bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Comparison of [ONS]‐Type and [ONO]‐Type Schiff Bases in the Acylphosphonylation of Aldehyde
Authors: Zhang Guangwei , Zhang Yuanyuan , Zhang Han , Wen Yeqian
Published: March 2022

Two novel [ONS]‐type tridentate Schiff base ligands were prepared and employed in the acylphosphonylation of aldehyde. Ligand L1 was derived from 2‐amino‐3‐methylbutane‐1‐thiol and 3,5‐di‐tert‐butyl salicylaldehyde, and L1/Ti(Oi‐Pr)4 exhibited moderate to good activities to produce α‐acyloxyphosphonate. Furthermore, the performance difference of L1 and the traditional [ONO]‐type tridentate Schiff base L3 coordinating with TiIV or AlIII was also investigated.
Coupling of N‐Doped Mesoporous Carbon and N‐Ti3C2 in 2D Sandwiched Heterostructure for Enhanced Oxygen Electroreduction
Authors: Gou Zhaolin , Qu Huiqi , Liu Hanfang , Ma Yiru , Zong Lingbo , Li Bin , Xie Congxia , Li Zhenjiang , Li Wei , Wang Lei
Published: March 2022

2D heterostructures provide a competitive platform to tailor electrical property through control of layer structure and constituents. However, despite the diverse integration of 2D materials and their application flexibility, tailoring synergistic interlayer interactions between 2D materials that form electronically coupled heterostructures remains a grand challenge. Here, the rational design and optimized synthesis of electronically coupled N‐doped mesoporous defective carbon and nitrogen modified titanium carbide (Ti3C2) in a 2D sandwiched heterostructure, is reported. First, a F127‐polydopamine single‐micelle‐directed interfacial assembly strategy guarantees the construction of two surrounding mesoporous N‐doped carbon monolayers assembled on both sides of Ti3C2 nanosheets. Second, the followed ammonia post‐treatment successfully introduces N elements into Ti3C2 structure and more defective sites in N‐doped mesoporous carbon. Finally, the oxygen reduction reaction (ORR) and theoretical calculation prove the synergistic coupled electronic effect between N‐Ti3C2 and defective N‐doped carbon active sites in the 2D sandwiched heterostructure. Compared with the control 2D samples (0.87–0.88 V, 4.90–5.15 mA cm−2), the coupled 2D heterostructure possesses the best onset potential of 0.90 V and limited density current of 5.50 mA cm−2. Meanwhile, this catalyst exhibits superior methanol tolerance and cyclic durability. This design philosophy opens up a new thought for tailoring synergistic interlayer interactions between 2D materials.
Sustained Exosome‐Guided Macrophage Polarization Using Hydrolytically Degradable PEG Hydrogels for Cutaneous Wound Healing: Identification of Key Proteins and MiRNAs, and Sustained Release Formulation
Authors: Kwak Gijung , Cheng Jing , Kim Hyosuk , Song Sukyung , Lee Su Jin , Yang Yoosoo , Jeong Ji Hoon , Lee Ji Eun , Messersmith Phillip B. , Kim Sun Hwa
Published: March 2022

Macrophages (Mφs) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti‐inflammatory (M2) Mφs during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2‐Mφs (M2‐Exos), which contain putative key regulators driving Mφ polarization, are used as local microenvironmental cues to induce reprogramming of M1‐Mφs toward M2‐Mφs for effective wound management. As an injectable controlled release depot for exosomes, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels (Exogels) are designed and employed for encapsulating M2‐Exos to maximize their therapeutic effects in cutaneous wound healing. The degradation time of the hydrogels is adjustable from 6 days or up to 27 days by controlling the crosslinking density and tightness. The localization of M2‐Exos leads to a successful local transition from M1‐Mφs to M2‐Mφs within the lesion for more than 6 days, followed by enhanced therapeutic effects including rapid wound closure and increased healing quality in an animal model for cutaneous wound healing. Collectively, the hydrolytically degradable PEG hydrogel‐based exosome delivery system may serve as a potential tool in regulating local polarization state of Mφs, which is crucial for tissue homeostasis and wound repair.
Automated and Dynamic Control of Chemical Content in Droplets for Scalable Screens of Small Animals
Authors: Aubry Guillaume , Milisavljevic Marija , Lu Hang
Published: March 2022

Screening functional phenotypes in small animals is important for genetics and drug discovery. Multiphase microfluidics has great potential for enhancing throughput but has been hampered by inefficient animal encapsulation and limited control over the animal's environment in droplets. Here, a highly efficient single‐animal encapsulation unit, a liquid exchanger system for controlling the droplet chemical environment dynamically, and an automation scheme for the programming and robust execution of complex protocols are demonstrated. By careful use of interfacial forces, the liquid exchanger unit allows for adding and removing chemicals from a droplet and, therefore, generating chemical gradients inaccessible in previous multiphase systems. Using Caenorhabditis elegans as an example, it is demonstrated that these advances can serve to analyze dynamic phenotyping, such as behavior and neuronal activity, perform forward genetic screen, and are scalable to manipulate animals of different sizes. This platform paves the way for large‐scale screens of complex dynamic phenotypes in small animals.
Surface Adsorption‐Mediated Ultrahigh Efficient Peptide Encapsulation with a Precise Ratiometric Control for Type 1 and 2 Diabetic Therapy
Authors: Zhang Pei , Du Chunyang , Huang Tianhe , Hu Shuai , Bai Yuancheng , Li Cong , Feng Guobing , Gao Yue , Li Zhi , Wang Baoxun , Hirvonen Jouni T. , Fan Jin , Santos Hélder A. , Liu Dongfei
Published: March 2022

A surface adsorption strategy is developed to enable the engineering of microcomposites featured with ultrahigh loading capacity and precise ratiometric control of co‐encapsulated peptides. In this strategy, peptide molecules (insulin, exenatide, and bivalirudin) are formulated into nanoparticles and their surface is decorated with carrier polymers. This polymer layer blocks the phase transfer of peptide nanoparticles from oil to water and, consequently, realizes ultrahigh peptide loading degree (up to 78.9%). After surface decoration, all three nanoparticles are expected to exhibit the properties of adsorbed polymer materials, which enables the co‐encapsulation of insulin, exenatide, and bivalirudin with a precise ratiometric control. After solidification of this adsorbed polymer layer, the release of peptides is synchronously prolonged. With the help of encapsulation, insulin achieves 8 days of glycemic control in type 1 diabetic rats with one single injection. The co‐delivery of insulin and exenatide (1:1) efficiently controls the glycemic level in type 2 diabetic rats for 8 days. Weekly administration of insulin and exenatide co‐encapsulated microcomposite effectively reduces the weight gain and glycosylated hemoglobin level in type 2 diabetic rats. The surface adsorption strategy sets a new paradigm to improve the pharmacokinetic and pharmacological performance of peptides, especially for the combination of peptides.
M‐Series Nonfullerene Acceptors with Varied Fluorinated End Groups: Crystal Structure, Intermolecular Interaction, Charge Transport, and Photovoltaic Performance
Authors: Li Zhijian , Ma Xiaoling , Liao Ruochuan , Tu Qisheng , Ma Yunlong , Zheng Qingdong
Published: March 2022

Intermolecular interaction of nonfullerene acceptors (NFAs) is essential for controlling their photovoltaic performance. Fluorinated substituents attached at the end groups of NFAs can significantly affect their frontier molecular orbitals and intermolecular interactions. Herein, four heteroheptacene‐based NFAs (ML‐1F, ML‐2FO, ML‐2FM, and ML‐2FP) with different fluorinated end groups are designed, synthesized, and characterized. The impact of the end group on the crystal structures, optical, electrochemical, charge transport, and photovoltaic properties of these NFAs are systematically studied. In comparison with the acceptor with monofluorinated end groups, the acceptors with difluorinated end groups show reduced bandgaps and downshifted energy levels. Single‐crystal results demonstrate that the intermolecular interactions including the π–π stacking distance and molecular aggregation behavior of these acceptors are also affected by the variation of end groups thereby leading to the acceptors with varied charge transport properties. In combination with the polymer donor of PM6, ML‐2FM exhibits the highest power conversion efficiency (PCE) of 15.33% with a short‐circuit current density of 23.73 mA cm−2 and a fill factor of 0.734. However, ML‐2FP displays an inferior PCE of 10.48% which is lower than that of ML‐1F (11.41% PCE). The results show that the fluorine substituent number and position of end group are of vital importance in determining their photovoltaic performance.
Experimental Analysis on Bending Behavior of Non‐Alloy Carbon Steel Sheets Using Laser‐Forming Process
Authors: Abedinzadeh Reza , Sattari Mehdi , Toghraie Davood
Published: March 2022

Herein, the laser‐forming process of nonalloy carbon steel sheets is investigated experimentally. First, it is necessary to consider how the material factor of carbon steels affects the bend angle during the laser‐forming process. Therefore, bend angle results of three grades of carbon steel sheets, including St 14, CK 45, and CK 75, are studied based on the Taguchi design of the experiment. Then, the effects of process parameters, as named laser power, beam diameter, and scan rate on bend angle, are investigated for the most formable steel. The results show that the steel grade factor exhibits an obvious effect on bend angle, but the laser power and laser beam scan rate as process parameters play a more dominant role in determining the magnitude of the bend angle. Moreover, for St 14 with the highest bend angle, the scan rate has the most significant effect on the bend angle. In addition, the laser beam diameter exhibits the least significant effect on the bend angle. It can be concluded that the laser scan rate is the fastest factor to adjust and the most efficient control parameter for the bend angle.
A natural disaster student support program for online students faces the challenge of COVID‐19
Authors: Sanders Jennie , Howlett Bernadette , Jungbauer Michelle , Koch Alonna , Bliven AnnaMaria , Velarde Jesse , Saulnier Heather
Published: March 2022

This article describes Western Governors University's emergency management student support program in place prior to the pandemic and the challenge to adapt and address the unprecedented needs students faced due to COVID‐19. Included are key lessons learned in addressing the impact of COVID‐19 and evidence‐based learnings in response to the large‐scale student needs during the prolonged pandemic.
Reconceptualizing student engagement: Supporting diverse students in medical school through holistic approaches
Authors: Blalock A. Emiko , Noble Chelsea E. , Chinchilla Jennifer , Flores Antonio , Lepe Paola R.
Published: March 2022

This article illustrates the important role family and community play in students’ sense of belonging, and the need for student services to look beyond the college campus to support student engagement.
Lessons for the future: Learning from virtual student services
Authors: Hugus Erin , Tkatchov Mary , Becker Brianna K. , Hunter Kendra , Brazelton G. Blue
Published: March 2022

In this final article, we revisit the issue and present the common themes described throughout this issue. We conclude with recommendations for continued practice of solutions that serve all students.
Xanthohumol targets the JNK1/2 signaling pathway in apoptosis of human nasopharyngeal carcinoma cells
Authors: Hsieh Ming‐Yu , Hsieh Ming‐Ju , Lo Yu‐Sheng , Lin Chia‐Chieh , Chuang Yi‐Ching , Chen Mu‐Kuan , Chou Ming‐Chih
Published: March 2022

Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 μM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis‐related pathways. Xn upregulated the expression of apoptosis‐related proteins, namely DR5, cleaved RIP, caspase‐3, caspase‐8, caspase‐9, PARP, Bim, and Bak, and it downregulated the expression of Bcl‐2. Xn upregulated the c‐Jun N‐terminal kinase (JNK) in the mitogen‐activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn‐activated cleaved caspase‐3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.
Burn‐out and employability rates are impacted by the level of job autonomy and workload among Dutch gastroenterologists
Authors: van Leeuwen Evelien H. , Kuyvenhoven Johan Ph. , Taris Toon W. , Verhagen Marc A. M. T.
Published: March 2022

Background

Increasing burn‐out rates among gastroenterologists make it necessary to find ways to prevent burn‐out and to stimulate their ability and willingness to continue working (i.e., their employability). Understanding their antecedents might help organizations to prevent burn‐out and to enhance employability among this occupational group.

Objective

The purpose of this study is to provide insight in the relationship between job characteristics and job crafting behavior on the one hand and job outcomes (burn‐out symptoms and employability) on the other hand.

Methods

Data from two surveys in 2020 and 2021 were collected in a longitudinal study among 238 Dutch gastroenterologists. The data were analyzed with multiple linear regression analyses and paired‐samples t‐tests.

Results

Job characteristics, specifically job aspects that require sustained physical and/or psychological effort or skills (i.e., job demands), are important predictors of burn‐out symptoms among gastroenterologists. Specifically, high quantitative and emotional workload are significantly related to more burn‐out symptoms. No strong relationship was found between job crafting and burn‐out symptoms. Furthermore, job aspects that reduce the negative impact of these demanding aspects and that help to achieve work goals (i.e., job resources), and job demands to some extent, significantly predict employability. In particular, high job autonomy is related to higher employability, and high quantitative workload is associated with lower employability. Job crafting does not significantly affect employability. Furthermore, levels of burn‐out symptoms and employability differed only little across time.

Conclusion

In gastroenterologists, a high quantitative workload and emotional workload are associated with a higher burn‐out risk, while low job autonomy and high quantitative workload are associated with more negative perceptions of employability. To prevent burn‐out and to create positive perceptions of employability, it is important to take these aspects into account.
Serological survey of anti‐Leptospira spp. antibodies in individuals with animal hoarding disorder and their dogs in a major city of Southern Brazil
Authors: Cunha Graziela Ribeiro da , Pellizzaro Maysa , Martins Camila Marinelli , Rocha Suzana Maria , Yamakawa Ana Carolina , da Silva Evelyn Cristine , dos Santos Andrea Pires , Morikawa Vivien Midori , Langoni Hélio , Biondo Alexander Welker
Published: March 2022

Background

Individuals with hoarding disorder (HD) presented a persistent difficulty in detaching from objects and/or animals. Unhealthy conditions, frequently found in cases of animal HD (AHD), may favour environmental contamination and the spread of zoonotic pathogens. Despite that, only one study of zoonotic diseases in individuals with AHD and their companion animals has been conducted to date.

Objectives

This study aimed to assess the seroprevalence of anti‐Leptospira spp. antibodies in individuals with AHD and their dogs in a major city of Southern Brazil.

Methods

Blood samples were obtained from 264 dogs (21 households) and 19 individuals with AHD (11 households) and tested by microscopic agglutination test.

Results

All human samples were seronegative. Seropositivity was found in 16/264 (6.1%; CI 95% 3.3–9.6%) dogs from 11/21 (52.38%) households, with titres ranging from 100 up to 400, and Copenhageni (10/16; 62.5%) was the most frequent serovar. Surprisingly, seropositivity of hoarded dogs found herein was among the lowest reportedly observed in other dog populations of Brazil. Two epidemiological variables were significantly associated with seropositivity in dogs: the presence of cat hoarding (p = 0.004) and the report of flood occurrence in the household (p = 0.031).

Conclusions

No individuals with AHD were seropositive, and besides the lower seroprevalence of dogs, they probably had contact with Leptospira spp. at some point in their life. Since dogs can be considered potential sentinels in leptospirosis, public health programs must become aware of the risk of leptospirosis cases in households of individuals with AHD and nearby communities.
Torsional oscillation damping in wind turbines with virtual synchronous machine‐based frequency response
Authors: Lu Liang , Saborío‐Romano Oscar , Cutululis Nicolaos A.
Published: March 2022

In the quest of improving the frequency response capability of wind turbines, control solutions trying to emulate synchronous machines have been proposed. While their performance in terms of frequency support is relatively good, they may trigger torsional oscillations, cause fatigue and damage in the drivetrain, and reduce its lifetime. In this paper, the torsional oscillations caused by a virtual synchronous machine (VSM)‐based frequency controller are illustrated, and methods for damping them are introduced. Two torsional oscillation damping methods are compared and combined to derive an improved method. Dynamic simulation results show better damping performance from the combined damping method.
Grundlegende semantische Aspekte der Ausdrücke
Authors: Neumair Phillip Alexander
Published: March 2022

Im Rahmen einer lexikalisch-semantischen Untersuchung sind der Gebrauch und die Bedeutung des Ausdrucks Flüchtling als juristisch-politische Kategorie zu nennen. Rechte und Pflichten der Menschen, denen der Status als Flüchtling verliehen wird, werden im Asylgesetz und der Genfer Flüchtlingskonvention festgelegt, wobei beide juristische Schriften ein enges Raster anlegen, das der Realität von Flucht im Kontext der sog. Flüchtlingskrise nicht gerecht wird. Zudem liegt in Flüchtling eine „Lebensrolle“ vor, die sich im artikellosen Gebrauch in einfachen Nominalphrasen zeigt. Migrant_in erfährt im Gegensatz zu Flüchtling keine juristisch fixierte Bedeutung, gleichwohl politische Definitionen eine Rolle spielen. Sie kennzeichnen den Ausdruck als übergreifende Personenbezeichnung im Kontext unterschiedlicher Arten von Menschenmobilität. Ausgehend von einer Betrachtung des Ausdrucks Migrationshintergrund wird gezeigt, dass in allen drei Ausdrücken differenz-konstruierende, Othering reflektierende und vollziehende Konzepte vorliegen, die per se zwar nicht problematisch sind, es jedoch werden, wenn ihre gebildeten Kategorien zu einer umfassenden, allerklärenden Identifikation von Personen herangezogen werden. Geflüchtete_r wird als politisch korrekte Bezeichnung insbesondere als Alternative zu Flüchtling betrachtet, wobei sich die Argumente vor allem auf folgende Aspekte beziehen: das eine abwertende Funktion attestierte Suffix -ling in Flüchtling, die Möglichkeit, in Geflüchtete_r eine weibliche Form zu bilden, ein höheres attributives Potenzial von Geflüchtete_r sowie der perfektive Aspekt in Geflüchtete_r, der die Flucht als abgeschlossen konzeptualisiere.
Wissenssemantische Analyse: die evozierten Frames
Authors: Neumair Phillip Alexander
Published: March 2022

Die wissens- bzw. frame-semantische Analyse der Ausdrücke, wie sie im untersuchten Diskursausschnitt in Pressetexten gebraucht werden, zeigt: Steht der Ausdruck Geflüchtete_r in einem engen konzeptuellen wie sprachlichen Verhältnis zu dem zwar nicht unproblematisierbaren, jedoch zukunftsorientierten sowie konstruktiven Themenkomplex der Integration, kennzeichnen Flüchtling eine stärkere Passivität der bezeichneten Personen sowie, in Verbindung dazu, der Umgang politischer Akteur_innen mit ihnen. Die Analyse zweier politischer Reden zeigt jedoch, dass Flüchtling nicht per se eine negative Konnotation zugeschrieben werden sollte. So perspektiviert etwa Heiko Maas das Konzept hinsichtlich Chancen und Perspektiven in der Aufnahmegesellschaft und verbindet dies mit (einem Aufruf zu) politischen Handlungen. Ein zentraler Unterschied zwischen Geflüchtete_r und Flüchtling besteht darin, dass mit ersterer Bezeichnung weitaus häufiger auf Personen verwiesen wird, die sich bereits in Deutschland befinden. Migrant_in gleicht sich hinsichtlich des kognitiv-semantischen wie epistemischen Gehalts und auch quantitativ stark an Flüchtling an. Dies ist u. a. an dem Umstand zu erkennen, dass – trotz seinem Dasein als Sammelbegriff – der Ausdruck im Gros der Fälle auf Menschen referiert, deren Fluchtbewegung noch andauert. Dieses sich im Diskurs zur sog. Flüchtlingskrise sprachlich manifestierende Wissen – in der vorliegenden Studie evoziert durch die jeweiligen instantiierten oder token-Frames der Ausdrücke Flüchtling, Geflüchtete_r und Migrant_in – kann in Form von type-Frames zu den jeweiligen Konzepten abgebildet werden.
PP2A-Cdc55 phosphatase regulates actomyosin ring contraction and septum formation during cytokinesis
Authors: Moyano-Rodríguez Yolanda , Vaquero David , Vilalta-Castany Odena , Foltman Magdalena , Sanchez-Diaz Alberto , Queralt Ethel
Published: March 2022

Eukaryotic cells divide and separate all their components after chromosome segregation by a process called cytokinesis to complete cell division. Cytokinesis is highly regulated by the recruitment of the components to the division site and through post-translational modifications such as phosphorylations. The budding yeast mitotic kinases Cdc28-Clb2, Cdc5, and Dbf2-Mob1 phosphorylate several cytokinetic proteins contributing to the regulation of cytokinesis. The PP2A-Cdc55 phosphatase regulates mitosis counteracting Cdk1- and Cdc5-dependent phosphorylation. This prompted us to propose that PP2A-Cdc55 could also be counteracting the mitotic kinases during cytokinesis. Here we show that in the absence of Cdc55, AMR contraction and the primary septum formation occur asymmetrically to one side of the bud neck supporting a role for PP2A-Cdc55 in cytokinesis regulation. In addition, by in vivo and in vitro assays, we show that PP2A-Cdc55 dephosphorylates the chitin synthase II (Chs2 in budding yeast) a component of the Ingression Progression Complexes (IPCs) involved in cytokinesis. Interestingly, the non-phosphorylable version of Chs2 rescues the asymmetric AMR contraction and the defective septa formation observed in cdc55∆ mutant cells. Therefore, timely dephosphorylation of the Chs2 by PP2A-Cdc55 is crucial for proper actomyosin ring contraction. These findings reveal a new mechanism of cytokinesis regulation by the PP2A-Cdc55 phosphatase and extend our knowledge of the involvement of multiple phosphatases during cytokinesis.
The subjective and objective very long-term outcomes of TVT in the COVID era: A 20-year follow-up
Authors: Braga Andrea , Caccia Giorgio , Papadia Andrea , Castronovo Fabiana , Salvatore Stefano , Scancarello Chiara , Torella Marco , Ghezzi Fabio , Serati Maurizio
Published: March 2022

Introduction and hypothesis

Few studies in literature have assessed the long-term durability and mesh-related complications of mid-urethral slings (MUSs). The aim of this study is to assess the efficacy and safety of retro-pubic tension-free vaginal tape (TVT) 20 years after implantation for the treatment of female stress urinary incontinence (SUI).

Methods

A prospective observational study was conducted in two urogynaecologic units in two countries. All the patients involved were consecutive women with urodynamically proven pure SUI treated by TVT. The patients underwent preoperative clinical and urodynamic evaluations. Subjective outcomes, objective outcomes and adverse events were recorded during the follow-up period.

Results

Fifty-two patients underwent a TVT surgical procedure. Twenty years after surgery, 32 out of 36 patients (88.8%) declared themselves cured (p = 0.98). Similarly, 33 out of these 36 patients (91.7%) were objectively cured (p = 0.98). No significant deterioration of subjective and objective cure rates was observed over time (p for trend 0.50 and 0.48). Fifteen of the 36 patients (41.6%) at the 20-year follow-up reported the onset of de novo overactive bladder (OAB) (p = 0.004). No significant vaginal bladder or urethral erosion or de novo dyspareunia was recorded and no patient required tape release or resection during this period. The cause of death of seven out of ten women who died in the last year of the follow-up period was coronavirus disease 19 (COVID 19).

Conclusions

The 20-year results of this study showed that TVT is a highly effective and safe option for the treatment of SUI. The impact of COVID 19 on the mortality rate of elderly women has drastically reduced the number of eligible patients for future evaluations in our region.
Low-entry-barrier point-of-care testing of anti-SARS-CoV-2 IgG in the population of Upper Austria from December 2020 until April 2021—a feasible surveillance strategy for post-pandemic monitoring?
Authors: Doppler Christian , Feischl Michael , Ganhör Clara , Puh Spela , Müller Marina , Kotnik Michaela , Mimler Teresa , Sonnleitner Max , Bernhard David , Wechselberger Christian
Published: March 2022

Already at the very beginning of the COVID-19 pandemic, an extensive PCR and antigen testing strategy was considered necessary and subsequently also proved successful in order to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on international and national levels. However, equally important will be the continuous monitoring of the seroprevalence status of populations from defined regions to detect—in a timely manner—any recurrence of infections or an eventual decline in antibody levels of vaccinated individuals, especially in the emerging post-pandemic situation. The aim of this study was to estimate the prevalence of SARS-CoV-2-specific immunoglobulin G antibodies in the federal state of Upper Austria (Austria) during the period of December 2020 until April 2021. To achieve this goal, we have analyzed anonymized data on the immune status of self-referral volunteers that have been determined at local pharmacies through a low-entry-barrier point-of-care analysis approach. The seroprevalence values for immunoglobulin type G antibodies against SARS-CoV-2 antigens obtained by rapid diagnostic testing on peripheral blood from volunteers reflect the current population-based estimates reported in the literature as well as the positivity rates detected by PCR-screening analyses. In conclusion, broad-based monitoring of IgG antibodies by means of a point-of-care testing network represents a valuable tool to assess the current immune situation within regionally defined populations.

Graphical abstract
Outcomes of clitoral reconstruction in women that experienced genital mutilation and/or genital cutting: 10 years of experience in the Netherlands
Authors: Karim Refaat Bari , Karim Disha Elizabeth Nihar Bari , Dekker Judith Johanna Maria Louise , Middelburg Maria Johanna
Published: March 2022

Background

The empowerment of women that migrated from Africa and the Middle East to the Netherlands increased the awareness and demand for clitoral reconstruction in women that experienced genital mutilation and/or genital cutting (FGM/C). Our aim was to investigate the outcomes of FGM/C-corrective surgeries conducted over a 10-year period.

Methods

We recruited 72 patients with FGM/C from January 2010 to January 2021. All patients received counseling and underwent strict selection for surgery. Clitoroplasty was performed according to the Foldès technique. Patients were followed for a mean of 13 months. Surgery outcomes were evaluated with a questionnaire.

Results

Of 72 women recruited, 19 (26%) were unsuitable for clitoral reconstructive surgery, due to comorbidities that required prior treatment (n = 5), unrealistic expectations about the surgery outcome (n = 12), a desire for information only about the procedure (n = 2), a choice to treat only a Bartholin cyst (n = 1), or previous surgery for FGM/C (n = 1). As of January 2021, 45 patients had undergone surgery and were included in the present study. After surgery, we performed primary clitoroplasty. Postoperatively, we observed four minor complications. Among all 45 patients, 35 (76%) reported satisfaction with the treatment and improvements in self-respect. Four woman reported disappointment in the aesthetic results, but they were satisfied with the surgery. Six women were lost to follow-up.

Conclusions

After well-specified preoperative patient selection, clitoral reconstructive surgery led to a high patient satisfaction rate with minor surgical complications. Among patients that desire reconstruction, this surgery can be performed after careful counseling.

Level of evidence: Level IV,  Risk/Prognostic study.
Intraoperative fluorescence molecular imaging accelerates the coming of precision surgery in China
Authors: Zhang Zeyu , He Kunshan , Chi Chongwei , Hu Zhenhua , Tian Jie
Published: March 2022

Purpose

China has the largest cancer population globally. Surgery is the main choice for most solid cancer patients. Intraoperative fluorescence molecular imaging (FMI) has shown its great potential in assisting surgeons in achieving precise resection. We summarized the typical applications of intraoperative FMI and several new trends to promote the development of precision surgery.

Methods

The academic database and NIH clinical trial platform were systematically evaluated. We focused on the clinical application of intraoperative FMI in China. Special emphasis was placed on a series of typical studies with new technologies or high-level evidence. The emerging strategy of combining FMI with other modalities was also discussed.

Results

The clinical applications of clinically approved indocyanine green (ICG), methylene blue (MB), or fluorescein are on the rise in different surgical departments. Intraoperative FMI has achieved precise lesion detection, sentinel lymph node mapping, and lymphangiography for many cancers. Nerve imaging is also exploring to reduce iatrogenic injuries. Through different administration routes, these fluorescent imaging agents provided encouraging results in surgical navigation. Meanwhile, designing new cancer-specific fluorescent tracers is expected to be a promising trend to further improve the surgical outcome.

Conclusions

Intraoperative FMI is in a rapid development in China. In-depth understanding of cancer-related molecular mechanisms is necessary to achieve precision surgery. Molecular-targeted fluorescent agents and multi-modal imaging techniques might play crucial roles in the era of precision surgery.
Multi-phase contrast-enhanced magnetic resonance image-based radiomics-combined machine learning reveals microscopic ultra-early hepatocellular carcinoma lesions
Authors: Sun Kui , Shi Liting , Qiu Jianfeng , Pan Yuteng , Wang Ximing , Wang Haiyan
Published: March 2022

Purpose

This study aimed to investigate whether models built from radiomics features based on multiphase contrast-enhanced MRI can identify microscopic pre-hepatocellular carcinoma lesions.

Methods

We retrospectively studied 54 small hepatocellular carcinoma (SHCC, diameter < 2 cm) patients and 70 patients with hepatocellular cysts or haemangiomas from September 2018 to June 2021. For the former, two MRI scans were collected within 12 months of each other; the 2nd scan was used to confirm the diagnosis. The volumes of interest (VOIs), including SHCCs and normal liver tissues, were delineated on the 2nd scans, mapped to the 1st scans via image registration, and enrolled into the SHCC and internal-control cohorts, respectively, while those of normal liver tissues from patients with hepatocellular cysts or haemangioma were enrolled in the external-control cohort. We extracted 1132 radiomics features from each VOI and analysed their discriminability between the SHCC and internal-control cohorts for intra-group classification and the SHCC and external-control cohorts for inter-group classification. Five radial basis-function, kernel-based support vector machine (SVM) models (four corresponding single-phase models and one integrated from the four-phase MR images) were established.

Results

Among the 124 subjects, the multiphase models yielded better performance on the testing set for intra-group and inter-group classification, with areas under the receiver operating characteristic curves of 0.93 (95% CI, 0.85–1.00) and 0.97 (95% CI, 0.92–1.00), accuracies of 86.67% and 94.12%, sensitivities of 87.50% and 94.12%, and specificities of 85.71% and 94.12%, respectively.

Conclusion

The combined multiphase MRI-based radiomics feature model revealed microscopic pre-hepatocellular carcinoma lesions.
Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma
Authors: Oosterveer Timo T. M. , van Erp Gonnie C. M. , Hendriks Pim , Broersen Alexander , Overduin Christiaan G. , van Rijswijk Carla S. P. , van Erkel Arian R. , van der Meer Rutger W. , Tushuizen Maarten E. , Moelker Adriaan , Meijerink Martijn R. , van Delden Otto M. , de Jong Koert P. , van der Leij Christiaan , Smits Maarten L. J. , Urlings Thijs A. J. , Braak Jeffrey P. B. M. , Meershoek-Klein Kranenbarg Elma , van Duijn-de Vreugd Bianca , Zeijdner Evelijn , Goeman Jelle J. , Fütterer Jurgen J. , Coenraad Minneke J. , Dijkstra Jouke , Burgmans Mark C.
Published: March 2022

Purpose

The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy.

Materials and Methods

This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival.

Discussion

It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success.

Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713.
Adaptive immunity, chronic inflammation and the clock
Authors: Gray Kathryn J. , Gibbs Julie E.
Published: March 2022

The adaptive arm of the immune system facilitates recognition of specific foreign pathogens and, via the action of T and B lymphocytes, induces a fine-tuned response to target the pathogen and develop immunological memory. The functionality of the adaptive immune system exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking and development of T lymphocyte subsets) and in responses to challenge. Here, we discuss how the circadian clock exerts influence over the function of the adaptive immune system, considering the roles of cell intrinsic clockwork machinery and cell extrinsic rhythmic signals. Inappropriate or misguided actions of the adaptive immune system can lead to development of autoimmune diseases such as rheumatoid arthritis, ulcerative colitis and multiple sclerosis. Growing evidence indicates that disturbance of the circadian clock has negative impact on development and progression of these chronic inflammatory diseases and we examine current understanding of clock-immune interactions in the setting of these inflammatory conditions. A greater appreciation of circadian control of adaptive immunity will facilitate further understanding of mechanisms driving daily variation in disease states and drive improvements in the diagnosis and treatment of chronic inflammatory diseases.
Coronary calcium scores on dual-source photon-counting computed tomography: an adapted Agatston methodology aimed at radiation dose reduction
Authors: van der Werf Niels R. , Greuter Marcel J. W. , Booij Ronald , van der Lugt Aad , Budde Ricardo P. J. , van Straten Marcel
Published: March 2022

Objectives

The aim of this study was to determine mono-energetic (monoE) level–specific photon-counting CT (PCCT) Agatston thresholds, to yield monoE level independent Agatston scores validated with a dynamic cardiac phantom. Also, we examined the potential of dose reduction for PCCT coronary artery calcium (CAC) studies, when reconstructed at low monoE levels.

Methods

Theoretical CAC monoE thresholds were calculated with data from the National Institute of Standards and Technology (NIST) database. Artificial CAC with three densities were moved in an anthropomorphic thorax phantom at 0 and 60–75 bpm, and scanned at full and 50% dose on a first-generation dual-source PCCT. For all densities, Agatston scores and maximum CT numbers were determined. Agatston scores were compared with the reference at full dose and 70 keV monoE level; deviations (95% confidence interval) < 10% were deemed to be clinically not-relevant.

Results

Averaged over all monoE levels, measured CT numbers deviated from theoretical CT numbers by 6%, 13%, and − 4% for low-, medium-, and high-density CAC, respectively. At 50% reduced dose and 60–75 bpm, Agatston score deviations were non-relevant for 60 to 100 keV and 60 to 120 keV for medium- and high-density CAC, respectively.

Conclusion

MonoE level–specific Agatston score thresholds resulted in similar scores as in standard reconstructions at 70 keV. PCCT allows for a potential dose reduction of 50% for CAC scoring using low monoE reconstructions for medium- and high-density CAC.

Key Points

• Mono-energy level–specific Agatston thresholds allow for reproducible coronary artery calcium quantification on mono-energetic images.

• Increased calcium contrast-to-noise ratio at reduced mono-energy levels allows for coronary artery calcium quantification at 50% reduced radiation dose for medium- and high-density calcifications.
High-power, high-brightness solid-state laser architectures and their characteristics
Authors: Brauch Uwe , Röcker Christoph , Graf Thomas , Abdou Ahmed Marwan
Published: March 2022

The development of high-power diode lasers enabled new solid-state laser concepts such as thin-disk, fiber, and Innoslab lasers based on trivalent ytterbium as the laser-active ion, which resulted in a tremendous increase in the efficiency and beam quality of cw lasers compared to previously used lamp-pumped rod or slab lasers and the realization of ultrafast lasers with several 100 W or even kilowatts of average power. In addition to their beneficial thermo-optical properties, these architectures offer characteristic benefits making them especially suitable to obtain dedicated laser properties. This review article comprises milestone developments, characteristic challenges, and benefits, and summarizes the state of the art of high-power solid-state lasers with the focus on ultrafast lasers.
Determination of cooling rates of glasses over four orders of magnitude
Authors: Scarani Alex , Vona Alessandro , Di Genova Danilo , Al-Mukadam Raschid , Romano Claudia , Deubener Joachim
Published: March 2022

Volcanic materials can experience up to eleven orders of magnitude of cooling rate (qc) starting from 10–5 K s−1. The glassy component of volcanic material is routinely measured via differential scanning calorimeter (DSC) to obtain qc through the determination of the glass fictive temperature (Tf). Conventional DSC (C-DSC), which has been employed for decades, can only access a relatively small range of qc (from ~ 10–2 to ~ 1 K s−1). Therefore, extrapolations up to six orders of magnitude of C-DSC data are necessary to derive qc of glasses quenched both at extremely low and high qc. Here, we test the reliability of such extrapolations by combining C-DSC with the recently introduced flash calorimetry (F-DSC). F-DSC enables to extend the qc exploration up to 104 K s−1. We use three synthetic glasses as analogs of volcanic melts. We first apply a normalization procedure of heat flow data for both C-DSC and F-DSC to derive Tf as a function of experimental qc, following the “unified area-matching” approach. The obtained Tf–qc relationship shows that Arrhenius models, widely adopted in previous studies, are only valid for qc determination within the calibration range. In contrast, a non-Arrhenius model better captures qc values, especially when a significant extrapolation is required. We, therefore, present a practical “how-to” protocol for estimating qc using DSC.
Development of a droplet digital polymerase chain reaction tool for the detection of Toxoplasma gondii in meat samples
Authors: Mancusi Andrea , Giordano Angela , Bosco Antonio , Girardi Santa , Proroga Yolande T. R. , Morena Luigi , Pinto Renato , Sarnelli Paolo , Cringoli Giuseppe , Rinaldi Laura , Capuano Federico , Maurelli Maria Paola
Published: March 2022

Toxoplasmosis is a zoonotic disease caused by the protozoan parasite Toxoplasma gondii. Infection in humans has usually been related to the consumption of raw, undercooked or cured meat. The aim of this study was to develop a droplet digital polymerase chain reaction (ddPCR)-based assay for the detection and quantification of T. gondii in meat samples. To optimize the ddPCR, T.gondii reference DNA aliquots at five known concentrations: 8000 cg/µl, 800 cg/µl, 80 cg/µl, 8 cg/µl were used. Moreover, results obtained by ddPCR and quantitative PCR (qPCR) were compared using 80 known samples (40 positive and 40 negative), as well as 171 unknown diaphragm tissue samples collected at slaughterhouses. The ddPCR showed a sensitivity of 97.5% and a specificity of 100%, with a detection limit of 8 genomic copy/µl of T. gondii. A nearly perfect agreement (κ = 0.85) was found between results obtained by ddPCR and qPCR for both positive and negative known samples analysed. On the 171 diaphragm tissue samples from field, 7.6% resulted positive by ddPCR and only 1.2% by qPCR. Therefore, this innovative method could be very useful for the detection of T. gondii in meat samples, aiming to prevent human infections.
Assessment of neuropsychological function in brain tumor treatment: a comparison of traditional neuropsychological assessment with app-based cognitive screening
Authors: Romero-Garcia Rafael , Owen Mallory , McDonald Alexa , Woodberry Emma , Assem Moataz , Coelho Pedro , Morris Rob C. , Price Stephen J. , Santarius Tom , Suckling John , Manly Tom , Erez Yaara , Hart Michael G.
Published: March 2022

Background

Gliomas are typically considered to cause relatively few neurological impairments. However, cognitive difficulties can arise, for example during treatment, with potential detrimental effects on quality of life. Accurate, reproducible, and accessible cognitive assessment is therefore vital in understanding the effects of both tumor and treatments. Our aim is to compare traditional neuropsychological assessment with an app-based cognitive screening tool in patients with glioma before and after surgical resection. Our hypotheses were that cognitive impairments would be apparent, even in a young and high functioning cohort, and that app-based cognitive screening would complement traditional neuropsychological assessment.

Methods

Seventeen patients with diffuse gliomas completed a traditional neuropsychological assessment and an app-based touchscreen tablet assessment pre- and post-operatively. The app assessment was also conducted at 3- and 12-month follow-up. Impairment rates, mean performance, and pre- and post-operative changes were compared using standardized Z-scores.

Results

Approximately 2–3 h of traditional assessment indicated an average of 2.88 cognitive impairments per patient, while the 30-min screen indicated 1.18. As might be expected, traditional assessment using multiple items across the difficulty range proved more sensitive than brief screening measures in areas such as memory and attention. However, the capacity of the screening app to capture reaction times enhanced its sensitivity, relative to traditional assessment, in the area of non-verbal function. Where there was overlap between the two assessments, for example digit span tasks, the results were broadly equivalent.

Conclusions

Cognitive impairments were common in this sample and app-based screening complemented traditional neuropsychological assessment. Implications for clinical assessment and follow-up are discussed.