bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Novel Pseudo‐Natural Product Type IV IDO1 Inhibitor Chemotype
Authors: Davies Caitlin , Dötsch Lara , Ciulla Maria Gessica , Hennes Elisabeth , Yoshida Kei , Gasper Raphael , Scheel Rebecca , Sievers Sonja , Strohmann Carsten , Kumar Kamal , Ziegler Slava , Waldmann Herbert
Published: August 2022

Natural product (NP)‐inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo‐natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo‐NP class, whereby indole‐ and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3‐dioxygenase 1 (IDO1), a heme‐containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo‐IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo‐IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research.
Non‐uniform Self‐folding of Helical Poly(fluorenevinylene) Derivatives in the Solid State Leading to Amplified Circular Dichroism and Circularly Polarized Light Emission
Authors: Wu Pengfei , Pietropaolo Adriana , Fortino Mariagrazia , Shimoda Shuhei , Maeda Katsuhiro , Nishimura Tatsuya , Bando Masayoshi , Naga Naofumi , Nakano Tamaki
Published: August 2022

An unprecedented non‐uniform self‐folding of artificial polymer chains composed of turn moieties and stretched segments is presented through the design of a set of optically active poly(fluorene‐2,7‐diylethene‐1,2‐diyl) (poly(fluorenevinylene)) derivatives bearing a neomenthyl group and a pentyl group attached at the 9‐position of fluorene backbone at various ratios. The folded structure is formed and stabilized through inter‐chain interactions in the solid state, leading to remarkably enhanced chiroptical properties (chirality amplification) in terms of circular dichroism (CD) and circularly polarized light (CPL) emission. This phenomenon is rationalized by experimental and theoretical CD and CPL spectral analyses. The polymer arrangements in the solid state were further assessed through transmission electron microscopic observations combined with enhanced sampling molecular dynamics simulations in the solid state revealing the thin film organizations.
Aktuelle Untersuchungen an Suction Buckets für Offshore‐Windenergieanlagen – das ProBucket‐Projekt
Authors: Foglia Aligi , Quiroz Tulio , Widerspan Viktor , Heinrich Dariya , Binsker Georg , Schenk Alexander , Sanders Immo , Achmus Martin , Collmann Mareike , Böhm Manuela , Schaumann Peter , Elsesser Waldemar , Schädlich Bert , Kirsch Fabian , Richter Thomas , Gose Manfred , Pehl Peter , Kleineidam Patric , Maas Justus , Ibis Sercan , Oltmann Klaas
Published: August 2022

Suction Buckets sind etablierte Gründungselemente für Offshore‐Öl‐ und ‐Gasplattformen, die bisher in der Offshore‐Windindustrie nur vereinzelt eingesetzt wurden. Diese Fundamente können zusammen mit der Unterstruktur installiert werden, wodurch zusätzliche Offshore‐Operationen wie das Grouting von Transition Pieces oder von Jacket‐Beinen vermieden werden. Außerdem werden bei der Installation von Suction Buckets, im Gegensatz zu Pfahlgründungen, minimale akustische Emissionen erzeugt, sodass zusätzliche schallreduzierende Maßnahmen überflüssig sind. Aus diesen Gründen gelten Suction Buckets als eine praktikable und potenziell kostengünstige Gründungslösung für Offshore‐Windenergieanlagen (OWEA). Das Forschungsvorhaben ProBucket wurde 2020 initiiert und wird vom Bundesministerium für Wirtschaft und Klimaschutz (BMWK) gefördert. Durch die geplanten vielfältigen physikalischen und numerischen Untersuchungen strebt das Vorhaben an, die Unsicherheiten der existierenden Bemessungsverfahren zu verringern. In diesem Beitrag werden die aktuellen Herausforderungen zum Design und zur wirtschaftlichen Umsetzung von Suction Buckets für OWEA erläutert. Darüber hinaus werden die Forschungsaktivitäten von ProBucket beschrieben.
In‐situ Lithiated SiO2 as Lithium‐Free Anode for Lithium‐Sulfur Batteries
Authors: Bosubabu Dasari , Ramakumar Sampathkumar , Jeevanantham Sivaraj , Kanagaraj Inthumathi , Bhargav Pamula Balaji , Ahmed Nafis , Ramesha Kannadka
Published: August 2022

Lithium‐sulfur (Li−S) batteries are attractive owing to their high energy density and cost‐effectiveness. However, the practical application of Li−S batteries is hindered by uncontrollable lithium dendrite growth and severe polysulfide shuttling during cycling. Here, we fabricated 100 nm thin SiO2 decorated on carbon cloth (SiO2@CC). It is observed that in‐situ lithiation of SiO2 forms a highly lithiophilic LixSiOy layer over SiO2 which further acts as an efficient host for dendrite‐free lithium metal deposition. So lithiated SiO2@CC shows high affinity for homogenous growth of Li while the carbon fibers control the volume change during the deposition/stripping process. Hence, the synergistic effect of LixSiOy layer and carbon cloth (CC) effectively suppresses dendritic Li growth. As a result, the symmetric cell exhibits an ultra‐stable cycling performance over 1000 h with a low overpotential of <25 mV even at a high current density of 1 mA cm−2. Further, the lithiated SiO2@CC is used as a lithium metal‐free anode (also a flexible electrode) for Li−S battery, which exhibits a stable capacity of 800 mAh g−1 over 500 cycles due to its unique structural properties. This work offers new insights and paves the way for developing dendrite‐free, high‐performance Li−S battery technology.
Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling
Authors: Walker Cierra J. , Batan Dilara , Bishop Carrie T. , Ramirez Daniel , Aguado Brian A. , Schroeder Megan E. , Crocini Claudia , Schwisow Jessica , Moulton Karen , Macdougall Laura , Weiss Robert M. , Allen Mary A. , Dowell Robin , Leinwand Leslie A. , Anseth Kristi S.
Published: August 2022

Aortic valve stenosis (AVS) is a progressive fibrotic disease that is caused by thickening and stiffening of valve leaflets. At the cellular level, quiescent valve interstitial cells (qVICs) activate to myofibroblasts (aVICs) that persist within the valve tissue. Given the persistence of myofibroblasts in AVS, epigenetic mechanisms have been implicated. Here, we studied changes that occur in VICs during myofibroblast activation by using a hydrogel matrix to recapitulate different stiffnesses in the valve leaflet during fibrosis. We first compared the chromatin landscape of qVICs cultured on soft hydrogels and aVICs cultured on stiff hydrogels, representing the native and diseased phenotypes respectively. Using assay for transposase‐accessible chromatin sequencing (ATAC‐Seq), we found that open chromatin regions in aVICs were enriched for transcription factor binding motifs associated with mechanosensing pathways compared to qVICs. Next, we used RNA‐Seq to show that the open chromatin regions in aVICs correlated with pro‐fibrotic gene expression, as aVICs expressed higher levels of contractile fiber genes, including myofibroblast markers such as alpha smooth muscle actin (αSMA), compared to qVICs. In contrast, chromatin remodeling genes were downregulated in aVICs compared to qVICs, indicating qVICs may be protected from myofibroblast activation through epigenetic mechanisms. Small molecule inhibition of one of these remodelers, CREB Binding Protein (CREBBP), prevented qVICs from activating to aVICs. Notably, CREBBP is more abundant in valves from healthy patients compared to fibrotic valves. Our findings reveal the role of mechanical regulation in chromatin remodeling during VIC activation and quiescence and highlight one potential therapeutic target for treating AVS.
Enzymatic Synthesis of the Unnatural Nucleotide 2’‐Deoxyisoguanosine 5’‐Monophosphate
Authors: Zhao Fuping , Wei Yifeng , Wang Xinyu , Zhou Yan , Tong Yang , Ang Ee Lui , Liu Shengnan , Zhao Huimin , Zhang Yan
Published: August 2022

Naturally occurring DNA contains four canonical bases, forming two Watson‐Crick base pairs (adenine‐thymine, guanine‐cytosine). Efforts over the past decades have led to the development of several unnatural base pairs, enabling the synthesis of unnatural DNA with an expanded genetic alphabet. The engineering of organisms capable of de novo biosynthesis of unnatural DNA would have significant technological and philosophical implications, but remains a challenge. Here we report the enzymatic conversion of 2’‐deoxyxanthosine 5’‐monophosphate (dXMP) into deoxyisoguanosine monophosphate (dBMP), a precursor of the unnatural isoguanine‐isocytosine base pair. The reaction is catalyzed by the bacteriophage enzyme PurZ and bacterial PurB, and is a key addition to the toolbox for de novo biosynthesis of unnatural DNA.
The System Role of Smart Bioenergy: A Multicriteria Assessment
Authors: Szarka Nora , Schmid Christopher , Pfeiffer Diana , Thrän Daniela
Published: August 2022

The smart bioenergy approach encompasses the further development of modern biomass utilization systems into integrated systems consisting of optimized interaction with various renewable energy sources and coupled material/energy utilization. This study introduces the development and application of a multilevel analytic hierarchy and network process (AHP‐ANP) tool – SMARTbioGO – to assess smart bioenergy concepts in a transparent manner. The results indicate that all 36 analyzed bioenergy concepts support the energy system via sustainable biomass use, smart conversion, and system‐beneficial integration. A comprehensive contribution to a sustainable energy system can be achieved through a network of bioenergy concepts.
Catalyst Activity Characterization and Proper Integration in Small‐Scale Biomass Combustion Systems
Authors: Müller Mirjam , Hartmann Ingo
Published: August 2022

Catalysts can reduce emissions from biomass combustion systems. Efficient use in small‐scale applications is challenging due to the variations of temperature, fluid flow, and flue gas composition. An analytical procedure was defined and evaluated with three commercial catalysts to realize efficient integration. The characterization included activity measurements at three facilities: a model gas analysis device, a laboratory‐scale combustion system, and a wood log stove. The results demonstrate the possibilities of model gas analysis to define a scope of application and also the need for catalyst characterization under real operation conditions to determine the performance and stability of the final process. Temperature and gas hourly space velocity are the two main parameters influencing catalyst activity.
Boron‐Catalyzed Electrochemical Si−C Bond Formation for Safe and Controllable Benzylation and Allylation of Hydrosilanes
Authors: Beck Alexander D. , Haufe Stefan , Waldvogel Siegfried R.
Published: August 2022

The range of possible applications of B(C6F5)3 extends into many areas of organic and inorganic chemistry. However, electrochemical synthesis with hydrosilanes using B(C6F5)3 to increase yield or scope has not yet been achieved. A comprehensive study on the use of Lewis acidic boron species, especially B(C6F5)3, for the activation of hydrosilanes in presence of commercially available supporting electrolyte for Si−C bond formation was presented. The benzylation and allylation of hydrosilane species was successfully conducted in presence of catalytic amounts of B(C6F5)3 in yields up to 86 %. Screening of electrode materials revealed leaded bronzes as superior for cathodic conversion without contamination of the electrolyte by heavy metals. Supported by cyclic voltammetry studies, B(C6F5)3 activated the hydrosilane for easier nucleophilic access, leading to significant increase in yield and enrichment of the target product in the reaction mixture.
Azobenzene‐based Photochromic Delivery Vehicles for Ions and Small Molecules
Authors: Sahid Hossain Munshi , Chatterjee Sheelbhadra , Bandyopadhyay Subhajit
Published: August 2022

Molecular switches have been used as delivery vehicles for various molecular and ionic species. The ones that reversibly operate with light are arguably the best candidates for the purpose as they can be operated using light. The two states of these photoswitchable systems often possess remarkable differences in terms of their structural features and electronic properties. Photochromic systems with the appropriate embellishment of functionalities at suitable positions have thus been used as photoresponsive receptors. The use of light‐driven alterations of the structural features has led to differential molecular recognition with these switchable host molecules. In this article, we discuss the use of such supramolecular systems as the delivery vehicles for ions and molecules that started with the pioneering work by Shinkai back in 1979. This review will explicitly cover the development from 2001 to 2022 with some past background and the future prospects of the field.
Stereoselective synthesis of 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐one derivatives as PIM kinase inhibitors inspired from marine alkaloids
Authors: Casuscelli Francesco , Ardini Elena , Avanzi Nilla , Badari Alessandra , Casale Elena , Disingrini Teresa , Donati Daniele , Ermoli Antonella , Felder Eduard R. , Galvani Arturo , Isacchi Antonella , Menichincheri Maria , Montemartini Marisa , Orrenius Christian , Piutti Claudia , Salom Barbara , Papeo Gianluca
Published: August 2022

We previously demonstrated that natural product‐inspired 3,4‐dihydropyrrolo[1,2‐a]pyrazin‐1(2H)‐ones derivatives delivered potent and selective PIM kinases inhibitors however with non‐optimal ADME/PK properties and modest oral bioavailability. Herein, we describe a structure‐based scaffold decoration and a stereoselective approach to this chemical class. The synthesis, structure–activity relationship studies, chiral analysis, and pharmacokinetic data of compounds from this inhibitor class are presented herein. Compound 20c demonstrated excellent potency on PIM1 and PIM2 with exquisite kinases selectivity and PK properties that efficiently and dose‐dependently promoted c‐Myc degradation and appear to be promising lead compounds for further development.
Quantification of the Strength of π‐Noncovalent Interactions in Molecular Balances using Density Functional Methods
Authors: Nunar Luka , Aliev Abil E.
Published: August 2022

Different molecular balances were designed previously to compare noncovalent interactions. However, some balances are difficult to synthesise and there is a need for developing a computational approach. In this work, we probe noncovalent interactions of π systems using DFT methods to assess their reliability in reproducing experimentally measured conformer populations. Based on our results, the PW6B95D3 functional performed best, followed by M11L and ωB97XD. Additionally, the simulation of the rotation of the hydroxyl group revealed stabilising OH⋯Alkyne and OH⋯Nitrile interactions that are difficult to identify experimentally. These methods were then applied to compare the strengths of sulfur⋯π interactions in molecules which have not been explored experimentally. Compared to the hydroxyl counterpart, the simulation of the thiol group rotation showed that the geometry of the conformer with the two sulfur lone pairs oriented towards the aromatic ring or the double bond is stabilised, suggesting that S(LP)⋯π interactions can be attractive in nature. The ability of sulfur to rearrange its electronic surrounding to form an attractive interaction with π systems, including those with either electron‐donating or withdrawing groups, was also confirmed. Overall, the results show a promising future for both qualitative and quantitative assessments of the strengths of noncovalent interactions using selected DFT techniques.
Impact of acupuncture and integrative therapies on chemotherapy‐induced peripheral neuropathy: A multicentered, randomized controlled trial
Authors: Ben‐Arye Eran , Hausner David , Samuels Noah , Gamus Dorit , Lavie Ofer , Tadmor Tamar , Gressel Orit , Agbarya Abed , Attias Samuel , David Adi , Schiff Elad
Published: August 2022

Background

To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy‐induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients.

Methods

In this prospective, pragmatic, and patient‐preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice‐weekly acupuncture‐only (group A) or acupuncture with additional manual‐movement or mind–body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy‐Taxane (FACT‐Tax) tool. Other QoL‐related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well‐being questionnaire. Von Frey measurements examined perception thresholds.

Results

Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline‐to‐6‐week assessment scores improved significantly in the intervention arm (vs controls) on FACT‐Tax (p = .038) and emotional well‐being (p = .04) scores; FACT‐TAX scores for hand numbness/tingling (p = .007) and discomfort (p < .0001); and EORTC physical functioning (p = .045). Intervention groups A and B showed improved FACT‐Tax physical well‐being (p < .001), FACT‐TAX total score (p < .001), FACT‐TAX feet discomfort (p = .003), and EORTC pain (p = .017) scores.

Conclusions

Acupuncture, with or without CIM modalities, can relieve CIPN‐related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.
Ten year age‐ and sex‐specific temporal trends in incidence and prevalence of heart failure in Västra Götaland, Sweden
Authors: Wideqvist Maria , Rosengren Annika , Schaufelberger Maria , Pivodic Aldina , Fu Michael
Published: August 2022

Aim

Heart failure (HF) is predominantly a disorder of the elderly. During the last decades, cardiovascular primary and secondary prevention and life expectancy have improved. Accordingly, trends in incidence and prevalence of HF are dynamic and may differ over time by age and gender. We aim to investigate the overall and age‐specific and sex‐specific trends, in incidence, prevalence, and the proportion with co‐morbidities of HF over a 10 year period in Region Västra Götaland, Sweden.

Methods and results

The VEGA database is an administrative database of all patients managed in hospital and/or in primary care (private and public) living in Region Västra Götaland. All patients with a main or contributory diagnosis of HF (I50) aged 18 years or older between 2008 and 2017 were included. Incidence and prevalence of HF were calculated based on the entire adult population of Region Västra Götaland. The adult population in Region Västra Götaland increased by 8% from 2008 (n = 1 234 609) to 2017 (n = 1 338 906). Half the population was female and 69% < 60 years of age, both constant over time. In total, 62 228 incident cases of HF were identified. In 2008, we identified 6464 cases, mean age 78.7 (11.5) years, and 49.8% (n = 3222) men, while in 2017, 5727 cases were identified, mean age 78.3 (11.8) years, and 52.5% (n = 3006) men. The overall yearly incidence rate of HF decreased by 3%, RR 0.97 (95% CI 0.96–0.97) per year, P < 0.0001, mainly driven by the age categories >75 years. A constantly higher incidence of HF was seen for men compared with women in all age categories, RR 1.46 (95% CI 1.44–1.49), P < 0.0001. During the same period, we observed a steady increase in overall prevalence from 1.8% for women and 2.0% for men in 2008, to 2.4% in women and 2.8% in men in 2017, particularly in those >85 years of age who had a prevalence of 16.5% (men) and 14.6% (women) in 2008 and 23.5% (men) and 21.5% (women) in 2017. The overall 1 year mortality rate was 22.7%. When adjusted for age, women had a lower risk for death by 13% compared with men [hazard ratio 0.87 (95% CI 0.84–0.90, P < 0.0001)].

Conclusion

We saw a decrease in overall incidence, but incidence of HF remains high, particularly in the oldest age groups. Prevalence of HF keeps increasing particularly in those aged >85 years. Our findings emphasize the need for implementation of effective preventive strategies for HF.
Selective Chemical Substitution of Cu in the Structure of TiAl3 Type InPd3: Experimental and Theoretical Studies
Authors: Roy Nilanjan , Kuila Sandip K. , Harshit  , Pramanik Parna , Jana Partha P.
Published: August 2022

InPd3‐xCux (x=0–1) were prepared by high temperature synthesis starting from the highly pure constituent elements. The crystal structures were determined by X‐ray diffraction. In the structure of InPd3‐xCux (x=0–1), Cu stabilizes the TiAl3‐type InPd3 and selectively substitutes one of the two Pd positions and at the limiting composition ordered InPd2Cu is formed where Cu completely occupies that position. The intriguing selective substitution was investigated by first‐principles total energy calculations followed by electronic structure and chemical bonding analysis.
Synthesis of Oxazole–Tetrahydropyran Hybrids and Study on Their Antiproliferative Activity Against Human Tumour Cells
Authors: Quintana Vanesa , González‐Bakker Aday , Padrón Juan I. , Martín Víctor S. , Padrón José M. , Davyt Danilo , Valdomir Guillermo
Published: August 2022

A series of triazole linked tetrahydropyran–oxazole hybrids was synthesized based on a previously reported lead compound with selective antiproliferative activity against human tumour cell lines. The series was prepared to evaluate the impact of LogP and different modifications in the activity, and the new compounds were assayed against A549, HBL‐100, HeLa, SW1573, T‐47D, and WiDr cell lines. Also, the potentiality to be P‐gp substrate was tested. The compounds exhibited good antiproliferative results when compared with the standards cisplatin and 5‐fluorouracil. In silico studies to evaluate pharmacokinetic properties using pkCSM software were also carried out.
Selective Electrochemical Dibromination of Terpenes and Naturally Derived Olefins
Authors: Gombos Lilla G. , Werner Leo , Schollmeyer Dieter , Martínez‐Huitle Carlos A. , Waldvogel Siegfried R.
Published: August 2022

A simple electrochemical protocol is established for the selective alkene dibromination of naturally derived olefins, such as terpenes. The use of hazardous Br2 or its analogues have been elegantly avoided by employing readily available, inexpensive, and harmless sodium bromide with a dual role as reagent and supporting electrolyte in combination with sustainable carbon‐based electrodes. This electrochemical protocol provides the desired products with good to excellent yields up to 82 % with 10 examples. Scalability has been proved by a 5‐fold scale‐up. Notably, higher yields and selectivity were achieved in comparison to conventional bromination by Br2 and DMSO/HBr system and the dibrominated compound was eligible for further functionalization, such as cyanation according to the Kolbe nitrile synthesis protocol.
The Path to UVCB Ecological Risk Assessment: Grappling with Substance Characterization
Authors: Salvito Daniel , Fernandez Marc , Arey Jeremy S. , Lyon Delina Y. , Lawson Nelson , Deglin Sandrine , MacLeod Matthew
Published: August 2022

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) pose a unique challenge to regulators and to product registrants, who are required to characterize their fate, exposure, hazard, and potential risks to human health and the environment. To address these challenges and ensure an efficient and fit-for-purpose process, it is proposed that the ecological risks of UVCBs be assessed following a tiered strategy. The development of this approach required exploring how substance composition ties into hazard and exposure information and determining the extent to which a UVCB needs to be characterized to ensure a robust risk assessment. The present study highlights the key aspects of this new method. It presents how a tiered substance characterization approach can be integrated into broader UVCB risk-assessment schemes to encourage an examination of data needs before a full substance characterization is performed. The first tier of the characterization process, Tier 0, is a fundamental step that includes data from basic, lower-resolution compositional analyses. Tier 0 assessments can be used to inform hazard and exposure for any substance of interest. The need for more sophisticated, higher-tier characterization is determined by the level of uncertainty of the risk assessment. The next step will integrate a tiered exposure assessment into the characterization scheme featured in the present study, to create a more complete risk-assessment framework. Environ Toxicol Chem 2022;41:2649–2657. © 2022 Her Majesty the Queen in Right of Canada, Health and Environmental Sciences Institute and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.
Young women's engagement with gambling: A critical qualitative inquiry of risk conceptualisations and motivations to gamble
Authors: McCarthy Simone , Thomas Samantha , Pitt Hannah , Marko Sarah , Randle Melanie , Cowlishaw Sean , Kairouz Sylvia , Daube Mike
Published: August 2022

Background

Younger women's engagement with gambling has changed over recent decades due to a range of socio‐cultural, environmental and commercial factors. However, younger women's distinct lived experiences with gambling have rarely been considered. The following critical qualitative inquiry explored factors that influenced younger women's engagement with gambling and their perceptions of gambling risks.

Methods

Semi‐structured interviews were conducted with 41 Australian women aged 18‐40 years. Participants were asked questions relating to their reasons for gambling, and the perceived risks associated with gambling. Reflexive thematic analysis was used to interpret the data.

Results

Five themes were constructed from the data. First, women reported that they gambled to escape their everyday lives, with some women reporting gambling within their own homes. Second, women reported gambling for financial reasons, particularly to change their life circumstances and outcomes. Third, gambling was used by women as a way to connect with social network members. Fourth, gambling was an incidental activity that was an extension of non‐gambling leisure activities. Finally, lower risk perceptions of participants' own gambling risk contributed to their engagement and continuation of gambling.

Conclusion

Public health and health promotion initiatives should recognise that young women's gambling practices are diverse, and address the full range of socio‐cultural, environmental and commercial factors that may influence younger women's engagement with gambling.
Alginate/polyvinyl alcohol films for wound healing: Advantages and challenges
Authors: Saraiva Matheus Morais , Campelo Matheus da Silva , Câmara Neto João Francisco , Lima Ana Beatriz Nogueira , Silva George de Almeida , Dias Andre Tavares de Freitas Figueredo , Ricardo Nágila Maria Pontes Silva , Kaplan David L. , Ribeiro Maria Elenir Nobre Pinho
Published: August 2022

The skin is the largest organ in the human body and its physical integrity must be maintained for body homeostasis and to prevent the entry of pathogenic microorganisms. Sodium alginate (SA) and polyvinyl alcohol (PVA) are two polymers widely used in films for wound dressing applications. Furthermore, blends between SA and PVA improve physical, mechanical and biological properties of the final wound healing material when compared to the individual polymers. Different drugs have been incorporated into SA/PVA‐based films to improve wound healing activity. It is noteworthy that SA/PVA films can be crosslinked with Ca2+ or other agents, which improves physicochemical and biological properties. Thus, SA/PVA associations are promising for the biomedical field, as a potential alternative for wound treatment. This review focuses on the main techniques for obtaining SA/PVA films, their physical–chemical characterization, drug incorporation, and the advantages and challenges of these films for wound healing.
Functional evaluation of the tachycardia patient‐derived iPSC cardiomyocytes carrying a novel pathogenic SCN5A variant
Authors: Goktas Sahoglu Sevilay , Kazci Yusuf Enes , Tuncay Erkan , Torun Tugce , Akdeniz Celal , Tuzcu Volkan , Cagavi Esra
Published: August 2022

Tachycardia is characterized by high beating rates that can lead to life‐threatening fibrillations. Mutations in several ion‐channel genes were implicated with tachycardia; however, the complex genetic contributors and their modes of action are still unclear. Here, we investigated the influence of an SCN5A gene variant on tachycardia phenotype by deriving patient‐specific iPSCs and cardiomyocytes (iPSC‐CM). Two tachycardia patients were genetically analyzed and revealed to inherit a heterozygous p.F1465L variant in the SCN5A gene. Gene expression and immunocytochemical analysis in iPSC‐CMs generated from patients did not show any significant changes in mRNA levels of SCN5A or gross NaV1.5 cellular mislocalization, compared to healthy‐derived iPSC‐CMs. Electrophysiological and contraction imaging analysis in patient iPSC‐CMs revealed intermittent fibrillation‐like states, occasional arrhythmic events, and sustained high‐paced contractions that could be selectively reduced by flecainide treatment. The patch‐clamp analysis demonstrated a negative shift in the voltage‐dependent activation at the patient‐derived iPSC‐CMs compared to the healthy control line, suggestive of a gain‐of‐function activity associated with the SCN5A+/p.F1465L variant. Our patient‐derived iPSC‐CM model recapitulated the clinically relevant characteristics of tachycardia associated with a novel pathogenic SCN5A+/p.F1465L variant leading to altered Na+ channel kinetics as the likely mechanism underlying high excitability and tachycardia phenotype.
Malunion deformity of the forearm: Three‐dimensional length variation of interosseous membrane and bone collision
Authors: Mania Sylvano , Zindel Christoph , Götschi Tobias , Carrillo Fabio , Fürnstahl Philipp , Schweizer Andreas
Published: August 2022

It remains unclear to what extent the interosseous membrane (IOM) is affected through the whole range of motion (ROM) in posttraumatic deformities of the forearm. The purpose of this study is to describe the ligament‐ and bone‐related factors involved in rotational deficit of the forearm. Through three‐dimensional (3D) kinematic simulations on one cadaveric forearm, angular deformities of 5° in four directions (flexion, extension, valgus, varus) were produced at two locations of the radius and the ulna (proximal and distal third). The occurrence of bone collision in pronation and the linear length variation of six parts of the IOM through the whole ROM were compared between the 32 types of forearm deformities. Similar patterns could be observed among four groups: 12 types of deformity presented increased bone collision in pronation, 8 presented an improvement of bone collision with an increase of the mean linear lengthening of the IOM in neutral rotation, 6 had an increased linear lengthening of the IOM in supination with nearly unchanged bone collision in pronation and 6 types presented nearly unchanged bone collision in pronation with a shortening of the mean linear length of IOM in supination or neutral rotation. This kinematic analysis provides a better understanding of the ligament‐ and bone‐related factors expected to cause rotational deficit in forearm deformity and may help to refine the surgical indications of patient‐specific corrective osteotomy.
Testing the use of the silica deposition fluorescent probe PDMPO to estimate in situ growth rates of diatoms
Authors: Husmann Eva , Klaas Christine
Published: August 2022

The fluorophore [2‐(4‐pyridyl)‐5{[4‐dimethylaminoethyl‐aminocarbamoyl‐methoxy]phenyl}oxazole], in short PDMPO, is incorporated in newly polymerized silica in diatom frustules and thereby provides a tool to estimate Si uptake, study diatom cell cycles but also determine mortality‐independent abundance‐based species specific‐growth rates in cultures and natural assemblages. In this study, the theoretical framework and applicability of the PDMPO staining technique to estimate diatom species specific‐growth rates were investigated. Three common polar diatom species, Pseudo‐nitzschia subcurvata, Chaetoceros simplex, and Thalassiosira sp., chosen in order to cover a broad range of species specific frustule and life‐cycle characteristics, were incubated over 24 h in control (no PDMPO) and with 0.125 and 0.6 μM PDMPO addition, respectively. Results indicate that specific‐growth rates of the species tested were not affected in both treatments with PDMPO addition. The specific‐growth rate estimates based on the PDMPO staining patterns (μPDMPO) were comparable and more robust than growth rates estimated from the changes in cell concentrations (μcc). This technique also allowed to investigate and highlight the importance of the illumination cycle (light and dark phases) on cell division in diatoms.
Characterization of the gassy sediment layer in shallow water using an acoustical method: Lake Kinneret as a case study
Authors: Katsnelson Boris , Uzhansky Ernst , Lunkov Andrey , Ostrovsky Ilia
Published: August 2022

Remote characterization and parameterization of gassy sediments have significant environmental importance for quantifying the global methane budget and assessing its impact on climate change. Acoustic techniques that have been developed hold advantages over direct sediment sampling (e.g., using pressurized and frozen cores), as they permit comparatively quick and cost‐effective assessments over the large bottom areas. This paper proposes a non‐invasive acoustic method that allows simultaneous assessments of the free gas content () and the thickness () of a gassy layer in the aquatic surface sediments. The method is based on amplitude measurements and frequency analysis of the bottom reflection coefficient in the wide frequency band (300–3500 Hz). The spatial variability of and in freshwater Lake Kinneret (Israel) is studied, where the upper sedimentary layer is characterized by a high organic matter content, high methane production rates, and a large . The assessed values of and varied from 0.1% to 0.6%, and from 20 to 40 cm, respectively, depending on the location of measurements. These results are in reasonable agreement with gas void fractions measured directly in frozen sediment cores, where the depth‐averaged varied from to . The suggested methodology should have considerable practical implementation for remote spatiotemporal monitoring of shallow gassy sediments in aquatic ecosystems.
Toward High‐Efficiency Ultrahigh Numerical Aperture Freeform Metalens: From Vector Diffraction Theory to Topology Optimization
Authors: Sang Di , Xu Mingfeng , Pu Mingbo , Zhang Fei , Guo Yinghui , Li Xiong , Ma Xiaoliang , Fu Yunqi , Luo Xiangang
Published: August 2022

Optical metasurface is a 2D array of subwavelength meta‐atoms that arbitrarily manipulates amplitude, polarization, and wavefront of incident light, offering great advantages in miniaturization and integration. However, the presuppositions hidden in conventional unit‐cell‐based design approach, including discrete phase sampling, local periodicity approximation, and normal response, imply that the responses and interactions of meta‐atoms are almost impossible to be accurately modeled, thus impeding the effective design of high‐efficiency ultrahigh numerical aperture (NA) metalens. Here, based on vector diffraction theory and plane wave expansion method, theoretical limitation of metalens efficiency is comprehensively investigated. It is identified that for high‐NA metalens, theoretical focusing efficiency is limited by diffraction capability of vector field, while evanescent wave attenuation dominates theoretical efficiency decline for ultrahigh‐NA metalens. It is also shown that the efficiency of conventional metalens has a huge gap from theoretical limitation, owing to imperfect diffractive focusing and impedance mismatch reflections. To fill such efficiency gap, the high‐efficiency high‐NA freeform metalens based on topology optimization is further demonstrated. Particularly, topology geometric constraints are utilized to reduce minimum feature size while keeping high efficiency. The results could shed new light on the understanding and design of ultrahigh‐NA metalens and find promising applications in optical imaging, microscopy, and lithography.
Electron ultra‐high dose rate FLASH irradiation study using a clinical linac: Linac modification, dosimetry, and radiobiological outcome
Authors: Xie De‐Huan , Li Yi‐Chuan , Ma Sai , Yang Xin , Lan Ruo‐Ming , Chen Ao‐Qiang , Zhu Hong‐Yu , Mei Yan , Peng Li‐Xia , Li Zuo‐Feng , Huang Bi‐Jun , Chen Yan , Huang Xiao‐Yan , Qian Chao‐Nan
Published: August 2022

Purpose

Ultra‐high dose rate FLASH irradiation (FLASH‐IR) has been shown to cause less normal tissue damage compared with conventional irradiation (CONV‐IR), this is known as the “FLASH effect.” It has attracted immense research interest because its underlying mechanism is scarcely known. The purpose of this study was to determine whether FLASH‐IR and CONV‐IR induce differential inflammatory cytokine expression using a modified clinical linac.

Materials and methods

An Elekta Synergy linac was used to deliver 6 MeV CONV‐IR and modified to deliver FLASH‐IR. Female FvB mice were randomly assigned to three different groups: a non‐irradiated control, CONV‐IR, or FLASH‐IR. The FLASH‐IR beam was produced by single pulses repeated manually with a 20‐s interval (Strategy 1), or single‐trigger multiple pulses with a 10 ms interval (Strategy 2). Mice were immobilized in the prone position in a custom‐designed applicator with Gafchromic films positioned under the body. The prescribed doses for the mice were 6 to 18 Gy and verified using Gafchromic films. Cytokine expression of three pro‐inflammatory cytokines (tumor necrosis factor‐α [TNF‐α], interferon‐γ [IFN‐γ], interleukin‐6 [IL‐6]) and one anti‐inflammatory cytokine (IL‐10) in serum samples and skin tissue were examined within 1 month post‐IR.

Results

The modified linac delivered radiation at an intra‐pulse dose rate of around 1 × 106 Gy/s and a dose per pulse over 2 Gy at a source‐to‐surface distance (SSD) of 13 to 15 cm. The achieved dose coverage was 90%–105% of the maximum dose within −20 to 20 mm in the X direction and 95% within −30 to 30 mm in the Y direction. The absolute deviations between the prescribed dose and the actual dose were 2.21%, 6.04%, 2.09%, and 2.73% for 6, 9, 12, and 15 Gy as measured by EBT3 films, respectively; and 4.00%, 4.49%, and 2.30% for 10, 14, and 18 Gy as measured by the EBT XD films, respectively. The reductions in the CONV‐IR versus the FLASH‐IR group were 4.89%, 10.28%, −7.8%, and −22.17% for TNF‐α, IFN‐γ, IL‐6, and IL‐10 in the serum on D6, respectively; 37.26%, 67.16%, 56.68%, and −18.95% in the serum on D31, respectively; and 62.67%, 35.65%, 37.75%, and −12.20% for TNF‐α, IFN‐γ, IL‐6, and IL‐10 in the skin tissue, respectively.

Conclusions

Ultra‐high dose rate electron FLASH caused lower pro‐inflammatory cytokine levels in serum and skin tissue which might mediate differential tissue damage between FLASH‐IR and CONV‐IR.
Cisco Aquaculture Best Practices: Randomized Experiments from Eggs to Juvenile
Authors: Fischer Gregory J. , Hartleb Christopher , Holmes Kendall , Hansum Chloe , Tintle Nathan
Published: August 2022

The Cisco Coregonus artedi (also known as Lake Herring), a coldwater salmonid found in the Great Lakes, is of interest to multiple agencies for restoration and conservation purposes due to its important ecological role. Further information on rearing and restocking of Cisco is needed, especially toward understanding the biological culture needs of Cisco eggs, larvae, and fingerlings. To address this gap in the literature and to provide essential fish culture information, we performed three preliminary studies in 2010 with Cisco: fertilization (wet versus dry fertilization), egg survival (pre-water-hardening versus post-water-hardening iodine treatment), and fry development (three different larval feed treatments that were commercially available at that time). The dry fertilization methodology (68%) yielded a significantly better eye-up percentage than wet fertilization (34%). Additionally, our testing revealed higher survival rates when iodophor treatment was used on fertilized eggs after water hardening (54%) in comparison with treatment before water hardening (43%). Although mean survival rates across the three diet treatments were not significantly different, larval Cisco that were fed brine shrimp Artemia replacement diets outperformed those fed the other diets, with the INVE Proton diet ranking highest. These early preliminary studies substantially increased the understanding of optimum culture parameters for Cisco in preparation for the widespread production of this important species, and the results provide propagation recommendations for conservation stocking programs.
Statistical characterization of patient response to offered access delays using healthcare transactional data
Authors: Kilinc Derya , Gel Esma S. , Sir Mustafa Y. , Pasupathy Kalyan S.
Published: August 2022

We present a novel framework to characterize the probability that an offered appointment with k‐days' access delay will be booked and subsequently attended by a patient. We refer to this probability as the “probability of realization” of an offered appointment, and demonstrate how empirical characterizations of this measure can be used to identify improved policies for managing patient demand and enabling the most intentional use of clinical care resources. We consider the estimation problem in the context of new patients looking to establish care at a clinic, and offer a model of patient responses during an appointment scheduling encounter with an agent. We define different cases of data availability and demonstrate the effectiveness of the framework in each case to ensure generalizability. We first demonstrate the accuracy of estimations using simulated data, and then highlight behavioral differences between different patient groups using real‐life transactional data from two clinical departments. Finally, we demonstrate a practical use case for the obtained realization probabilities by showing that they can be reliably used as input to a novel time windows‐based patient prioritization protocol that allows effective management of demand from different classes by explicitly considering wait sensitivities of patients.
Multiphysics mixed finite element method with Nitsche's technique for Stokes‐poroelasticity problem
Authors: Ge Zhihao , Pang Jin'ge , Cao Jiwei
Published: August 2022

In this article, we propose a multiphysics mixed finite element method with Nitsche's technique for Stokes‐poroelasticity problem. Firstly, we reformulate the poroelasticity part of the original problem by introducing two pseudo‐pressures to into a “fluid–fluid” coupled problem so that we can use the classical stable finite element pairs to deal with this problem conveniently. Then, we prove the existence and uniqueness of weak solution of the reformulated problem. And we use Nitsche's technique to approximate the coupling condition at the interface to propose a loosely‐coupled time‐stepping method to solve three subproblems at each time step–a Stokes problem, a generalized Stokes problem and a mixed diffusion problem. And the proposed method does not require any restriction on the choice of the discrete approximation spaces on each side of the interface provided that appropriate quadrature methods are adopted. Also, we give the stability analysis and error estimates of the loosely‐coupled time‐stepping method. Finally, we give the numerical tests to show that the proposed numerical method has a good stability and no “locking” phenomenon.
Genomic features of Helicobacter pylori‐naïve diffuse‐type gastric cancer
Authors: Namikawa Ken , Tanaka Norio , Ota Yuki , Takamatsu Manabu , Kosugi Mayuko , Tokai Yoshitaka , Yoshimizu Shoichi , Horiuchi Yusuke , Ishiyama Akiyoshi , Yoshio Toshiyuki , Hirasawa Toshiaki , Amino Sayuri , Furuya Rie , Gotoh Osamu , Kaneyasu Tomoko , Nakayama Izuma , Imamura Yu , Noda Tetsuo , Fujisaki Junko , Mori Seiichi
Published: August 2022

Helicobacter pylori (HP) is a major etiologic driver of diffuse‐type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP‐naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP‐exposed and HP‐naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP‐exposed and 27 HP‐naïve DGCs from sporadic, early‐stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP‐exposed and 17 HP‐naïve samples had been preserved as fresh‐frozen samples. HP infection status was determined using stringent criteria. HP‐exposed DGCs exhibited an increased single nucleotide variant burden (HP‐exposed DGCs; 1.97 [0.48–7.19] and HP‐naïve DGCs; 1.09 [0.38–3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm‐level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA–ARHGAP pathway misregulation was exclusive to HP‐exposed DGCs (p = 0.0167). HP‐exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP‐exposed DGCs. HP‐naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP‐naïve and HP‐exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.