bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid and High‐Throughput SARS‐CoV‐2 RNA Detection without RNA Extraction and Amplification by Using a Microfluidic Biochip
Authors: Chu Yujin , Qiu Jiaoyan , Wang Yihe , Wang Min , Zhang Yu , Han Lin
Published: February 2022

The ongoing outbreak of the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) has spread globally and poses a threat to public health and National economic development. Rapid and high‐throughput SARS‐CoV‐2 RNA detection without the need of RNA extraction and amplification remain a key challenge. In this study, a new SARS‐CoV‐2 RNA detection strategy using a microfluidic biochip for the rapid and ultrasensitive detection of SARS‐CoV‐2 without RNA extraction and amplification was developed. This new strategy takes advantage of the specific SARS‐CoV‐2 RNA and probe DNA reaction in the microfluidic channel, fluorescence signal regulation by nanomaterials, and accurate sample control by the microfluidic chip. It presents an ultralow limit of detection of 600 copies mL−1 in a large linear detection regime from 1 aM to 100 fM. Fifteen samples were simultaneously detected in 40 min without the need for RNA purification and amplification. The detection accuracy of the strategy was validated through quantitative reverse transcription polymerase chain reaction (qRT‐PCR), with a recovery of 99–113 %. Therefore, the SARS‐CoV‐2 RNA detection strategy proposed in this study can potentially be used for the quantitative diagnosis of viral infectious diseases.
Fast and Cysteine‐Specific Modification of Peptides, Proteins and Bacteriophage Using Chlorooximes
Authors: Chen Fa‐Jie , Zheng Mengmeng , Nobile Vincent , Gao Jianmin
Published: February 2022

This work reports a novel chlorooxime mediated modification of native peptides and proteins under physiologic conditions. This method features fast reaction kinetics (apparent k2=306±4 M−1s−1 for GSH) and exquisite selectivity for cysteine residues. This cysteine conjugation reaction can be carried out with just single‐digit micromolar concentrations of the labeling reagent. The conjugates show high stability towards acid, base, and external thiol nucleophiles. A nitrile oxide species generated in situ is likely involved as the key intermediate. Furthermore, a bis‐chlorooxime reagent is synthesized to enable facile Cys‐Cys stapling in native peptides and proteins. This highly efficient cysteine conjugation and stapling was further implemented on bacteriophage to construct chemically modified phage libraries.
Klimaschutz und nachhaltige Mobilität durch grünen Wasserstoff
Authors: Zellner Reinhard
Published: February 2022

Wasserstoff als Energieträger oder industrieller Rohstoff kommt auf dem Weg zu einer klimaneutralen Gesellschaft eine besondere Bedeutung zu. Kein anderer energiereicher Stoff ist gleichermaßen gut geeignet, in Mobilität, Wärmeversorgung und als Rohstoff in der industriellen Produktion den Weg in die Nachhaltigkeit zu ebnen. Die deutsche Politik setzt derzeit auf den Ausbau der regenerativen Stromerzeugung und die batterie‐elektrischen Fahrzeuge, die großzügig gefördert werden. Es ist aber seit langem erkennbar, dass mit einer Direktnutzung von erneuerbarem Strom allein eine Defossilierung der Energiewirtschaft nicht möglich sein dürfte. Dies kann nach heutiger Meinung nur durch „grünen”, klimaneutralen Wasserstoff erreicht werden. Wasserstoff als Baustein für gasförmige und flüssige Energieträger im Sinne der Power‐to‐X‐Strategie ist aus heutiger Sicht quasi unverzichtbar für alle Anwendungen, bei denen die direkte Stromnutzung technisch oder wirtschaftlich weder möglich noch sinnvoll ist.
Synthesis of Thin Film of a Three‐Dimensional Covalent Organic Framework as Anti‐counterfeiting Label
Authors: Dong Xin , Yang Jing , Wang Honglei , Zhao Pei , Tan Fanglin , Zhou Zhipeng , Ou Zhaowei , Gong Li , Liu Wei , Chen Xudong , Zheng Zhikun
Published: February 2022

Comprehensive Summary

Film plays a key role in the sustainable development of our society. Freestanding thin films of two‐dimensional covalent organic frameworks (COFs) have been produced by interface, spin coating, microwave‐assisted synthesis, and screen printing methods and are applied in nanofiltration, molecular separation, photochemical sensing, anion transport, heat conduction, and proton conduction. On the other hand, the synthesis of their three‐dimensional (3D) analogues and subsequent integration in devices remains challenging. Herein, self‐supporting thin films of a three‐dimensional COF with tunable thickness was created by a stearic acid mediated synthesis methodology on water surface at room temperature in air. The film could be transferred onto arbitrary substrate, and when supported on indium tin oxide glass, it exhibited irreversible electrochromism. The optical feature made it act as a one‐time anti‐counterfeiting label in an electrochemical device. This work will inspire the synthesis of thin films of 3D COFs as well as other 3D materials, and boost their property and application exploration.
Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma
Authors: O’Donnell Elizabeth K. , Shapiro Yael N. , Yee Andrew J. , Nadeem Omar , Hu Bonnie Y. , Laubach Jacob P. , Branagan Andrew R. , Anderson Kenneth C. , Mo Clifton C. , Munshi Nikhil C. , Ghobrial Irene M. , Sperling Adam S. , Agyemang Emerentia A. , Burke Jill N. , Harrington Cynthia C. , Richardson Paul G. , Raje Noopur S. , El‐Jawahri Areej
Published: February 2022

Background

Multiple myeloma (MM) is an incurable hematologic malignancy requiring long‐term, continuous therapy. Despite its chronic and unrelenting course, studies examining quality of life (QOL), psychological distress, and perceptions of prognosis by line of therapy are lacking.

Methods

The authors conducted a cross‐sectional, multisite study of patients undergoing treatment for MM (excluding maintenance) between June 2020 and January 2021. The authors conducted purposeful sampling and recruited patients to 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first‐line therapy; 2) 2 to 3 lines; and 3) 4 or more lines. Patients completed validated questionnaires to assess their QOL, fatigue, psychological distress, and perceptions of prognosis.

Results

A total of 180 patients with MM were enrolled (newly diagnosed [n = 60], 2 to 3 lines [n = 60], and ≥4 lines of therapy [n = 60]). QOL, symptom burden, and fatigue scores did not differ by lines of therapy. There were no statistically significant differences in psychological distress by line of therapy. The rates of clinically significant depression, anxiety, and post‐traumatic stress disorder symptoms were 23.9% (43 of 180), 23.9% (43 of 180), and 24.4% (44 of 180), respectively. Most patients (84.7%, 149 of 176) reported that their oncologist told them their cancer was incurable, but only 30.6% (53 of 173) acknowledged that they were terminally ill, and 42.0% (73 of 174) reported that they thought their cancer was incurable.

Conclusions

Patients with MM undergoing treatment experience impaired QOL and elevated psychological distress across the disease continuum, regardless of line of therapy. A substantial proportion of patients with MM have significant misperceptions about their prognosis and the curability of their illness despite reporting being informed of the prognosis by their oncologist.

Lay Summary

This study discusses 180 patients with MM (newly diagnosed [n = 60], 2‐3 lines [n = 60], and ≥4 lines of therapy [n = 60]). Quality of life, symptom burden, and fatigue scores do not differ by lines of therapy. There are also no statistically significant differences in psychological distress by line of therapy.

The rates of clinically significant depression, anxiety, and post‐traumatic stress disorder symptoms are 23.9%, 23.9%, and 24.4%, respectively.

Most patients (84.7%) report that their oncologist told them their cancer was incurable, but only 30.6% acknowledge that they are terminally ill, and 42.0% report that they thought their cancer was incurable.
A novel voltage boosting switched‐capacitor 19‐level inverter with reduced component count
Authors: Tayyab Mohammad , Sarwar Adil , Hussan Md Reyaz , Murshid Shadab , Tariq Mohd , Alamri Basem
Published: February 2022

A dual‐source switched‐capacitor multilevel inverter (SCMLI) topology utilizing 13 switches, one diode, and two switched capacitors is presented in this paper. The proposed topology is capable of operating in both asymmetrical and symmetrical modes. In asymmetrical mode, it produces 19‐level output voltage, whereas, in symmetrical mode, it produces 13‐level output voltage. The capacitor voltages are self‐balanced in the presented SCMLI topology. A detailed comparative analysis has been carried to show the advantages of the proposed topology in terms of the number of switches, number of capacitors, number of sources, and boosting of the converter with the recently published multilevel inverter topologies. The nearest level control (NLC)‐based algorithm is used for generating switching signals for the IGBTs present in the circuit. The reliability assessment is carried to assess the life span of the proposed SCMLI. Experimental results are obtained for different loading conditions using a laboratory hardware prototype. The fluke‐based power analyzer is used to record the inverter voltage and corresponding THD values at different modulation indexes. The efficiency of the proposed inverter is 97.35% for 200‐W load.
A novel semantic representation approach for web documents using deep entity linking and multidocument support
Authors: Urkude Giridhar , Pandey Manju
Published: February 2022

Representing semantic web information in the form of existing formats like extensible mark‐up language (XML), resource description framework (RDF) or web ontology language (OWL) is limited by the inability to maintain intradocument relationships between different semantic entities. Moreover, these standards are built for generic data representation and thus do not have inherent support for the semantic description of the document and, consequently, do not support features like multidocument linkages and context‐sensitivity. In order to remove these drawbacks, a semantic web‐specific document representation approach, namely, deep semantic XML (DS‐XML) using deep linking and machine learning, is presented in this paper. The DS‐XML approach facilitates the use of semantics with the help of a novel document structure that focuses on defining any web document in a semantic form. It includes ontologies and linkage between different vocabularies, which assists in achieving semantic interoperability. In order to make this approach future proof, a novel deep linking approach is integrated at the document level, which allows DS‐XML to understand more about the contents of the document and represent information in an aggregated manner. The deep linking layer is combined with the machine learning‐based classification layer that allows the document information to be represented in an interactive manner. The proposed DS‐XML approach is tested on different document retrieval applications, including a few Internet of Things (IoT) applications, and the representation performance is found to be superior to the existing semantic approach (XML, RDF and OWL).
Digital storytelling brings assessment data to life
Authors: McCarthy Claudine
Published: February 2022

Digital stories presented on social media platforms can become powerful tools for building empathy and can play an important role in presenting assessment data in a way that's engaging and effective, according to Lesley D'Souza, Director of Digital Engagement and Storytelling at Western University (Ontario), and Joseph D. Levy, Ed.D., Executive Director of Assessment and Accreditation at National Louis University Illinois. They gave a presentation on the topic during the virtual Assessment Institute, hosted by Indiana University–Purdue University Indianapolis.
Consider digital badges for your students — and your faculty
Authors: Sutton Halley
Published: February 2022

Andrea Carroll‐Glover, Ed.D., was planning on transitioning out of higher education when she received an  offer she couldn't refuse: the position of Vice Provost of Online Strategy and Programs at Saint Mary's University of Minnesota. It was a perfect marriage of Carroll‐Glover's passions: technology, innovation, and education.
The drivers of avian‐haemosporidian prevalence in tropical lowland forests of New Guinea in three dimensions
Authors: Vinagre‐Izquierdo Celia , Bodawatta Kasun H. , Chmel Kryštof , Renelies‐Hamilton Justinn , Paul Luda , Munclinger Pavel , Poulsen Michael , Jønsson Knud A.
Published: February 2022

Haemosporidians are among the most common parasites of birds and often negatively impact host fitness. A multitude of biotic and abiotic factors influence these associations, but the magnitude of these factors can differ by spatial scales (i.e., local, regional and global). Consequently, to better understand global and regional drivers of avian‐haemosporidian associations, it is key to investigate these associations at smaller (local) spatial scales. Thus, here, we explore the effect of abiotic variables (e.g., temperature, forest structure, and anthropogenic disturbances) on haemosporidian prevalence and host–parasite networks on a horizontal spatial scale, comparing four fragmented forests and five localities within a continuous forest in Papua New Guinea. Additionally, we investigate if prevalence and host–parasite networks differ between the canopy and the understory (vertical stratification) in one forest patch. We found that the majority of Haemosporidian infections were caused by the genusHaemoproteusand that avian‐haemosporidian networks were more specialized in continuous forests. At the community level, only forest greenness was negatively associated withHaemoproteusinfections, while the effects of abiotic variables on parasite prevalence differed between bird species.Haemoproteusprevalence levels were significantly higher in the canopy, and an opposite trend was observed forPlasmodium. This implies that birds experience distinct parasite pressures depending on the stratum they inhabit, likely driven by vector community differences. These three‐dimensional spatial analyses of avian‐haemosporidians at horizontal and vertical scales suggest that the effect of abiotic variables on haemosporidian infections are species specific, so that factors influencing community‐level infections are primarily driven by host community composition.
Diphosphorus Release and Heterocumulene Oligomerisation by Nickel Complexes
Authors: Hierlmeier Gabriele , Wolf Robert
Published: February 2022

The generation of diphosphorus molecules P2 under mild conditions in solution is a useful strategy to generate diphosphines via [4+2] cycloadditions. We recently described the release of P2 units from the nickel butterfly complex [{(IMes)Ni(CO)}2(μ2,η2:η2‐P2)] (IMes=1,3‐bis(2,4,6‐trimethylphenyl)imidazolin‐2‐ylidene) upon addition of CO gas. Herein, we developed an alternative protocol for the same process using heterocumulenes. In addition to formation of P4 (the dimerisation product of P2), the reactions afford nickel complexes of novel pincer‐type ligands. Aryl isothiocyanates undergo a trimerisation within the coordination sphere of nickel and afford square planar nickel complexes with S−C−S pincer‐ligand frameworks. Carbon disulfide coordinates to the [(IMes)Ni]‐fragment in an η2‐fashion, affording a dinuclear complex. Similar products are formed when the N‐heterocyclic carbene nickel(0) complex [(IMes)Ni(vtms)2] is used as a precursor (vtms=vinyltrimethylsilane).
Heterotriptycene Containing an Unsubstituted Bispyrrole: Synthesis, Crystal Structures, and 2D Nested Hexagonal Arrays Constructed by NH⋅⋅⋅π Intermolecular Interactions
Authors: Inoue Ryo , Furumoto Kyosuke , Osada Toshiki , Morisaki Yasuhiro
Published: February 2022

Herein, we report the synthesis, crystal structure, and optical properties of a heterotriptycene consisting of an unsubstituted bispyrrole, 2,4,6,8‐tetrahydro‐4,8‐benzobenzo[1,2‐c:4,5‐c′]dipyrrole, which was synthesized via hetero‐Diels‐Alder reaction of a novel benzobicyclo[2.2.2]octane derivative. The compound formed a 2D nested hexagonal array with NH⋅⋅⋅π interactions in the crystalline state; whereas, in the solution state, it exhibited through‐space intramolecular charge transfer (ICT) induced emission in the solution state.
Electrolyte formulation strategies for potassium‐based batteries
Authors: Ni Ling , Xu Gaojie , Li Chuanchuan , Cui Guanglei
Published: February 2022

Potassium (K)‐based batteries are viewed as the most promising alternatives to lithium‐based batteries, owing to their abundant potassium resource, lower redox potentials (−2.97 V vs. SHE), and low cost. Recently, significant achievements on electrode materials have boosted the development of potassium‐based batteries. However, the poor interfacial compatibility between electrode and electrolyte hinders their practical. Hence, rational design of electrolyte/electrode interface by electrolytes is the key to develop K‐based batteries. In this review, the principles for formulating organic electrolytes are comprehensively summarized. Then, recent progress of various liquid organic and solid‐state K+ electrolytes for potassium‐ion batteries and beyond are discussed. Finally, we offer the current challenges that need to be addressed for advanced K‐based batteries.
A Family Matter: Responsibility and Selfishness in Spanish Households
Authors: Weiss Hadas
Published: February 2022

Under the pressure of work's devaluation and the state's retrenchment, men and women in Spain manage their extended family resources in a struggle to provide for their dependents. These resources have become the main axis of inequality in Spain's financialized economy. Drawing on fieldwork in Madrid, I show that men and women understand themselves in terms of this responsibility, internalizing capitalist pressures on social reproduction as a family matter. This self‐identification cuts through the solidarities that exploited waged work and gendered domestic work might generate, and it makes family one's ultimate reference point. Instead of the refusal of a responsibility that used to be socialized being a principled and political stance, then, it is dismissed as selfish.
Increasing the resilience of ecological restoration to extreme climatic events
Authors: Zabin Chela J , Jurgens Laura J , Bible Jillian M , Patten Melissa V , Chang Andrew L , Grosholz Edwin D , Boyer Katharyn E
Published: February 2022

Extreme climatic events (ECEs) are increasing in frequency and magnitude as part of global climate change, with severe consequences for both nature and human societies. While many restoration projects account for gradual climate change, ECEs are rarely considered. Through a literature search and the use of expert opinion, we reviewed the impacts of ECEs on habitat restoration projects, and the degree to which they were resilient. ECEs had overwhelmingly negative impacts on habitat restoration, although some projects also reported positive outcomes. The severity of impact varied among and within projects. Nearly all projects that included more than one focal species, life stage or genotype, restoration method, site, habitat type, or microhabitat reported better outcomes for at least one of these project aspects. We suggest that practitioners may be able to reduce risk from future ECEs through a portfolio approach, incorporating heterogeneity into project design, including in site selection and propagule choices.
Drones address an observational blind spot for biological oceanography
Authors: Gray Patrick Clifton , Larsen Gregory D , Johnston David W
Published: February 2022

Marine biological communities are dynamic across many scales in both space and time. Such multi‐scale complexity complicates efforts to fully characterize these communities. Critical processes unfold on the order of 0.1–10 kilometers and 0.1–10 days, but conventional oceanographic techniques generally do not observe or model at this scale. Small aerial drones conveniently achieve scales of observation between satellite resolutions and in‐situ sampling, and effectively diminish the “blind spot” between these established measurement techniques. Despite this promise, drone‐based techniques face challenges inherent to optical oceanography, as well as logistical and regulatory barriers relating to both aerial and marine operations. Such obstacles have slowed adoption of drones for marine biological study, but best practices are emerging alongside new techniques that facilitate robust study designs and rigorous data collection. With such advancements, drones promise to complement conventional approaches in biological oceanography to more fully capture the spatiotemporal complexity of the marine environment.
Genetic linkage map construction and identification of QTLs associated with agronomic traits in bambara groundnut (Vigna subterranea (L.) Verdc.) using DArTseq‐based SNP markers
Authors: Gao Xiuqing , Chai Hui Hui , Ho Wai Kuan , Kundy Aloyce Callist , Mateva Kumbirai Ivyne , Mayes Sean , Massawe Festo
Published: February 2022

Bambara groundnut [Vigna subterranea (L.) Verdc.] is an underutilised, protein‐rich and self‐pollinating legume that can withstand high temperature and drought stress and is mainly grown in semi‐arid Africa. In order to dissect the complexity of drought resistance and to use genomic tools for yield enhancement of bambara groundnut in response to drought stress, yield‐related and morphological traits under drought‐stressed (DS) and well‐watered (WW) conditions were evaluated in the F3 and F4 segregating generations derived from a cross between two genotypes selected from landraces S19‐3 (originally from Namibia) and DodR (originally from Tanzania). Significant quantitative trait loci (QTLs) for shoot dry weight (SDW) were mapped on LG10 accounting for 15.5% of the phenotypic variation explanation (PVE) under well‐watered conditions and a putative quantitative trait locus (QTL) for the same trait mapped on LG10 with reduced PVE (10.10%) under drought‐stressed conditions in the F3 segregating population. Significant QTLs associated with the number of seeds per plant (NS), number of double‐seeded pods per plant (NDP), seed weight per plant (SW) and pod weight per plant (PW) were mapped on LG4 (nearest marker: 4181663 and 4175954) with overlapping confidence intervals and explained 21.9%, 21.8%, 23.5% and 19.9% of the PVE, respectively, under well‐watered conditions in the F4 population, which could be considered as the major QTL involved in the control of these traits. Seven consensus QTLs for yield‐related and morphological traits were mapped on LG2, LG3, LG4, LG7A and LG10. The study provides fundamental knowledge of QTLs associated with yield‐related and morphological traits under drought‐stressed and well‐watered conditions in bambara groundnut, which is also essential for yield improvement of bambara groundnut in response to drought stress.
Fusion‐positive skin/adnexal carcinomas
Authors: Agaimy Abbas
Published: February 2022

Gene fusions have been increasingly identified as central events driving oncogenesis in a variety of benign and malignant neoplasms of different histogenesis originating in diverse organs. While some fusion‐driven neoplasms may occur at any body site, certain genotypes and their associated phenotypic entities cluster to specific body site/organ, albeit with variable frequencies among anatomic locations. In the last two decades, several skin adnexal entities driven by specific fusions have been described; some of them represent new entities (eg, secretory carcinoma harboring NTRK fusions), while others are old established entities with newly discovered underlying gene fusions (eg, poroid neoplasms harboring NUTM1, YAP1, and WWTR1 fusions). While limited availability of next generation sequencing tools in routine practice has largely limited and delayed discovery of fusions in old entities, the increasing availability of novel immunoantibodies as surrogates to recognize gene fusions (such as NUT and YAP1 immunohistochemistry) represents a relatively cheap, quick, and reliable routine tool for their proper recognition and appropriate classification. This review highlights the main, recently defined skin adnexal carcinomas carrying gene fusions.
Palaeoenvironment, palaeogeography, and palaeoclimatology of the Mississippian carbonate ramp in the Alborz tectonostratigraphic zone: Implications for deciphering the controlling factors on ramp evolution
Authors: Zandkarimi Keyvan , Bayet‐Goll Aram , Falahatgar Mostafa , Sharafi Mahmoud , Amani Hamed , Hasanlou Mitra
Published: February 2022

The Mississippian successions of the Alborz tectonostratigraphic zone have been studied in several sections (Dozdehban, Naserabad, Shahmirzad, and Mighan) extending from north to southeast. The sedimentological data indicate three main facies associations (FA): (FA1) a basin to distal outer ramp of low‐energy, low‐oxygen environment with low bioturbation and less developed in situ fossils; (FA2) a middle ramp facies accompanied by storm‐induced sediments (tempestites), echinoderm‐dominated mud mounds, and high fragmentation of skeletal components; and (FA3) an inner ramp facies, represented by sand shoal, and lagoonal/back‐barrier, mainly characterized by the dominance of oolitic, bioclast, and intraclast grainstones. The sedimentary features imply the formation of the succession on a broad flat‐topped, high‐to‐moderate‐energy shelfal carbonate ramp which had been open to the N/NE, the downslope direction, as revealed by local palaeoenvironmental reconstructions. Analysis of several proxies indicates a subtropical palaeoclimate evidenced by (a) widespread tempestite facies and occurrence of storm‐depositional processes, (b) diverse and abundant pellet‐forming thalassinoideans and burrowing echinoids trace fossil assemblages, (c) geochemical proxy indicating a palaeotemperature of 23°–25°, and (d) a rich subtropical heterozoan fossil association. The data provided here imply the palaeolatitudinal position of the Alborz Mississippian ramp is 30–40°S along the southern margin of the Palaeotethys.
Fabrication of portable solar thermal bank for indoor cooking
Authors: Kumar Uttam , Agrawal Himanshu , Chandrashekara M. , Yadav Avadhesh
Published: February 2022

The aim of this report is to build a portable solar thermal bank based on a Scheffler reflector that is capable of boiling‐type cooking using HITEC as a thermal storage material. This report reviews the problems related to solar cooking and evaluates the novel layout of a portable solar thermal bank which includes a daily thermal storage vessel. This stove is in the shape of a cylindrical container filled with phase‐changing latent heat storage material. Inside the container, we provide a small gap taking into account the volumetric expansion of the phase change material (PCM) during the melting process. The solar thermal bank is charged in the sun. It is placed directly for a few hours under the focus of a Scheffler reflector, which charges the solar thermal bank with enough thermal energy stored. After a while, the cooking process can be completed by users using that stored heat. The top cavity is used as a cooking pot in a solar thermal bank. Cooking meals do not require direct sunlight, which is typical for most solar cookers. The portable solar thermal bank is an alternative for low‐income households and adapts to local traditions of indoor cooking. It is portable and can be used safely to cook indoors or outdoors. In this study, a solar cooker with a thermal storage device was developed using a PCM. The size of the stove has been calculated by calculating the energy consumption for two to three people. HITEC salt has been chosen as a phase change material for thermal storage, which will be used for cooking when there is no sunlight. It enhances the applicability of solar cooking and preserves cooking possibilities using energy stored throughout the day at low production costs.
Pelvic organ prolapse and vaginal cancer: A systematic literature review
Authors: Frigerio Matteo , Inzoli Alessandra , Barba Marta
Published: February 2022

Background

Primary vaginal cancer is a rare gynecologic malignancy. Few cases describing the concurrence of a vaginal tumor with advanced genital prolapse are reported in the literature and there is no consensus on optimal treatment.

Objectives

To investigate available evidence on presentation, treatment, and outcomes of these concurrent conditions.

Search Strategy

We performed a systematic search of literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “pelvic organ prolapse”, “genital prolapse”, and “vaginal cancer”, “vaginal carcinoma”.

Selection Criteria

No article type restrictions were applied.

Data Collection and Analysis

Twenty‐one studies (case reports and two small case series) were incorporated into the review process, for a total of 27 patients.

Main Results

Management usually involved surgery or primary external beam radiation therapy. External beam radiation therapy was reported to be highly associated with the development of vesicovaginal fistula. A surgical approach was the treatment of choice in most cases. Exclusive interstitial brachytherapy was rarely performed.

Conclusion

A multidisciplinary approach considering risks and benefits is of the utmost importance to provide counseling and tailor treatment strategy in these complex cases.
The golf course as an outdoor classroom—A proof of concept project
Authors: Szczepanski Anders , Strandberg Maria
Published: February 2022

Pupils’ learning experience can be improved if part of the teaching takes place in a natural outdoor environment. Golf courses and the land that surrounds them as outdoor classrooms could become particularly important at a time when most of the world's population lives in urban landscapes and when local areas suitable for outdoor activities are becoming scarce. A consequence of the Coronavirus crisis is higher demand for outdoor activities in the urban landscape, including outdoor teaching. The Swedish National Curriculum advocates the development of cognitive as well as affective competencies and skills, which makes outdoor teaching a natural and integrated part of today's school and education, where outdoor and indoor learning activities complement each other. In this project, at Motala Golf Club, in collaboration with the Smedsby School in Motala, methods for outdoor teaching on golf courses and the most suitable areas of the golf course for use as an outdoor classroom were investigated. A training course for participating teachers was held in autumn 2017, and the children visited their new classroom at the golf course in spring 2018. Through this project, Motala Golf Club has become a pilot model for outdoor teaching on golf courses. The concept of the golf course as an outdoor classroom is being implemented in Stockholm municipality and Jönköping municipality.
The ins and outs of the flavin mononucleotide cofactor of respiratory complex I
Authors: Curtabbi Andrea , Enríquez José Antonio
Published: February 2022

The flavin mononucleotide (FMN) cofactor of respiratory complex I occupies a key position in the electron transport chain. Here, the electrons coming from NADH start the sequence of oxidoreduction reactions, which drives the generation of the proton‐motive force necessary for ATP synthesis. The overall architecture and the general catalytic proprieties of the FMN site are mostly well established. However, several aspects regarding the complex I flavin cofactor are still unknown. For example, the flavin binding to the N‐module, the NADH‐oxidizing portion of complex I, lacks a molecular description. The dissociation of FMN from the enzyme is beginning to emerge as an important regulatory mechanism of complex I activity and ROS production. Finally, how mitochondria import and metabolize FMN is still uncertain. This review summarizes the current knowledge on complex I flavin cofactor and discusses the open questions for future research.
Bacillus subtilis chassis in biomanufacturing 4.0
Authors: Zhang Wenbo , Zhu Xinshu , Wang Yan , Li Tao
Published: February 2022

Synthetic biology, an emerging research field, can promote biomanufacturing 4.0 by offering various efficient chassis. Engineering Bacillus subtilis, a prominent workhorse in industrial biotechnology, through synthetic biology approaches may be a disruptive innovation. Diverse chassis forms are envisaged to deal with challenges in metabolic complexity, metabolic burden, and systems robustness. Thus, advancements in chassis engineering, a synthetic biology strategy for genome‐reduced cell factories, cell‐free systems, and synthetic microbial consortia would be a driving force facilitating microbial production. In this review article, we summarized chassis engineering categories and applications for B. subtilis. Prospects and challenges for chassis engineering in B. subtilis were also discussed. © 2022 Society of Chemical Industry (SCI).
Three leading coupled modes of summer rainfall with atmospheric circulations over northern East Asia
Authors: Lin Zhongda , Yang Qin
Published: February 2022

Northern East Asia (NEA) is characterized by wet monsoon region in the east and mid‐latitude westerly‐controlled dry inland in the west in summer, where ecosystem and environment are vulnerable to rainfall variability. Previous studies found close relationship between summer rainfall in NEA and local large‐scale atmospheric circulation systems including East Asian upper‐tropospheric westerly jet (EAJ) and middle‐tropospheric trough (EAT), and lower‐tropospheric low over NEA (NEAL). However, major features of rainfall–circulation coupling over NEA are still not fully understood. This study addresses this issue using multivariate empirical orthogonal functions method based on the ERA‐Interim reanalysis dataset and the GPCP precipitation data for 1979–2018. Three leading coupled modes are identified, together accounting for 30–50% of summer rainfall year‐to‐year variance in most of NEA. The first mode features consistent decrease of rainfall in NEA related to the decelerated EAJ, southward shifted EAT, and weakened NEAL, with a significant interdecadal change in late 1990s. The second mode exhibits a meridional dipole rainfall pattern, with less rainfall along the East Asian subtropical rainy belt and more rainfall in southern Russian Far East, coupled with the northward shifted EAJ, weakened EAT, and intensified NEAL. The third mode presents a zonal dipole rainfall pattern, with suppressed rainfall in southern Russia east of northeast China and enhanced rainfall around the Lake Baikal related to the decelerated EAJ, and westward shifted EAT and NEAL. Further investigation shows that the first mode is remotely modulated by summer rainfall anomalies in the Sahel region and Atlantic Multidecadal Oscillation (AMO) on the interdecadal timescales, and by the Polar/Eurasia teleconnection on the interannual timescales. The second and third modes are, respectively, modulated by summer rainfall in the western North Pacific and north central‐eastern India through the East Asia‐Pacific and circumglobal teleconnection patterns.
The Cognitive–Creative Profiles of Insightful Problem Solvers: A Person‐Centered Insight Study
Authors: Salmon‐Mordekovich Nirit , Leikin Mark
Published: February 2022

This study aimed to portray insightful problem solvers. Participants solved classic insight problems and rebuses and completed cognitive and creativity tasks. Grouping the participants based on their success in solving insight problems of different modalities revealed that 95% of the spatial problem solvers succeeded in solving verbal ones (spatial verbal solvers) but not vice versa. Verbal problem solvers were not necessarily able to solve spatial ones. A latent class analysis (LCA) based on relationships among the cognitive and creativity variables confirmed these two types of insightful solvers. It portrayed two compatible classes of experts and successful solvers alongside two classes of low‐level solvers. The former classes excelled in solving rebuses and verbal problems, yet the experts outperformed the others in spatial problems. Both classes scored higher in spatial divergent thinking measures than the low‐level solvers. However, the experts benefited additionally from verbal divergent thinking and associative combination ability. Seemingly, should retrieval of diverse ideas be insufficient to solve the problem, the experts combine ideas by a novel association, thereby generating an insight. Moreover, individual differences in working memory indicated that experts favor associative–automatic strategy, whereas successful solvers utilize analytic strategy. These profiles illuminate “insight” in terms of cognitive and creative styles.
Composing in the scanner: A functional magnetic resonance imaging single case study on visual and auditory imagery
Authors: Izadifar Morteza , Yang Taoxi , Paolini Marco , Formuli Arusu , Bao Yan
Published: February 2022

“Seeing with the mind's eye” and “hearing with the mind's ear” are two common indicators of musical imagery, and they can be referred to as “visual” and “auditory” musical imagery. However, a question remains open, that is, whether visual and auditory imagery of the same musical composition share the same neural mechanisms. Moreover, how can neural mechanisms guarantee the temporal flow of “musical imagery”? To answer these questions, we report here a preliminary single case study using functional magnetic resonance imaging with an eminent composer who imagined one of his compositions in two states of mind as compared to his resting‐state activity. In the visual imagery condition, he imagined visually the score of his composition in a continuous way. In the auditory imagery condition, he imagined auditorily the same musical composition with pauses. In spite of the modality and temporal differences, the two types of mental imagery showed similar temporal durations for the same musical composition. However, different patterns of neural activation were observed for visual and auditory imagery with one important exception, that is, a common activation pattern was observed in the left medial temporal gyrus in both visual and auditory imagery. We speculate that the left medial temporal gyrus may play an important role in the creation of apparent temporal continuity in musical imagery and perhaps even in conscious information processing in general.
Prenatal hydronephrosis: Bridging pre‐ and postnatal management
Authors: Rickard Mandy , Dos Santos Joana , Keunen Johannes , Lorenzo Armando J.
Published: February 2022

Urinary tract dilation (UTD), including hydronephrosis (HN) is the most common prenatally detected anomaly and affects up to 1%–2% of pregnancies. Postnatally, it resolves without surgical intervention in approximately 75%–80% of children, however this may take several years to occur, necessitating repeated clinic visits and additional invasive testing for many. For the remainder, a surgical intervention will be offered to relieve obstruction or to correct vesicoureteral reflux. During the monitoring period, many of these infants will be offered continuous antibiotic prophylaxis for the prevention of urinary tract infections, however this remains a controversial topic among pediatric urologists and nephrologists. Herein, we present an up‐to‐date review of the early management of prenatally detected UTD including timing of postnatal imaging, the use of antibiotics, when circumcision may be beneficial and long term outcomes of the most common HN etiologies. We also propose a decision making tool to help guide the care of infants with UTD.
The cost of caring: How advanced cancer patients affect Caregiver's employment in Singapore
Authors: Su Jasmine , Malhotra Chetna
Published: February 2022

Background

With ageing populations and rising cancer incidence, more people are becoming informal caregivers. Informal caregivers are less likely to work than non‐caregivers, yet little is known about how their employment changes over time. This study aimed to examine the association between decline in cancer patient's health (termed health shock) and caregiver's employment. A secondary aim was to assess characteristics of caregivers who stayed employed despite the health shock and the burden of caring for advanced stage cancer patients.

Method

This study used data from 270 dyads of advanced cancer patients and their caregivers who participated in the Cost of Medical Care of Patients with Advanced Serious Illness in Singapore study. The dyads were interviewed every 3 months for 2 years. Fixed‐effects regression was used to analyse the association between patient health shock and two caregiver employment outcomes (i.e., employment status and work disruptions).

Results

Ninety‐seven% of caregivers whose patient experienced a health shock reported work disruptions. About 13% of caregivers whose patient experienced at least one health shock left employment, compared to 5% of those whose patient did not experience any health shock. Following a patient health shock, caregivers were significantly less likely to be employed (β: −0.03; 95% CI, −0.05 to −0.001) and more likely to experience work disruptions (β: 0.06; 95% confidence interval [CI], −0.01 to 0.12). Caregivers who were young, educated, unmarried, not spousal caregivers, and not living with their patients were more likely to stay employed despite patient health shock (p < 0.01 for all).

Conclusion

Findings show that caregivers' employment is affected by their patients' health through the caregiving trajectory. Continuous support for caregivers catered to specific vulnerable subgroups may be important to keeping caregivers in the workforce.
Development of a novel castration‐resistant orthotopic prostate cancer model in New Zealand White rabbit
Authors: Wang Yu , Abenojar Eric C. , Wang Jing , de Leon Al C. , Tavri Sidhartha , Wang Xinning , Gopalakrishnan Ramamurthy , Walker Ethan , MacLennan Gregory T. , Giles Anoja , Czarnota Gregory J. , Basilion James P. , Exner Agata A.
Published: February 2022

Background

Prostate cancer (PCa) models in mice and rats are limited by their size and lack of a clearly delineated or easily accessible prostate gland. The canine PCa model is currently the only large animal model which can be used to test new preclinical interventions but is costly and availability is sparse. As an alternative, we developed an orthotopic human prostate tumor model in an immunosuppressed New Zealand White rabbit. Rabbits are phylogenetically closer to humans, their prostate gland is anatomically similar, and its size allows for clinically‐relevant testing of interventions.

Methods

Rabbits were immunosuppressed via injection of cyclosporine. Human PC3pipGFP PCa cells were injected into the prostate via either (a) laparotomy or (b) transabdominal ultrasound (US) guided injection. Tumor growth was monitored using US and magnetic resonance imaging (MRI). Contrast‐enhanced ultrasound (CEUS) imaging using nanobubbles and Lumason microbubbles was also performed to examine imaging features and determine the optimal contrast dose required for enhanced visualization of the tumor. Ex vivo fluorescence imaging, histopathology, and immunohistochemistry analyses of the collected tissues were performed to validate tumor morphology and prostate‐specific membrane antigen (PSMA) expression.

Results

Immunosuppression and tumor growth were, in general, well‐tolerated by the rabbits. Fourteen out of 20 rabbits, with an average age of 8 months, successfully grew detectable tumors from Day 14 onwards after cell injection. The tumor growth rate was 39 ± 25 mm2 per week. CEUS and MRI of tumors appear hypoechoic and T2 hypointense, respectively, relative to normal prostate tissue. Minimally invasive US‐guided tumor cell injection proved to be a better method compared to laparotomy due to the shorter recovery time required for the rabbits following injection. Among the rabbits that grew tumors, seven had tumors both inside and outside the prostate, three had tumors only inside the prostate, and four had tumors exclusively outside of the prostate. All tumors expressed the PSMA receptor.

Conclusions

We have established, for the first time, an orthotopic PCa rabbit model via percutaneous US‐guided tumor cell inoculation. This animal model is an attractive, clinically relevant intermediate step to assess preclinical diagnostic and therapeutic compounds.
Model‐informed drug development supporting the approval of the avelumab flat‐dose regimen in patients with advanced renal cell carcinoma
Authors: Masters Joanna C. , Khandelwal Akash , di Pietro Alessandra , Dai Haiqing , Brar Satjit
Published: February 2022

Avelumab is an anti–PD‐L1 monoclonal antibody approved as monotherapy for Merkel cell carcinoma (MCC) and urothelial carcinoma (UC), and in combination with axitinib for advanced renal cell carcinoma (aRCC). Although initially approved with weight‐based dosing (10 mg/kg intravenously [IV] every 2 weeks [Q2W]), avelumab was subsequently approved for flat dosing (800 mg IV Q2W) based on population pharmacokinetic (PopPK), exposure‐efficacy, and exposure‐safety modeling in MCC and UC. Here, through modeling and simulation, we provide justification for a flat‐dose regimen of avelumab plus axitinib in aRCC. Simulated exposure metrics from the previous monotherapy PopPK model (1827 patients) for both weight‐based and flat‐dose regimens were compared with exposure metrics from treatment‐naive patients with aRCC who received avelumab plus axitinib (488 patients). The aRCC population exposures were derived from a fit‐for‐purpose PopPK model developed using data from monotherapy and combination studies and the existing base structural PopPK model. Exposure‐response relationships for safety were analyzed, including grade ≥3 treatment‐emergent adverse events (TEAEs), any‐grade infusion‐related reactions, and TEAE any‐grade immune‐related adverse events (irAEs). Weight‐based dosing of avelumab in the aRCC population yielded similar PK exposures to the flat‐dose regimen reference exposures in the monotherapy population. Increased avelumab exposure was not associated with increased probabilities of grade ≥3 TEAEs or any‐grade IRRs, although there was a weak association with an increased probability of any‐grade irAEs. Overall, models in aRCC suggest that the avelumab 800‐mg Q2W flat‐dose regimen would provide similar benefits compared with weight‐based dosing with no meaningful change in the probability of AEs.