bluuebunny/crossref_metadata_2025 huggingface dataset:
A pharmacokinetic–pharmacodynamic model for chemoprotective agents against malaria
Authors: Cherkaoui‐Rbati Mohammed H. , Andenmatten Nicole , Burgert Lydia , Egbelowo Oluwaseun F. , Fendel Rolf , Fornari Chiara , Gabel Michael , Ward John , Möhrle Jörg J. , Gobeau Nathalie
Published: November 2022

Chemoprophylactics are a vital tool in the fight against malaria. They can be used to protect populations at risk, such as children younger than the age of 5 in areas of seasonal malaria transmission or pregnant women. Currently approved chemoprophylactics all present challenges. There are either concerns about unacceptable adverse effects such as neuropsychiatric sequalae (mefloquine), risks of hemolysis in patients with G6PD deficiency (8‐aminoquinolines such as tafenoquine), or cost and daily dosing (atovaquone–proguanil). Therefore, there is a need to develop new chemoprophylactic agents to provide more affordable therapies with better compliance through improving properties such as pharmacokinetics to allow weekly, preferably monthly, dosing. Here we present a pharmacokinetic–pharmacodynamic (PKPD) model constructed using DSM265 (a dihydroorotate dehydrogenase inhibitor with activity against the liver schizonts of malaria, therefore, a prophylaxis candidate). The PKPD model mimics the parasite lifecycle by describing parasite dynamics and drug activity during the liver and blood stages. A major challenge is the estimation of model parameters, as only blood‐stage parasites can be observed once they have reached a threshold. By combining qualitative and quantitative knowledge about the parasite from various sources, it has been shown that it is possible to infer information about liver‐stage growth and its initial infection level. Furthermore, by integrating clinical data, the killing effect of the drug on liver‐ and blood‐stage parasites can be included in the PKPD model, and a clinical outcome can be predicted. Despite multiple challenges, the presented model has the potential to help translation from preclinical to late development for new chemoprophylactic candidates.
Emodin inhibiting epithelial‐mesenchymal transition in pulmonary fibrosis through the c‐MYC/miR‐182‐5p/ZEB2 axis
Authors: Yang Jia , Jiang Gangdan , Ni Kaiwen , Fan Liming , Tong Wang , Yang Junchao
Published: November 2022

Emodin is a natural anthraquinone compound, which is the main component found in the traditional Chinese herb Polygonum cuspidatum. The anti‐fibrosis effects of Emodin have been reported. This study aimed to explore the specific mechanism of Emodin in the epithelial‐mesenchymal transition (EMT) of pulmonary fibrosis. The pulmonary fibrosis mice models were constructed with bleomycin, the EMT models of alveolar epithelial cells were stimulated by TGF‐β1, and Emodin was used for intervention. c‐MYC and miR‐182‐5p were overexpressed or silenced by cell transfection. Our results demonstrated that Emodin attenuated pulmonary fibrosis induced by bleomycin in mice, and inhibited EMT, meanwhile downregulated c‐MYC, upregulated miR‐182‐5p, and downregulated ZEB2 in vitro and vivo. Next, overexpression of c‐MYC promoted EMT, while silencing c‐MYC and overexpressing miR‐182‐5p inhibited EMT. Then, c‐MYC negatively regulated the expression of miR‐182‐5p with a direct binding relationship. And miR‐182‐5p inhibited ZEB2 expression in a targeted manner. Finally, Emodin inhibited EMT that had been promoted by overexpression of c‐MYC. In conclusion, Emodin could attenuate pulmonary fibrosis and EMT by regulating the c‐MYC/miR‐182‐5p/ZEB2 axis, which might provide evidence for the application of Emodin in the treatment of pulmonary fibrosis.
Chemical mass shifts of cluster ions and adduct ions in quadrupolar ion traps revisited and extended
Authors: Romson Joakim , Emmer Åsa
Published: November 2022

Rationale

Chemical mass shifts in quadrupolar ion traps have been studied previously but only for a limited number of analytes and mass ranges. Here, mass shifts of cluster ions, commonly used as calibrants, and other analytes are qualitatively evaluated on the Bruker amaZon spherical ion trap (QIT) and the Finnigan LXQ linear ion trap (LIT). To extend the mass range from previous experiments m/z up to 4000 are investigated.

Methods

Chemical mass shifts of CsI, Y(HCOO)3, and NaCF3COO cluster ions, CF3COO−, Na+, and Cs+ adduct ions, protonated commercial calibration solutions and peptides, and deprotonated peptides were investigated on the Bruker amaZon speed QIT and some of these were also investigated on the Finnigan LXQ LIT.

Results

On both instruments, peak distortions and mass shifts toward lower m/z became apparent as m/z approached 1000. To some extent, the issues were more severe at slower scans. Peak distortions included loss of resolution, tailing, or fronting and were different between the amaZon QIT and the LXQ LIT. The noncluster and nonadduct ions analyzed showed no obvious mass shifts or peak distortions under the same analysis conditions.

Conclusions

As expected, the ion traps investigated here showed mass shift and peak distortion issues, and such issues persisted at m/z up to 4000 on both instruments. Peak distortions were different between the amaZon QIT and the LXQ LIT, and were not always visible despite mass shifts. Both mass shifts and peak distortions make cluster ions and some adduct ions unsuitable for ion trap calibration.
Sequential measurement of 13C, 15N, and 34S isotopic composition on nanomolar quantities of carbon, nitrogen, and sulfur using nano‐elemental analysis/isotope ratio mass spectrometry
Authors: Baczynski Allison A. , Brodie Christopher R. , Kracht Oliver , Freeman Katherine H.
Published: November 2022

Rationale

We report modifications to a commercial elemental analyzer‐isotope ratio mass spectrometer that permit high‐precision isotopic analysis of nanomoles of carbon (C), nitrogen (N), and sulfur (S) on a single sample without chemical or cryogenic trapping of gases. The sample size required for measurement by our system is about two orders of magnitude less than that for conventional analyses.

Methods

Our system builds on the analytical advancements offered by the EA IsoLink IRMS System and employs simple modifications to reduce the diameter of the flow path (reactors, water trap, and transfer lines), enhance peak separation (gas chromatography capillary column), and improve sample transfer to the ion source of the mass spectrometer (reduced flow rates).

Results

Conventional precision (<0.2‰) can be achieved down to c. 500 nmol C, N, and S for samples analyzed without modification of the commercial system. Further reduction in sample size (<50 nmol C, N, and S) was achieved with minor modifications. There is a significant carbon blank and a small nitrogen blank that can be measured directly and a sulfur blank that can be calculated using regression. Only 30 nmol of N, 22 nmol of C, and 12 nmol of S are needed to achieve better than 1‰ precision (1σ) from a single measurement. Larger samples and more replicate measurements provide better precision.

Conclusions

The nano‐EA method described here reduces sample size requirements by two orders of magnitude compared to traditional approaches and improves the accuracy and precision of isotope measurements on sample sizes less than 1 μmol. These advancements simplify the analytical technique and broaden the range and type of samples amenable to EA analysis.
Accuracy of cortical bone trajectory screw fixation guided by spinous process clamp guide in lumbosacral vertebrae: A cadaver study
Authors: Zhang Xi‐Nuo , Zhou Li‐Jin , Su Qing‐Jun , Guan Li , Li Dong‐Yue , Pei Bao‐Qing , Pan Ai‐Xing , Yang Hong‐Hao , Ding Hong‐Tao , Liu Yu‐Zeng , Hai Yong
Published: November 2022

Background

The purpose of this study was to access the accuracy of cortical bone trajectory screw placement guided by spinous process clamp (SPC).

Methods

Eight formalin‐treated cadaveric lumbar specimens with T12‐S1 were used. A total of 96 screws were implanted in eight lumbar specimens.

Results

In the freehand (FH) group, clinically acceptable placement (grade A and B) was 40 screws (83.3%), meanwhile 44 screws (91.7%) in the SPC guide group (p = 0.217). The grade A screws in the SPC guide group were much more than that in the FH group (n = 40 vs. n = 31, p = 0.036). The misplacement screws (grade C, D, and E) and proximal facet joint violation (FJV) in the SPC group was comparable to the FH group.

Conclusions

This cadaveric study demonstrate that implanting CBT screws guided by SPC guide was more accuracy and reduces severe deviations in important directions.
Modification of Nias’ Cacao Pod Husk Cellulose through Carboxymethylation Stages by Using MAOS Method and Its Application as Li‐ion Batteries’ Biopolymer Electrolyte Membrane**
Authors: Ndruru Sun Theo Constan Lotebulo , Widiarto Sonny , Pramono Edi , Wahyuningrum Deana , Bundjali Bunbun , Arcana I Made
Published: November 2022

This research aimed to modify the Nias’ cacao pod husk cellulose by using Microwave‐assisted Organic Synthesis (MAOS) method to produce carboxymethyl cellulose and its application as lithium‐ion batteries’ biopolymer electrolyte membrane. There were two main stages of modification of Nias’ cacao pod husk cellulose i. e. cellulose alkalization and cellulose carboxymethylation process (etherification stage). Lithium‐ion batteries’ biopolymer electrolyte membrane was fabricated through the casting solution technique, where the blend of Methylcellulose/Carboxymethyl cellulose (MC/CMC) (80/20) (w/w) was complexed to 10 % (w/w) of lithium perchlorate. The determinations of functional groups, molecular structure, crystallinities, and thermal stability were conducted using Fourier Transform Infrared, Nuclear Magnetic Resonance, X‐Ray Diffraction, and Thermogravimetry Analysis, respectively. The lithium‐ion biopolymer electrolyte of the 10 % lithium perchlorate‐complexed MC/CMC (80/20) blend shows ionic conductivity, tensile strength/elongation at break, thermal stability are 5.91×10−3 S cm−1, 30.69 MPa/31.83 %, and 279.40–341.05 °C. Based on the results, the prepared biopolymer electrolyte of 10 % lithium perchlorate‐complexed MC/CMC (80/20) fulfills the separator (solid electrolyte) requirement for lithium‐ion battery application.
Total synthesis of selected tyrosine‐derived alkaloids: A comparative analysis of tyrosine‐based chiral pool vs other synthetic approaches
Authors: Banerjee Arpita , Chatterjee Indranil , Panda Gautam
Published: November 2022

Alkaloids are secondary metabolites and they continue to be investigated owing to their mesmerizing architectural features having potent medicinal properties. Due to the presence of stereogenic center resulting into inherent chirality and configurational integrity, alkaloids have become the area under the countless discussion in synthetic studies. In biological systems, uniqueness of tyrosine rests on phenolic −OH which acts as both hydrogen bond donor, acceptor and its aromatic ring is capable of engaging in π–π stacking interactions. Moreover, tyrosine serves as an economical and adaptable chiral pool in asymmetric synthesis of alkaloids. Herein, we discussed total syntheses of selected alkaloids via tyrosine and non‐tyrosine‐based routes along with comparison of synthetic steps based on strategy, total number of steps, use of complex reagents, overall yield, ee etc. It is first critical review about tyrosine as a chiral pool over other strategies towards alkaloids.
One‐Pot Multicomponent Synthesis of Bis(diamino‐1,3,5‐triazines) under Microwave Irradiation
Authors: Bin Shahari Muhammad Syafiq , Tiekink Edward R. T. , Dolzhenko Anton V.
Published: November 2022

A new method for the synthesis of bis(1,3,5‐triazine‐2,4‐diamines) was developed using a one‐pot multicomponent approach. The synthesis was performed using the acid‐catalyzed reaction of cyanoguanidine with amines and aldehydes, followed by dehydrogenative aromatization of the dihydrotriazine intermediates upon heating with alkali. Two types of bis(1,3,5‐triazine‐2,4‐diamines) were prepared using either piperazine as the bifunctional amine or terephthaldehyde as the bifunctional aldehyde thus affording products with a piperazine or p‐phenylene link between two 1,3,5‐triazine rings. The microwave‐assisted method allows fast and convenient synthesis of diverse bis(1,3,5‐triazine‐2,4‐diamines).
Meta‐analysis of the corporate planning–organizational performance relationship: A research note
Authors: Hamann Peter Maik , Halw Oliver , Guenther Thomas W.
Published: November 2022

Research Summary

Despite a plethora of studies, the moderating effects of contingency factors regarding the relationship between corporate planning (CP) and organizational performance (OP) remain open to discussion. Our meta‐analysis analyzes 183 independent study samples, 84 of which are examined for the first time. We expand on previous meta‐analyses by correcting for measurement error and dichotomization, and we use moderation analyses and meta‐analytical regressions to explain heterogeneity in these studies. We find evidence for the moderating effects of task interdependence and uncertainty avoidance as contingency factors. Unexpectedly, we identify an interaction of the measurements of OP and CP with uncertainty avoidance. Our results provide new insights into the relationship between CP and OP.

Management Summary

Managers who may doubt whether planning is still fruitful in turbulent times obtain a clear answer from our study: Yes, it is. CP is definitely correlated with OP. The effect sizes are stable over time and for different types of planning. However, the effect of CP on performance depends on the organizational context. Manufacturing firms benefit more than nonmanufacturing firms, and larger firms benefit more than smaller firms. Organizations in countries with high uncertainty avoidance show larger effects in relation to those in countries with low uncertainty avoidance. Finally, organizations facing high environmental uncertainty show higher effects of CP than organizations in more stable environments. However, the identified effects are conditional on the type of measurement of performance and CP.
Rutin alleviates bisphenol A‐glycidyl methacrylate‐induced generation of proinflammatory mediators through the MAPK and NF‐κB pathways in macrophages
Authors: Huang Fu‐Mei , Chang Yu‐Chao , Lee Min‐Wei , Su Ni‐Yu , Yang Li‐Chiu , Kuan Yu‐Hsiang
Published: November 2022

Bisphenol A‐glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three‐dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti‐inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti‐inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 μM for 30 min before being incubated with BisGMA at 0 or 3 μM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme‐linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA‐induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, and PGE2, in macrophages. Rutin also suppressed the BisGMA‐induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration‐dependent manner. Furthermore, rutin suppressed the mitogen‐activated protein kinase (MAPK) phosphorylation in a concentration‐dependent manner. Finally, rutin suppressed the BisGMA‐induced phosphorylation of nuclear factor (NF)‐κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF‐κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti‐inflammatory agent for BisGMA‐stimulated macrophages through NF‐κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.
Natural Language Processing
Authors: Wüthrich Mario V. , Merz Michael
Published: November 2022

This chapter discusses natural language processing (NLP) which deals with regression modeling of non-tabular or unstructured text data. We explain how words can be embedded into low-dimension spaces that serve as numerical word encodings. These can then be used for text recognition, either using RN networks or attention layers. We give an example where we aim at predicting claim perils from claim descriptions.
Appendix B: Data and Examples
Authors: Wüthrich Mario V. , Merz Michael
Published: November 2022

This chapter illustrates the data used in this book. These are a French motor third party liability (MTPL) claims data set, a Swedish motorcycle claims data set, a Wisconsin Local Government Property Insurance Fund data set, and a Swiss compulsory accident insurance data set.
Estimation Theory
Authors: Wüthrich Mario V. , Merz Michael
Published: November 2022

This chapter is on classical statistical decision theory. It is an important chapter for historical reasons, but it also provides the right mathematical grounding and intuition for more modern statistical tools from data science and machine learning. In particular, we discuss maximum likelihood estimation (MLE), unbiasedness, consistency and asymptotic normality of MLEs in this chapter.
Convolutional Neural Networks
Authors: Wüthrich Mario V. , Merz Michael
Published: November 2022

This chapter considers convolutional neural (CN) networks. These are special network architectures that are useful for time-series and spatial data modeling, e.g., applied to image recognition problems. Time-series and images have a natural topology, and CN networks try to benefit from this additional structure (over tabular data). We introduce these network architectures and provide insurance-relevant examples related to telematics data and mortality forecasting.
Components
Authors: Keller Reto B.
Published: November 2022

In order to choose the right components for EMI filters, it is essential to understand the properties and nonideal behavior of passive filter components. Therefore, in this chapter, the high-frequency behavior and other undesirable effects of conductors (wires, cables, PCB traces), resistors, capacitors, inductors, ferrite beads, common-mode chokes, baluns, varistors, and TVS diodes are presented.
Grounding
Authors: Keller Reto B.
Published: November 2022

Considering grounding in EMC is fundamental. Grounding has to be considered from the very beginning of a hardware development project. This chapter presents the basic grounding concepts and how to apply them.
RF Parameters
Authors: Keller Reto B.
Published: November 2022

This section introduces some of the most common radio-frequency (RF) parameters used in the field of EMC and high-frequency circuit design and measurement. A particular emphasis lays on the term impedance matching and distinguishing between good and poor impedance matching.
Antennas
Authors: Keller Reto B.
Published: November 2022

This chapter is a brief introduction to antennas and electromagnetic radiation, focusing on antennas for EMC tests. We skip the math intense part around Maxwell’s Equations.

The formulas and statements in this chapter apply to the far-field (not the near-field), free-space, matched impedances (of antennas and receiver/transmitter equipment), and matched polarization (of the electromagnetic waves and the antenna polarization).
The Research on English Medium Instruction and a Proposed Constructivist EMI Teaching Framework
Authors: Han Jinghe
Published: November 2022

This chapter revisits the problems and challenges in current EMI research, reflecting on issues of theoretical scope and methodological validity. It provides a summary of the findings from this research and its implications for EMI pedagogy in higher education. This Chapter concludes by proposing a practical EMI teaching framework. Its development is based on the insights gleaned from this research and the years of my experience as an EMI facilitator for academics’ professional learning in higher education settings.
Erratum zu: Theoretischer und empirischer Hintergrund
Authors: Knauf Rhea-Katharina
Published: November 2022

Ein bedauerlicher Fehler im Verlag hat dazu geführt, dass auf Seite 34 in Tabelle 1.4 ein Zahlendreher enthalten war. Dies wurde nachträglich durch den Verlag korrigiert.
Diskriminierungssensible Sprache in der Forschung zu Migration und Gesundheit – eine Handreichung
Authors: Bilgic Leman , Sarma Navina , Loer Anne-Kathrin M. , Koschollek Carmen , Bozorgmehr Kayvan , Razum Oliver , Hövener Claudia , Kajikhina Katja
Published: November 2022

Hintergrund

In der Public-Health-Forschung ist Migration als eine Determinante von Gesundheit zunehmend in den Fokus gerückt. Verantwortungsvolle Forschung in diesem Bereich setzt eine antidiskriminierende Vorgehensweise in der Durchführung, Berichterstattung und Ergebnisdissemination voraus. Ein diskriminierungssensibler Sprachgebrauch ist dabei ein zentrales Element. Handreichungen hierzu gibt es im deutschsprachigen Raum für den Bereich Public Health bisher nicht.

Methoden

Im Rahmen des ProjektesImproving Health Monitoring in Migrant Populations (IMIRA)am Robert Koch-Institut wurde eine Handreichung zu antidiskriminierender Sprache in der Forschung zu Migration und Gesundheit entwickelt, die aus einem Leitfaden und einer Übersicht über relevante Begriffe und Konzepte besteht. Die Bedarfe, Inhalte und Form dazu wurden in einem Aktionsforschungsprozess mit Projektmitarbeitenden aus demIMIRA-Projekt erarbeitet.

Ergebnisse

Der Leitfaden zeigt 5 Grundprinzipien für einen antidiskriminierenden Sprachgebrauch auf: 1. Generalisierungen und Verallgemeinerungen vermeiden, 2. diskriminierungssensibel formulieren, 3. Selbst- und Fremdbezeichnungen berücksichtigen, 4. Begriffe unterliegen einem ständigen Wandel und 5. eigene Unsicherheiten offen kommunizieren. Die Übersicht, welche online als „Living Document“ zur Verfügung steht, beinhaltet Begriffe und Konzepte, die im Zusammenhang mit dem Thema Gesundheit und Migration häufig verwendet werden.

Fazit

Die Handreichung soll Forschende dafür sensibilisieren und dabei unterstützen, Sprache antidiskriminierend anzuwenden. Dies geht mit einer Reflexion der eigenen Sprache einher und stärkt verantwortungsvolle Forschung zum Thema Migration und Gesundheit. Die Nutzung und der Nutzen der Handreichung können Gegenstand zukünftiger Evaluationen sein.
Ambulantes Langzeit-Video-EEG als neuer diagnostischer Ansatz in Deutschland: Ergebnisse einer Machbarkeitsstudie
Authors: Meisel Christian , Holtkamp Martin , Vock Simon
Published: November 2022

Das Langzeit-Video-EEG als Goldstandarddiagnostik bei Epilepsie und anderen Anfallsleiden ist in Deutschland derzeit nur in wenigen spezialisierten Zentren zur stationären Überwachung verfügbar. Diese begrenzten Überwachungskapazitäten und der damit verbundene hohe Zeit- und Arbeitsaufwand führen bundesweit zu einer erheblichen Wartezeit für diese wichtige Diagnostik. Neue, tragbare Sensortechnologien und automatisierte Datenanalysemethoden schaffen Möglichkeiten für Video-EEG-Langzeituntersuchungen nach dem Goldstandard im ambulanten Bereich, die dazu beitragen können, diese Barriere zu überwinden. Hier berichten wir über die Ergebnisse einer Machbarkeitsstudie an einem Zentrum, in der das ambulante Langzeit-Video-EEG (ALVEEG) als diagnostischer Weg in Deutschland eingeführt wurde. In dem neuen Diagnostikpfad soll der Einsatz innovativer, tragbarer Video-EEG-Monitoringsysteme zusammen mit einer durch künstliche Intelligenz unterstützten Datenanalyse den von Anfallsleiden betroffenen Patienten einen schnelleren, effizienteren und sektorübergreifenden Zugang zu einer Goldstandarddiagnostik in der häuslichen Umgebung ermöglichen. Die Diagnostik wurde von Patienten und Klinikern gut angenommen und könnte eine ergänzende Option zur stationären Überwachung darstellen, um die derzeitigen Engpässe in Diagnostik und Versorgung zu beseitigen.
Immune biology of NSCLC revealed by single-cell technologies: implications for the development of biomarkers in patients treated with immunotherapy
Authors: Wlosik J. , Fattori S. , Rochigneux P. , Goncalves A. , Olive D. , Chretien A. S.
Published: November 2022

First-line immunotherapy in non-small-cell lung cancer largely improved patients’ survival. PD-L1 testing is required before immune checkpoint inhibitor initiation. However, this biomarker fails to accurately predict patients’ response. On the other hand, immunotherapy exposes patients to immune-related toxicity, the mechanisms of which are still unclear. Hence, there is an unmet need to develop clinically approved predictive biomarkers to better select patients who will benefit the most from immune checkpoint inhibitors and improve risk management. Single-cell technologies provide unprecedented insight into the tumor and its microenvironment, leading to the discovery of immune cells involved in immune checkpoint inhibitor response or toxicity. In this review, we will underscore the potential of the single-cell approach to identify candidate biomarkers improving non-small-cell lung cancer patients’ care.
Patient characteristics, treatment patterns, and outcomes of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer patients prescribed cyclin-dependent kinase 4 and 6 inhibitors: large-scale data analysis using a Japanese claims database
Authors: Kawai Masaaki , Takada Masahiro , Nakayama Takahiro , Masuda Norikazu , Shiheido Hirokazu , Cai Zhihong , Huang Yu-Jing , Kawaguchi Tsutomu , Tanizawa Yoshinori
Published: November 2022

Purpose

The aim was to understand real-world cyclin-dependent kinase (CDK) 4 and 6 inhibitor use in Japan.

Methods

This retrospective observational study used a Japanese administrative claims database and included patients with presumptive hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) prescribed CDK4 and 6 inhibitor therapy between December 2017 and March 2021. Patient characteristics, treatment patterns, and selected clinical and safety outcomes were descriptively summarized. Time to discontinuation (TTD) and chemotherapy-free survival (CFS) were examined using Kaplan–Meier estimates.

Results

The study cohort (N = 6442) was predominantly female (99.4%; median [range] age 64 [26–99] years) with records of metastases (79.6%) within 1 year prior to initiating CDK4 and 6 inhibitor therapy. In total, 4463 (69.3%) and 1979 (30.7%) were prescribed palbociclib and abemaciclib, respectively, as their first CDK4 and 6 inhibitor, most commonly in combination with fulvestrant (n = 3801; 59.0%). Overall, 3756 patients initiated a subsequent anticancer treatment, of whom 748 (19.9%) initiated a different CDK4 and 6 inhibitor in combination with the same or different endocrine therapy. Median TTD (95% confidence interval) was 9.7 (9.3, 10.1) months for the first CDK4 and 6 inhibitor therapy. Median CFS was 26.1 (24.6, 27.8) months. Incidence of clinically relevant diarrhea was higher after abemaciclib initiation (9.8%) than after palbociclib initiation (1.5%). More patients experienced dose reduction with palbociclib (69.3%) than with abemaciclib (53.0%).

Conclusion

The data provide insights into current clinical practices for CDK4 and 6 inhibitor use in Japan that could help establish future treatment strategies for ABC.
Factors affecting in vitro regeneration in the model tree Populus trichocarpa I. Medium, environment, and hormone controls on organogenesis
Authors: Ma Cathleen , Goddard Amanda , Peremyslova Ekaterina , Duan Chenyang , Jiang Yuan , Nagle Michael , Strauss Steven H.
Published: November 2022

In preparation for a major GWAS (Genome Wide Association Study) of plant regeneration and transformation, a large number of factors were examined for their effects on indirect regeneration rate in diverse wild genotypes—seeking a high rate of regeneration, but also highly genetically variable and heritable treatments. Many of the factors examined have never before been reported on for their effects on callus, shoot, or root organogenesis in poplar (Populus). Stems had the highest regeneration potential, followed by petioles and leaves, with greenhouse grown explant sources superior to in vitro growth explant sources. Changes of ± 50% to Murashige and Skoog (MS) basal medium salts and micronutrients had a minor effect on regeneration. Many popular treatments that were evaluated also had little to no useful effect at the levels studied, including activated charcoal, ascorbic acid, silver nitrate, melatonin, serotonin, sucrose concentration, and lipoic acid. As a result of this wide exploration, treatment combinations that substantially elevated regeneration in diverse genotypes were identified, enabling GWAS.
Short-term outcomes of robot-assisted versus conventional laparoscopic surgery for mid and low rectal cancer after neoadjuvant chemoradiotherapy: a propensity score-matched analysis
Authors: Yamanashi Takahiro , Miura Hirohisa , Tanaka Toshimichi , Watanabe Akiko , Yokoi Keigo , Kojo Ken , Niihara Masahiro , Yamashita Keishi , Sato Takeo , Kumamoto Yusuke , Hiki Naoki , Naitoh Takeshi
Published: November 2022

The benefits of robot-assisted laparoscopic surgery (RALS) for rectal cancer remain controversial. Only a few studies have evaluated the safety and feasibility of RALS following neoadjuvant chemoradiotherapy (NCRT). This study aimed to compare the short-term outcomes of RALS versus conventional laparoscopic surgery (CLS) after NCRT for rectal cancer. Propensity score matching of 111 consecutive patients who underwent RALS or CLS after NCRT for rectal adenocarcinoma between February 2014 and February 2022 was performed. Among them, 60 matched patients were enrolled and their short-term outcomes were compared. Although operative time, conversion rate to open laparotomy and blood loss were comparable, the incidence of postoperative complications, including anastomotic leakage, was significantly lower, urinary retention tended to be lower, and the days to soft diet intake and postoperative hospital stay were significantly shorter in the RALS than the CLS group. No postoperative mortality was observed in either group, and there were no significant differences in terms of resection margins and number of lymph nodes dissected. RALS after NCRT for rectal cancer is safe and technically feasible, and has acceptable short-term outcomes. Further studies are required for validation of the long-term oncological outcomes.
Populist radical right parties and discursive opportunities during Covid-19. Blame attribution in times of crisis
Authors: Schwörer Jakob , Fernández-García Belén
Published: November 2022

This study examines how populist radical right parties (PRRP) adapt to the discursive opportunities delivered by the Covid-19 pandemic. Conducting manual content analyses of discourses on Twitter in six Western European countries between February and October 2020 we show that PRRP frame the pandemic as a domestic political crisis attacking primarily national political elites. While PRRP occasionally link their initial support for measures against the pandemic to blame attribution towards immigrants accusing them of spreading the virus, nativist messages almost disappear when PRRP became less supportive of restrictions. Instead, in countries less affected by the pandemic (Austria, Germany) as well as in Spain, PRRP compensate the lack of nativist messages by using anti-elitist demonizing discourses against the national government accusing it of abolishing democracy and undermining freedom. The study shows how PRRP electorally “survive” periods with scarce nativist discursive opportunities by emphasizing on anti-elitist discourses.
Identification of Explainable Structures in Data with a Human-in-the-Loop
Authors: Thrun Michael C.
Published: November 2022

Explainable AIs (XAIs) often do not provide relevant or understandable explanations for a domain-specific human-in-the-loop (HIL). In addition, internally used metrics have biases that might not match existing structures in the data. The habilitation thesis presents an alternative solution approach by deriving explanations from high dimensional structures in the data rather than from predetermined classifications. Typically, the detection of such density- or distance-based structures in data has so far entailed the challenges of choosing appropriate algorithms and their parameters, which adds a considerable amount of complex decision-making options for the HIL. Central steps of the solution approach are a parameter-free methodology for the estimation and visualization of probability density functions (PDFs); followed by a hypothesis for selecting an appropriate distance metric independent of the data context in combination with projection-based clustering (PBC). PBC allows for subsequent interactive identification of separable structures in the data. Hence, the HIL does not need deep knowledge of the underlying algorithms to identify structures in data. The complete data-driven XAI approach involving the HIL is based on a decision tree guided by distance-based structures in data (DSD). This data-driven XAI shows initial success in the application to multivariate time series and non-sequential high-dimensional data. It generates meaningful and relevant explanations that are evaluated by Grice’s maxims.
Alternatives to Adjudication in International Law: A Case Study of the Ombudsperson to the ISIL and Al-Qaida Sanctions Regime of the UN Security Council
Authors: Lang Andrej
Published: November 2022

The “temporary golden age” of international courts is likely over. States seeking to provide oversight mechanisms and individual remedies at the international level are likely to opt for less intrusive and more flexible alternatives to adjudication. This Article analyzes the phenomenon of international complaint mechanisms through a detailed case study of the Ombudsperson to the ISIL and Al-Qaida sanctions regime. The analysis reveals an in-built tension between principle and pragmatism: the Ombudsperson's institutional design falls short of the requirements that are essential for adjudication, but it nevertheless proves to be a surprisingly effective remedy for persons wrongfully listed. The Article makes the case for the establishment of such bodies, despite some of their inherent shortcomings.
Looking beyond challenging student behaviour: Utilising the teacher relationship interview
Authors: Spilt Jantine L. , Koomen Helma M. Y.
Published: November 2022

Intervention is considered the ultimate goal of the diagnostic process. However, when diagnostic assessment is largely focused on student (mal)adjustment and when the role and perspective of the teacher is not systematically evaluated, the assessment may fail to generate useful recommendations for intervention or teacher consultation. Based on a descriptive case report, the potential contribution of the Teacher Relationship Interview in making the assessment phase more relevant to intervention is outlined and illustrated.
Coexistence and correlates of forms of malnutrition among mothers and under-five child pairs in Tanzania
Authors: Faustini Fina T. , Mniachi Ali R. , Msengwa Amina S.
Published: November 2022

Improving the health and well-being of mothers and children is a priority worldwide. The present study aimed to examine the coexistence and correlates of malnutrition among mothers and under-five child pairs using Tanzania Demographic Health Survey 2015–16 data. Height-for-age, height-for-weight and weight-for-age Z-scores were used to assess the nutritional status of children, while body mass index was used to assess the nutritional status of mothers. Correlates of forms of malnutrition were assessed using multinomial logistic regression. Among 8083 pairs, 40⋅9 % were normal, 30⋅3 % were underweight, 17⋅5 % overweight and 11⋅3 % had double burden of malnutrition. The risk of being underweight is highest among the pairs with; children aged 13–59 months (relative risk ratio (RRR) = 2⋅33) and children with small birth weight (RRR = 2⋅67). Overweight is highest among pairs with; mothers aged 35–49 (RRR = 3⋅36), mothers with secondary education and above (RRR = 1⋅85), fathers aged 35+ (RRR = 1⋅38), professional fathers (RRR = 4⋅10) and richer households (RRR = 2⋅06). The double burden of malnutrition is highest among pairs with; children with small birth weight (RRR = 2⋅76), from rural households (RRR = 1⋅24) and from richer households (RRR = 1⋅41). There is a coexistence of forms of malnutrition among mothers and under-five child pairs in Tanzania. The study recommends using multidimensional approaches such as double-duty action for nutrition to eradicate all forms of malnutrition.
Risk and demand for social protection in an era of populism
Authors: Baldwin Kate , Mares Isabela
Published: November 2022

Economic and health crises have profound political consequences for public support for social policy, historically setting in motion a massive expansion of governmental programs. Is demand for social protection likely to increase among citizens exposed to risk in an era in which populist messages are prominent? We show that this depends critically on the precise targets that populists evoke as enemies of the people. We distinguish between two types of political rhetoric deployed by populist politicians in their claims to represent the authentic people—one opposing the authority of domestic elites, including technocrats, and one attacking foreigners. We examine the extent to which each rhetorical strategy reduces or enhances popular demand for social policies by randomly exposing Americans to these frames as part of a public opinion survey conducted during the Covid-19 pandemic. Our results show that the two messages have different consequences for support for redistribution among respondents exposed to risk: populist anti-foreign rhetoric that blames foreign countries for the onset of the pandemic increases demand for expansion of social protection compared to populist anti-elite rhetoric.
THE LANGUAGE OF ROADS AND TRAVEL IN HOMER: HODOS AND KELEUTHOS
Authors: Folit-Weinberg Benjamin
Published: November 2022

The aim of this article is to map the relationship between the main words that comprise the Homeric lexicon of roads, journeys, paths and travel. The central task is to explore the relationship between the words hodos and keleuthos; along the way, the article will also address other terms that appear less frequently, such as atarp(it)os and poros. The article first teases out a difference in sense between keleuthos in the singular and in the plural. The discussion of keleuthos provides a key distinction, namely between ‘object-concepts’ and ‘activity-concepts’, that proves valuable in discussing different senses of the word hodos. Rather than differentiating the words keleuthos and hodos as others have suggested, however, this distinction should be used to differentiate domains of meaning within each word. The result will be what might be conceived of as a four-part grid, with the two words hodos and keleuthos split into two distinct parts along the ‘activity-concept’/‘object-concept’ axis. Finally, concepts drawn from discussions of verbal aspect and philosophy of action are deployed heuristically to develop further the analysis of this semantic field.
Dirichlet vs Neumann
Authors: Marušić-Paloka Eduard
Published: November 2022

We study the asymptotic behaviour of the periodically mixed Zaremba problem. We cover the part of the boundary by a chess board with a small period (square size) $\varepsilon$ and impose the Dirichlet condition on black and the Neumann condition on white squares. As $\varepsilon \to 0$, we get the effective boundary condition which is always of the Dirichlet type. The Dirichlet data on the boundary, however, depend on the ratio between the magnitudes of the two boundary values.
Famines in the manorial economy of eighteenth-century Poland
Authors: Miodunka Piotr
Published: November 2022

On the basis of eight available terriers of a large royal estate of Niepołomice in southern Poland and of the vital records of two parishes located on its area, all dating from the early eighteenth century, this article examines the effect of famines on the economic situation of both feudal lords and their peasant tenants. The restrictive framework of the second serfdom in Poland did not prevent two severe mortality crises at the time triggered by crop failures. The key hazards caused by the famines for demesne economy were shortages of corvée labour and peasant-owned draught animals. While the famine mortality that affected the peasants reported as farmers in the terriers was not high, the famines were conducive to peasant impoverishment and reshuffled groups of various financial statuses.
EMT Response in COVID-19 Pandemic: Best Practices from Deployment of UK-MED and PCPM’s EMTs
Authors: Vadi Ramnath , Wilk Wojtek
Published: November 2022

Background/Introduction:

As part of EU (Horizon 2020) HERoS program, UK-MED and PCPM compiled main operational difficulties faced by the two EMTs in 25 and seven COVID-19 deployments, respectively. In particular, the paper discusses the changing role of EMTs, as well as challenges faced in meeting high expectations of the respective Ministries of Health (MOH).

Objectives:

Documenting challenges faced by EMTs in COVID-19 response, lessons learned, and best practices.

Method/Description:

Review of mission reports; interviews with mission members; input from other EMTs (TBC).

Results/Outcomes:

The paper lists best practices of the two EMTs and recommendations to donors and EMT Secretariat, particularly linked to mission duration and collaboration with MOH.

Conclusion:

The paper lists best practices of the two EMTs and recommendations to donors and EMT Secretariat, particularly linked to mission duration and collaboration with MOH.
Violence Against Health Care in Nigeria and South Sudan: Frontline Health Worker Perspectives on Threats and Solutions
Authors: Adams Ali , Ojemu Francis , Ogueji Okechi , Tax Leonie
Published: November 2022

Background/Introduction:

Health staff in South Sudan and Nigeria face extreme risks while providing services: in 2021, at least 18 health care workers were killed in South Sudan and Nigeria, while 32 were kidnapped. Reporting of such incidents takes place via the WHO coordinated SS. However, such event reporting is not designed to capture “lower scale” security incidents, nor does it capture possible solutions. As such, the IRC in coordination with the Health Cluster and national organizations are conducting a survey to complement the existing analysis with insights of frontline health care workers, to support program design, funding requests, and advocacy activities. Research questions include:

What are the most common incidents of violence against health care workers?

What has been the impact of these incidents on staff well-being, on the health system/sector, and on access to health care for the wider community?

What are the priorities in preventing such incidents and reducing their impact?

Objectives:

To identify incidents of violence against health care as experienced by health care staff in 2022.

To identify health workers perspective on causes, impact, and what works in terms of prevention and response.

Method/Description:

A self-administered, online survey targeting all health staff working for the humanitarian community in South Sudan and Northeastern Nigeria.

Results/Outcomes:

This study is on-going with results expected by early September.

Conclusion:

This study is on-going with results expected by early September.
WHO Emergency Medical Teams Minimal Data Set in Conflict-Stricken Ukraine: Comparative Analysis of a New Primary Health Care Coding Tool
Authors: Armitage Richard , Afonso Ana Teresa
Published: November 2022

Background/Introduction:

The WHO EMT Minimum Data Set (EMT-MDS) was designed for data collection in sudden-onset disasters. Using EMT-MDS in the context of primary health care (PHC) generated large quantities of low granularity data that threatened the successful delivery of UK-Med’s clinical programs in Ukraine. Accordingly, UK-Med developed, piloted, and implemented a new coding tool (PHC-CT) tailored to PHC presentations prevalent in humanitarian settings.

Objectives:

To assess the performance of EMT-MDS and PHC-CT in the generation of programmatically-useful diagnostic codes from data collected in mobile PHC clinics in Ukraine during active conflict.

To compare the performance of EMT-MDS and PHC-CT in this setting and to suggest recommendations for data collection tool improvements.

Method/Description:

After multiple iterations, the final version of PHC-CT was used to collect clinical data from all UK-Med clinical encounters in Ukraine from March 28, 2022-May 13, 2022. Clinical data using EMT-MDS were collected simultaneously. The prevalence of each diagnostic code was calculated using both EMT-MDS and PHC-CT, expressed as a proportion of the total diagnoses, and compared between the two coding tools.

Results/Outcomes:

1,390 clinical encounters took place during the study. Data coded using EMT-MDS generated 1,756 diagnoses (86.8% of total diagnoses) categorized as “Other Diagnosis” while the same data coded using PHC-CT generated 37 diagnoses (1.8% of total diagnoses) categorized as “Other Diagnosis.” Only seven of the available 25 diagnostic codes in EMT-MDS were used, while 48 of the 67 available diagnostic codes in PHC-CT were used.

Conclusion:

PHC-CT offers substantial benefits beyond those provided by EMT-MDS when utilized in mobile PHC clinics in humanitarian settings.

Tables and Figures (optional)

Table 1.

Number of Clinical Encounters, Unique Diagnoses, and Frequency of Selected Diagnostic Codes for EMT-MDS and PHC-CT. (Note: % refers to proportion of diagnoses made)
Sharing of Best Practices from an Emergency Medical Team Deployment in Papua New Guinea: Piloting a Health Promotion Program Targeting COVID-19 Vaccine Uptake
Authors: Vadi Ramnath , Maddah Diana , Marmont Lizzi
Published: November 2022

Background/Introduction:

COVID-19 tremendously affected Papua New Guinea in late 2021, which accompanied by a low vaccination rate (<4%), lead to an International EMT Request for Assistance.

Objectives:

Study’s aim is to share how UK-Med, a part of the UK EMT, developed best practices related to risk communication and community engagement integration within a COVID-19 emergency response.

Method/Description:

A participatory health promotion program was piloted in Western Highland Province among 71 health care workers. Training of trainers approach was adopted to build the capacity of health workers in advocating for vaccines uptake. Perception survey was used at the baseline and at the end of the program to assess the knowledge, skills, and attitude of the participants towards COVID-19 vaccine acceptance. A descriptive analysis and paired t-test were used.

Results/Outcomes:

Health care professionals are not well-equipped with accurate, scientific, and up-to-date information related to COVID-19 vaccines; which leads to increase in concern and fear among them. Health care workers affect community members’ decision to take the COVID-19 vaccine, being viewed as referents within their communities. The paired t-test showed a significant increase in the knowledge, skills, and attitude (P value <.001) of the participants toward COVID-19 vaccines. Participants described being ready to engage community influencers and cascade training to further reach out to community groups.

Conclusion:

Integrating RCCE within EMT deployments plays a crucial role in leveraging health care capabilities to influence community members and advocate for COVID-19 vaccines uptake; which will ultimately decrease morbidity and mortality. Further research is required to strengthen the role of health promotion in emergencies.