bluuebunny/crossref_metadata_2025 huggingface dataset:
Applications of Fuzzy Theory-Based Approaches in Tunnelling Geomechanics: a State-of-the-Art Review
Authors: Madanda Vhutali Carol , Sengani Fhatuwani , Mulenga François
Published: May 2023

The first introduction of fuzzy theory in the nineteenth century created room for continuous research and application in various fields. Fuzzy set theory has been globally applied in geotechnical engineering, and research in this field continues to date. The fuzzy inference system is considered to be one of the most popular techniques adopted to resolve some of the geomechanical challenges faced in both surface and underground excavations. This paper unpacks fuzzy theory-based approaches in mine geomechanics with the aim of expanding the innovative application of the same approach specifically in tunnel geomechanics. This aim was achieved by conducting a review of recent successful and unsuccessful applications of fuzzy inference systems in underground excavations/tunnelling geomechanics. Indeed, this review has outlined some cardinal points associated with the ability of the technique to solve complex geomechanics problems. However, the success of the technique was accompanied by a few limitations associated with the methodology. Finally, a future outlook associated with the technique has been established.
Flying against the clock – risk management and resilience in Arctic search and rescue and casualty evacuation flights
Authors: Ash John
Published: May 2023

Despite the successful conclusion of the 2011 Arctic Search and Rescue Agreement, the resources available for search and rescue operations in the High North remain limited. Rescue flights are time critical. Survival times – especially in the Arctic – are severely curtailed by the environment. At the same time, clinical evidence supports the need to provide critical casualty care within the first, or ‘golden’ hour following injury. The selection, training and management of personnel lies at the heart of addressing the risks attendant upon both flying and rendering appropriate casualty care under such circumstances. Despite technological advances, human decisions remain pivotal. This paper examines recent advances in decision enhancement techniques and their application in improving the safety and resilience of future Arctic rescue flight operations.
Doing Archaeology without Strings
Authors: Hazell Sarah M. , Hawkins Alicia L.
Published: May 2023

In the province of Ontario, Canada, it is estimated that 80% of archaeological sites are Indigenous, yet there are very few Indigenous archaeologists involved in management and decision-making about Indigenous heritage. Systemic barriers, particularly around licensing and regulations for curatorial facilities, continue to prevent Indigenous people from directly managing and protecting their own cultural heritage. Recognizing that Indigenous communities in northeastern Ontario have had little exposure or opportunity to learn about archaeology, for several years we have been involved in educational programs to train Indigenous youth, staff in First Nations government offices, and others. We illustrate with two examples: the monitor training program undertaken in northeastern Ontario and a project to catalog artifacts from the legacy collection from the La Cloche site.
Distributional weighting and welfare/equity tradeoffs: a new approach
Authors: Acland Daniel J. , Greenberg David H.
Published: May 2023

There are increasing calls for concrete suggestions on how to account for distributional impacts in policy analysis. Within the context of benefit-cost analysis, per se, one possibility is to apply “distributional weights,” to inflate costs and benefits experienced by poor or disadvantaged groups. We distinguish between “utility-weights,” intended to correct for the bias in willingness to pay caused by diminishing marginal utility of income, and “equity-weights,” intended to account for the possibility that decision makers might have disproportional concern about the welfare of the poor or other disadvantaged groups. We argue that utility-weights are appropriate and necessary to maintain the legitimacy of BCA as a measure of aggregate welfare, but that equity-weights are inappropriate because they involve moral judgments that should remain in the domain of democratically accountable decision makers, and because they conflate information about both the welfare and equity impacts of policies, making it impossible for decision-makers to apply their own moral values to the assessment of tradeoffs between welfare and equity. We offer concrete suggestions regarding the application of utility-weights and the calculation of a set of metrics to provide intuitively comprehensible and useful information about, and allow decision makers to quantitatively assess the tradeoffs between, welfare and equity caused by specific policies.
Equidistribution for matings of quadratic maps with the modular group
Authors: MATUS DE LA PARRA V.
Published: May 2023

We study the asymptotic behavior of the family of holomorphic correspondences
$\lbrace \mathcal {F}_a\rbrace _{a\in \mathcal {K}}$
, given by
$$ \begin{align*}\bigg(\frac{az+1}{z+1}\bigg)^2+\bigg(\frac{az+1}{z+1}\bigg)\bigg(\frac{aw-1}{w-1}\bigg)+\bigg(\frac{aw-1}{w-1}\bigg)^2=3.\end{align*} $$
It was proven by Bullet and Lomonaco [Mating quadratic maps with the modular group II. Invent. Math.220(1) (2020), 185–210] that
$\mathcal {F}_a$
is a mating between the modular group
$\operatorname {PSL}_2(\mathbb {Z})$
and a quadratic rational map. We show for every
$a\in \mathcal {K}$
, the iterated images and preimages under
$\mathcal {F}_a$
of non-exceptional points equidistribute, in spite of the fact that
$\mathcal {F}_a$
is weakly modular in the sense of Dinh, Kaufmann, and Wu [Dynamics of holomorphic correspondences on Riemann surfaces. Int. J. Math.31(05) (2020), 2050036], but it is not modular. Furthermore, we prove that periodic points equidistribute as well.
The extreme right and the democratic institutions in Italy. The response of the regions to a national and trans-national phenomenon (1973–1975)
Authors: Borri Michelangelo , Marinelli Valerio
Published: May 2023

This essay aims to analyse the presence of neofascist organisations and far-right terrorism in Italy in the early 1970s from a new perspective. Firstly, it will focus on the activities to combat the subversive structures of the ‘black galaxy’ carried out by regional institutions through the creation of special ‘regional commissions of inquiry on the problems of neofascism’. Between 1974 and 1975, these commissions carried out an extensive inventory of the movements, associations and organisations of the Italian far right. Their aim was to show the spread of the phenomenon and its local roots. Building upon the information gathered by the regional commissions, the essay will analyse the relationships between the various far-right groups in Italy and their European counterparts. The final part of the article will focus on the influence of local specificities in defining the relations between extremist movements beyond national borders.
Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene–environment interactions in patients with autoimmune thyroiditis
Authors: Zhou Zheng , Jin Meihui , Li Baoxiang , He Yanhong , Liu Lixiang , Ren Bingxuan , Li Jianshuang , Li Fan , Liu Jinjin , Chen Yun , Wan Siyuan , Shen Hongmei
Published: May 2023

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene–environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.
Depression and risk of gastrointestinal disorders: a comprehensive two-sample Mendelian randomization study of European ancestry
Authors: Chen Dongze , Zhang Yali , Huang Tao , Jia Jinzhu
Published: May 2023

Background

Major depressive disorder (MDD) is clinically documented to co-occur with multiple gastrointestinal disorders (GID), but the potential causal relationship between them remains unclear. We aimed to evaluate the potential causal relationship of MDD with 4 GID [gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), peptic ulcer disease (PUD), and non-alcoholic fatty liver disease (NAFLD)] using a two-sample Mendelian randomization (MR) design.

Methods

We obtained genome-wide association data for MDD from a meta-analysis (N = 480 359), and for GID from the UK Biobank (N ranges: 332 601–486 601) and FinnGen (N ranges: 187 028–218 792) among individuals of European ancestry. Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses to test the hypothesis of MR. Individual study estimates were pooled using fixed-effect meta-analysis.

Results

Meta-analyses IVW MR found evidence that genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Additionally, reverse MR found evidence of genetically predicted GERD or IBS may increase the risk of MDD.

Conclusions

Genetically predicted MDD may increase the risk of GERD, IBS, PUD and NAFLD. Genetically predicted GERD or IBS may increase the risk of MDD. The findings may help elucidate the mechanisms underlying the co-morbidity of MDD and GID. Focusing on GID symptoms in patients with MDD and emotional problems in patients with GID is important for the clinical management.
Theorizing about Christian faith in God with John Bishop
Authors: McKaughan Daniel J. , Howard-Snyder Daniel
Published: May 2023

We assess John Bishop's theory of the nature of Christian faith in God, as most recently expressed in ‘Reasonable Faith and Reasonable Fideism’, although we dip into other writings as well. We explain several concerns we have about it. However, in the end, our reflections lead us to propose a modified theory, one that avoids our concerns while remaining consonant with some of his guiding thoughts about the nature of Christian faith in God. We also briefly examine three normative issues Bishop's views present.
Kababurun: investigations of an eastern Aegean village in the Late Chalcolithic to Early Bronze Age transition
Authors: Çilingiroğlu Çiler , Schwall Christoph , Sezgin Ece , Çakırlar Canan
Published: May 2023

The Late Chalcolithic and Early Bronze Age (EBA) 1 are dynamic prehistoric eras, encapsulating crucial political, social and economic developments in western Anatolia and the adjacent regions. Although recent fieldwork and synthesis on this transition in western Turkey provide a general framework for this important transitional period, we still lack a holistic understanding of settlement types, subsistence patterns and socio-economic interaction zones. Discovery of the coastal site of Kababurun during surveys on the Karaburun Peninsula enhances understanding of the Late Chalcolithic–EBA 1 transition by providing data on settlement characteristics, material technologies and subsistence strategies. Kababurun is currently the only absolutely dated prehistoric site in the Karaburun Peninsula, offering a reliable chronological basis for comparisons in the region and beyond. In this article, we first introduce and then contextualise the Kababurun data within the eastern Aegean and western Anatolian research problems, then discuss how that data might contribute to a more refined understanding of Late Chalcolithic to EBA 1 communities. In particular, we argue that the site of Kababurun represents a form of community that is vitally important but poorly understood for this period: a small-scale rural settlement, connected to local networks but without a specialised function.
Surrogacy and the Fiction of Medical Necessity
Authors: Baron Teresa
Published: May 2023

A number of countries and states prohibit surrogacy except in cases of “medical necessity” or for those with specific medical conditions. Healthcare providers in some countries have similar policies restricting the provision of clinical assistance in surrogacy. This paper argues that surrogacy is never medically necessary in any ordinary understanding of this term. The author aims to show first that surrogacy per se is a socio-legal intervention and not a medical one and, second, that the intervention in question does not treat, prevent, or mitigate any actual or potential harm to health. Legal regulations and healthcare-provider policies of this kind therefore codify a fiction—one which both obscures the socio-legal motivations for surrogacy and inhibits critical examination of those motivations while mobilizing normative connotations of appeals to medical need. The persisting distinction, in law and in moral discourse, between “social” and “medical” surrogacy, is unjustified.
Die Entwicklung der Rolle einer Advanced Practice Nurse (APN) für das Ernährungsmanagement
Authors: Möcking Kerstin , Hosters Bernadette
Published: May 2023

Zusammenfassung. Hintergrund: Pflegefachpersonen wird eine Schlüsselrolle im Ernährungsmanagement zugeschrieben. Dieser Bereich wurde als ein Schwerpunkt der Entwicklung einer Advanced Nursing Practice identifiziert. Ziel: Bedarfsanalyse zum Rollenprofil einer Advanced Practice Nurse (APN) entsprechend dem PEPPA-Rahmenmodell. Methodik: Mixed Methods-Design. In einer Querschnittserhebung zum Ist-Stand wurde die diagnostische Genauigkeit des pflegerischen Ernährungsscreenings mittels Nutritional Risk Screening (NRS 2022) im Vergleich zur Einschätzung durch eine Ernährungsexpertin mittels NRS 2022 untersucht. Bei positivem Befund wurden Gründe mithilfe eines vertieften Assessments ermittelt. Ergänzend wurden halbstrukturierte, leitfadengestützte Interviews geführt und inhaltsanalytisch ausgewertet. Ergebnisse: Die Identifikation von Risikopatient_innen im pflegerischen Screening wies Verbesserungsbedarf auf (Sensitivität: 56%, Spezifität: 96%; n = 195). Häufig identifizierte Gründe (des Risikos) einer Mangelernährung ( n = 51) waren die fehlende Lust zum Essen/Appetitlosigkeit oder ein krankheitsbedingter erhöhter Bedarf. Entwicklungsmöglichkeiten und Erwartungen an eine APN wurden anhand der Interviews ( n = 20) konkretisiert. Sie beziehen sich auf Kompetenzerweiterung, Support im interprofessionellen Team bei komplexen Behandlungsfällen und einer stärkeren pflegerischen Rolle im Ernährungsmanagement. Schlussfolgerungen: Anhand der Bedarfsanalyse konnten Aufgabenbereiche der APN benannt, dem Modell nach Hamric zugeordnet und Umsetzungsstrategien abgeleitet werden.
Einfluss der digitalen Dokumentation auf die Arbeitszeit und den Arbeitsablauf auf der Intensivstation
Authors: Zoller Richard , Weiß Claudia , Kießling Patrick Joachim , Wittmann Maria
Published: May 2023

Zusammenfassung: Hintergrund: Die Einführung digitaler Patientendokumentationssysteme im Krankenhaus und auf den Intensivstationen nimmt in Deutschland zu. Die Auswirkungen dieser Systeme auf den Workflow der Pflegefachpersonen sind kaum untersucht. Ziel: Analysiert wird, wie hoch der Arbeitsaufwand mit einem digitalen Dokumentationssystem im Vergleich zur papiergestützten Dokumentation ist, wie sich der Workflow ändert und wie die digitale Dokumentation im Vergleich zur papiergestützten hinsichtlich Nutzbarkeit, zeitlichem Aufwand und Dokumentationsqualität bewerten wird. Methoden: Vor (to) und nach Einführung des digitalen Patientendokumentationssytems (t1) wurde die Zeit für die Dokumentation und die Dokumentationshäufigkeit in einer prospektiven Prä-Post-Beobachtungsstudie mit Hilfe einer eigens dafür konfigurierten App gemessen und beide Erhebungszeiträume statistisch verglichen (Mann-Whitney-U-Test). Des Weiteren wurde eine Befragung der Pflegefachpersonen zur digitalen Patientendokumentation durchgeführt. Ergebnisse: Die Arbeitszeit für die Dokumentation bleibt nach der Digitalisierung gleich. Allerdings geben 80% der Befragten an, die Dokumentationszeit hätte sich verringert. Außerdem sinkt die Anzahl der Dokumentationsvorgänge signifikant (p = 0,03). Zusätzlich wird mehrheitlich (55 %) eine Erhöhung der Dokumentationsqualität angegeben. Schlussfolgerungen: Eine digitale Patientendokumentation spart nicht zwingend Arbeitszeit, defragmentieren aber den Ablauf der Dokumentationsarbeit und hat das Potential, den Dokumentationsworkflow positiv zu beeinflussen.
On a Scientific Approach for Deep Time Investigations
Authors: Harrison T. Mark
Published: May 2023

I came to geology through a metaphoric back door and was gifted a series of visionary mentors who imbued me with an outside‐the‐box view of Earth history. Coupled with remarkable advances in microscale analytical capabilities that arose just as I was graduating into the field, that unorthodox view permitted my research group to explore an alternate conception of the longstanding paradigm of earliest Earth history. As I look back on how the field has evolved in my 40 year career, I see a mixed record of significant advances in our understanding alongside a persistent groupthink that discourages creativity and individual responsibility. I've come to understand this as reflecting different intellectual requirements of deep time geology relative to the study of modern processes. This difference between the general understanding of the scientific method and our needs has given cover to an unconstructive habit. My field is ripe for a fundamental change in the way we address the meager and almost certainly biased geologic record. This disruption could lead younger scientists and future generations away from poorly justified consensus models toward a more complete understanding of the darkest age of our planet's history.
Validation of OMPS Suomi NPP and OMPS NOAA‐20 Formaldehyde Total Columns With NDACC FTIR Observations
Authors: Kwon H.‐A. , Abad G. González , Nowlan C. R. , Chong H. , Souri A. H. , Vigouroux C. , Röhling A. , Kivi R. , Makarova M. , Notholt J. , Palm M. , Winkler H. , Té Y. , Sussmann R. , Rettinger M. , Mahieu E. , Strong K. , Lutsch E. , Yamanouchi S. , Nagahama T. , Hannigan J. W. , Zhou M. , Murata I. , Grutter M. , Stremme W. , De Mazière M. , Jones N. , Smale D. , Morino I.
Published: May 2023

We validate formaldehyde (HCHO) vertical column densities (VCDs) from Ozone Mapping and Profiler Suite Nadir Mapper (OMPS‐NM) instruments onboard the Suomi National Polar‐orbiting Partnership (Suomi NPP) satellite for 2012–2020 and National Oceanic and Atmospheric Administration‐20 (NOAA‐20) satellite for 2018–2020, hereafter referred to as OMPS‐NPP and OMPS‐N20, with ground‐based Fourier‐Transform Infrared (FTIR) observations of the Network for the Detection of Atmospheric Composition Change (NDACC). OMPS‐NPP/N20 HCHO products reproduce seasonal variability at 24 FTIR sites. Monthly variability of OMPS‐NPP/N20 has a very good agreement with FTIR, showing correlation coefficients of 0.83 and 0.88, respectively. OMPS‐NPP (N20) biases averaged over all sites are −0.9 (4) ± 3 (6)%. However, at clean sites (with VCDs < 4.0 × 1015 molecules cm−2), positive biases of 20 (32) ± 6 (18)% occur for OMPS‐NPP (N20). At sites with HCHO VCDs > 4.0 × 1015 molecules cm−2, negative biases of −15% ± 4% appear for OMPS‐NPP, but OMPS‐N20 shows smaller bias of 0.5% ± 6% due to its smaller ground pixel footprints. Therefore, smaller satellite footprint sizes are important in distinguishing small‐scale plumes. In addition, we discuss a bias correction and provide lower limit for the monthly uncertainty of OMPS‐NPP/N20 HCHO products. The total uncertainty for OMPS‐NPP (N20) at clean sites is 0.7 (0.8) × 1015 molecules cm−2, corresponding to a relative uncertainty of 32 (30)%. In the case of HCHO VCDs > 4.0 × 1015 molecules cm−2, however, the relative uncertainty in HCHO VCDs for OMPS‐NPP (N20) decreases to 31 (18)%.
Radial Transport of Io Plasma From the Inner Magnetosphere to the Tail
Authors: Tanaka T. , Ebihara Y. , Watanabe M. , Fujita S. , Kataoka R.
Published: May 2023

The solar wind‐Jovian magnetosphere‐ionosphere interaction is studied from the global magnetohydrodynamic simulation. The calculation considers the high‐speed solar wind, Io plasma emission, high‐speed rotation, ionospheric ions, and precession of magnetic field, and consequently reproduces the confinement of Jovian magnetic field, distributions of O+ and H+, supply of H+ by the polar wind, the interchange instability, and the current system that maintains co‐rotation. The radial transport process of plasma generated from Io is traceable from this solution, such that the transport mechanism gradually changes from the Io torus to the distant tail. In the transport of Io plasma, the precession plus interchange instability is effective near 10–15 Rj, interchange instability is predominant around 15–20 Rj, and the centrifugal force is predominant beyond 25 Rj. The current system supplies torque from the planet to co‐rotating plasma beyond 25 Rj to compensate the rotation delay. The associated upward field‐aligned current (FAC) is connected to the main emission (ME) in the ionosphere. The polar emission (PE) position coincides with that of downward feedback current of upward FAC causing the ME. High‐speed polar wind develops in the ME and in the polar cap, while slow polar wind develops in lower latitudes. In the middle of transport, Io plasma is mixed around 15 Rj with H+ supplied from the ionosphere by the low‐speed polar wind. Afterward, mixed plasma diffuses outward. The equatorial diffuse emission occurs in the projected position of the plasma mixing process.
RUNX1 mutation has no prognostic significance in paediatric AML: a retrospective study of the AML-BFM study group
Authors: Sendker Stephanie , Awada Amani , Domagalla Sophia , Sendker Michael , Orhan Eser , Hoffmeister Lina Marie , Antoniou Evangelia , Niktoreh Naghmeh , Reinhardt Dirk , von Neuhoff Nils , Schneider Markus
Published: May 2023

In acute myeloid leukaemia (AML) RUNX1 mutation is characterised by certain clinicopathological features with poor prognosis and adverse risk by the European LeukemiaNet recommendation. Though initially considered as provisional category, the recent World Health Organisation (WHO) classification of 2022 removed RUNX1-mutated AML from the unique entity. However, the significance of RUNX1 mutation in paediatric AML remains unclear. We retrospectively analysed a German cohort of 488 paediatric patients with de novo AML, enroled in the AMLR12 or AMLR17 registry of the AML-BFM Study Group (Essen, Germany). A total of 23 paediatric AML patients (4.7%) harboured RUNX1 mutations, 18 of which (78%) had RUNX1 mutation at initial diagnosis. RUNX1 mutations were associated with older age, male gender, number of coexisting alterations and presence of FLT3-ITD but mutually exclusive of KRAS, KIT and NPM1 mutation. RUNX1 mutations did not prognostically impact overall or event-free survival. Response rates did not differ between patients with and without RUNX1 mutations. This comprehensive study, comprising the largest analysis of RUNX1 mutation in a paediatric cohort to date, reveals distinct but not unique clinicopathologic features, with no prognostic significance of RUNX1-mutated paediatric AML. These results broaden the perspective on the relevance of RUNX1 alterations in leukaemogenesis in AML.
SUMO specific peptidase 3 halts pancreatic ductal adenocarcinoma metastasis via deSUMOylating DKC1
Authors: Wu Xiao , Li Jian-Hui , Xu Long , Li Ya-Xiong , Zhu Xiao-Xu , Wang Xi-Yu , Wu Xingmei , Zhao Wei , Ni Xuhao , Yin Xiao-Yu
Published: May 2023

In the past few decades, advances in the outcomes of patients suffering from pancreatic ductal adenocarcinoma (PDAC) have lagged behind these gained in the treatment of many other malignancies. Although the pivotal role of the SUMO pathway in PDAC has been illustrated, the underlying molecule drivers have yet to be fully elucidated. In the present study, we identified SENP3 as a potential suppressor of PDAC progression through an in vivo metastatic model. Further studies revealed that SENP3 inhibited PDAC invasion in a SUMO system dependent fashion. Mechanistically, SENP3 interacted with DKC1 and, as such, catalyzed the deSUMOylation of DKC1, which accepted SUMO3 modifiers at three lysine residues. SENP3-mediated deSUMOylation caused DKC1 instability and disruption of the interaction between snoRNP proteins, which contributed to the impaired migration ability of PDAC. Indeed, overexpression of DKC1 abated the anti-metastasis effect of SENP3, and DKC1 was elevated in PDAC specimens and associated with a poor prognosis in PDAC patients. Collectively, our findings shed light on the essential role of SENP3/DKC1 axis in the progression of PDAC.
Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial
Authors: Nassiri Farshad , Patil Vikas , Yefet Leeor S. , Singh Olivia , Liu Jeff , Dang Rachel M. A. , Yamaguchi Takafumi N. , Daras Mariza , Cloughesy Timothy F. , Colman Howard , Kumthekar Priya U. , Chen Clark C. , Aiken Robert , Groves Morris D. , Ong Shirley S. , Ramakrishna Rohan , Vogelbaum Michael A. , Khagi Simon , Kaley Thomas , Melear Jason M. , Peereboom David M. , Rodriguez Analiz , Yankelevich Maxim , Nair Suresh G. , Puduvalli Vinay K. , Aldape Kenneth , Gao Andrew , López-Janeiro Álvaro , de Andrea Carlos E. , Alonso Marta M. , Boutros Paul , Robbins Joan , Mason Warren P. , Sonabend Adam M. , Stupp Roger , Fueyo Juan , Gomez-Manzano Candelaria , Lang Frederick F. , Zadeh Gelareh
Published: May 2023

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2–20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1–69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7–13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05–0.87). A total of 56.2% (95% CI 41.1–70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).
Design and experiments with a single spiral fixed depth ditching and fertilizing machine
Authors: Zhan Caixue , Ding Wenqin , Han Yu , Jiang Qinghai , Zhao Ying , Zhao Liang , Song Zhiyu
Published: May 2023

Aiming at the problems of low fertilization efficiency, mainly the process operation and inconsistent fertilization depth of domestic tea garden fertilizer machines, a single-spiral fixed depth ditching and fertilizing machine is appropriately designed. This machine is capable of performing the integrated operation of ditching, fertilization, and covering soil at the same time through the operation mode of single-spiral ditching and fertilization. The theoretical analysis and design of the structure of the main components are properly carried out. The fertilization depth can be adjusted through the established depth control system. The performance test reveals that the single-spiral ditching and fertilizing machine exhibits a maximum stability coefficient of 96.17% and a minimum of 94.29% in terms of trenching depth and a maximum of 94.23% and a minimum of 93.58% in terms of fertilization uniformity, meeting the production requirements of tea plantations.
Influence of the modifiers in polyol method on magnetically induced hyperthermia and biocompatibility of ultrafine magnetite nanoparticles
Authors: Radoń Adrian , Włodarczyk Agnieszka , Sieroń Łukasz , Rost-Roszkowska Magdalena , Chajec Łukasz , Łukowiec Dariusz , Ciuraszkiewicz Agnieszka , Gębara Piotr , Wacławek Stanisław , Kolano-Burian Aleksandra
Published: May 2023

Magnetite nanoparticles (Fe3O4 NPs) are widely tested in various biomedical applications, including magnetically induced hyperthermia. In this study, the influence of the modifiers, i.e., urotropine, polyethylene glycol, and NH4HCO3, on the size, morphology, magnetically induced hyperthermia effect, and biocompatibility were tested for Fe3O4 NPs synthesized by polyol method. The nanoparticles were characterized by a spherical shape and similar size of around 10 nm. At the same time, their surface is functionalized by triethylene glycol or polyethylene glycol, depending on the modifiers. The Fe3O4 NPs synthesized in the presence of urotropine had the highest colloidal stability related to the high positive value of zeta potential (26.03 ± 0.55 mV) but were characterized by the lowest specific absorption rate (SAR) and intrinsic loss power (ILP). The highest potential in the hyperthermia applications have NPs synthesized using NH4HCO3, for which SAR and ILP were equal to 69.6 ± 5.2 W/g and 0.613 ± 0.051 nHm2/kg, respectively. Their application possibility was confirmed for a wide range of magnetic fields and by cytotoxicity tests. The absence of differences in toxicity to dermal fibroblasts between all studied NPs was confirmed. Additionally, no significant changes in the ultrastructure of fibroblast cells were observed apart from the gradual increase in the number of autophagous structures.
Dysbiosis of the gut microbiome in elderly patients with hepatocellular carcinoma
Authors: Zhang Weizheng , Xu Xiaosong , Cai Liping , Cai Xiangsheng
Published: May 2023

Fecal samples from participants aged 60–80 were collected and sequenced by a high-throughput second-generation sequencer to explore the structural composition of gut microbiota in elderly patients with hepatocellular carcinoma(HCC). Comparison of gut microbiota between patients with hepatocellular carcinoma and healthy controls, α diversity and β diversity were statistically different. At the genus level, compared with the normal group, the abundance of A Blautia, Fusicatenibacter, Anaerostipes, Lachnospiraceae_ND3007_group, CAG-56, Eggerthella, Lachnospiraceae_FCS020_group and Olsenella were decreased significantly in the LC group. In contrast, the abundance of Escherichia-Shigella, Fusobacterium, Megasphaera, Veillonella, Tyzzerella_4, Prevotella_2 and Cronobacter increased significantly. The KEGG and COG pathway analyses showed that the dysbiosis of gut bacteria in primary liver carcinoma is associated with several pathways, including amino acid metabolism, replication and repair, nucleotide metabolism, cell motility, cell growth and death, and transcription. Age is negatively associated with the abundance of Bifidobacterium. Lachnospiraceae_ ND3007_ group, [Eubacterium]_hallii_group, Blautia, Fuscatenibacter and Anaerostipes are negatively correlated with ALT, AST and GGT levels (p < 0.05), respectively. Alpha-fetoprotein (AFP) is positively associated with the abundance of Erysipelatoclostridium, Magasphaera, Prevotella 2, Escherichia-Shigella, Streptococcus and [Eubacterium]_eligens_group (p < 0.05), respectively. A random forest model showed that the genera Eggerthella, Anaerostipes, and Lachnospiraceae_ ND3007_ group demonstrated the best predictive capacity. The area under the Receiver Operating Characteristic Curve of Eggerthella, Anaerostipes and Lachnospiraceae_ ND3007_ group are 0.791, 0.766 and 0.730, respectively. These data are derived from the first known gut microbiome study in elderly patients with hepatocellular carcinoma. Potentially, specific microbiota can be used as a characteristic index for screening, diagnosis, and prognosis of gut microbiota changes in elderly patients with hepatocellular carcinoma and even as a therapeutic clinical target.
Computer-assisted diagnosis for an early identification of lung cancer in chest X rays
Authors: Juan Judith , Monsó Eduard , Lozano Carme , Cufí Marta , Subías-Beltrán Paula , Ruiz-Dern Laura , Rafael-Palou Xavier , Andreu Marta , Castañer Eva , Gallardo Xavier , Ullastres Anna , Sans Carles , Lujàn Manel , Rubiés Carles , Ribas-Ripoll Vicent
Published: May 2023

Computer-assisted diagnosis (CAD) algorithms have shown its usefulness for the identification of pulmonary nodules in chest x-rays, but its capability to diagnose lung cancer (LC) is unknown. A CAD algorithm for the identification of pulmonary nodules was created and used on a retrospective cohort of patients with x-rays performed in 2008 and not examined by a radiologist when obtained. X-rays were sorted according to the probability of pulmonary nodule, read by a radiologist and the evolution for the following three years was assessed. The CAD algorithm sorted 20,303 x-rays and defined four subgroups with 250 images each (percentiles ≥ 98, 66, 33 and 0). Fifty-eight pulmonary nodules were identified in the ≥ 98 percentile (23,2%), while only 64 were found in lower percentiles (8,5%) (p < 0.001). A pulmonary nodule was confirmed by the radiologist in 39 out of 173 patients in the high-probability group who had follow-up information (22.5%), and in 5 of them a LC was diagnosed with a delay of 11 months (12.8%). In one quarter of the chest x-rays considered as high-probability for pulmonary nodule by a CAD algorithm, the finding is confirmed and corresponds to an undiagnosed LC in one tenth of the cases.
Characterization of Duffy Binding Protein II-specific CD4+T cell responses in Plasmodium vivax patients
Authors: Thawornpan Pongsakorn , Malee Chayapat , Kochayoo Piyawan , Wangriatisak Kittikorn , Leepiyasakulchai Chaniya , Ntumngia Francis B. , De Sai Lata , Adams John H. , Chootong Patchanee
Published: May 2023

Plasmodium vivax Duffy Binding Protein region II (PvDBPII) is a leading vaccine candidate against blood-stage vivax malaria. Anti-PvDBPII antibodies potentially block parasite invasion by inhibition of erythrocyte binding. However, knowledge of PvDBPII-specific T cell responses is limited. Here, to assess the responses of PvDBPII-specific CD4+T cells in natural P. vivax infection, three cross-sectional studies were conducted in recovered subjects. In silico analysis was used for potential T cell epitope prediction and selection. PBMCs from P. vivax subjects were stimulated with selected peptides and examined for cytokine production by ELISPOT or intracellular cytokine staining. Six dominant T cell epitopes were identified. Peptide-driven T cell responses showed effector memory CD4+T cell phenotype, secreting both IFN-γ and TNF-α cytokines. Single amino acid substitutions in three T cell epitopes altered levels of IFN-γ memory T cell responses. Seropositivity of anti-PvDBPII antibodies were detected during acute malaria (62%) and persisted up to 12 months (11%) following P. vivax infection. Further correlation analysis showed four out of eighteen subjects had positive antibody and CD4+T cell responses to PvDBPII. Altogether, PvDBPII-specific CD4+T cells were developed in natural P. vivax infections. Data on their antigenicity could facilitate development of an efficacious vivax malaria vaccine.
Time domain self-bending photonic hook beam based on freezing water droplet
Authors: Minin Oleg V. , Minin Igor V. , Cao Yinghui
Published: May 2023

Tunable optical devices are of great interest as they offer adjustability to their functions. Temporal optics is a fast-evolving field, which may be useful both for revolutionizing basic research of time-dependent phenomena and for developing full optical devices. With increasing focus on ecological compatibility, bio-friendly alternatives are a key subject matter. Water in its various forms can open up new physical phenomena and unique applications in photonics and modern electronics. Water droplets freezing on cold surfaces are ubiquitous in nature. We propose and demonstrate the effectual generation of time domain self-bending photonic hook (time–PH) beams by using mesoscale freezing water droplet. The PH light bends near the shadow surface of the droplet into large curvature and angles superior to a conventional Airy beam. The key properties of the time–PH (length, curvature, beam waist) can be modified flexibly by changing the positions and curvature of the water–ice interface inside the droplet. Due to the modifying internal structure of freezing water droplets in real time, we showcase the dynamical curvature and trajectory control of the time–PH beams. Compared with the traditional methods, our phase-change- based materials (water and ice) of the mesoscale droplet have advantages of easy fabrication, natural materials, compact structure and low cost. Such PHs may have applications in many fields, including temporal optics and optical switching, microscopy, sensors, materials processing, nonlinear optics, biomedicine, and so on.
Projecting malaria elimination in Thailand using Bayesian hierarchical spatiotemporal models
Authors: Rotejanaprasert Chawarat , Lawpoolsri Saranath , Sa-angchai Patiwat , Khamsiriwatchara Amnat , Padungtod Chantana , Tipmontree Rungrawee , Menezes Lynette , Sattabongkot Jetsumon , Cui Liwang , Kaewkungwal Jaranit
Published: May 2023

Thailand has set a goal of eliminating malaria by 2024 in its national strategic plan. In this study, we used the Thailand malaria surveillance database to develop hierarchical spatiotemporal models to analyze retrospective patterns and predict Plasmodium falciparum and Plasmodium vivax malaria incidences at the provincial level. We first describe the available data, explain the hierarchical spatiotemporal framework underlying the analysis, and then display the results of fitting various space–time formulations to the malaria data with the different model selection metrics. The Bayesian model selection process assessed the sensitivity of different specifications to obtain the optimal models. To assess whether malaria could be eliminated by 2024 per Thailand’s National Malaria Elimination Strategy, 2017–2026, we used the best-fitted model to project the estimated cases for 2022–2028. The study results based on the models revealed different predicted estimates between both species. The model for P. falciparum suggested that zero P. falciparum cases might be possible by 2024, in contrast to the model for P. vivax, wherein zero P. vivax cases might not be reached. Innovative approaches in the P. vivax-specific control and elimination plans must be implemented to reach zero P. vivax and consequently declare Thailand as a malaria-free country.
Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer’s disease
Authors: Merchant Julie P. , Zhu Kuixi , Henrion Marc Y. R. , Zaidi Syed S. A. , Lau Branden , Moein Sara , Alamprese Melissa L. , Pearse Richard V. , Bennett David A. , Ertekin-Taner Nilüfer , Young-Pearse Tracy L. , Chang Rui
Published: May 2023

Despite decades of genetic studies on late-onset Alzheimer’s disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We delineate bulk-tissue gene expression into single cell-type gene expression and integrate clinical and pathologic traits, single nucleotide variation, and deconvoluted gene expression for the construction of cell type-specific predictive network models. Here, we focus on neuron-specific network models and prioritize 19 predicted key drivers modulating Alzheimer’s pathology, which we then validate by knockdown in human induced pluripotent stem cell-derived neurons. We find that neuronal knockdown of 10 of the 19 targets significantly modulates levels of amyloid-beta and/or phosphorylated tau peptides, most notablyJMJD6. We also confirm our network structure by RNA sequencing in the neurons following knockdown of each of the 10 targets, which additionally predicts that they are upstream regulators of REST and VGF. Our work thus identifies robust neuronal key drivers of the Alzheimer’s-associated network state which may represent therapeutic targets with relevance to both amyloid and tau pathology in Alzheimer’s disease.
Content aware image restoration improves spatiotemporal resolution in luminescence imaging
Authors: Boothe Tobias , Ivanković Mario , Grohme Markus A. , Markus M. Andrea , Dullin Christian , Xu Xingbo , Rink Jochen C.
Published: May 2023

Luminescent reporters are due to their intrinsically high signal-to-noise ratio a powerful labelling tool for microscopy and macroscopic in vivo imaging in biomedical research. However, luminescence signal detection requires longer exposure times than fluorescence imaging and is consequently less suited for applications requiring high temporal resolution or throughput. Here we demonstrate that content aware image restoration can drastically reduce the exposure time requirements in luminescence imaging, thus overcoming one of the major limitations of the technique.
Mental health penalties of having a child: findings from the China family panel studies
Authors: Shi Xinjie , Shen Yu
Published: May 2023

In recent years, the birth rate in China has rapidly declined. While much research has been done on the penalties in earnings that women incur when they fall behind men in the labor market due to childbirth, there has been little to no research on the mental health effects. This study addresses the gap in current literature by examining the mental health penalties that women experience after having a child in comparison to men. We applied econometric modeling to data collected from China Family Panel Studies (CFPS) and found that women experienced a significant, immediate, and long-run decline (4.3%) in life satisfaction after their first child, while men were unaffected. We also found that women experienced a significant increase in depression after their first child. This suggests mental health penalties since the mental health risk proxied by these two measurements is only significant for women. This is likely related to child penalties in labor market performance and childbirth-related physical health issues. When countries adopt multiple tools to stimulate the birth rate for economic growth, they must consider the implicit burden on women—especially the long-term negative effects on mental health.
Enhanced Raman scattering based on a ZnO/Ag nanostructured substrate: an in-depth study of the SERS mechanism
Authors: Tran Thu Trang , Vu Xuan Hoa , Ngo Thi Lan , Pham Thi Thu Ha , Nguyen Dac Dien , Nguyen Van Dang
Published: May 2023

Using Herzberg–Teller-surface selection rules in combination with the results of DFT calculations, the SERS mechanism based on the ZnO/Ag substrate has indicated a significant electromagnetic contribution versus the Ag substrate, in which charge transfer plays a pivotal role.
Heterobimetallic 21,23-dimetallaporphyrin: activation of metal–metal interactions within the porphyrinoid macrocycle
Authors: Vetter Grzegorz , Białońska Agata , Jezierska Aneta , Panek Jarosław J. , Pacholska-Dudziak Ewa
Published: May 2023

The incorporation of two metal atoms, platinum and rhodium, in place of NH groups in the porphyrin macrocycle brings them into close proximity. The weak metal–metal bond is switched on and off depending on the oxidation state of the platinum ion.
Correction: One-step mild preparation of tough and thermo-reversible poly(vinyl alcohol) hydrogels induced by small molecules
Authors: Dong Chuang , Zhou Jiahua , Shi Dongjian , Song Yufang , Yu Xi , Dong Weifu , Chen Mingqing , Kaneko Daisaku
Published: May 2023

Correction for ‘One-step mild preparation of tough and thermo-reversible poly(vinyl alcohol) hydrogels induced by small molecules’ by Chuang Dong et al., Chem. Commun., 2021, 57, 3789–3792, https://doi.org/10.1039/D1CC00578B.
Polymorphs, cocrystal and hydrate of nilutamide
Authors: Prashanth Jupally , Surov Artem O. , Drozd Ksenia V. , Perlovich German L. , Balasubramanian Sridhar
Published: May 2023

Nilutamide (Nil), commercialized under the trade names Nilandron and Anandron, is a nonsteroidal antiandrogen drug used in prostate cancer treatment.
DFT-based microkinetic studies on methanol synthesis from CO2 hydrogenation over In2O3 and Zr–In2O3 catalysts
Authors: Li Kun , Wei Zhangqian , Chang Qingyu , Li Shenggang
Published: May 2023

CO2 conversion to methanol and CO were studied by DFT-based microkinetic simulations over the In2O3 and Zr–In2O3 catalyst models.
First-principles study of O2 and H2O adsorption on the Mg3Sb2(10−11) surface
Authors: Li Juan , Han Kai , Sun Bing , Cao Lianzhen , Zhang Shuai
Published: May 2023

Sb termination and Al doping are beneficial to reduce the interaction between O2 or H2O with Mg atoms and thus improve the performance stability of Mg3Sb2.
Direct chemical dynamics simulations of CN− + CH3I bimolecular nucleophilic substitution reaction
Authors: Gutal Akash , Paranjothy Manikandan
Published: May 2023

Atomistic simulations of a substitution reaction involving ambidentate nucleophile.
Synthesis, characterization, and photocatalytic CO2 reduction evaluation of the CaWxMo1−xO4 (x = 0–1) solid solution
Authors: Garay-Rodríguez Luis F. , Ibarra-Rodríguez Luz I. , Torres-Martínez Leticia M. , Juárez-Ramírez I.
Published: May 2023

A solid solution with the formula CaWxMo1−xO4 (x = 0–1) was synthesized using a microwave-assisted hydrothermal method.
Mechanistic insights into the catalytic transfer hydrogenation of furfural to furfuryl alcohol over a N-doped carbon-supported Ni single atom catalyst from first principles
Authors: Yang Fan , Lai Wenzhen
Published: May 2023

First-principles calculations reveal the catalytic active sites and the reaction mechanism of the catalytic transfer hydrogenation of furfural to furfuryl alcohol over a N-doped carbon-supported Ni single atom catalyst.
Correction: NHC–Zn alkyl catalyzed cross-dehydrocoupling of amines and silanes
Authors: Harinath Adimulam , Karmakar Himadri , Kisan Devadkar Ajitaro , Nayek Hari Pada , Panda Tarun K.
Published: May 2023

Correction for ‘NHC–Zn alkyl catalyzed cross-dehydrocoupling of amines and silanes’ by Adimulam Harinath et al., Org. Biomol. Chem., 2023, https://doi.org/10.1039/d3ob00453h.