bluuebunny/crossref_metadata_2025 huggingface dataset:
Wettability and Treatability of Sengon (Paraserianthes falcataria (L.) I.C. Nielsen) wood from NTB
Authors: Lestari A T , Wahyuningsih E , Syaputra M , Anwar H , Suparyana P K , Ritonga F N
Published: December 2021

The supply of wood from natural forests is decreasing as a result of the imbalance between harvesting and planting. The lack of wood supply from natural forests has resulted in relatively expensive wood prices. This can be anticipated by using fast-growing wood species. One type of fast-growing wood which is very abundantly available in NTB is sengon wood (Paraserianthes falcataria (L.) I.C. Nielsen). However, sengon wood has low durability so it is easily attacked by wood-destroying organisms. This condition can be overcome by making efforts to prevent wood damage in the form of preservation. This study aims to determine the wettability and treatability properties of sengon wood. The results of this study are expected to be basic information to improve the quality of sengon wood. The wettability test was carried out by measuring the contact angle between the liquid and the sample surface using the sessile drop method and the wood durability testing was carried out by measuring the retention and penetration of preservatives. The treatability test was carried out by measuring the absorption, retention, and penetration of preservatives. The results showed that the wettability of sengon is high with an equilibrium contact angle (θe) of 16.88 in the radial section and 12.51 in the tangential section. This shows that sengon wood has a good adhesion system for preservation. Treatability of sengon wood showed that the average retention and penetration are 10,21 kg/m3 and 7,33 mm. Based on the results of these measurements, sengon wood has met SNI 03-5010.1-1999 (wood preservation for housing and buildings).
The Properties of OPEFB Cellulose Nanofibrils Produced by A Different Mode of Ultrafine Grinding
Authors: Amanda P , Nabila S , Qonita N , Ningrum R S , Ismadi  , Masruchin N
Published: December 2021

Cellulose Nanofibrils (CNFs) was resulted from deconstruction of the hierarchical structure of cellulose. CNFs are commonly obtained by mechanical fibrillation, such as ultrafine grinding processes and its variation. Nevertheless, the influence of different treatments on the properties of the resulting CNF especially from variety of ultrafine grinding mode has not been reported. This study investigates the properties of cellulose nanofibrils (CNF) produced from bleached pulp oil palm empty fruit bunch (OPEFB) Kraft pulp through an ultrafine grinder with two different treatments in the fibrillation process. These two treatments were: 1) ultrafine grinder with increasing gaps distances; -30, -50, -70, and -90 µm with five cycles in every gap, 2) ultrafine grinder on constant gaps (-30µm) with increasing grinding cycles: 5, 10, 15, 30, and 40 cycles through the grinder. The influence of the treatment was evaluated through particle size distribution, crystallinity index, and morphological properties. The result showed that the increasing gaps treatment efficiently improved the size uniformity of CNFs, length 147-139.5 nm, and scanning electron microscope micrograph confirmed that the diameter of CNF was smaller with the increasing grinding gaps than increasing grinding cycles. However, the increasing cycle’s treatment produced CNF with a higher crystallinity index. The crystallinity index (CrI) of the CNF decreased from 71.27 to 62.25% with increasing gaps, whereas the CrI of the CNF from increasing cycles was 69.35%. This study provides a valuable guideline for determining the appropriate process to produce CNF especially by mechanical grinding using ultrafine grinder from OPEFB according to the desired result.
Biopellet from demineralized oil palm trunk
Authors: Wistara N J , Diputra P , Hendra D
Published: December 2021

Oil palm trunk (OPT) is a potential raw material for biopellet manufacturing. This study aimed to reduce the ash content of biopellet through pre-treatment with sulfuric acid. The moisture content, durability, ash content, density, and calorific values of the biopellet were determined according to DIN EN 14961-2 and 51731 standards. Scanning electron microscopy (SEM) indicated the presence of inter-particle interlocking in the highly durable biopellet. Thermal analysis indicated that the mass and water loss, hemicellulose, cellulose, and lignin decomposition occurred at 76.12 ºC, 113.97-200 ºC, 310-360 ºC, and >400 ºC, respectively. Biopellet produced retained a moisture content of 3.40-8.90%, the durability of 97.75-99.38%, ash content after pre-treatment with H2SO4of 1.02-1.47%, control ash content of 2.20-3.31%, the density of 1.03-1.30 g/cm3, and the calorific value of 3954-4608 kcal/kg. The biopellet quality fulfilled the requirements of DIN EN 14961-2, 51731, and SNI 8021-2014 standard,except for the ash content of the control.
The Use of Marketing Monitoring Web System Application to Estimate Cempaka Wood Product Consumption Level in North Sulawesi, Indonesia
Authors: Abdulah L , Irawan A , Arini D I D , Suryaningsih R
Published: December 2021

Cempaka or Magnolia spp. is categorised into primary local wood mostly used by the people in North Sulawesi. Efforts to cultivate cempaka and supply of raw materials continue to be carried out. However, there is no measurement of consumption of cempaka wood at the industrial and household levels. This will threaten the existence of cempaka or cempaka cultivation is not attractive to the Minahasa community. The objective of this study was to obtain the information of consumption ratio of cempaka wood in North Sulawesi in household scale. This study was carried out for approximately eight months in Minahasa, South Minahasa, and North Minahasa. There are 13 industries of cempaka wood in household scale, and 99 respondents are gathered successfully. The study findings indicated that cempaka wood products identified were not only wooden houses construction but also furniture. Average consumption of cempaka wood products in North Sulawesi reached 0.17 m3/capita/annual. If the total population of North Sulawesi reached 2,5 million, the total consumption of cempaka timber was estimated to reach 435,000 m3 annually. With enormous demands for cempaka wood in North Sulawesi compared to its inefficient availability, it is recommended to promote more intensive cempaka plantation development in the region.
Land Use Conflict Mapping in Mount Rinjani National Park Pesangrahan Village East Lombok District
Authors: Ichsan A C , Anwar H , Aji I M L , Webliana K , Waru T , Febryano I G , Salampessy M L
Published: December 2021

This study aims to map the conflict in the use of forest resources in the area of Mount Rinjani National Park as an implication of the management model implemented, then formulate several alternative solutions to reduce the negative impact of the conflict. This research used a case study approach. The data collected in this research was through several data collection methods such as field observations, interviews using questionnaires, in-depth interviews, Focus Group Discussions, Participatory Rural Appraisal, and literature studies. Analysis of the data used in this study adopted the concept of dispute style analysis. Based on the results, using Analysis of Dispute Mode (AGATA), in the Pesangrahan village, the actors are divided into three categories, namely compromise, negotiation, and collaboration. The results also illustrate that there are still multiple interpretations related to the utilization of national park areas in the region, and thus, a definite collaboration mechanism is needed principle-based on principles of co-ownership, co-operation, and responsibility.
The experimental results of the geophysical pulse voltage generator
Authors: Gulyakov S A , Stovbun N S
Published: December 2021

The paper is devoted to the development process of the geophysical pulse voltage generator. The peculiarity of the generator lies in the non-specific purpose of this type of construction. Its main function is the controlled effect on the active faults of seismically dangerous zones. The results of the field experiment with the constructed device from 2018 to 2020 are presented. During the experiments, estimations and theoretical analysis we have obtained the seismic noise recorded by means of molecular electronic instruments and determined the periods of the electrical pulses. Operational parameters of the generator were identified on the basis of experiment results. The software and hardware elements of the system were upgraded and, as a result, a new version of the geophysical pulse voltage generator was developed.
Dirty thunderstorms caused by volcano explosive eruptions in Kamchatka by the data of electromagnetic radiation
Authors: Malkin E I , Cherneva N V , Firstov P P , Druzhin G I , Sannikov D V
Published: December 2021

During volcano eruptions, so called dirty thunderstorms are the sources of electromagnetic radiation. They are caused by ash-gas clouds formed during explosive eruptions. Thunderstorm activity in an ash-gas cloud during volcano eruption is monitored by radio equipment. The VLF direction finder, located at Paratunka, monitors thunderstorm activity in the region of Kamchatka Peninsula including dirty thunderstorms accompanying explosive eruptions of Shiveluch and Bezymyanniy volcanoes. In the paper, we analyze records of electromagnetic radiation associated with dirty thunderstorms occurring during volcano eruptions from 2017 to 2020. During that period 24 eruptions of Shiveluch volcano and 5 eruptions of Bezymyanniy volcano occurred. Seventeen and three of them, respectively, caused dirty thunderstorms. Two-stage scenario of development is typical for all the dirty thunderstorms. The first stage lasts for 5–7 minutes and accompanies eruptive column development. However, if the eruption begins according to a smooth scenario, the first stage may be weak. The second stage lasts for 20–80 minutes and is associated with eruptive cloud formation and propagation. The intensity of this dirty thunderstorm stage depends on eruption power as well as on the interaction of an eruptive cloud during its propagation with the clouds of meteorological origin. Based on the obtained data, that is indicated by the increase of cloud-to-cloud stroke number.
Materials for the database on the largest lakes of the Kuril Islands (morphometry, genesis and geographic distribution)
Authors: Kozlov D N
Published: December 2021

This paper presents generalized modern data on the location, morphometry, and genesis of the largest lake basins of the Kuril Islands, obtained in a series of expeditions of the laboratory of volcanology and volcanic hazard of the Institute of Marine Geology and Geophysics FEB RAS in 2005–2020. The data is supplemented with modern geoinformation open access resources. A sample of the largest of 1099 Kuril lakes has been made according to the areal criterion, thus, 20 objects have been included in the list of studied water bodies, which are represented by 7 volcanic and 13 lagoon lakes. The considered lakes are clearly divided according to genesis, area and height of the mirror, maximum depth, as well as the ratio of the main morphometric characteristics. This information is part of a database currently being created on the largest lakes in the region.
Accumulative landforms in valleys with gas-hydrothermal manifestations of the Kuril-Kamchatka region
Authors: Lebedeva E V , Zharkov R V
Published: December 2021

Within the watercourse valleys of geothermal zones, where manifestations of gas-hydrothermal activity are noted, the processes of relief formation are accompanied by chemical and thermal effects. Thermal waters contribute to the formation of specific accumulative landforms both directly in the channel and in the bottom and on the sides of river valleys. Similar phenomena have been studied in river valleys draining the slopes of the Mendeleev volcano (Kunashir Island), Baransky volcano (Iturup Island), Mutnovsky volcano and Uzon-Geyzernaya caldera (Kamchatka). The typification of accumulative relief forms is carried out, the influence of gas-hydrothermal manifestations on fluvial and slope processes is determined.
Possibility of using satellite-based monitoring for large-scale mapping and research of dynamics of mud volcanic landscapes
Authors: Kopanina A V , Shvidskaya K A
Published: December 2021

Currently Earth remote probing to study vegetation dynamics and monitor volcanic activity is of great scientific interest. The purpose of this study is to create a large-scale outline map of Yuzhno-Sakhalinsk mud volcano which will include the topography objects, mud fields of eruptions of various years and gryphons, and to perform semi-automatic classification of Yuzhno-Sakhalinsk mud volcano. Work was performed with QGIS software using the following modules: «QuickMapServices», «Freehandrastergeoreference», «LatLanTools», and «Semi-AutomaticClassificationPlugin». We developed an outline map of Yuzhno-Sakhalinsk mud volcano on a scale of 1:10000, which shows how the mud flows have changed directions over the last 70 years, as well as mud fields have been formed over the last 20 years. Using semi-automatic classification of satellite images from Sentinel-2A satellite in various color channel sets, we obtained two premaps of Yuzhno-Sakhalinsk mud volcano vegetation on a scale of 1:50 000. Satellite monitoring of YuSMV activity allows us to track the eruptive activity of the volcano, and assess its impact on vegetation.
Trophic migrations of the brown bear in the forest landscapes of the Vostochny Nature Reserve on Sakhalin Island
Authors: Nikulina I V , Sabirov R N
Published: December 2021

The article deals with trophic migrations of the brown bear in the characteristic forest landscapes of the Vostochny Nature Reserve. Active life of a bear in the reserve begins after hibernation and is directly related to foraging in different seasons of the year. In the spring-early summer period, bears concentrate in valley forest complexes and coastal-marine landscapes, where, along with plant food, they obtain various products of animal origin thrown out of the sea. During the summer period, from the beginning of the course of salmon and until the end of their spawning, the animals mainly live in the mouths of rivers, and as the fish move, they go upstream and are distributed among their numerous tributaries. During the autumn period, bears concentrate mainly in mountainous forest landscapes and high-altitude natural complexes of the reserve, where they eat ripe berries and pine nuts, their trophic migrations are significantly reduced.
Application of local Monte Carlo method in neutronics calculation of EAST radial neutron camera
Authors: HUANG Liangsheng , HU Liqun , NIU Luying , ZHOU Mengjie , HONG Bing , LI Kai , ZHANG Ruixue , ZHONG Guoqiang
Published: December 2021

The Local Monte Carlo (LMC) method is used to solve the problems of deep penetration and long time in the neutronics calculation of the radial neutron camera (RNC) diagnostic system on the experimental advanced superconducting tokamak (EAST), and the radiation distribution of the RNC and the neutron flux at the detector positions of each channel are obtained. Compared with the results calculated by the global variance reduction method, it is shown that the LMC calculation is reliable within the reasonable error range. The calculation process of LMC is analyzed in detail, and the transport process of radiation particles is simulated in two steps. In the first step, an integrated neutronics model considering the complex window environment and a neutron source model based on EAST plasma shape are used to support the calculation. The particle information on the equivalent surface is analyzed to evaluate the rationality of settings of equivalent surface source and boundary. Based on the characteristic that only a local geometric model is needed in the second step, it is shown that the LMC is an advantageous calculation method for the nuclear shielding design of tokamak diagnostic systems.
Stereotypes, conditions and binaries: Analysing processes of social disqualification towards children and parents living in precarity
Authors: Jacquet Nicolas , Van Haute Dorien , Schiettecat Tineke , Roets Griet
Published: December 2021

In contemporary European welfare states, poverty reduction strategies can currently be characterised as individualistic rather than solidaristic, focusing on welfare recipients’ merit rather than securing their rights. Based on the findings of a recent research project in Belgium, we explore how social workers develop strategies to combat child poverty in local municipalities. Inspired by the work of the critical French scholars Robert Castel and Serge Paugam, our qualitative analysis reveals how social workers construct stereotypes, conditions and binaries between ‘deserving’ and ‘undeserving’ poor in their everyday practice. Our results elucidate how social workers strengthen processes of social disqualification when they support children and sanction parents living in poverty. Interestingly, our analysis also shows how social work takes a critical stance in relation to the recent shifts in the normative value orientation of social policy and social work.
Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations
Authors: Pottier Cyril , Mateiu Ligia , Baker Matthew C , DeJesus-Hernandez Mariely , Teixeira Vicente Cristina , Finch NiCole A , Tian Shulan , van Blitterswijk Marka , Murray Melissa E , Ren Yingxue , Petrucelli Leonard , Oskarsson Björn , Biernacka Joanna M , Graff-Radford Neill R , Boeve Bradley F , Petersen Ronald C , Josephs Keith A , Asmann Yan W , Dickson Dennis W , Rademakers Rosa
Published: December 2021

Frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) is a complex heterogeneous neurodegenerative disorder for which mechanisms are poorly understood.

To explore transcriptional changes underlying FTLD-TDP, we performed RNA-sequencing on 66 genetically unexplained FTLD-TDP patients, 24 FTLD-TDP patients with GRN mutations and 24 control participants. Using principal component analysis, hierarchical clustering, differential expression and coexpression network analyses, we showed that GRN mutation carriers and FTLD-TDP-A patients without a known mutation shared a common transcriptional signature that is independent of GRN loss-of-function. After combining both groups, differential expression as compared to the control group and coexpression analyses revealed alteration of processes related to immune response, synaptic transmission, RNA metabolism, angiogenesis and vesicle-mediated transport. Deconvolution of the data highlighted strong cellular alterations that were similar in FTLD-TDP-A and GRN mutation carriers with NSF as a potentially important player in both groups. We propose several potentially druggable pathways such as the GABAergic, GDNF and sphingolipid pathways.

Our findings underline new disease mechanisms and strongly suggest that affected pathways in GRN mutation carriers extend beyond GRN and contribute to genetically unexplained forms of FTLD-TDP-A.
Precision medicine in stroke: towards personalized outcome predictions using artificial intelligence
Authors: Bonkhoff Anna K , Grefkes Christian
Published: December 2021

Stroke ranks among the leading causes for morbidity and mortality worldwide. New and continuously improving treatment options such as thrombolysis and thrombectomy have revolutionized acute stroke treatment in recent years. Following modern rhythms, the next revolution might well be the strategic use of the steadily increasing amounts of patient-related data for generating models enabling individualized outcome predictions. Milestones have already been achieved in several health care domains, as big data and artificial intelligence have entered everyday life.

The aim of this review is to synoptically illustrate and discuss how artificial intelligence approaches may help to compute single-patient predictions in stroke outcome research in the acute, subacute and chronic stage. We will present approaches considering demographic, clinical and electrophysiological data, as well as data originating from various imaging modalities and combinations thereof. We will outline their advantages, disadvantages, their potential pitfalls and the promises they hold with a special focus on a clinical audience. Throughout the review we will highlight methodological aspects of novel machine-learning approaches as they are particularly crucial to realize precision medicine. We will finally provide an outlook on how artificial intelligence approaches might contribute to enhancing favourable outcomes after stroke.
Differentially targeted seeding reveals unique pathological alpha-synuclein propagation patterns
Authors: Rahayel Shady , Mišić Bratislav , Zheng Ying-Qiu , Liu Zhen-Qi , Abdelgawad Alaa , Abbasi Nooshin , Caputo Anna , Zhang Bin , Lo Angela , Kehm Victoria , Kozak Michael , Yoo Han Soo , Dagher Alain , Luk Kelvin C.
Published: December 2021

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the intracellular accumulation of insoluble alpha-synuclein aggregates into Lewy bodies and neurites. Increasing evidence indicates that Parkinson’s disease progression results from the spread of pathologic alpha-synuclein through neuronal networks. However, the exact mechanisms underlying the propagation of abnormal proteins in the brain are only partially understood. The objective of this study was first to describe the long-term spatiotemporal distributions of Lewy-related pathology in mice injected with alpha-synuclein preformed fibrils and then to recreate these patterns using a computational model that simulates in silico the spread of pathologic alpha-synuclein.

In this study, 87 2–3-month-old non-transgenic mice were injected with alpha-synuclein preformed fibrils to generate a comprehensive post-mortem dataset representing the long-term spatiotemporal distributions of hyperphosphorylated alpha-synuclein, an established marker of Lewy pathology, across the 426 regions of the Allen Mouse Brain Atlas. The mice were injected into either the caudoputamen, nucleus accumbens or hippocampus, and followed over 24 months with pathologic alpha-synuclein quantified at seven intermediate time points. The pathologic patterns observed at each time point in this high-resolution dataset were then compared to those generated using a Susceptible-Infected-Removed (SIR) computational model, an agent-based model that simulates the spread of pathologic alpha-synuclein for every brain region taking simultaneously into account the effect of regional brain connectivity and Snca gene expression.

Our histopathological findings showed that differentially targeted seeding of pathological alpha-synuclein resulted in unique propagation patterns over 24 months and that most brain regions were permissive to pathology. We found that the SIR model recreated the observed distributions of pathology over 24 months for each injection site. Null models showed that both Snca gene expression and connectivity had a significant influence on model fit.

In sum, our study demonstrates that the combination of normal alpha-synuclein concentration and brain connectomics contributes to making brain regions more vulnerable to the pathological process, providing support for a prion-like spread of pathologic alpha-synuclein. We propose that this rich dataset and the related computational model will help test new hypotheses regarding mechanisms that may alter the spread of pathologic alpha-synuclein in the brain.
Neuronal synchrony abnormalities associated with subclinical epileptiform activity in early-onset Alzheimer’s disease
Authors: Ranasinghe Kamalini G , Kudo Kiwamu , Hinkley Leighton , Beagle Alexander , Lerner Hannah , Mizuiri Danielle , Findlay Anne , Miller Bruce L , Kramer Joel H , Gorno-Tempini Maria Luisa , Rabinovici Gil D , Rankin Katherine P , Garcia Paul A , Kirsch Heidi E , Vossel Keith , Nagarajan Srikantan S
Published: December 2021

Since the first demonstrations of network hyperexcitability in scientific models of Alzheimer’s disease, a growing body of clinical studies have identified subclinical epileptiform activity and associated cognitive decline in patients with Alzheimer’s disease. An obvious problem presented in these studies is lack of sensitive measures to detect and quantify network hyperexcitability in human subjects. In this study we examined whether altered neuronal synchrony can be a surrogate marker to quantify network hyperexcitability in patients with Alzheimer’s disease. Using magnetoencephalography (MEG) at rest, we studied 30 Alzheimer’s disease patients without subclinical epileptiform activity, 20 Alzheimer’s disease patients with subclinical epileptiform activity and 35 age-matched controls. Presence of subclinical epileptiform activity was assessed in patients with Alzheimer’s disease by long-term video-EEG and a 1-h resting MEG with simultaneous EEG. Using the resting-state source-space reconstructed MEG signal, in patients and controls we computed the global imaginary coherence in alpha (8–12 Hz) and delta–theta (2–8 Hz) oscillatory frequencies. We found that Alzheimer’s disease patients with subclinical epileptiform activity have greater reductions in alpha imaginary coherence and greater enhancements in delta–theta imaginary coherence than Alzheimer’s disease patients without subclinical epileptiform activity, and that these changes can distinguish between Alzheimer’s disease patients with subclinical epileptiform activity and Alzheimer’s disease patients without subclinical epileptiform activity with high accuracy. Finally, a principal component regression analysis showed that the variance of frequency-specific neuronal synchrony predicts longitudinal changes in Mini-Mental State Examination in patients and controls. Our results demonstrate that quantitative neurophysiological measures are sensitive biomarkers of network hyperexcitability and can be used to improve diagnosis and to select appropriate patients for the right therapy in the next-generation clinical trials. The current results provide an integrative framework for investigating network hyperexcitability and network dysfunction together with cognitive and clinical correlates in patients with Alzheimer’s disease.
Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy
Authors: Bernard-Valnet Raphaël , Frieser David , Nguyen Xuan Hung , Khajavi Leila , Quériault Clémence , Arthaud Sébastien , Melzi Silvia , Fusade-Boyer Maxime , Masson Frederick , Zytnicki Matthias , Saoudi Abdelhadi , Dauvilliers Yves , Peyron Christelle , Bauer Jan , Liblau Roland S
Published: December 2021

Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009–2010 pandemic ‘influenza’ virus strain. The potential immunological link between the Pandemrix® vaccination and narcolepsy remains, however, unknown. Deciphering these mechanisms may reveal pathways potentially at play in most cases of narcolepsy.

Here, we developed a mouse model allowing to track and study the T-cell response against ‘influenza’ virus haemagglutinin, which was selectively expressed in the orexinergic neurons as a new self-antigen. Pandemrix® vaccination in this mouse model resulted in hypothalamic inflammation and selective destruction of orexin-producing neurons. Further investigations on the relative contribution of T-cell subsets in this process revealed that haemagglutinin-specific CD4 T cells were necessary for the development of hypothalamic inflammation, but insufficient for killing orexinergic neurons. Conversely, haemagglutinin-specific CD8 T cells could not initiate inflammation but were the effectors of the destruction of orexinergic neurons. Additional studies revealed pathways potentially involved in the disease process. Notably, the interferon-γ pathway was proven essential, as interferon-γ-deficient CD8 T cells were unable to elicit the loss of orexinergic neurons.

Our work demonstrates that an immunopathological process mimicking narcolepsy can be elicited by immune cross-reactivity between a vaccine antigen and a neuronal self-antigen. This process relies on a synergy between autoreactive CD4 and CD8 T cells for disease development. This work furthers our understanding of the mechanisms and pathways potentially involved in the development of a neurological side effect due to a vaccine and, likely, to narcolepsy in general.
Decline in Pneumococcal Disease in Young Children During the Coronavirus Disease 2019 (COVID-19) Pandemic in Israel Associated With Suppression of Seasonal Respiratory Viruses, Despite Persistent Pneumococcal Carriage: A Prospective Cohort Study
Authors: Danino Dana , Ben-Shimol Shalom , van der Beek Bart Adriaan , Givon-Lavi Noga , Avni Yonat Shemer , Greenberg David , Weinberger Daniel M , Dagan Ron
Published: December 2021

Background

The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis.

Methods

The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016–2019 [expected rates]) adjusted for age and ethnicity were compared.

Results

CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]: .07 and .19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs: .46 and .42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels.

Conclusions

Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses.
Nutritional Supplementation Would Be Cost-Effective for Reducing Tuberculosis Incidence and Mortality in India: The Ration Optimization to Impede Tuberculosis (ROTI-TB) Model
Authors: Sinha Pranay , Lakshminarayanan Subitha L , Cintron Chelsie , Narasimhan Prakash Babu , Locks Lindsey M , Kulatilaka Nalin , Maloomian Kimberly , Prakash Babu Senbagavalli , Carwile Madeline E , Liu Anne F , Horsburgh C Robert , Acuna-Villaorduna Carlos , Linas Benjamin P , Hochberg Natasha S
Published: December 2021

Background

Undernutrition is the leading cause of tuberculosis (TB) in India and is associated with increased TB mortality. Undernutrition also decreases quality of life and economic productivity.

Methods

We assessed the cost-effectiveness of providing augmented rations to undernourished Indians through the government’s Targeted Public Distribution System (TPDS). We used Markov state transition models to simulate disease progression and mortality among undernourished individuals in 3 groups: general population, household contacts (HHCs) of people living with TB, and persons living with human immunodeficiency virus (HIV). The models calculate costs and outcomes (TB cases, TB deaths, and disability-adjusted life years [DALYs]) associated with a 2600 kcal/day diet for adults with body mass index (BMI) of 16–18.4 kg/m2 until they attain a BMI of 20 kg/m2 compared to a status quo scenario wherein TPDS rations are unchanged. We employed deterministic and probabilistic sensitivity analyses to test result robustness.

Results

Over 5 years, augmented rations could avert 81% of TB cases and 88% of TB deaths among currently undernourished Indians. Correspondingly, this intervention could forestall 78% and 48% of TB cases and prevent 88% and 70% of deaths among undernourished HHCs and persons with HIV, respectively. Augmented rations resulted in 10-fold higher resolution of undernutrition and were highly cost-effective with (incremental cost-effectiveness ratio [ICER] of $470/DALY averted). ICER was lower for HHCs ($360/DALY averted) and the HIV population ($250/DALY averted).

Conclusions

A robust nutritional intervention would be highly cost-effective in reducing TB incidence and mortality while reducing chronic undernutrition in India.
Randomized clinical study to evaluate the effect of personalized therapy on patients with immunoglobulin A nephropathy
Authors: Schena Francesco P , Tripepi Giovanni , Rossini Michele , Abbrescia Daniela I , Manno Carlo
Published: December 2021

Background

Randomized controlled trials (RCTs) have been conducted, stratifying idiopathic immunoglobulin A nephropathy (IgAN) patients based on the laboratory findings [serum creatinine, estimated glomerular filtration rate (eGFR) and daily proteinuria]. In contrast, data from kidney biopsy have been used only for clinical diagnosis. Therefore, IgAN patients with active or chronic renal lesions have been receiving the same therapy in experimental and control arms of randomized clinical trials (RCTs).

Methods

Our clinical study of IgAN (CLIgAN) is a multicentre, prospective, controlled and open-label RCT based on patients’ stratification at the time of their kidney biopsy. We will consider, first, the type of renal lesions, followed by serum creatinine values, eGFR and proteinuria. Primary and secondary endpoints will be monitored. Then, we will determine whether personalized therapy can slow the decline of renal function and delay end-stage kidney disease.

Results

We will enrol 132 IgAN patients with active renal lesions (66 patients per arm) in the first RCT (ACIgAN). They will receive corticosteroids combined with renin–angiotensin system blockers (RASBs) or only RASBs. A total of 294 IgAN patients with chronic or moderate renal lesions at high or very high risk of chronic kidney disease (147 patients per arm) will be enrolled in the second RCT (CHRONIgAN), in which they will receive dapagliflozin, a sodium–glucose cotransporter 2 inhibitor, combined with RASBs, or RASBs alone.

Conclusion

Using this approach, we hypothesize that patients could receive personalized therapy based on renal lesions to ensure that the right drug gets to the right patient at the right time.
The year in cardiovascular medicine 2021: diabetes and metabolic disorders
Authors: Cosentino Francesco , Bhatt Deepak L. , Marx Nikolaus , Verma Subodh
Published: December 2021

In the current paper, we review recently published studies that are helping us to understand how the treatment landscape for glucagon-like peptiide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors is moving forward. We have also included relevant articles related to cardiovascular disease prevention in the setting of obesity, atherogenic dyslipidaemia and chronic kidney disease.
Measurement of obesity in primary care practice: chronic conditions matter
Authors: Lindeman Cliff , Jones Allyson , Klein Doug , Prado Carla M , Pham Anh N Q , Spence John C , Drummond Neil
Published: December 2021

Lay Summary

Primary care providers can deliver tailored advice and support to patients who are overweight or have obesity. The 2020 Canadian Adult Obesity Practice Guideline for primary care providers recommended that patients’ waist circumference (WC) be measured if their height and weight place them in the overweight or Class I obesity category. The guideline does not recommend how often providers should measure WC nor describe how often this is measured in current practice. We reviewed electronic medical records (EMRs) of 707,819 Canadian adult patients aged 40 and older. Among them, 48.7% had 1 or more body mass index (BMI) recorded; 11.5% had at least 1 waist measurement recorded. Of those with a BMI classified as overweight or having Class I obesity, 23.7% had at least 1 WC measurement recorded, which differed by chronic disease. WC was documented in more patients who had diabetes mellitus (36.8%) than hypertension (26.1%), or osteoarthritis (24.3%). This difference may be reflective of more specific advice in diabetes guidelines. To our knowledge, this is the first study to describe documentation of WC measurement for patients who are overweight or have Class I obesity in Canadian primary care EMRs across obesity-related conditions.
Efficient ancestry and mutation simulation with msprime 1.0
Authors: Baumdicker Franz , Bisschop Gertjan , Goldstein Daniel , Gower Graham , Ragsdale Aaron P , Tsambos Georgia , Zhu Sha , Eldon Bjarki , Ellerman E Castedo , Galloway Jared G , Gladstein Ariella L , Gorjanc Gregor , Guo Bing , Jeffery Ben , Kretzschumar Warren W , Lohse Konrad , Matschiner Michael , Nelson Dominic , Pope Nathaniel S , Quinto-Cortés Consuelo D , Rodrigues Murillo F , Saunack Kumar , Sellinger Thibaut , Thornton Kevin , van Kemenade Hugo , Wohns Anthony W , Wong Yan , Gravel Simon , Kern Andrew D , Koskela Jere , Ralph Peter L , Kelleher Jerome
Published: December 2021

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime’s many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.
N-glycan profiles of acute myocardial infarction patients reveal potential biomarkers for diagnosis, severity assessment and treatment monitoring
Authors: Lim Si Ying , Hendra Christopher , Yeo Xin Hao , Tan Xin Yi , Ng Bao Hui , Laserna Anna Karen Carrasco , Tan Sock Hwee , Chan Mark Y , Khan Shaheer H , Chen Shiaw-Min , Li Sam Fong Yau
Published: December 2021

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. Diagnostic challenges remain in this highly time-sensitive condition. Using capillary electrophoresis-laser-induced fluorescence, we analyzed the blood plasma N-glycan profile in a cohort study comprising 103 patients with AMI and 69 controls. Subsequently, the data generated was subjected to classification modeling to identify potential AMI biomarkers. An area under the Receiving Operating Characteristic curve (AUCROC) of 0.81 was obtained when discriminating AMI vs. non-MI patients. We postulate that the glycan profile involves a switch from a pro- to an anti-inflammatory state in the AMI pathophysiology. This was supported by significantly decreased levels in galactosylation, alongside increased levels in sialylation, afucosylation and GlcNAc bisection levels in the blood plasma of AMI patients. By substantiating the glycomics analysis with immunoglobulin G (IgG) protein measurements, robustness of the glycan-based classifiers was demonstrated. Changes in AMI-related IgG activities were also confirmed to be associated with alterations at the glycosylation level. Additionally, a glycan-biomarker panel derived from glycan features and current clinical biomarkers performed remarkably (AUCROC = 0.90, sensitivity = 0.579 at 5% false positive rate) when discriminating between patients with ST-segment elevation MI (n = 84) and non-ST-segment elevation MI (n = 19). Moreover, by applying the model trained using glycomics information, AMI and controls can still be discriminated at 1 and 6 months after baseline. Thus, glycomics biomarkers could potentially serve as a valuable complementary test to current diagnostic biomarkers. Additional research on their utility and associated biomechanisms via a large-scale study is recommended.
Mammalian sialyltransferases allow efficient Escherichia coli-based production of mucin-type O-glycoproteins but can also transfer Kdo
Authors: Sim Lyann , Thompson Nicole , Geissner Andreas , Withers Stephen G , Wakarchuk Warren W
Published: December 2021

The prospect of producing human-like glycoproteins in bacteria is becoming attractive as an alternative to already-established but costly mammalian cell expression systems. We previously described an Escherichia coli expression platform that uses a dual-plasmid approach to produce simple mucin type O-glycoproteins: one plasmid encoding the target protein and another O-glycosylation machinery. Here, we expand the capabilities of our platform to carry out sialylation and demonstrate the high-yielding production of human interferon α2b and human growth hormone bearing mono- and disialylated T-antigen glycans. This is achieved through engineering an E. coli strain to produce CMP-Neu5Ac and introducing various α-2,3- and α-2,6 mammalian or bacterial sialyltransferases into our O-glycosylation operons. We further demonstrate that mammalian sialyltransferases, including porcine ST3Gal1, human ST6GalNAc2 and human ST6GalNAc4, are very effective in vivo and outperform some of the bacterial sialyltransferases tested, including Campylobacter jejuni Cst-I and Cst-II. In the process, we came upon a way of modifying T-Antigen with Kdo, using a previously uncharacterised Kdo-transferase activity of porcine ST3Gal1. Ultimately, the heterologous expression of mammalian sialyltransferases in E. coli shows promise for the further development of bacterial systems in therapeutic glycoprotein production.
Selective retinal ganglion cell loss and optic neuropathy in a humanized mouse model of familial dysautonomia
Authors: Chekuri Anil , Logan Emily M , Krauson Aram J , Salani Monica , Ackerman Sophie , Kirchner Emily G , Bolduc Jessica M , Wang Xia , Dietrich Paula , Dragatsis Ioannis , Vandenberghe Luk H , Slaugenhaupt Susan A , Morini Elisabetta
Published: December 2021

Familial dysautonomia (FD) is an autosomal recessive neurodegenerative disease caused by a splicing mutation in the gene encoding Elongator complex protein 1 (ELP1, also known as IKBKAP). This mutation results in tissue-specific skipping of exon 20 with a corresponding reduction of ELP1 protein, predominantly in the central and peripheral nervous system. Although FD patients have a complex neurological phenotype caused by continuous depletion of sensory and autonomic neurons, progressive visual decline leading to blindness is one of the most problematic aspects of the disease, as it severely affects their quality of life. To better understand the disease mechanism as well as to test the in vivo efficacy of targeted therapies for FD, we have recently generated a novel phenotypic mouse model, TgFD9; IkbkapΔ20/flox. This mouse exhibits most of the clinical features of the disease and accurately recapitulates the tissue-specific splicing defect observed in FD patients. Driven by the dire need to develop therapies targeting retinal degeneration in FD, herein, we comprehensively characterized the progression of the retinal phenotype in this mouse, and we demonstrated that it is possible to correct ELP1 splicing defect in the retina using the splicing modulator compound (SMC) BPN-15477.
Patterns of integration in global value chains and the changing structure of employment in Europe
Authors: Bontadini Filippo , Evangelista Rinaldo , Meliciani Valentina , Savona Maria
Published: December 2021

This paper aims at revisiting the empirical evidence on the recent trends of countries’ integration in global value chains (GVCs) in Europe. It investigates two potential sources of unbalances that these processes might relate to (i) the sectoral specialization of the patterns of international fragmentation, whether high-technology manufacturing or knowledge-intensive business services (KIBS), and (ii) the occupational categories that have benefited or been penalized by these trends. A rich empirical mapping of these trends in the European countries is provided, based on World Input–Output Database and European Union Labour Force Survey (EU LFS) data. The results on the overall and sectoral-specific trends of integration in GVCs and the associated changes in the shares of managers and manual workers show dual-speed and qualitatively different integration patterns in Europe, with Eastern European (EE) countries rapidly integrating in high-tech manufacturing and the core of Western countries strengthening their mutual integration in the KIBS area. Despite the relatively “good quality” integration of EE countries, the evidence does not seem to reveal a mirroring upgrading of employment structures. While this empirical contribution does not attempt to identify causal relationships, the picture provided in the paper shows that, overall, integration in GVCs seems to reproduce and perhaps exacerbate the initial asymmetries in the sectoral and employment structure, with employment shares of manual workers reducing on the whole and knowledge-intensive occupations concentrating in Western Europe.
BSAC Vanguard Series: The future role of laboratories in relation to antimicrobial resistance
Authors: Wells David
Published: December 2021

The COVID-19 pandemic has shown that the management of infectious diseases is of global importance. It is clear that a greater more complex pandemic will emerge through antimicrobial resistance (AMR) if we don’t embrace the lessons from this one. Earlier diagnostic testing, in the right place at the right time, using data to drive better public health approaches, should be our response. Proactive diagnostics as a paradigm shift from reactive diagnostics are essential and should be factored into the design of future services. By building on and capitalizing on the lessons on how to handle data, deploy technology and understand the spread of disease, we will improve the response of laboratories, and improve patient outcomes, and through that improve public health. The digital tools of the future will be a huge enabler of this, and this will be made more effective though sharing of data seamlessly. Action needs to be taken now to ensure that this change is implemented at the pace required to tackle AMR.