bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Increasing Patient Complexity Have an Effect on Medical Outcomes and Lengths-of-Stay after Total Knee Arthroplasty?
Authors: Anis Hiba K. , Sodhi Nipun , Acuña Alexander J. , Roth Alexander , Vakharia Rushabh , Newman Jared M. , Mufarrih Syed H. , Grossman Eric , Roche Martin W. , Mont Michael A.
Published: April 2020

A greater number of medically complex patients with multiple comorbidities are now more readily considered for total knee arthroplasty (TKA). Therefore, the purpose of this study was to determine whether comorbidity burden, measured with the Elixhauser Comorbidity Index (ECI), correlated with 90-day medical complications and longer in-hospital lengths-of-stay (LOS) in TKA patients. The PearlDiver supercomputer was queried for all primary TKA patients in the Medicare Standard Analytic Files from 2005 to 2014 using International Classification of Disease, 9th edition codes. Patients were included based on ECI scores, ranging from 1 to 5. ECI 1 patients served as the control cohort, while ECI 2, 3, 4, and 5 patients were considered study cohorts. Each study cohort was matched based on age and gender to the control cohort, resulting in a total of 715,398 patients included for analysis (ECI 1, n = 144,072; ECI 2, n = 144,072; ECI 3, n = 144,072; ECI 4, n = 144,072; ECI 5, n = 139,110). Logistic regression analyses were performed to compare 90-day medical complications and Welch's t-tests were performed to compare LOS between the cohorts. Patients with higher ECI scores were more likely to develop medical complications and have longer LOS compared with matched patients in the control cohort. Compared with matched ECI 1 patients, patients with ECI scores of 2 (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.14–1.24), 3 (OR: 1.27, 95% CI: 1.21–1.32), 4 (OR: 1.32, 95% CI: 1.27–1.38), and 5 (OR: 1.33, 95% CI: 1.27–1.39) were significantly more likely to develop 90-day medical complications. Additionally, the mean LOS of patients in the ECI 2 (2.59 ± 1.49 vs. 2.73 ± 1.52 days), ECI 3 (2.59 ± 1.49 vs. 2.88 ± 1.51 days; p < 0.001), ECI 4 (2.59 ± 1.49 vs. 3.01 ± 1.56 days; p < 0.001), and ECI 5 (2.61 ± 1.49 vs. 3.14 ± 1.61 days; p < 0.001) groups were significantly longer than the mean LOS in the control ECI 1 group. In an increasingly complex patient population, associations between comorbidities and outcomes after TKA procedures can guide providers on how to modify their pre- and postoperative care. These results demonstrate that higher ECI scores are associated with a greater likelihood of 90-day medical complications and longer in-hospital LOS.
Treatment of Concomitant ACL and MCL Injuries: Spontaneous Healing of Complete ACL and MCL Tears
Authors: Razi Mohammad , Soufali Amir Payman , Ziabari Elaheh Ziaei , Dadgostar Haleh , Askari Alireza , Arasteh Peyman
Published: April 2020

The mainstay of treatment for anterior cruciate ligament (ACL) tear is considered to be surgery, especially when associated with medial collateral ligament (MCL) tears. We aimed to evaluate our hypothesis that some patients with concomitant ACL and MCL tears may develop spontaneous healing without surgical intervention. This study was conducted during 2013 to 2017. A total of 707 patient referred with combined ACL and MCL injuries. Patients were divided into three groups according to type of ACL and MCL management as follows: (1) group 1 as those who only had ACL reconstruction without any surgical treatment of MCL; (2) group 2 as those who had ACL reconstruction and MCL surgery (reconstruction, reefing, or both); (3) group 3 as those who showed spontaneous healing of ACL and MCL. Overall, 206 and 129 patients entered groups 1 and 2, respectively. Overall, 15 patients showed spontaneous healing of ACL and entered group 3. Skiing and soccer were the most common causes of injury within the third group, followed by traffic accidents (35.7%, 35.7% and 21.4%, respectively). All these were noncontact injuries within this groups. In group 3 only three patients had concomitant meniscal injury. Mean healing time for patient with spontaneous healing was 8.66 ± 3.41 months. All patients showed ACL tears at the proximal part of its attachment. During follow-up, all pivot shift, Lachman and MCL tests were either negative or one plus. All these individuals returned to previous physical activity. Among the total number of patients with skiing injuries presenting with concomitant ACL/MCL injuries (27 patients), five patients (18.5%) showed spontaneous healing. Valgus and external rotation injuries with dominancy of valgus force, apart from a MCL tear, may lead to proximal tear of ACL as well, and the inflammation from the torn MCL can potentiate and stimulate the healing process of ACL; thus, patient with this mechanism of injury is better followed before surgical intervention is planned as spontaneous healing may occur.
Initial data and first evolutions of dust clouds in bimetric relativity
Authors: Kocic Mikica , Torsello Francesco , Högås Marcus , Mörtsell Edvard
Published: April 2020

We present a method for solving the constraint equations in the Hassan–Rosen bimetric theory to determine the initial data for the gravitational collapse of spherically symmetric dust. The setup leads to equations similar to those for a polytropic fluid in general relativity, here called Lane–Emden-like equations. Using a numerical code which solves the evolution equations in the standard 3 + 1 form, we also obtain a short-term development of the initial data for these bimetric spherical clouds. The evolution highlights some important features of the bimetric theory such as the interwoven and oscillating null cones representing the essential nonbidiagonality in the dynamics of the two metrics. The simulations are in the strong-field regime and show that, at least at an early stage, if the bimetric initial data are close to those for general relativity, the bimetric evolution stays close to the evolution in general relativity as well, and with no instabilities, albeit with small oscillations in the metric fields. In addition, we determine initial data and first evolution for vacuum bimetric spherically symmetric nonstationary solutions, providing generic counterexamples to a statement analog to Jebsen–Birkhoff theorem in bimetric relativity.
Vibrationally resolved electron impact electronic excitation of BeH
Authors: Darby-Lewis D , Tennyson J , Yurchenko S N , Lawson K D
Published: April 2020

Beryllium is being adopted for plasma facing walls in fusion reactors. This has led to the observation of emissions from the A 2Π state of beryllium hydride. Use of these emissions to monitor Be erosion requires electron impact excitation rates. Cross sections for electron impact vibrational excitation within the X 2Σ+ state and vibrationally resolved electronic excitation to the A 2Π state are reported for BeH, BeD and BeT. Electron collisions are studied at a range of internuclear separations using the UK molecular R-matrix (UKRmol+) codes. Electronic excitation is studied both within the Franck–Condon approximation and by explicit averaging of the T-matrix elements. It is found that (a) inclusion of the effect of higher partial waves using the Born approximation leads to significant increases in the cross sections and (b) the Franck–Condon approximation underestimates the importance of collisions for which the vibrational state changes during electronic excitation.
Pushing Cherenkov PET with BGO via coincidence time resolution classification and correction
Authors: Kratochwil Nicolaus , Gundacker Stefan , Lecoq Paul , Auffray Etiennette
Published: April 2020

Bismuth germanate (BGO) shows good properties for positron emission tomography (PET) applications, but was substituted by the development of faster crystals like lutetium oxyorthosilicate (LSO) for time-of-flight PET (TOF-PET). Recent improvements in silicon photomultipliers (SiPMs) and fast readout electronics make it possible to access the Cherenkov photon signal produced upon 511 keV interaction, which makes BGO a cost-effective candidate for TOF-PET.

Tails in the time-delay distribution, however, remain a challenge. These are mainly caused by the high statistical fluctuation on the Cherenkov photons detected. To select fast events with a high detected Cherenkov photon number, the signal rise time of the SiPM was used for discrimination. The charge, time delay and signal rise time was measured for two different lengths of BGO crystals coupled to FBK NUV-HD SiPMs and high frequency readout in a coincidence time resolution setup. The recorded events were divided into 5 × 5 categories based on the signal rise time, and time resolutions of 200 ± 3 ps for 2 × 2 × 20 mm3 and 117 ± 3 ps for 2 × 2 × 3 mm3 were measured for the fastest 20% of the events (4% in coincidence). These good timing events can provide additional information for the image reconstruction in order to increase the SNR significantly, without spoiling the detector sensitivity. Putting all photopeak events together and correcting for the time bias introduced by different numbers of Cherenkov photons detected, time resolutions of 259 ± 3 ps for 20 mm long and 151 ± 3 ps for 3 mm long crystals were measured. For a small fraction of events sub-100 ps coincidence time resolution with BGO was reached for a 3 mm short pixel.
Dynamical properties of a few mass-imbalanced ultra-cold fermions confined in a double-well potential
Authors: Nandy Dillip K , Sowiński Tomasz
Published: April 2020

A comprehensive analysis of the exact unitary dynamics of two-component mass-imbalanced fermions in a one-dimensional double-well potential is accomplished by considering the total number of particles maximum up to six. The simultaneous effect of mass imbalance between the flavors and their mutual interactions on the dynamics is scrutinized through the exact diagonalization. In particular, we investigate the occupation dynamics of such systems being initially prepared in experimentally accessible states in which opposite components occupy opposite wells. Moreover, to capture the role of interactions, we also inspect situations in which initial states contain an opposite-spin pair localized in a chosen well. Finally, to assess the amount of quantum correlations produced during the evolution, we analyze the behavior of the von Neumann entanglement entropy between components.
The effect of microwave irradiation on reduced graphene oxide from coconut shells
Authors: Yanti D R , Hikmah U , Prasetyo A , Hastuti E
Published: April 2020

Reduced graphene oxide has been synthesized by microwave irradiation assisted. The effect of microwave irradiation on its crystal structure and electrical conductivity was investigated. Graphene oxide was synthesized using a modified hummers method then reduced by LAA (L-Ascorbic Acid) as a reducing agent with microwave irradiation assisted. The irradiation time varied by 10, 20, 30, and 40 minutes. The samples characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy-EDAX (SEMEDAX), X-Ray Diffractometer (XRD), and Inductance Capacitance and Resistance Meters (LCR-Meters).
Pilot-scale production of Boletus colossus culture for promoting the growth of Para rubber trees
Authors: Dechmahitkul W , Khumvongsa K , Mekvichitsaeng P
Published: April 2020

Boletus colossus is an Ectomycorrhiza fungi. It grows on roots of big trees such as Rubber tree, Mango tree and etc. This mushroom grows by using the organic materials released from the roots. The moisture adsorbed on the fungi makes the roots resist the drought better. The mushroom can also turn some insoluble inorganic materials into the form that plants can make use of. This research is to study the production of the starter culture by using low-cost media. The result shows that the fungi can grow best in whey to 9.2 g/L (dry weight) in 10 days. The liquid broth can inhibit the growth of pathogens (Alternaría brasicola, Alternaría pori, and Fusarium solani) on Potato-Dextrose agar. The starter culture can also be produced in a 50L fermenter to the dry weight of 8.1 g/L in 6 days. Loam is the best as solid carrier followed by peat moss. The result in one year shows that the Para rubber trees grow with the fungi that have significantly longer stems, leaves, and roots.
Assessment of agronomic performance and shattering resistance of F7 soybean lines
Authors: Krisnawati A , Soegianto A , Waluyo B , Kuswanto
Published: April 2020

Soybean productivity can be increased through optimizing the agronomic performance and minimizing the yield losses due to pod shattering. The objectives of this studywere to evaluate the agronomic performance and shattering resistance of F7 soybean lines. Twenty-one F7 lines including three check varieties (Dega 1, Detap 1, and Anjasmoro) were evaluated in two soybean production centers (Blitar and Mojokerto, East Java, Indonesia) from July to October 2018. The field experiment was arranged in a randomized block design with four replications. The screening for shattering resistance was done by the oven-dry method. The results showed that the plant height, number of filled pods, seed size, and seed yield were higher in Mojokerto than in Blitar, meanwhile, the average branches number in Blitar was higher than in Mojokerto. The yield of Detap 1 (2.89 t/ha) was highest than the two other check varieties. Three lines produce higher yield than Detap 1, namely Anjs/G100H-44 (3.33 t/ha), Anjs/Rajabasa-306 (3.22 t/ha), and Anjs/Rajabasa-311 (3.26 t/ha). The agronomic traits for determining high yields differ between locations. The assessment for shattering resistance resulted in seven highly resistant lines, twelve resistant lines, three moderately resistant lines, one susceptible line, and one highly susceptible line. Three selected lines with high yield and resistant to pod shattering were recommended to be tested in the various environments.
Study of house orientation and their placement towards sustainable Islamic residential area
Authors: Junara N , Mutiara E , Senjana S
Published: April 2020

Indonesia is a country which exhibits full of dynamic in its physical development. There are existing kampongs, within the city rapid development growth, preserve with their abundant cultural and traditional potentials. Muslim kampongs are one of the traditional settlements embedded with significant Islamic characteristics. Religious or belief factor is one of the issues that determine occupational typology. In traditional society, this is a dominant aspect that signifies their community identity. In this research, the leading indicators include the nature of law, faith in religion and culture, design principal from Sharia law, and social principal. This study aims to investigate the relationship between traditional settlement patterns with religious influences, especially Islam in Indonesia through house orientation and their placement. This paper adopts a content analysis method to achieve the research objective of “Islamic Housing Typology.” From the content analysis, it is discovered that the orientation and house placement has a significant relationship with the Muslim worldview. The existence of mosques and boarding schools are some of the factors forming the orientation of Muslim residential areas. This study enhances the existing literature on the importance of house orientation and their placement in the Muslim residential area.
Implementation green industry standard at textile industry and textile product
Authors: Indrayani L , Triwiswara M
Published: April 2020

At present industrialists must begin to shift from the industry as usual to an environmental industry or what is now known as a green industry. An important issue in the principle of green industry that needs to be understood and implemented is industries in their production processes implement sustainable efficiency and effectiveness in resources. The green industry is not only oriented towards improving the economic sector but also concerned with environmental sustainability. So the negative impact on the environment and the use of natural resources providers of industrial supports, does not result in a decrease in the carrying capacity and capacity of the environment. Therefore to realize the textile industry and textile products that are environmentally friendly, the necessity to develop industrial performance by integrating the principles of the green industry into the production process. This paper will explain the implementation of green industry characteristics that can be adapted into each stage of the production process in the textile industry and textile products, especially the batik industry. The characteristics of the green industry include the efficiency of the use of input materials, namely raw materials and auxiliary materials and the use of alternative materials that are more environmentally friendly, low energy and water intensity, minimization of waste both liquid and solid waste and reducing emissions due to the use of low-carbon technology. Each characteristic is equipped with criteria in the green industry standard (GIS) that can be used by textile and textile products industrialists, especially the batik industry in implementing the principles of the green industry.
Sprinkler irrigation design with microcontroller based on IoT
Authors: Noerhayati E , Margianto  , Dwisulo B , Rahmawati A
Published: April 2020

Sprinkler irrigation is an alternative irrigation technology application that theoretically has a higher efficiency than open irrigation channels. In the form of the field, production of high- efficiency irrigation is achieved when most of the irrigation network is designed correctly and use an excellent tool and smooth operation. 4.0 to support the industry, irrigation precipitation can automatically be developed using the ESP8266 NodeMCU Android-based microcontroller. Tests in the laboratory by direct observation method. The statistical data analysis using the analytical statistic results of the T-test showed that the distribution of the automatic sprinkler water distribution compared to manual testing meets the T-test.
Diversity and clustering analysis of Sterculia quadrifida R.Br from Kupang, East Nusa Tenggara, Indonesia based on morphological and anatomical characters
Authors: Uslan  , Asmiati  , Lestari N
Published: April 2020

This study aimed to determine the diversity and clustering of Faloak (Sterculia quadrifida R.Br) from Kupang District based on morphological and anatomical characters. This research used descriptive qualitative and quantitative methods. To show the clustering relationship, we used the UPGMA method similarity by the Nei Li coefficient through the MVSP software program version 3.2. Results showed that there was a relationship of Faloak plants from both locations in Kupang district forming 4 groups including Group I (Kupang Barat populations); Group II (Taebenu 3 pupulation), Group III (Kupang Barat 3 and Taebenu 2 populations) and Group IV (Kupang Barat 2 and Taebenu 1 populations). The anatomical characters showed a clear similarity on the epidermal cell, thick inner wall, guard cell, and stomatal pore. The type of trichome on the leaves of Faloak plants from these two sub-districts also showing a similarity, namely non-glandular trichome type.
Synthesis of nanomagnetite coated with carboxymethyl kappa carrageenan (CMKC) as a binder of sodium diclofenac
Authors: Zuhroti B , Kusumaningrum I K , Wijaya A R , Purnama N N
Published: April 2020

To increase the effectiveness of therapy and prevent such damage, nanocarriers can be used as drug carriers through intraarticular injection. The active ingredient of the drug is bound to the nanoparticle-wrapping membrane which is controlled by a magnetic field from the outside. The nanoparticles used in this study were nanomagnetites which were synthesized by the coprecipitation method. Then nanomagnetite is coated with a coating agent that can bind the active ingredients of the drug while preventing agglomeration and oxidation. The coating used carboxymethyl kappa-carrageenan (CMKC). CMKC synthesis was carried out by modifying kappa-carrageenan through two steps, alkalization of k-carrageenan using NaOH, to form alkoxy-k-carrageenan, then etherification of alkoxy-k-carrageenan with monochloroacetic acid (MCA) as reactant to produce carboxymethyl k-carrageenan (CMKC) in isopropanol and ethanol solvent media. The absorption of diclofenac sodium into nanomagnetite coatings was carried out on a phosphate buffer media of pH 7.4 with an absorption time of 30 minutes at room temperature. From the results of the research note that sodium diclofenac successfully adsorbed onto nanomagnetite coatings.
Properties of cassava starch-based bioplastics and CMC with sorbitol as A plasticizer
Authors: Tamara T , Sumari  , Nazriati  , Arni S
Published: April 2020

This research aims to synthesize and characterize the properties of starch and starch/CMC-based bioplastics and to know the effect of sorbitol concentration on bioplastics produced. Characterization the bioplastics used SEM, FTIR and XRD as well as thickness, tensile strength, elongation at break, and resistant to water and acid. The result showed that synthesis of starch and starch-bioplastic success and the surface of bioplastics is uniform, except bioplastic from pure starch. Starch/CMC-based bioplastics is thinner (106.67 ± 5.13 μm), lower tensile strength (8.95 N), more easily degraded by water (33 hours) and acid (15 hours) but highest elongation at breaks (48.15%) than starch based-bioplastics. Sorbitol concentration is proportional to the level of elongation at break and the optimum concentration which added to starch-based bioplastic is 15 mL/20g starch.
Designing a Green Food Delivery Packaging with QFD for Environment (QFDE) and TRIZ
Authors: Harahap M F B , Mubarak A , Suzianti A
Published: April 2020

The Indonesian food delivery service market is projected to grow until 2020. Looking at these trends, food packaging plays an important role in the running of the system. However, until now the packaging on the delivery order is still similar to the package on take-out orders. Seeing this, several problems might occur such as changes in food temperature during transportation, poor presentation of food, changing food tastes, and other causes that impact on decreasing customer satisfaction with the quality of food delivery services and restaurants. The existence of food packaging is very close to the waste it produces. Responding to the problem, this study attempts to examine the proper food delivery packaging (tertiary packaging) design so that food quality can still be maintained by applying the Quality Function Deployment for Environment (QFDE) and Teorija Rezhenija Izobretatelskih Zadach (TRIZ) methods. This study succeeded in answering the research objectives, namely to find out the attributes of customer needs and weighing their importance to the quality of food packaging, as well as succeed in providing food packaging design recommendations with a function focus to maintain food hygiene during the delivery process and considering environmental aspect along the design process.
Investigation on Capacitance Regeneration Characteristics of Supercapacitors during the Aging Tests
Authors: Zhang L , Shi H L , Wang L Q , Wang N
Published: April 2020

The lifetime prediction of supercapacitors is of great significance to the management of energy storage systems, but the phenomenon of capacitance regeneration may occur in the aging cycle experiment of supercapacitors, which will bring about interference to its lifetime prediction. In this paper, the critical factors affecting the capacitance regeneration of supercapacitors are investigated, so as to analyze the influence of the regeneration phenomenon on the lifetime prediction of supercapacitors. The results show that the regeneration performance of supercapacitors is closely related to the working voltage, temperature, aging depth and recovery time. When the charging voltage is increased, the amplitude of the capacitance regeneration decreases, and with the deepening of aging degree, the amplitude of the capacitance regeneration decreases gradually. The temperature has little effect on the amplitude of the capacitance regeneration, but the higher the temperature, the longer the recovery time of capacitance regeneration. In addition, the regeneration capacitance of supercapacitors decays faster than its inherent capacitance under the same aging test conditions. Considering the capacitance regeneration characteristics, the aging trend of supercapacitors is predicted by using support vectors machines method. The prediction results are basically identical with the experimental results.
The changing ecosystem of Dutch BITs
Authors: Lavranos Nikos
Published: April 2020

This article reviews the recent changes of the Dutch model BIT text. It provides a background of the political changes at the domestic as well as the European Union (EU) level, which have been driving these changes. The consequences of the Achmea judgment are of particular importance for the intra-EU BITs and potentially for the Energy Charter Treaty. Subsequently, the article highlights the most dramatic changes compared to the previous Dutch model BIT text and Dutch BIT practice. The author concludes that these changes will ultimately result in a lowering of the level of investor and investment protection.
Development and validation of an interpretable deep learning framework for Alzheimer’s disease classification
Authors: Qiu Shangran , Joshi Prajakta S , Miller Matthew I , Xue Chonghua , Zhou Xiao , Karjadi Cody , Chang Gary H , Joshi Anant S , Dwyer Brigid , Zhu Shuhan , Kaku Michelle , Zhou Yan , Alderazi Yazan J , Swaminathan Arun , Kedar Sachin , Saint-Hilaire Marie-Helene , Auerbach Sanford H , Yuan Jing , Sartor E Alton , Au Rhoda , Kolachalama Vijaya B
Published: April 2020

Alzheimer’s disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer’s disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer’s disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer’s disease and cognitively normal subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer’s Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer’s disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease.
18F-fluorodeoxyglucose positron emission tomography in dementia with Lewy bodies
Authors: Graff-Radford Jonathan , Lesnick Timothy G , Savica Rodolfo , Chen Qin , Ferman Tanis J , Przybelski Scott A , Jones David T , Senjem Matthew L , Gunter Jeffrey L , Kremers Walter K , Jack Clifford R , Lowe Val J , Petersen Ronald C , Knopman David S , Boeve Bradley F , Murray Melissa E , Dickson Dennis W , Kantarci Kejal
Published: April 2020

Among individuals with dementia with Lewy bodies, pathologic correlates of clinical course include the presence and extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease. The objectives of this study are to determine (i) whether 18F-fluorodeoxyglucose PET signature patterns of dementia with Lewy bodies are associated with the extent of coexisting Alzheimer’s pathology and the presence of transitional or diffuse Lewy body disease and (ii) whether these 18F-fluorodeoxyglucose pattern(s) are associated with clinical course in dementia with Lewy bodies. Two groups of participants were included: a pathology-confirmed subset with Lewy body disease (n = 34) and a clinically diagnosed group of dementia with Lewy bodies (n = 87). A subset of the clinically diagnosed group was followed longitudinally (n = 51). We evaluated whether 18F-fluorodeoxyglucose PET features of dementia with Lewy bodies (higher cingulate island sign ratio and greater occipital hypometabolism) varied by Lewy body disease subtype (transitional versus diffuse) and Braak neurofibrillary tangle stage. We investigated whether the PET features were associated with the clinical trajectories by performing regression models predicting Clinical Dementia Rating Scale Sum of Boxes. Among autopsied participants, there was no difference in cingulate island sign or occipital hypometabolism by Lewy body disease type, but those with a lower Braak tangle stage had a higher cingulate island sign ratio compared to those with a higher Braak tangle stage. Among the clinically diagnosed dementia with Lewy bodies participants, a higher cingulate island ratio was associated with better cognitive scores at baseline and longitudinally. A higher 18F-fluorodeoxyglucose PET cingulate island sign ratio was associated with lower Braak tangle stage at autopsy, predicted a better clinical trajectory in dementia with Lewy body patients and may allow for improved prognostication of the clinical course in this disease.
Foxg1 Upregulation Enhances Neocortical Activity
Authors: Tigani Wendalina , Rossi Moira Pinzan , Artimagnella Osvaldo , Santo Manuela , Rauti Rossana , Sorbo Teresa , Ulloa Severino Francesco Paolo , Provenzano Giovanni , Allegra Manuela , Caleo Matteo , Ballerini Laura , Bozzi Yuri , Mallamaci Antonello
Published: April 2020

Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity. We found that mice overexpressing Foxg1 in neocortical pyramidal cells displayed an electroencephalography (EEG) with increased spike frequency and were more prone to kainic acid (KA)-induced seizures. Consistently, primary cultures of neocortical neurons gain-of-function for Foxg1 were hyperactive and hypersynchronized. That reflected an unbalanced expression of key genes encoding for ion channels, gamma aminobutyric acid and glutamate receptors, and was likely exacerbated by a pronounced interneuron depletion. We also detected a transient Foxg1 upregulation ignited in turn by neuronal activity and mediated by immediate early genes. Based on this, we propose that even small changes of Foxg1 levels may result in a profound impact on pyramidal cell activity, an issue relevant to neuronal physiology and neurological aberrancies associated to FOXG1 copy number variations.
Comparative Replication and Immune Activation Profiles of SARS-CoV-2 and SARS-CoV in Human Lungs: An Ex Vivo Study With Implications for the Pathogenesis of COVID-19
Authors: Chu Hin , Chan Jasper Fuk-Woo , Wang Yixin , Yuen Terrence Tsz-Tai , Chai Yue , Hou Yuxin , Shuai Huiping , Yang Dong , Hu Bingjie , Huang Xiner , Zhang Xi , Cai Jian-Piao , Zhou Jie , Yuan Shuofeng , Kok Kin-Hang , To Kelvin Kai-Wang , Chan Ivy Hau-Yee , Zhang Anna Jinxia , Sit Ko-Yung , Au Wing-Kuk , Yuen Kwok-Yung
Published: April 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that has resulted in more than 2 000 000 laboratory-confirmed cases including over 145 000 deaths. Although SARS-CoV-2 and SARS-CoV share a number of common clinical manifestations, SARS-CoV-2 appears to be highly efficient in person-to-person transmission and frequently causes asymptomatic or presymptomatic infections. However, the underlying mechanisms that confer these viral characteristics of high transmissibility and asymptomatic infection remain incompletely understood.

Methods

We comprehensively investigated the replication, cell tropism, and immune activation profile of SARS-CoV-2 infection in human lung tissues with SARS-CoV included as a comparison.

Results

SARS-CoV-2 infected and replicated in human lung tissues more efficiently than SARS-CoV. Within the 48-hour interval, SARS-CoV-2 generated 3.20-fold more infectious virus particles than did SARS-CoV from the infected lung tissues (P < .024). SARS-CoV-2 and SARS-CoV were similar in cell tropism, with both targeting types I and II pneumocytes and alveolar macrophages. Importantly, despite the more efficient virus replication, SARS-CoV-2 did not significantly induce types I, II, or III interferons in the infected human lung tissues. In addition, while SARS-CoV infection upregulated the expression of 11 out of 13 (84.62%) representative proinflammatory cytokines/chemokines, SARS-CoV-2 infection only upregulated 5 of these 13 (38.46%) key inflammatory mediators despite replicating more efficiently.

Conclusions

Our study provides the first quantitative data on the comparative replication capacity and immune activation profile of SARS-CoV-2 and SARS-CoV infection in human lung tissues. Our results provide important insights into the pathogenesis, high transmissibility, and asymptomatic infection of SARS-CoV-2.
All-Cause Mortality and Serious Non-AIDS Events in Adults With Low-level Human Immunodeficiency Virus Viremia During Combination Antiretroviral Therapy: Results From a Swedish Nationwide Observational Study
Authors: Elvstam Olof , Marrone Gaetano , Medstrand Patrik , Treutiger Carl Johan , Sönnerborg Anders , Gisslén Magnus , Björkman Per
Published: April 2020

Background

The impact of low levels of human immunodeficiency virus (HIV) RNA (low-level viremia [LLV]) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAEs).

Methods

We grouped individuals starting cART 1996–2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load, 50–999 copies/mL), and nonsuppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50–199 and 200–999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes.

Results

A total of 6956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.3–3.6). This association was also observed for LLV 50–199 copies/mL (aHR, 2.2; 95% CI, 1.3–3.8), but was not statistically significant for LLV 200–999 copies/mL (aHR, 2.1; 95% CI, .96–4.7). LLV 50–999 copies/mL was not linked to increased risk of AIDS or SNAEs, but in subanalysis, LLV 200–999 copies/mL was associated with SNAEs (aHR, 2.0; 95% CI, 1.2–3.6).

Conclusions

In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.
Long-term success of flexible endoscopic septal division with the stag beetle knife for Zenker’s diverticulum: a tertiary center study
Authors: Ishaq Sauid , Siau Keith , Lee Minhong , Sultan Haleema , Mohaghegh Shalmani H , Kuwai Toshio , Mulder Chris J , Neumann Helmut
Published: April 2020

Objectives

Flexible endoscopic septum division is an established treatment for Zenker’s diverticulum (ZD); however, long-term outcome data are lacking. We aimed to evaluate the long-term efficacy of flexible endoscopic septal division (FESD) using the stag beetle knife for ZD and identify predictors of symptom recurrence.

Methods

Patients undergoing the procedure between 2013 and 2018 were prospectively enrolled. Procedures were performed by a single operator. Symptom severity pre- and postprocedure was recorded using the dysphagia, regurgitation, and complications scale. Symptom recurrence was defined as a total score > 1 after the index procedure. Time-to-event analyses were performed using Kaplan–Meier plots, with multivariable analyses performed using Cox regression models.

Results

Altogether, 65 patients (mean age 74.0 years, 60% male) were included. Previous stapling had been performed in 44.6% of patients. Over the mean posttreatment follow-up period of 19 months, 5.6% of the treatment naïve group and 34.5% of the recurrent group underwent repeated FESD (P = 0.003), with rates of symptom remission and improvement of 75.4% and 92.7%, respectively. Recurrence at 48 months was higher in patients with recurrent ZD (84.7%) than in treatment-naïve patients (10.7%). On multivariable analysis, recurrent disease (hazard ratio [HR] 20.8, P = 0.005) and younger age (HR 0.96/year, P = 0.047) were associated with symptom recurrence.

Conclusions

In patients with treatment-naïve ZD, flexible endoscopic septal division is safe and provides durable symptom remission. However, in patients with poststapling recurrence, the risk of recurrence is high and time-dependent.
Results of the Patient-Related Outcomes of Mechanical lead Extraction Techniques (PROMET) study: a multicentre retrospective study on advanced mechanical lead extraction techniques
Authors: Starck Christoph T , Gonzalez Elkin , Al-Razzo Omar , Mazzone Patrizio , Delnoy Peter-Paul , Breitenstein Alexander , Steffel Jan , Eulert-Grehn Jürgen , Lanmüller Pia , Melillo Francesco , Marzi Alessandra , Sohal Manav , Domenichini Giulia , Gallagher Mark M
Published: April 2020

Aims

Several large studies have documented the outcome of transvenous lead extraction (TLE), focusing on laser and mechanical methods. To date there has been no large series addressing the results obtained with rotational lead extraction tools. This retrospective multicentre study was designed to investigate the outcomes of mechanical and rotational techniques.

Methods and results

Data were collected on a total of 2205 patients (age 66.0 ± 15.7 years) with 3849 leads targeted for extraction in six European lead extraction centres. The commonest indication was infection (46%). The targeted leads included 2879 pacemaker leads (74.8%), 949 implantable cardioverter-defibrillator leads (24.6%), and 21 leads for which details were unknown; 46.6% of leads were passive fixation leads. The median lead dwell time was 74 months [interquartile range (IQR) 41–112]. Clinical success was obtained in 97.0% of procedures, and complete extraction was achieved for 96.5% of leads. Major complications occurred in 22/2205 procedures (1%), with a peri-operative or procedure-related mortality rate of 4/2205 (0.18%). Minor complications occurred in 3.1% of procedures. A total of 1552 leads (in 992 patients) with a median dwell time of 106 months (IQR 66–145) were extracted using the Evolution rotational TLE tool. In this subgroup, complete success was obtained for 95.2% of leads with a procedural mortality rate of 0.4%.

Conclusion

Patient outcomes in the PROMET study compare favourably with other large TLE trials, underlining the capability of rotational TLE tools and techniques to match laser methods in efficacy and surpass them in safety.
Patterns of Cardiovascular Risk Factors in Old Age and Survival and Health Status at 90
Authors: Odden Michelle C , Rawlings Andreea M , Arnold Alice M , Cushman Mary , Biggs Mary L , Psaty Bruce M , Newman Anne B
Published: April 2020

Background

The population age 90 years and older is the fastest growing segment of the U.S. population. Only recently is it possible to study the factors that portend survival to this age.

Methods

Among participants of the Cardiovascular Health Study, we studied the association of repeated measures of cardiovascular risk factors measured over 15–23 years of follow-up and not only survival to 90 years of age, but also healthy aging outcomes among the population who reached age 90. We included participants aged 67–75 years at baseline (n = 3,613/5,888) to control for birth cohort effects, and followed participants until death or age 90 (median follow-up = 14.7 years).

Results

Higher systolic blood pressure was associated with a lower likelihood of survival to age 90, although this association was attenuated at older ages (p-value for interaction <.001) and crossed the null for measurements taken in participants’ 80’s. Higher levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and body mass index (BMI) were associated with greater longevity. Among the survivors to age 90, those with worse cardiovascular profile (high blood pressure, LDL cholesterol, glucose, and BMI; low HDL cholesterol) had lower likelihood of remaining free of cardiovascular disease, cognitive impairment, and disability.

Conclusion

In summary, we observed paradoxical associations between some cardiovascular risk factors and survival to old age; whereas, among those who survive to very old age, these risk factors were associated with higher risk of adverse health outcomes.
Metabolic Rate and Oxygen Radical Levels Increase But Radical Generation Rate Decreases with Male Age in Drosophila melanogaster Sperm
Authors: Turnell Biz R , Reinhardt Klaus
Published: April 2020

Oxidative damage increases with age in a variety of cell types, including sperm, which are particularly susceptible to attack by reactive oxygen species (ROS). While mitochondrial respiration is the main source of cellular ROS, the relationship between the rates of aerobic metabolism and ROS production, and how this relationship may be affected by age, both in sperm and in other cell types, is unclear. Here, we investigate in Drosophila melanogaster sperm, the effects of male age on (i) the level of hydrogen peroxide in the mitochondria, using a transgenic H2O2 reporter line; (ii) the in situ rate of non-H2O2 ROS production, using a novel biophysical method; and (iii) metabolic rate, using fluorescent lifetime imaging microscopy. Sperm from older males had higher mitochondrial ROS levels and a higher metabolic rate but produced ROS at a lower rate. In comparison, a somatic tissue, the gut epithelium, also showed an age-related increase in mitochondrial ROS levels but a decrease in metabolic rate. These results support the idea of a tissue-specific optimal rate of aerobic respiration balancing the production and removal of ROS, with aging causing a shift away from this optimum and leading to increased ROS accumulation. Our findings also support the view that pathways of germline and somatic aging can be uncoupled, which may have implications for male infertility treatments.
Olfaction and Changes in Body Composition in a Large Cohort of Older U.S. Adults
Authors: Purdy Frank , Luo Zhehui , Gardiner Joseph C , Pinto Jayant M , Shiroma Eric J , Simonsick Eleanor M , Harris Tamara B , Chen Honglei
Published: April 2020

Background

Poor sense of smell in older adults may lead to weight loss, which may further contribute to various adverse health outcomes. However, empirical prospective evidence is lacking. We aimed to longitudinally assess whether poor olfaction is associated with changes in body composition among older adults.

Methods

A total of 2,390 participants from the Health ABC Study had their olfaction assessed using the Brief Smell Identification Test in 1999–2000. Based on the test score, olfaction was defined as poor (0–8), moderate (9–10), or good (11–12). Total body mass, lean mass, and fat mass were measured by dual-energy X-ray absorptiometry annually or biennially from 1999 to 2007.

Results

At baseline, compared to participants with good olfaction, those with poor olfaction weighed on average 1.67 kg less (95% CI: −2.92, −0.42) in total mass, 0.53 kg less (95% CI: −1.08, 0.02) in lean mass, and 1.14 kg less (95% CI: −1.96, −0.31) in fat mass. In longitudinal analyses, compared to participants with good olfaction, those with poor olfaction had a greater annual decline in both total mass (−234 g, 95% CI: −442, −26) and lean mass (−139 g, 95% CI: −236, −43). They also tended to have a greater annual loss of fat mass (−113 g, 95% CI: −285, 59), but the difference was not statistically significant.

Conclusions

Our results indicate poor olfaction is associated with lower body weight and greater weight loss in older adults. It is imperative for future studies to investigate potential underlying mechanisms and associated adverse health consequences.
Glycan characterization of pregnancy-specific glycoprotein 1 and its identification as a novel Galectin-1 ligand
Authors: Mendoza Mirian , Lu Dongli , Ballesteros Angela , Blois Sandra M , Abernathy Kelsey , Feng Chiguang , Dimitroff Charles J , Zmuda Jonathan , Panico Maria , Dell Anne , Vasta Gerardo R , Haslam Stuart M , Dveksler Gabriela
Published: April 2020

Pregnancy-specific beta 1 glycoprotein (PSG1) is secreted from trophoblast cells of the human placenta in increasing concentrations as pregnancy progresses, becoming one of the most abundant proteins in maternal serum in the third trimester. PSG1 has seven potential N-linked glycosylation sites across its four domains. We carried out glycomic and glycoproteomic studies to characterize the glycan composition of PSG1 purified from serum of pregnant women and identified the presence of complex N-glycans containing poly LacNAc epitopes with α2,3 sialyation at four sites. Using different techniques, we explored whether PSG1 can bind to galectin-1 (Gal-1) as these two proteins were previously shown to participate in processes required for a successful pregnancy. We confirmed that PSG1 binds to Gal-1 in a carbohydrate-dependent manner with an affinity of the interaction of 0.13 μM. In addition, we determined that out of the three N-glycosylation-carrying domains, only the N and A2 domains of recombinant PSG1 interact with Gal-1. Lastly, we observed that the interaction between PSG1 and Gal-1 protects this lectin from oxidative inactivation and that PSG1 competes the ability of Gal-1 to bind to some but not all of its glycoprotein ligands.