bluuebunny/crossref_metadata_2025 huggingface dataset:
A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor
Authors: Morton Terri L. , Laskin Oscar L. , Kaushik Diksha , Lee Lucy , Ma Jiyuan , Bar Cristian M. , Kristensen Allan , O’Keefe Kylie , Golden Lee , Klein Matthew , Kong Ronald
Published: June 2023

Purpose

A therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome corona virus 2 (SARS-CoV-2, coronavirus disease 2019, COVID-19) management. Emvododstat (PTC299; 4-chlorophenyl 6-chloro-1-[4-methoxyphenyl]-1,3, 4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate) was found to be a potent inhibitor of immunomodulatory and inflammation-related processes by inhibition of dihydroorotate dehydrogenase to reduce the severity of SARS-CoV-2 infections This drug interaction study was performed to determine if emvododstat was an inhibitor of CYP2D6.

Methods

Potential drug-drug interactions between emvododstat and a CYP2D6 probe substrate (dextromethorphan) were investigated by measuring plasma dextromethorphan and metabolite (dextrorphan) concentrations before and after emvododstat administration. On day 1, 18 healthy subjects received an oral dose of 30 mg dextromethorphan followed by a 4-day washout period. On day 5, subjects received an oral dose of 250 mg emvododstat with food. Two hours later, 30 mg dextromethorphan was administered.

Results

When given with emvododstat, plasma dextromethorphan concentrations increased substantially, while metabolite levels (dextrorphan) remained essentially the same. Maximum plasma dextromethorphan concentration (Cmax) increased from 2006 to 5847 pg/mL. Dextromethorphan exposure (AUC) increased from 18,829 to 157,400 h·pg/mL for AUC0-last and from 21,585 to 362,107 h·pg/mL for AUC0-inf following administration of emvododstat. When dextromethorphan parameters were compared before and after emvododstat, least squares mean ratios (90% confidence interval) were found to be 2.9 (2.2, 3.8), 8.4 (6.1, 11.5), and 14.9 (10.0, 22.1) for Cmax, AUC0-last, and AUC0-inf, respectively.

Conclusion

Emvododstat appears to be a strong CYP2D6 inhibitor. No drug-related treatment emergent adverse effects (TEAEs) were considered to be severe or serious.

Trial registration

EudraCT 2021-004626-29, 11 May 2021.
Injective Split Systems
Authors: Hellmuth M. , Huber K. T. , Moulton V. , Scholz G. E. , Stadler P. F.
Published: June 2023

A split system$$\mathcal S$$Son a finite setX,$$|X|\ge 3$$|X|≥3, is a set of bipartitions or splits ofXwhich contains all splits of the form$$\{x,X-\{x\}\}$${x,X-{x}},$$x \in X$$x∈X. To any such split system$$\mathcal S$$Swe can associate the Buneman graph$$\mathcal B(\mathcal S)$$B(S)which is essentially a median graph with leaf-setXthat displays the splits in$$\mathcal S$$S. In this paper, we consider properties of injective split systems, that is, split systems$$\mathcal S$$Swith the property that$${{\,\textrm{med}\,}}_{\mathcal B(\mathcal S)}(Y) \ne {{\,\textrm{med}\,}}_{\mathcal B(\mathcal S)}(Y')$$medB(S)(Y)≠medB(S)(Y′)for any 3-subsets$$Y,Y'$$Y,Y′inX, where$${{\,\textrm{med}\,}}_{\mathcal B(\mathcal S)}(Y)$$medB(S)(Y)denotes the median in$$\mathcal B(\mathcal S)$$B(S)of the three elements inYconsidered as leaves in$$\mathcal B(\mathcal S)$$B(S). In particular, we show that for any setXthere always exists an injective split system onX, and we also give a characterization for when a split system is injective. We also consider how complex the Buneman graph$$\mathcal B(\mathcal S)$$B(S)needs to become in order for a split system$$\mathcal S$$SonXto be injective. We do this by introducing a quantity for |X| which we call the injective dimension for |X|, as well as two related quantities, called the injective 2-split and the rooted-injective dimension. We derive some upper and lower bounds for all three of these dimensions and also prove that some of these bounds are tight. An underlying motivation for studying injective split systems is that they can be used to obtain a natural generalization of symbolic tree maps. An important consequence of our results is that any three-way symbolic map onXcan be represented using Buneman graphs.
Mit RheMIT können Rheumazentren an der bundesweiten Kerndokumentation teilnehmen – Erweiterung der rheumatologischen Langzeitdokumentation
Authors: Callhoff Johanna , Feuchtenberger Martin , Karberg Kirsten , Kiltz Uta , Aringer Martin , Baraliakos Xenofon , Muth Theresia , Regierer Anne C. , Richter Jutta G. , Thiele Katja , Zinke Silke , Albrecht Katinka
Published: June 2023

Die Kerndokumentation der Regionalen kooperativen Rheumazentren wurde im vergangenen Jahr auf die Dokumentationssoftware RheMIT umgestellt. Damit können Einrichtungen, die RheMIT bereits für Versorgungsverträge oder andere Forschungsvorhaben nutzen, zukünftig auch an der Kerndokumentation teilnehmen. Erfahrungsberichte aus einer Klinik, einem Medizinischen Versorgungszentrum und einer Schwerpunktpraxis zeigen, wie die Umstellung auf RheMIT von einem bestehenden Dokumentationssystem bzw. eine neue Teilnahme an der Kerndokumentation mit RheMIT umsetzbar ist. Das Team Kerndokumentation am Deutschen Rheuma-Forschungszentrum Berlin (DRFZ) heißt neue teilnehmende rheumatologische Einrichtungen herzlich willkommen.
Morphological and molecular comparison of HIV-associated and sporadic inclusion body myositis
Authors: Vogt Sinja , Kleefeld Felix , Preusse Corinna , Arendt Gabriele , Bieneck Stefan , Brunn Anna , Deckert Martina , Englert Benjamin , Goebel Hans-Hilmar , Masuhr Anja , Neuen-Jacob Eva , Kornblum Cornelia , Reimann Jens , Montagnese Federica , Schoser Benedikt , Stenzel Werner , Hahn Katrin
Published: June 2023

Objective

The molecular characteristics of sporadic inclusion body myositis (sIBM) have been intensively studied, and specific patterns on the cellular, protein and RNA level have emerged. However, these characteristics have not been studied in the context of HIV-associated IBM (HIV-IBM). In this study, we compared clinical, histopathological, and transcriptomic patterns of sIBM and HIV-IBM.

Methods

In this cross-sectional study, we compared patients with HIV-IBM and sIBM based on clinical and morphological features as well as gene expression levels of specific T-cell markers in skeletal muscle biopsy samples. Non-disease individuals served as controls (NDC). Cell counts for immunohistochemistry and gene expression profiles for quantitative PCR were used as primary outcomes.

Results

14 muscle biopsy samples (7 HIV-IBM, 7 sIBM) of patients and 6 biopsy samples from NDC were included. Clinically, HIV-IBM patients showed a significantly lower age of onset and a shorter period between symptom onset and muscle biopsy. Histomorphologically, HIV-IBM patients showed no KLRG1+or CD57+cells, while the number of PD1+cells did not differ significantly between the two groups. All markers were shown to be significantly upregulated at gene expression level with no significant difference between the IBM subgroups.

Conclusion

Despite HIV-IBM and sIBM sharing important clinical, histopathological, and transcriptomic signatures, the presence of KLRG1+cells discriminated sIBM from HIV-IBM. This may be explained by longer disease duration and subsequent T-cell stimulation in sIBM. Thus, the presence of TEMRA cells is characteristic for sIBM, but not a prerequisite for the development of IBM in HIV+patients.
Picking up speed: cell cycle regulation during effector CD8+ T cell differentiation
Authors: Kretschmer Lorenz , Fuchs Noémie , Busch Dirk H. , Buchholz Veit R.
Published: June 2023

Clonal expansion and development of immunological memory are two hallmarks of adaptive immune responses. Resolving the intricate pathways that regulate cell cycle activity and lead to the generation of diverse effector and memory T cell subsets is essential for improving our understanding of protective T cell immunity. A deeper knowledge of cell cycle regulation in T cells also has translational implications for adoptive cell therapies and vaccinations against infectious diseases. Here, we summarize recent evidence for an early diversification of effector and memory CD8+ T cell fates and discuss how this process is coupled to discrete changes in division speed. We further review technical advances in lineage tracing and cell cycle analysis and outline how these techniques have shed new light on the population dynamics of CD8+ T cell responses, thereby refining our current understanding of the developmental organization of the memory T cell pool.
Visual Image Annotation for Bowel Obstruction: Repeatability and Agreement with Manual Annotation and Neural Networks
Authors: Murphy Paul M.
Published: June 2023

Bowel obstruction is a common cause of acute abdominal pain. The development of algorithms for automated detection and characterization of bowel obstruction on CT has been limited by the effort required for manual annotation. Visual image annotation with an eye tracking device may mitigate that limitation. The purpose of this study is to assess the agreement between visual and manual annotations for bowel segmentation and diameter measurement, and to assess agreement with convolutional neural networks (CNNs) trained using that data. Sixty CT scans of 50 patients with bowel obstruction from March to June 2022 were retrospectively included and partitioned into training and test data sets. An eye tracking device was used to record 3-dimensional coordinates within the scans, while a radiologist cast their gaze at the centerline of the bowel, and adjusted the size of a superimposed ROI to approximate the diameter of the bowel. For each scan, 59.4 ± 15.1 segments, 847.9 ± 228.1 gaze locations, and 5.8 ± 1.2 m of bowel were recorded. 2d and 3d CNNs were trained using this data to predict bowel segmentation and diameter maps from the CT scans. For comparisons between two repetitions of visual annotation, CNN predictions, and manual annotations, Dice scores for bowel segmentation ranged from 0.69 ± 0.17 to 0.81 ± 0.04 and intraclass correlations [95% CI] for diameter measurement ranged from 0.672 [0.490–0.782] to 0.940 [0.933–0.947]. Thus, visual image annotation is a promising technique for training CNNs to perform bowel segmentation and diameter measurement in CT scans of patients with bowel obstruction.
The effect of defatted black soldier fly meal (Hermetia illucens) inclusion in the formulated diet on the growth, gene expression, and histopathology of juvenile lobster (Panulirus ornatus Fabricius, 1798)
Authors: Saputra Ishaaq , Fotedar Ravi
Published: June 2023

The present study investigated the potential use of defatted black soldier fly (Hermetia illucens) meal as a protein source in the formulated feed for juvenile lobsters, Panulirus ornatus. A total of 160 heads of juvenile lobsters with initial weight of 0.24 ± 0.01 g and initial length of 21.77 ± 0.32 mm were distributed evenly into 16 rectangular fiberglass aquaria and kept individually for 8 weeks of the feeding experiment. Four formulated feeds containing defatted BSF meal as fishmeal replacements at 0%, 25%, 35%, and 50% and total dietary protein to energy ratio of ~ 26 g CP MJ−1 were prepared and assigned as BSF0, BSF25, BSF35, and BSF50, respectively. Fishmeal is technically a suitable aquafeed ingredient in terms of crude protein, moisture, and amino acid compositions. The partially substituted defatted BSF meal has higher crude lipid and ash content than fishmeal. At the end of week 8 of feeding trial, the specific growth rate, length increment, survival rate, and moulting rate of juvenile lobster were not significantly (P > 0.05) affected by the fishmeal replacement. The fishmeal replacement with the defatted BSF meal did not significantly (P > 0.05) alter the whole-body proximate composition of the juvenile lobster. However, it significantly (P < 0.05) affected the superoxidase dismutase of juvenile lobsters. The cytokine cell expression analysis indicated that up to 35% of fishmeal replacement increased the inflammatory cytokine cells (Interleukin 8 and 17) of juvenile lobster, while an adverse impact was observed on juvenile lobster receiving 50% of fishmeal replacement by BSF meal. Histopathological analysis showed that the hepatopancreas cells of juvenile lobsters were damaged following fishmeal replacement beyond 35%. The present study indicated that up to 35% of defatted BSF meal can be used as fishmeal replacement in the formulated feed of juvenile lobster.
Influence of analytic methods, data sources, and repeated measurements on the population attributable fraction of lifestyle risk factors
Authors: Wu You , Kim Hanseul , Wang Kai , Song Mingyang , Wang Molin , Tamimi Rulla , Eliassen Heather , Smith-Warner Stephanie A. , Willett Walter. C. , Giovannucci Edward L.
Published: June 2023

Population attributable risk (PAR%) reflects the preventable fraction of disease. However, PAR% estimates of cancer have shown large variation across populations, methods, data sources, and timing of measurements. Three statistical methods to estimate PAR% were identified from a systematic literature review: the Levin’s formula, the comparative incidence rate method, and the comparative risk assessment method. We compared the variations in PAR% of postmenopausal breast cancer in the Nurses’ Health Study to evaluate the influence by method choice, source of prevalence data, use of single vs repeated exposure measurements, and potential joint effects of obesity, alcohol, physical activity, fruit and vegetable intake. Across models of the three methods, the estimated PAR% using repeated measurements were higher than that using baseline measurement; overall PAR% for the baseline, simple update, and cumulative average models were 13.8%, 21.1%, 18.6% by Levin’s formula; 13.7%, 28.0%, 31.2% by comparative risk assessment; and 17.4%, 25.2%, 29.3% by comparative incidence rate method. The estimated PAR% of the combination of multiple risk factors was higher than the product of the individual PAR%: 18.9% when assuming independence and 31.2% when considering the risk factors jointly. The three methods provided similar PAR% based on the same data source, timing of measurements, and target populations. However, sizable increases in the PAR% were observed for repeated measures over a single measure and for calculations based on achieving all recommendations jointly rather than individually.
Performance of Normal Strength Concrete Slab Strengthened with High-Performance Concrete After Exposure to Elevated Temperature
Authors: Ghazy Mariam F. , Abd Elaty Metwally A. , Zalhaf Nagat M.
Published: June 2023

Reinforced concrete as the most important construction material suffers from long-term deterioration due to different exposure conditions. Fire attack is a critical exposure condition as it can lead to complete collapse of the structure. On the other hand, the repair and strengthening of existing structures have become necessary both technically and financially. Moreover, since high-performance concretes (HPCs) are extensively used as repairing or strengthening materials for different structures, their performance after exposure to elevated temperature needs to be investigated. Therefore, this study is directed to investigate the post-fire flexural behavior of RC slabs cast with traditional normal strength concrete (NSC) and strengthened with HPC. Twenty-one RC slabs were prepared and tested including casting the full thickness with the same mixture (single-concrete slabs) and composite slabs (cast with NSC and HPC). Different variables were considered; using high strength concrete, 30% fly ash, 30% slag, 0.5% polypropylene, 0.5% steel fibers, hybrid fibers (0.5% steel + 0.5% polypropylene), reinforcement ratio, the side exposed to elevated temperature (tension or compression), and joining the HPC layer to the NSC (shear studs or epoxy resin). The slabs were exposed to the required temperature of 600°C for 2 h. The results show that strengthening the RC slab in tension or compression by using HPC remarkably enhanced the slab’s performance after exposure to elevated temperature. Specially, composite slabs containing hybrid fibers in tension side when exposed to elevated temperature from the tension side recorded the highest cracking load, ultimate load, stiffness, toughness, and ductility index as compared to the NSC slab, with increases of 92.8%, 116%, 157%, 335%, and 86.9%, respectively.
Behavior of a Composite Steel Decking and Boarding System in Fire Based on Large-Scale Experimental Testing and Numerical Modelling
Authors: Claasen Jaleel , Cicione Antonio , Streicher Dirk , Walls Richard
Published: June 2023

This paper presents experimental and numerical results of an investigation into the thermal and structural behaviour of an innovative modular structural steel system, which includes cellular beams, that was tested in a 1-h standard fire scenario while loaded. The modular system consists of a 5.66 × 3.8 m rectangular steel frame, with a profiled steel sandwich decking (SD) system attached, which comprises of (a) profiled steel decking, (b) fibre cement, and (c) calcium silicate boards and strips. The SD system is suspended from the underside of the horizontal structural members to provide inherent fire protection to the steel beams from the bottom and acts as the load-bearing component of the flooring. The purpose of the experiment was to determine the fire resistance of the structural system, whilst under load, which is primarily based on the fire resistance of the SD system. Temperature data for the SD system was collected during the experiment and used to validate a numerical finite element analysis model. This study shows that the SD system was able to achieve a fire resistance rating of 57 min in the experiment which was governed by insulation resistance. A lower fire resistance rating is estimated based on numerical models. Structural resistance was maintained throughout the test. During preliminary testing structural collapse was observed in a separate experiment which highlights how the system is sensitive to damage to the ceiling boards. Numerical results highlight that thermal bowing and movement may result in changes in thermal interactions between adjacent elements. This paper provides novel large-scale experimental data on a loaded flooring system in fire.
Efficient Key Generation Techniques for Wireless Body Area Network
Authors: Divya S. , Prema K. V. , Muniyal Balachandra
Published: June 2023

In wireless body area network health care applications, energy-constraint wearable devices are used to monitor patient physiological parameters. The security of the private health information of a person plays a significant role because if it is captured and read by an unauthorized person, the confidentiality of the patient data is lost. Therefore, there is a requirement to secure the data by performing encryption to transfer it into an unreadable form. Since the resources used for encryption should be kept to a minimum as the devices are attached to the human body, a lightweight encryption algorithm has to be used. Therefore, the generation of a unique key used for encryption plays a significant role. In work, generating a unique key uses the ECG values taken from MIT-BIH Arrhythmia database. Four unique keys are generated, which can be used for encryption. The uniqueness and randomness of the keys generated are proved using the runs test and frequency test within the block. Also, the average hamming distance calculated between the ECG keys generated from two different ECG signals is 62.5% ($$\approx$$
≈
80 bits), which proves the distinctiveness of the keys generated. Implementation of the work is performed using Matlab.
Combining historical aerial photography with machine learning to map landscape change impacts on dry grasslands in the Central Alps
Authors: Kindermann Elisabeth , Hölzel Norbert , Wellstein Camilla
Published: June 2023

Context

Striking land-use changes after WW II characterize the past century in the European Alps with impact on ecosystems and biodiversity. Documenting land-use changes is often difficult due to limited information from the past. Mapping landscape history with aerial photography can foster the understanding of human-induced changes in vulnerable ecosystems, such as the remnants of dry grasslands in the Central Alps.

Objectives

We aimed to assess changes in grassland vegetation and their current extent in Val Venosta (European Alps, Italy) in relation to overall landscape settings, anthropogenic drivers of change and the effectiveness of the protected areas.

Methods

We performed a land-cover classification based on a mixed machine learning approach including several auxiliary classifiers in a random forest model to characterise the extent and state of (dry) grasslands. We calculated landscape metrics between 1945 and 2015 to assess shape-related changes, especially regarding their landscape embedding and the protection status of sites.

Results

Three main processes related to a changing extent in grassland habitat prevail: (i) agricultural intensification, (ii) settlement expansion at the valley bottom and (iii) forest expansion (afforestation and encroachment due to decreasing pasture activities) on the valley slopes. The remaining grassland habitat is increasingly isolated and fragmented, leaving only few core areas of dry grassland, which tended to be better conserved within protected areas.

Conclusion

The changes in extent of dry grasslands revealed marked changes. Transformations are assumed to be predominantly caused by human impact and successional changes. Our results confirm the importance of protected area networks. The pronounced landscape changes underline the urgent need for future research with explicit focus on the changes at community level and the underlying causes. Identifying all relevant drivers of change should be a key element in targeted conservation efforts.
In situ electron microscopy techniques for nanoparticle dispersion analysis of commercial sunscreen
Authors: Ilett M. , Naveed E. , Roncal-Herrero T. , Aslam Z. , Micklethwaite S. , Hondow N.
Published: June 2023

Nanoparticles are common active ingredients within many commercial products including sunscreen. Consequently, accurate characterisation of nanoparticles in these products is vital to enhance product design, whilst also understanding the toxicological implications of these nanoparticles. Whilst bulk techniques are useful in providing some information, they often cannot resolve individual particles, and therefore electron microscopy can be used for high-resolution nanoparticle characterisation. However, conventional high vacuum dry TEM does not accurately represent nanoparticle dispersions and other in situ methods must be used. Here, we use a combination of techniques including liquid cell transmission electron microscopy (LCTEM), cryogenic (cryo)-TEM and cryo-scanning electron microscopy (SEM) to characterise a commercial sunscreen containing titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles. Our work illustrates that whilst LCTEM does not require any sample preparation more beam artefacts can occur causing ZnO dissolution with only TiO2 nanoparticles visualised. Comparatively, cryo-TEM allows characterisation of both ZnO and TiO2, yet only cryo-SEM could be used to analyse the pure product (without dilution) but biased the characterisation to the larger fraction of nanoparticles and agglomerates. Ultimately, only with a combination of different in situ EM techniques can an accurate characterisation of commercial products be achieved in order to ensure effective and safe product design and manufacture.
Computing corporate bond returns: a word (or two) of caution
Authors: Andreani Martina , Palhares Diogo , Richardson Scott
Published: June 2023

We offer several suggestions for researchers using corporate bond return data. First, despite clear instructions from older papers (e.g., Bessembinder et al., The Review of Financial Studies 22:4219–4258, 2009) about ways to compute credit excess returns, a lot of recent research simply subtracts a Treasury Bill return. We show that this imprecision is likely to contaminate inferences, as the rate component of returns is negatively correlated to the spread component. This is a problem for all research looking at corporate bond returns, especially time series analysis and safer corporate bonds (e.g., investment grade). We provide a simple approach using Wharton Research Data Services (WRDS) data to remove the interest rate component of corporate bond returns. Second, we note significant differences in the coverage of corporate bonds across the Trade Reporting and Compliance Engine (TRACE) platform and typical corporate bond indices. We provide some simple rules for researchers who are using TRACE to select a subset of bonds closest to those contained inside corporate bond indices used by institutional investors. Third, we note differential quality in the prices and hence returns between TRACE and typical corporate bond indices. Corporate bond returns provided by corporate bond indices (i) correctly estimate credit excess returns, (ii) are synchronous for the entire set of bonds, allowing for consistent cross-sectional comparability, and (iii) suffer less from stale pricing issues. Due to these coverage and data quality issues, researchers should try, where possible, to source return data from multiple sources to ensure the robustness of their results.
GEnZ explorer: a tool for visualizing agroclimate to inform research and regulatory risk assessment
Authors: Melnick Rachel L. , Jarvis Larissa , Hendley Paul , Garcia-Alonso Monica , Metzger Marc J. , Ramankutty Navin , Teem John L. , Roberts Andrew
Published: June 2023

Confined field trials (CFT) of genetically engineered (GE) crops are used to generate data to inform environmental risk assessments (ERA). ERAs are required by regulatory authorities before novel GE crops can be released for cultivation. The transportability of CFT data to inform risk assessment in countries other than those where the CFT was conducted has been discussed previously in an analysis showing that the primary difference between CFT locations potentially impacting trial outcomes is the physical environment, particularly the agroclimate. This means that data from trials carried out in similar agroclimates could be considered relevant and sufficient to satisfy regulatory requirements for CFT data, irrespective of the country where the CFTs are conducted. This paper describes the development of an open-source tool to assist in determining the transportability of CFT data. This tool provides agroclimate together with overall crop production information to assist regulators and applicants in making informed choices on whether data from previous CFTs can inform an environmental risk assessment in a new country, as well as help developers determine optimal locations for planning future CFTs. The GEnZ Explorer is a freely available, thoroughly documented, and open-source tool that allows users to identify the agroclimate zones that are relevant for the production of 21 major crops and crop categories or to determine the agroclimatic zone at a specific location. This tool will help provide additional scientific justification for CFT data transportability, along with spatial visualization, to help ensure regulatory transparency.
Environmental heterogeneity affecting spatial distribution of phytoplankton community structure and functional groups in a large eutrophic lake, Lake Chaohu, China
Authors: Cao Huijuan , Zhang Kun , Deng Daogui , Qi Huiying , Li Jun , Cao Yaqin , Jin Qide , Zhao Yajie , Wang Yeping , Wu Zhou , Li Xinyue , Li Ying
Published: June 2023

The growth and development of phytoplankton are influenced by physico-chemical parameters, which can also affect the spatial distribution of phytoplankton community structure. However, it is unclear whether environmental heterogeneity caused by multiple physico-chemical factors can affect the spatial distribution of phytoplankton and its functional groups. In this study, we investigated the seasonal variation and spatial distribution of phytoplankton community structure and its relationships with environmental factors in Lake Chaohu from August 2020 to July 2021. We recorded a total of 190 species from 8 phyla, which were divided into 30 functional groups, including 13 dominating functional groups. The average annual phytoplankton density and biomass were (5.46 ± 7.17) × 107 cells/L and 4.80 ± 4.61 mg/L, respectively. The density and biomass of phytoplankton were higher in summer ((14.64 ± 20.34) × 107 cells/L, 10.61 ± 13.16 mg/L) and autumn ((6.79 ± 3.97) × 107 cells/L, 5.57 ± 2.40 mg/L), with the M and H2 of dominant functional groups. The dominant functional groups were N, C, D, J, MP, H2, and M in spring, whereas functional groups C, N, T, and Y dominated in winter. The distribution of phytoplankton community structure and dominant functional groups exhibited significant spatial heterogeneity in the lake, which was consistent with the environmental heterogeneity of the lake and could be classified into four locations. Location I had higher phytoplankton density and biomass than the other three locations. Additionally, dominant functional groups M, C, and H2 were present throughout the lake, and all 13 dominant functional groups were observed in Location II. Our findings suggest that environmental heterogeneity is a key factor influencing the spatial distribution of phytoplankton functional groups in Lake Chaohu.
Die Anwendung der Propensity-Score-Methode
Authors: Matteucci Gothe Raffaella
Published: June 2023

Hintergrund

Bei der Ermittlung von Behandlungseffekten mit Real World Data (RWD) kann die Gefahr bestehen, verzerrte Ergebnisse zu erhalten, wenn die Verteilung der Vorbehandlungscharakteristika der Studienteilnehmer in den zu vergleichenden Gruppen unterschiedlich ist (Confounding). Propensity Scores (PS) sind eine geeignete Methode zur Bildung von Gruppen mit vergleichbarer Verteilung von Charakteristika, um anschließend den interessierenden Behandlungseffekt zu schätzen.

Ziel der Arbeit

Ziel des vorliegenden Beitrags ist eine Einführung in die Berechnung und Anwendung von PS.

Material und Methoden

Die Methode der PS wird beschrieben und mit Bezug zur Übersichtsliteratur erläutert. Vor- und Nachteile der Methodik werden aufgezeigt.

Ergebnisse

Es wird dargestellt, wie PS berechnet und angewendet werden. Varianten der Berechnung sind: die logistische oder die Probit-Regression, die Diskriminanzanalyse, „classification and regression trees“ (CART), neuronale Netze und andere Methoden. PS werden zum Matching, zur Stratifizierung, zur Gewichtung und im Rahmen einer Regression angewandt.

Schlussfolgerung

Die Anwendung der PS führt zu einem quasiexperimentellen Studiendesign und hilft ggf. unverzerrte Behandlungseffekte im Rahmen der Analyse von RWD zu schätzen.
Introducing the Intergovernmental Policy Output Dataset (IPOD)
Authors: Lundgren Magnus , Squatrito Theresa , Sommerer Thomas , Tallberg Jonas
Published: June 2023

There is a growing recognition that international organizations (IOs) formulate and adopt policy in a wide range of areas. IOs have emerged as key venues for states seeking joint solutions to contemporary challenges such as climate change or COVID-19, and to establish frameworks to bolster trade, development, security, and more. In this capacity, IOs produce both extraordinary and routine policy output with a multitude of purposes, ranging from policies of historic significance like admitting new members to the more mundane tasks of administering IO staff. This article introduces the Intergovernmental Policy Output Dataset (IPOD), which covers close to 37,000 individual policy acts of 13 multi-issue IOs in the 1980–2015 period. The dataset fills a gap in the growing body of literature on the comparative study of IOs, providing researchers with a fine-grained perspective on the structure of IO policy output and data for comparisons across time, policy areas, and organizations. This article describes the construction and coverage of the dataset and identifies key temporal and cross-sectional patterns revealed by the data. In a concise illustration of the dataset’s utility, we apply models of punctuated equilibria in a comparative study of the relationship between institutional features and broad policy agenda dynamics. Overall, the Intergovernmental Policy Output Dataset offers a unique resource for researchers to analyze IO policy output in a granular manner and to explore questions of responsiveness, performance, and legitimacy of IOs.
Effects of site productivity on individual tree maximum basal area growth rates of Eucalyptus pilularis in subtropical Australia
Authors: West P. W.
Published: June 2023

Inventory data were available from 96 plots of even-aged, monoculture, tall-open forests of Eucalyptus pilularis Smith, aged 2–63 years, growing in sub-tropical regions along the east coast of Australia. A model was developed relating the maximum possible stem basal area growth rate of individual trees to their stem basal area. For any tree size, this maximum increased as site productivity increased. However, the size at which this maximum occurred decreased as productivity increased. Much research has shown that, at any stand age, trees of a particular stem basal area are taller on more productive sites than on less productive ones. Taller trees incur greater respiratory costs to ensure maintenance of the photosynthetic capacity of their canopies; this reduces their growth rates. It was concluded that trees with larger basal areas will have the maximum possible growth rate on a less productive site, whilst trees with smaller basal areas will have the maximum possible on a more productive site. The model developed may constitute the first stage of a complete individual tree growth model system to predict wood yields from these forests.
Smart and sustainable scheduling of charging events for electric buses
Authors: Jarvis Padraigh , Climent Laura , Arbelaez Alejandro
Published: June 2023

This paper presents a framework for the efficient management of renewable energies to charge a fleet of electric buses (eBuses). Our framework starts with the prediction of clean energy time windows, i.e., periods of time when the production of clean energy exceeds the demand of the country. Then, the optimization phase schedules charging events to reduce the use of non-clean energy to recharge eBuses while passengers are embarking or disembarking. The proposed framework is capable of overcoming the unstable and chaotic nature of wind power generation to operate the fleet without perturbing the quality of service. Our extensive empirical validation with real instances from Ireland suggests that our solutions can significantly reduce non-clean energy consumed on large data sets.
Biological effects of particulate matter samples during the COVID-19 pandemic: a comparison with the pre-lockdown period in Northwest Italy
Authors: Gea Marta , Macrì Manuela , Marangon Daniele , Pitasi Francesco Antonio , Fontana Marco , Schilirò Tiziana , Bonetta Sara
Published: June 2023

In 2020, during the COVID-19 pandemic, containment measures were applied inducing potential changes in air pollutant concentrations and thus in air toxicity. This study evaluates the role of restrictions on biological effects of particulate matter (PM) in different Northwest Italy sites: urban background, urban traffic, rural, and incinerator. Daily PM samples collected in 2020 were pooled according to restrictions: January/February (no restrictions), March and April (first lockdown), May/June and July/August/September (low restrictions), October/November/December (second lockdown). The 2019 samples (pre-pandemic period) were pooled as 2020 for comparison. Pools were extracted with organic solvents and extracts were tested to assess cytotoxicity (WST-1 assay) and genotoxicity (comet assay) on BEAS-2B cells, mutagenicity (Ames test) on TA98 and TA100 Salmonella typhimurium strains, and estrogenic activity (gene reporter assay) on MELN cells. Pollutant concentrations were also analyzed (PM10, PM2.5, polycyclic aromatic hydrocarbons). No difference was observed for PM and polycyclic aromatic hydrocarbon concentrations between 2020 and 2019. During lockdown months (2020), PM cytotoxicity/genotoxicity was significantly lower in some sites than during 2019, while considering PM mutagenicity/estrogenic activity some differences were detected but without statistical significance. PM extract effects decreased in some sites during 2020; this may be due to lockdowns that reduced/modified pollutant emissions and may be related also to complex PM origin/formation and to meteorological conditions. In conclusion, the study confirms that PM biological effects cannot be assessed considering only the PM concentration and suggests to include a battery of bioassay for air quality monitoring in order to protect human health from air pollution effects.

Graphical Abstract
Direct Oral Anticoagulants for Cancer-Associated Venous Thromboembolism
Authors: Masini Marta , Toma Matteo , Spallarossa Paolo , Porto Italo , Ameri Pietro
Published: June 2023

Purpose of Review

To present the randomized controlled trial (RCT) evidence and highlight the areas of uncertainty regarding direct oral anticoagulants (DOAC) for cancer-associated venous thromboembolism (CAT).

Recent Findings

In the last years, four RCTs have shown that rivaroxaban, edoxaban, and apixaban are at least as effective as low-molecular-weight heparin (LMWH) for the treatment of both incidental and symptomatic CAT. On the other hand, these drugs increase the risk of major gastrointestinal bleeding in patients with cancer at this site. Another two RCTs have demonstrated that apixaban and rivaroxaban also prevent CAT in subjects at intermediate-to-high risk commencing chemotherapy, albeit at the price of higher likelihood of bleeding. By contrast, data are limited about the use DOAC in individuals with intracranial tumors or concomitant thrombocytopenia. It is also possible that some anticancer agents heighten the effects of DOAC via pharmacokinetic interactions, up to making their effectiveness-safety profile unfavorable.

Leveraging the results of the aforementioned RCTS, current guidelines recommend DOAC as the anticoagulants of choice for CAT treatment and, in selected cases, prevention. However, the benefit of DOAC is less defined in specific patient subgroups, in which the choice of DOAC over LMWH should be carefully pondered.
Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers
Authors: Jansen Mark , Schmidt A. F. , Jans J. J. M. , Christiaans I. , van der Crabben S. N. , Hoedemaekers Y. M. , Dooijes D. , Jongbloed J. D. H. , Boven L. G. , Lekanne Deprez R. H. , Wilde A. A. M. , van der Velden J. , de Boer R. A. , van Tintelen J. P. , Asselbergs F. W. , Baas A. F.
Published: June 2023

Hypertrophic cardiomyopathy (HCM) is a relatively common genetic heart disease characterised by myocardial hypertrophy. HCM can cause outflow tract obstruction, sudden cardiac death and heart failure, but severity is highly variable. In this exploratory cross-sectional study, circulating acylcarnitines were assessed as potential biomarkers in 124 MYBPC3 founder variant carriers (59 with severe HCM, 26 with mild HCM and 39 phenotype-negative [G + P-]). Elastic net logistic regression identified eight acylcarnitines associated with HCM severity. C3, C4, C6-DC, C8:1, C16, C18 and C18:2 were significantly increased in severe HCM compared to G + P-, and C3, C6-DC, C8:1 and C18 in mild HCM compared to G + P-. In multivariable linear regression, C6-DC and C8:1 correlated to log-transformed maximum wall thickness (coefficient 5.01, p = 0.005 and coefficient 0.803, p = 0.007, respectively), and C6-DC to log-transformed ejection fraction (coefficient -2.50, p = 0.004). Acylcarnitines seem promising biomarkers for HCM severity, however prospective studies are required to determine their prognostic value.

Graphical abstract
Integration of GIS and Machine Learning Techniques for Mapping the Landslide-Prone Areas in the State of Goa, India
Authors: Ganesh Babitha , Vincent Shweta , Pathan Sameena , Benitez Silvia Raquel Garcia
Published: June 2023

A landslide susceptibility map (LSM) assists in reducing the danger of landslides by locating the landslide-prone locations within the designated area. One of the locations that are prone to landslides in India's Western Ghats of which Goa is a part. This article presents the LSMs prepared for the state of Goa using four standard machine learning algorithms, namely Logistic Regression (LR ), Support Vector Machine (SVM), K-Nearest Neighbour (KNN), and Random Forest (RF). In order to create LSMs, a 78-point landslide inventory, as well as 14 landslide conditioning factors, has been used, including slope, elevation, aspect, total curvature, plan curvature, profile curvature, yearly rainfall, Stream Power Index, Topographic Wetness Index, distance to road, depth to bedrock/soil depth, soil type, lithology, and land use land cover. The most pertinent features for the models' construction have been chosen using the Pearson correlation coefficient test and the Random Forest method. The presence of landslides is shown to be strongly influenced by the distance to road, slope of the terrain, and the annual rainfall. The LSMs generated were classified into five levels ranging from very low susceptibility level to very high susceptible. The prediction accuracy, precision, recall, F1-score, area under the ROC (AUC-ROC), and True Skill Statistics (TSS) have been used to analyse and compare the LSMs created using various methodologies. All of these algorithms perform pretty well, as evidenced by the overall accuracy scores of 81.90% for LR, 83.33% for SVM, 81.94% for KNN, and 86.11% for RF. SVM and RF are the better approaches for forecasting landslide vulnerability in the research area, according to TSS data. The maximum AUC-ROC of 86% was achieved by the RF algorithm. The results of performance metrics lead to the conclusion that the tree-based RF approach is most appropriate for producing LSM for the state of Goa. The results of this study indicate that more landslide-prone areas can be found in the Sattari, Dharbandora, Sanguem, and Canacona regions of Goa.
Holistic anti-tumor resistance mechanism of YBX1 and its potential as a chemoresistance target in pancreatic ductal adenocarcinoma
Authors: Li Zheng , Chen Haidi , Li Borui , Wang Ting , Ji Shunrong , Qin Yi , Xu Xiaowu , Yu Xianjun
Published: June 2023

The overall survival rate of pancreatic ductal adenocarcinoma (PDAC) is the worst among all cancers, which is mainly due to the fact that most patients are in the late tumor stage when diagnosed, lacking effective treatment options. Although targeted therapy has shown some prospects in PDAC, its efficacy is limited to patients with specific gene mutation or target gene expression. A large number of patients have no other treatment options except chemotherapy. However, the high drug resistance rate of chemotherapy for PDAC severely limits the improvement of curative effect. Therefore, determining the key factors that lead to drug resistance in PDAC is crucial to improve the prognosis of patients. Multifunctional oncoprotein Y-box binding protein 1 (YBX1) may be one of such potential targets. Studies have confirmed that YBX1 is associated with the inherent behavior of a variety of cancers, such as proliferation, invasion, metastasis, and cancer cell stemness. Herein, we integrated and analyzed the resistance mechanism of YBX1 in anti-tumor therapy, and discussed its potential as a therapeutic target to reverse the chemotherapy resistance of PDAC.
Motion Tracking in Diagnosis: Gait Disorders Classification with a Dual-Head Attentional Transformer-LSTM
Authors: Shayestegan Mohsen , Kohout Jan , Trnková Kateřina , Chovanec Martin , Mareš Jan
Published: June 2023

Gait and motion stability analysis in gait dysfunction problems is a very interesting research area. Usually, patients who undergo vestibular deafferentation are affected by changes in their dynamic balance. Therefore, it is important both patients and physicians are able to monitor the progress of the so-called vestibular compensation to observe the rehabilitation process objectively. Currently, the quantification of their progress is highly dependent on the physician’s opinion. In this article, we designed a novel methodology to classify the gait disorders associated with unilateral vestibular deafferentation in patients undergoing vestibular schwannoma surgery (model of complete vestibular loss associated with imbalance due to vestibular nerve section and eventual labyrinthectomy). We present a dual-head attentional transformer-LSTM (DHAT-LSTM) to evaluate the problem of rehabilitation from gait dysfunction, which is observed by a Kinect. A system consisting of a key-point-RCNN detector is used to compute body landmark measures and evaluate gait dysfunction based on a DHAT-LSTM network. This structure is used to quantitatively assess gait classification by tracking skeletal features based on the temporal variation of feature sequences. The proposed deep network analyses the features of the patient’s movement. These extracted high-level representations are then fed to the final evaluation of gait dysfunction. The result analytically demonstrates its effectiveness in classification evaluation when used in conjunction with state-of-the-art pose estimation and feature extraction techniques. An accuracy greater than 81% was achieved for given sets of individuals using velocity-based, angle-based, and position features for both the whole body and the symmetric features of the body.
Protecting Reproductive Rights Post-Roe: Can Companies Keep Your Data Safe?
Authors: Barrera Meagan , Rayman Labrin Danny
Published: June 2023

The United States Supreme Court decision in Dobbs v Jackson Women’s Health Organization brought to the forefront the intersections between technology and reproductive rights. As the country grappled with the impact of Dobbs on reproductive rights, digital and human rights experts warned that the vast amounts of data collected by companies could now be used to target and punish people seeking or facilitating access to abortions. This is the most recent manifestation of the negative impact technology can have on women, girls and persons of diverse sexual orientations and gender identities, and represents a global challenge for companies that collect, store, share and process user data. To fulfill their responsibility to respect human rights, companies should take steps to prevent the risks associated with collecting, storing, sharing and processing user data, and adapt these steps to respond to emerging risks, such as those now posed by the Dobbs decision.
The Interconnected Nature of Family Indebtedness: The Halliday Family of Frome, Somerset (1733–1752)
Authors: Collins Aidan
Published: June 2023

This article analyzes a single bankruptcy case—Hancock v Halliday (1742–1752)—as it was litigated in the Court of Chancery across a ten-year period. By incorporating local sources, the work attempts to move away from assumptions surrounding the “implicit contract” of family, and to provide a more nuanced analysis of “family strategies” in action. I argue that business historians—looking at networks—and economic and social historians—analyzing the use and implementation of credit—should continue to explore the divisions within families, which will help to reemphasize the role of women within business transactions and the wider credit-based economy. Ultimately, this article makes a significant contribution to the burgeoning scholarship on the negative aspects of familial networks of credit and debt, demonstrating how the complex and multifaceted nature of family indebtedness has been overlooked, and misunderstood, in the existing literature.