower the temperature, the greater the reduction. IR spectral analysis shows that the additive does not react with asphalt—only physical blending occurs. The addition of a surfactant warm mix additive to asphalt allows asphalt mixtures to be more easily mixed and compacted at lower temperatures, thereby saving energy.
Hypercalcemia of Malignancy Revealing a Parathyroid Carcinoma with Hepatic Metastasis: A Case Report and Literature Review
Authors: Mellagui Yassine , Jabi Rachid , Haouli Inass , Kora Christine , Ouachaou Jamal , Aabdi Mohammed , Bkiyar Houssam , Bouziane Mohammed , Housni Brahim
Published: November 2020

Parathyroid carcinoma is a very rare malignant tumor of the parathyroid gland. This cancer poses a great diagnostic and therapeutic difficulty due to its rarity and the absence of a characteristic clinical and paraclinical picture. The diagnosis is histological but is not always easy. Surgery remains the only curative treatment, and cervical radiotherapy can be discussed. Good prognostic factors are complete monobloc tumor resection, and bad prognostic factors are the presence of lymph node metastases at diagnosis, distant metastases, and nonsecreting carcinomas.
Reliability Analysis of a Direct Shear Test of Modified Iron Tailings Based on the Monte Carlo Algorithm
Authors: Jiang Ping , Qian Jian , Li Na
Published: November 2020

The resource utilization of iron tailings is of great significance for all countries in the world. Considering the particle composition and physicochemical characteristics of iron tailings, fiber and lime were used to modify iron tailings. The fiber content was 0%, 0.25%, 0.5%, 0.75%, and 1%, and the lime content was 0%, 2%, 4%, 8%, and 10%, respectively. Through a direct shear test, the shear stress displacement (τ‐δ) curves and shear strength of modified iron tailings, under the action of a 0 freeze‐thaw cycle and 1 freeze‐thaw cycle, were tested. As statistics have shown that there are uncertainty factors associated with direct shear tests, the shear strength index cohesion c and internal friction angle φ of the modified iron tailings were analyzed using the Monte Carlo method. The results show that the τ‐δ curve of the fiber‐modified iron tailings is a hardening‐type curve and that of the lime‐modified iron tailings is a softening‐type curve. In the direct shear tests, the main uncertain factors are the specimen diameter, vertical force, and horizontal force. The diameter of the sample obeys a normal distribution, and the vertical and horizontal forces obey a uniform distribution. The results of the Monte Carlo simulation show that both c and φ obey a normal distribution. Under a 95% confidence condition, the effect of fiber on the cohesion on iron tailings is obvious, but the effect on the internal friction angle is not obvious. However, the values of c and φ of the iron tailings are clearly improved by lime. Additionally, the iron tailings modified by a fiber content of 1% and those modified by a lime content of 8% have the best frost resistance.
Effects of Dietary Self-Monitoring, Physical Activity, Liraglutide 3.0 mg, and Placebo on Weight Loss in the SCALE IBT Trial
Authors: Tronieri Jena S. , Fabricatore Anthony N. , Wadden Thomas A. , Auerbach Pernille , Endahl Lars , Sugimoto Danny , Rubino Domenica
Published: November 2020

Introduction: Individuals who enroll in intensive behavioral therapy (IBT) programs are asked to make several lifestyle changes simultaneously. However, few studies have examined the relative effects of adherence to different treatment components on weight loss. Objective: This secondary analysis of the SCALE IBT trial assessed adherence to the medication regimen, dietary self-monitoring, and physical activity recommendations and their relative contributions to weight change in individuals with obesity who were provided with IBT combined with either liraglutide 3.0 mg or placebo. Methods: SCALE IBT was a double-blinded, multicenter, randomized controlled trial comparing 56-week weight losses in individuals with obesity who received liraglutide 3.0 mg (n = 142) or placebo (n = 140), as an adjunct to IBT. Adherence to dietary self-monitoring, physical activity, and medication usage (liraglutide or placebo) were measured during the 56-week treatment period. A regression model was used to estimate the relative contribution of adherence to each treatment component to weight loss at week 56. Results: The proportion of individuals who adhered to each intervention component decreased over time. Compared with non-adherence, complete adherence to dietary self-monitoring and physical activity recommendations were associated with estimated weight changes of −7.2% (95% CI –10.4 to –4.0; p < 0.0001) and –2.0% (95% CI –3.2 to –0.8; p = 0.0009), respectively. Complete adherence to liraglutide predicted an additional weight loss of –6.5% (95% CI –10.2 to –2.9; p = 0.0005) relative to individuals who did not adhere to the medication regimen, while adherence to placebo did not have a statistically significant effect on weight loss (p = 0.33). Conclusions: High adherence to dietary self-monitoring and use of liraglutide 3.0 mg was associated with clinically relevant weight loss with IBT and adjunctive pharmacotherapy. The effect of adherence to physical activity was significant but smaller.
Impact of Vein of Marshall Ethanol Infusion on Mitral Isthmus Block
Authors: Nakashima Takashi , Pambrun Thomas , Vlachos Konstantinos , Goujeau Cyril , André Clémentine , Krisai Philipp , Ramirez F. Daniel , Kamakura Tsukasa , Takagi Takamitsu , Nakatani Yosuke , Kitamura Takeshi , Takigawa Masateru , Roux Jean-Rodolphe , Cheniti Ghassen , Tixier Romain , Chauvel Remi , Welte Nicolas , Duchateau Josselin , Sacher Frédéric , Cochet Hubert , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre , Derval Nicolas
Published: November 2020

Background:

Achieving bidirectional mitral isthmus (MI) block using radiofrequency catheter ablation (RFCA) alone is challenging, and MI reconnection is common. Adjunctive vein of Marshall (VOM) ethanol infusion (VOM-Et) can facilitate acute MI block. However, little is known about its long-term success. This study sought to evaluate the impact of adjunctive VOM-Et on MI block achievement and durability compared with RFCA alone.

Methods:

Patients undergoing the first attempt of posterior MI ablation were grouped according to their MI block index strategy: adjunctive VOM-Et and RFCA alone. Rates of acute MI block and MI reconnection observed during repeat procedures were compared between the 2 groups.

Results:

The VOM-Et group consisted of 152 patients (63.8±9.4 years) undergoing adjunctive VOM-Et for MI block. The RFCA group consisted of 110 patients (60.9±9.2 years) undergoing MI ablation using RFCA alone. Acute MI block was more frequently achieved in the VOM-Et group (98.7% [150/152] versus 63.6% [70/110];
P
<0.001) with shorter RFCA duration (5.00 [3.00–7.00] versus 19.0 [13.6–22.0] minutes;
P
<0.001). Of the 220 patients with MI block achieved during the index procedure, 81 underwent a repeat procedure during follow-up (VOM-Et group: 23.3% [35/150] versus RFCA group: 65.7% [46/70], respectively;
P
<0.001). A significantly greater number of patients exhibited durable MI block in the VOM-Et group (62.9% [22/35] versus 32.6% [15/46], respectively;
P
=0.008).

Conclusions:

Beyond facilitating acute MI block, VOM-Et is associated with greater lesion durability as evidenced by higher rates of MI block during repeat procedures.
Early Onset of Coronary Artery Calcification in Women With Previous Preeclampsia
Authors: Benschop Laura , Brouwers Laura , Zoet Gerbrand A. , Meun Cindy , Boersma Eric , Budde Ricardo P.J. , Fauser Bart C.J.M. , de Groot Christianne M.J. , van der Schouw Yvonne T. , Maas Angela H.E.M. , Velthuis Birgitta K. , Linstra Katie M. , Kavousi Maryam , Duvekot Johannes J. , Franx Arie , Steegers Eric , van Rijn Bas B. , Roeters van Lennep Jeanine E. ,   on behalf of the CREW Consortium
Published: November 2020

Background:

Preeclampsia, coronary artery calcification (CAC), and atherosclerotic plaque are risk factors for the development of cardiovascular disease. We determined at what age CAC becomes apparent on coronary computed tomography after preeclampsia and to what extent modifiable cardiovascular risk factors were associated.

Methods:

We measured cardiovascular risk factors, CAC by coronary computed tomography, and coronary plaque by coronary computed tomography angiography in 258 previously preeclamptic women aged 40-63. Results were compared to 644 age- and ethnicity-equivalent women from the Framingham Heart Study with previous normotensive pregnancies.

Results:

Any CAC was more prevalent after preeclampsia than after a normotensive pregnancy (20% versus 13%). However, this difference was greatest and statistically significant only in women ages 45 to 50 (23% versus 10%). The degree of CAC advanced 4× faster between the ages of 40 to 45 and ages 45 to 50 in women with a history of preeclampsia (odds ratio, 4.3 [95% CI, 1.5–12.2] versus odds ratio, 1.2 [95% CI, 0.6–2.3]). Women with a preeclampsia history maintained greater advancement of CAC with age into their early 60s, although this difference declined after the perimenopausal years. Women with a previous normotensive pregnancy were 4.9 years (95% CI, 1.8–8.0) older when they had similar CAC scores as previously preeclamptic women. These observations were not explained by the greater prevalence of cardiovascular disease risk factors, and the higher Framingham Risk Scores also observed in women with a history of preeclampsia.

Conclusions:

Previously preeclamptic women have more modifiable cardiovascular risk factors and develop CAC ≈5 years earlier from the age of 45 years onwards compared to women with normotensive pregnancies. Therefore, women who experienced preeclampsia might benefit from regular cardiovascular screening and intervention before this age.

Registration:

URL:
https://www.trialregister.nl/trial/5406
; Unique identifier: NTR5531.
A Book Review in the Form of a Polemic Chad Elias's Posthumous Images: Contemporary Art and Memory Politics in Post-Civil War Lebanon and the Old New World Order
Authors: Saadawi Ghalya
Published: November 2020

Chad Elias' 2018 book Posthumous Images: Contemporary Art and Memory Politics in Post-Civil War Lebanon attempts to deal with the question of post-civil war representation, image-making and contemporary art from the perspective of memory studies in Lebanon. Dealing with a particular group of artists working since the 1990's in installation, video, film, and performance, the book attempts to create a relation between their artistic propositions and narratives on the one hand, and the post-war reckoning with the missing and disappeared, the history of former Leftist combatants, neglected space programs, reconstruction and urban space, on the other. The book has a series of shortcomings and structural, theoretical blind spots that this review essay attempts to redress. For instance, Posthumous Images has no framework for the notions of communities of witnessing, collective memory, or post-war amnesia that seems to underpin its claims, as they seem to figure only nominally. In these theoretical omissions, the essay argues, the book adopts and furthers the ideology human rights as this relates to the politics of remembrance, as well as to Lebanon's neoliberal post-war realities. Moreover, it lacks a rigorous art historical frame to study the given artworks formally, or theoretically, leaving the book open to a post-historical method that disavows a critical, social history of art needed for an analysis of post-civil war and post-Cold war art forms in Lebanon and beyond.
‘An Arabic Qurʾān, That You Might Understand’
Authors: Connolly Magdalen M. , Posegay Nick
Published: November 2020

The Arabic-script Qurʾān fragments of the Cairo genizah collections have not yet drawn much interest among Arabic and genizah scholars. This paper aims to bring them to the attention of a broader audience by presenting the palaeographic features (§ 3) and vocalisation systems (§ 4) of eleven Arabic-script Qurʾān fragments from the Cambridge University Library’s Taylor-Schechter Arabic collection. While the focus of this paper is the physical appearance of these Qurʾān leaves, their presence in the Cairo genizah (§ 1.1)—a Jewish ‘storeroom’ for retired sacred texts—is also tentatively explored (§ 1.2, § 5).
Evaluating the Accuracy and Consistency in Rendering Qurʾanic Terms with Overlapping Meanings into English
Authors: Al-Abbas Linda S , Haider Ahmad S.
Published: November 2020

The Holy Qurʾan has many terms that exhibit a great similarity in meaning and may not be easily rendered into another language. The present study attempts to explore the accuracy of the lexical choices used to render the Arabic near-synonyms ʿfawa, ṣafaḥa, and ġafara into English in three Translations of the Holy Qurʾan; namely, Pickthall (1999), Ali (2001), and Al-Hilali and Khan (2018). The researchers carried out a componential analysis for the Arabic words under study and their English equivalents based on their explanation in different Arabic and English dictionaries and exegeses. The study also investigates whether the translators maintain consistency in translating these words when they occur within the same verse and elsewhere. The findings show that the translators tended to use different English equivalents to the three Arabic words especially when they occur within the same verse, and sometimes failed to reflect the slight differences between them in their translations that they use them interchangeably. With regard to consistency, the study found that the three translators used various English equivalents to refer to the same Arabic word, but Al-Hilali & Khan and Ali were more consistent than Pickthall.
اسم (الرحمن) في القرآن، الدلالة والسياق: دراسة موضوعية
Authors: al-Majali Muhammad Khazir
Published: November 2020

This paper examines one of Allah’s names (Al-Raḥmān, the Merciful), and the unique manner in which it appears within some verses, in contexts that do not reflect its meaning – derived from ‘Mercy’. In light of multiple perspectives by scholars on this, it was imperative to read into the name’s mention in the Quran, study what has been introduced by scholars, and differentiate Al-Raḥmān from Al-Raḥīm (also derived from Mercy). Additionally, it was important to examine the various contexts to better comprehend the name’s definition and address the primary question of why it appears in contexts that do not reflect its original meaning. This paper also sheds light on Surah Al-Raḥmān, as it bears the name, in search for some of its secrets. The study concluded that the placement of the name did not contradict its linguistic status. Appearing in varying contexts is intended as a message, to remind of Allah’s mercy and grace, and that Islam is built on the principle of mercy, which is a message to all humanity, Muslims and particularly preachers, to embody the mercy that Allah sent His Messenger (PBUH).
The cicadas (Hemiptera: Cicadidae) of Ecuador including the description of five new species, a new subtribe, four new synonymies, and fifteen new records
Authors: SANBORN ALLEN F.
Published: November 2020

The known cicada fauna of Ecuador is identified. Durangona exechopyga n. sp., Calyria chaetoacontia n. sp., Calyria xiphion n. sp., Carineta coronida n. sp., and Carineta tiarata n. sp. are described as new. The subtribe Plautillina Distant, 1905h rev. stat. is formed for the genera Plautilla Stål, 1865 and Onoralna Boulard, 1996 within the Zammarini Distant, 1905b. Zammara erna Schmidt, 1919 n. syn., Orellana brunneipennis Goding, 1925 n. syn. and Orellana pulla Goding, 1925 n. syn. are reported to be junior synonyms of Zammara intricata Walker, 1850 and Coata facialis var. Jacobi 1907a n. syn. is shown to be unavailable and a junior synonym of Coata facialis Distant 1906b. The first records of Fidicinoides besti Boulard & Martinelli, 1996, Fidicinoides brunnea Boulard & Martinelli, 1996, Fidicinoides descampsi Boulard & Martinelli, 1996, Fidicinoides ptychodiropeda Sanborn 2020b, Ariasa bilaqueata (Uhler, 1903), Guyalna bicolor (Olivier, 1790), Guyalna dyticamazona Sanborn, 2020b, Calyria fenestrata (Fabricius, 1803), Taphura boulardi Sanborn, 2011a, Carineta lichiana Boulard, 1986a, Carineta peruviana Distant, 1905c, Carineta producta Walker, 1858b, Carineta rufescens (Fabricius, 1803), Herrera concolor Sanborn, 2019b and Toulgoetalna tavakiliani Boulard, 1982 are provided. The new records represent the first records for Ariasa Distant 1905d, Calyria Stål, 1862, the tribe Parnisini Distant, 1905e, and Toulgoetalna Boulard, 1982, in Ecuador. The record for Calyria fenestrata is the first known specific locality for the species. An additional first record of Fidicinoides besti is provided for Colombia to expand the known distribution of this species. Previous records of Zammara calochroma Walker, 1858a, Dorisiana semilata (Walker, 1850), Carineta bilineosa Walker, 1858b, Carineta fasciculata (Germar, 1821), and Selymbria stigmatica (Germar, 1834) are considered to be misidentifications of Dorisiana metcalfi Sanborn & Heath, 2014 (= Cicada viridis Olivier, 1790), C. maculosa Torres, 1848, C. pilifera Walker, 1858a, and S. ecuadorensis Sanborn, 2019a, respectively, so that Z. calochroma, D. semilata, C. bilineosa, C. fasciculata, and S. stigmatica are removed from the cicada fauna of Ecuador. In addition, Chilecicada occidentis (Walker, 1850) is removed from the Ecuadorian cicada fauna as the species is restricted to Chile. The currently known Ecuadorian cicada fauna is comprised of 98 species from 24 genera, nine tribes and three subfamilies.
A Variational Method for Analyzing Vortex Flows in Radar-Scanned Tornadic Mesocyclones. Part I: Formulations and Theoretical Considerations
Authors: Xu Qin
Published: November 2020

A variational method is formulated with theoretical considerations for analyzing vortex flows in Doppler radar–scanned tornadic mesocyclones. The method has the following features. (i) The vortex center axis (estimated as a continuous function of time and height in the four-dimensional space) is used as the vertical coordinate, so the coordinate system used for the analysis is slantwise curvilinear and nonorthogonal in general. (ii) The vortex flow (VF), defined by the three-dimensional vector wind minus the horizontal moving velocity of vortex center axis, is expressed in terms of the covariant basis vectors (tangent to the coordinate curves), so its axisymmetric part can be properly defined in that slantwise-curvilinear coordinate system. (iii) To satisfy the mass continuity automatically, the axisymmetric part is expressed by the scalar fields of azimuthally averaged tangential velocity and cylindrical streamfunction and the remaining asymmetric part is expressed by the scalar fields of streamfunction and vertically integrated velocity potential. (iv) VF-dependent covariance functions are formulated for these scalar variables and then deconvoluted to construct the square root of background error covariance matrix analytically with the latter used to transform the control vector to precondition the cost function. (v) The deconvoluted covariance functions and their transformed control variables satisfy two required boundary conditions (i.e., zero vertical velocity at the lower rigid boundary and zero cross-axis velocity along the vortex center axis), so the analyzed VF satisfies not only the mass continuity but also the two boundary conditions automatically.
The Modulation of Daily Southern Africa Precipitation by El Niño–Southern Oscillation across the Summertime Wet Season
Authors: Hoell Andrew , Gaughan Andrea E. , Magadzire Tamuka , Harrison Laura
Published: November 2020

The spatiotemporal evolution of daily southern Africa precipitation characteristics, and associated atmospheric circulation, related to El Niño and La Niña is examined across the region’s November–April wet season. Precipitation characteristics are examined in terms of monthly changes in daily average precipitation, the number of precipitation days, and the number of heavy precipitation days in three independently constructed estimates of observed precipitation during 1983–2018. Mechanisms related to precipitation changes, including contributions from mass divergence, water vapor transports, and transient eddies, are diagnosed using the atmospheric moisture budget based on the ERA5 reanalysis. El Niño is related to precipitation anomalies that build during December–March, the core of the rainy season, culminating in significantly below average values stretching across a semiarid region from central Mozambique to southeastern Angola. A broad anticyclone centered over Botswana drives these precipitation anomalies primarily through anomalous mass divergence, with moisture advection and transient eddies playing secondary roles. La Niña is related to significantly above average daily precipitation characteristics over all Africa south of 20°S in February and much less so during the other five months. February precipitation anomalies are primarily driven through mass divergence due to a strong anomalous cyclonic circulation, whereas a similar circulation is more diffuse during the other months. The spatiotemporal evolutions of anomalies in daily precipitation characteristics across southern Africa related to El Niño and La Niña are not equal and opposite. The robustness of an asymmetric evolution, which could have implications for subseasonal forecasts, needs to be confirmed with analysis of additional empirical data and established with climate model experimentation.
Classification of Precipitation Type in North China Using Model-Based Explicit Fields of Hydrometeors with Modified Thermodynamic Conditions
Authors: Yang Lu , Chen Mingxuan , Wang Xiaoli , Song Linye , Yang Meilin , Qin Rui , Cheng Conglan , Li Siteng
Published: November 2020

The ability to forecast thermodynamic conditions aloft and near the surface is critical to the accurate forecasting of precipitation type at the surface. This paper presents an experimental version of a new scheme for diagnosing precipitation type. The method considers the optimum surface temperature threshold associated with each precipitation type and combines model-based explicit fields of hydrometeors with higher-resolution modified thermodynamic and topographic information to determine precipitation types in North China. Based on over 60 years of precipitation-type samples from North China, this study explores the climatological characteristics of the five precipitation types—snow, rain, ice pellets (IP), rain/snow mix (R/S MIX), and freezing rain (FZ)—as well as the suitable air temperature Ta and wet-bulb temperature Tw thresholds for distinguishing different precipitation types. Direct output from numerical weather prediction (NWP) models, such as temperature and humidity, was modified by downscaling and bias correction, as well as by incorporating the latest surface observational data and high-resolution topographic data. Validation of the precipitation-type forecasts from this scheme was performed against observations from the 2016 to 2019 winter seasons and two case studies were also analyzed. Compared with the similar diagnostic routine in the High-Resolution Rapid Refresh (HRRR) forecasting system used to predict precipitation type over North China, the skill of the method proposed here is similar for rain and better for snow, R/S MIX, and FZ. Furthermore, depiction of the diagnosed boundary between R/S MIX and snow is good in most areas. However, the number of misclassifications for R/S MIX is significantly larger than for rain and snow.
Heparin-mediated dimerization of follistatin
Authors: Walker Ryan G , Kattamuri Chandramohan , Goebel Erich J , Zhang Fuming , Hammel Michal , Tainer John A , Linhardt Robert J , Thompson Thomas B
Published: November 2020

Heparin and heparan sulfate (HS) are highly sulfated polysaccharides covalently bound to cell surface proteins, which directly interact with many extracellular proteins, including the transforming growth factor-β (TGFβ) family ligand antagonist, follistatin 288 (FS288). Follistatin neutralizes the TGFβ ligands, myostatin and activin A, by forming a nearly irreversible non-signaling complex by surrounding the ligand and preventing interaction with TGFβ receptors. The FS288-ligand complex has higher affinity than unbound FS288 for heparin/HS, which accelerates ligand internalization and lysosomal degradation; however, limited information is available for how FS288 interactions with heparin affect ligand binding. Using surface plasmon resonance (SPR) we show that preincubation of FS288 with heparin/HS significantly decreased the association kinetics for both myostatin and activin A with seemingly no effect on the dissociation rate. This observation is dependent on the heparin/HS chain length where small chain lengths less than degree of polymerization 10 (dp10) did not alter association rates but chain lengths >dp10 decreased association rates. In an attempt to understand the mechanism for this observation, we uncovered that heparin induced dimerization of follistatin. Consistent with our SPR results, we found that dimerization only occurs with heparin molecules >dp10. Small-angle X-ray scattering of the FS288 heparin complex supports that FS288 adopts a dimeric configuration that is similar to the FS288 dimer in the ligand-bound state. These results indicate that heparin mediates dimerization of FS288 in a chain-length-dependent manner that reduces the ligand association rate, but not the dissociation rate or antagonistic activity of FS288.
Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review
Authors: Miró Òscar , Rossello Xavier , Platz Elke , Masip Josep , Gualandro Danielle M , Peacock W Frank , Price Susanna , Cullen Louise , DiSomma Salvatore , de Oliveira Jr Mucio Tavares , McMurray John JV , Martín-Sánchez Francisco J , Maisel Alan S , Vrints Christiaan , Cowie Martin R , Bueno Héctor , Mebazaa Alexandre , Mueller Christian ,   The Study Group on Acute Heart Failure of the Acute Cardiovascular Care Association of the European Society of Cardiology
Published: November 2020

Aims

This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients.

Methods and results

A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4–13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74–0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80–0.84.

Conclusions

There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.
Halting the FGF/FGFR axis leads to antitumor activity in Waldenström macroglobulinemia by silencing MYD88
Authors: Sacco Antonio , Federico Cinzia , Giacomini Arianna , Caprio Cinzia , Maccarinelli Federica , Todoerti Katia , Favasuli Vanessa , Anastasia Antonella , Motta Marina , Russo Domenico , Rossi Giuseppe , Bozza Nicole , Castelli Riccardo , Neri Antonino , Ronca Roberto , Cattaneo Chiara , Tucci Alessandra , Mor Marco , Presta Marco , Roccaro Aldo M.
Published: November 2020

The human fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) axis deregulation is largely involved in supporting the pathogenesis of hematologic malignancies, including Waldenström macroglobulinemia (WM). WM is still an incurable disease, and patients succumb because of disease progression. Therefore, novel therapeutics designed to specifically target deregulated signaling pathways in WM are required. We aimed to investigate the role of FGF/FGFR system blockade in WM by using a pan-FGF trap molecule (NSC12). Wide-transcriptome profiling confirmed inhibition of FGFR signaling in NSC12-treated WM cells; unveiling a significant inhibition of MYD88 was also confirmed at the protein level. Importantly, the NSC12-dependent silencing of MYD88 was functionally active, as it led to inhibition of MYD88-driven pathways, such as BTK and SYK, as well as the MYD88-downstream target HCK. Of note, both canonical and noncanonical NF-κB cascades were downregulated in WM cells upon NSC12 treatment. Functional sequelae exerted by NSC12 in WM cells were studied, demonstrating significant inhibition of WM cell growth, induction of WM cell apoptosis, halting MAPK, JAK/STAT3, and PI3K-Akt pathways. Importantly, NSC12 exerted an anti-WM effect even in the presence of bone marrow microenvironment, both in vitro and in vivo. Our studies provide the evidence for using NSC12 as a specific FGF/FGFR system inhibitor, thus representing a novel therapeutic strategy in WM.
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells
Authors: Surka Christine , Jin Liqing , Mbong Nathan , Lu Chin-Chun , Jang In Sock , Rychak Emily , Mendy Derek , Clayton Thomas , Tindall Elizabeth , Hsu Christy , Fontanillo Celia , Tran Eileen , Contreras Adrian , Ng Stanley W. K. , Matyskiela Mary , Wang Kai , Chamberlain Philip , Cathers Brian , Carmichael James , Hansen Joshua , Wang Jean C. Y. , Minden Mark D. , Fan Jinhong , Pierce Daniel W. , Pourdehnad Michael , Rolfe Mark , Lopez-Girona Antonia , Dick John E. , Lu Gang
Published: November 2020

A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009. Biochemical, structural, and molecular characterization demonstrates that CC-90009 coopts the CRL4CRBN to selectively target GSPT1 for ubiquitination and proteasomal degradation. Depletion of GSPT1 by CC-90009 rapidly induces acute myeloid leukemia (AML) apoptosis, reducing leukemia engraftment and leukemia stem cells (LSCs) in large-scale primary patient xenografting of 35 independent AML samples, including those with adverse risk features. Using a genome-wide CRISPR-Cas9 screen for effectors of CC-90009 response, we uncovered the ILF2 and ILF3 heterodimeric complex as a novel regulator of cereblon expression. Knockout of ILF2/ILF3 decreases the production of full-length cereblon protein via modulating CRBN messenger RNA alternative splicing, leading to diminished response to CC-90009. The screen also revealed that the mTOR signaling and the integrated stress response specifically regulate the response to CC-90009 in contrast to other cereblon modulators. Hyperactivation of the mTOR pathway by inactivation of TSC1 and TSC2 protected against the growth inhibitory effect of CC-90009 by reducing CC-90009-induced binding of GSPT1 to cereblon and subsequent GSPT1 degradation. On the other hand, GSPT1 degradation promoted the activation of the GCN1/GCN2/ATF4 pathway and subsequent apoptosis in AML cells. Collectively, CC-90009 activity is mediated by multiple layers of signaling networks and pathways within AML blasts and LSCs, whose elucidation gives insight into further assessment of CC-90009s clinical utility. These trials were registered at www.clinicaltrials.gov as #NCT02848001 and #NCT04336982).
Altered phenotype in LMAN1-deficient mice with low levels of residual LMAN1 expression
Authors: Everett Lesley A. , Khoriaty Rami N. , Zhang Bin , Ginsburg David
Published: November 2020

Combined deficiency of coagulation factors V and VIII (F5F8D) is an autosomal recessive bleeding disorder caused by loss-of-function mutations in either LMAN1 or MCFD2. The latter genes encode 2 components of a mammalian cargo receptor that facilitates secretion of coagulation factor V (FV) and factor VIII (FVIII) from the endoplasmic reticulum (ER) to the Golgi via coat protein complex II vesicles. F5F8D patients exhibit FV and FVIII levels that are ∼10% to 15% of normal. We report herein a comparative analysis for a series of murine Lman1 alleles. Consistent with previous reports, mice completely deficient in LMAN1 (Lman1−/−) exhibit ∼50% FV and FVIII levels. In contrast, mice carrying a hypomorphic Lman1 allele (Lman1cgt/cgt) that expresses ∼6% to 8% of wild-type Lman1 mRNA levels exhibit intermediate plasma FV and FVIII reductions (∼70% of wild-type levels). Lman1−/− mice exhibit ER accumulation of another LMAN1 cargo, alpha-1 antitrypsin (A1AT), with an intermediate level of A1AT ER retention observed in Lman1cgt/cgt mice. Finally, the previously reported strain-specific, partially penetrant, perinatal lethality of LMAN1-deficient mice (Lman1gt1/gt1) was confirmed in Lman1−/− mice, although it was not observed in Lman1cgt/cgt mice. Taken together, these results show a dose-dependent effect of residual LMAN1 on the secretion of its cargo proteins. The results also suggest that human subjects with hypomorphic LMAN1 mutations might present with mild bleeding phenotypes resulting from more modest reductions in FV and FVIII, which could be missed by routine clinical evaluation. Finally, these findings suggest that therapeutic targeting of LMAN1 to reduce FV and FVIII as an anticoagulant strategy may only require partial inhibition of LMAN1 function.
The clinical spectrum of ocular bartonellosis: a retrospective study at a tertiary centre in Malaysia
Authors: Tey Michele Shi-Ying , Govindasamy Gayathri , Vendargon Francesca Martina
Published: November 2020

Background

Cat scratch disease (CSD) is a systemic illness caused by the gram-negative bacillus, Bartonella henselea, which can occasionally involve the ocular structures. The objective of this study is to evaluate the various clinical presentations of ocular bartonellosis at our institution. A retrospective review of the clinical records of 13 patients (23 eyes) with ocular manifestations of Bartonella infections over a 3-year period between January 2016 to December 2018 was undertaken at our institution.

Results

The diagnosis was made based on clinical findings and in addition, with the support of the evidence of Bartonella hensalae IgG and/or IgM. Small retinal white lesions were the most common ocular findings in this series of patients (82.6% of eyes, 76.9% of patients). Neuroretinitis was the second most common finding (47.8% of eyes, 69.2% of patients), followed by exudative retinal detachment involving the macula (34.8% of eyes, 53.8% of patients) and Parinaud’s oculoglandular syndrome (17.4% of eyes, 23.1% of patients). Other findings like isolated optic disc oedema without macular star (8.7% of eyes, 15.4% of patients) and vitritis (4.3% of eyes, 7.7% of patients) were also observed. Ten patients (76.9%) had bilateral ocular involvement. Most of the patients were young, immunocompetent and had systemic symptoms like fever prior to their ocular symptoms. The visual acuity (VA) at initial presentation ranged from 6/6 to hand movement (mean, 6/20), and at final visit 6/6 to 6/60, (mean, 6/9). 91.7% of patients were treated with antibiotics. Only 2 patients received oral corticosteroids together with antibiotics due to very poor vision on presentation. The visual prognosis of ocular bartonellosis is generally good with 16 (88.9%) of 23 eyes having VA of 6/12 or better at final follow-up visit.

Conclusion

Small foci of retinal white lesions were the most common manifestation of ocular bartonellosis in this series, followed by neuroretinitis, though an array of other ocular findings may also occur. Therefore, we should consider bartonella infection as a possible differential diagnosis in those patients.
Predictive accuracy of a hierarchical logistic model of cumulative SARS-CoV-2 case growth until May 2020
Authors: Kriston Levente
Published: November 2020

Background

Infectious disease predictions models, including virtually all epidemiological models describing the spread of the SARS-CoV-2 pandemic, are rarely evaluated empirically. The aim of the present study was to investigate the predictive accuracy of a prognostic model for forecasting the development of the cumulative number of reported SARS-CoV-2 cases in countries and administrative regions worldwide until the end of May 2020.

Methods

The cumulative number of reported SARS-CoV-2 cases was forecasted in 251 regions with a horizon of two weeks, one month, and two months using a hierarchical logistic model at the end of March 2020. Forecasts were compared to actual observations by using a series of evaluation metrics.

Results

On average, predictive accuracy was very high in nearly all regions at the two weeks forecast, high in most regions at the one month forecast, and notable in the majority of the regions at the two months forecast. Higher accuracy was associated with the availability of more data for estimation and with a more pronounced cumulative case growth from the first case to the date of estimation. In some strongly affected regions, cumulative case counts were considerably underestimated.

Conclusions

With keeping its limitations in mind, the investigated model may be used for the preparation and distribution of resources during the initial phase of epidemics. Future research should primarily address the model’s assumptions and its scope of applicability. In addition, establishing a relationship with known mechanisms and traditional epidemiological models of disease transmission would be desirable.
Association between platelet count and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study
Authors: Furukawa Shinya , Yagi Sen , Shiraishi Kana , Mori Kenichirou , Ninomiya Tomoyuki , Kawasaki Keitarou , Mizukami Yuji , Suzuki Seiyuu , Uraoka Masayoshi , Shibata Naozumi , Nakamura Sanae , Imamine Satoshi , Murakami Hidehiro , Ohashi Katsuhisa , Torisu Masamoto , Hasebe Aki , Yano Harumi , Murakami Masato , Takeshita Eiji , Ikeda Yoshio , Hiasa Yoichi
Published: November 2020

Background

Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC.

Methods

The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0–1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors.

Results

The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI 0.19–0.810], very high: OR 0.37 [95%CI 0.17–0.77], p for trend = 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI 0.18–0.73], high: OR 0.41 [95% CI 0.19–0.83], and very high: OR 0.45 [95% CI 0.21–0.94], p for trend = 0.033) after adjustment for confounding factors.

Conclusions

Among patients with UC, platelet count was independently inversely associated with MH