bluuebunny/crossref_metadata_2025 huggingface dataset:
Voxel‐wise intermodal coupling analysis of two or more modalities using local covariance decomposition
Authors: Hu Fengling , Weinstein Sarah M. , Baller Erica B. , Valcarcel Alessandra M. , Adebimpe Azeez , Raznahan Armin , Roalf David R. , Robert‐Fitzgerald Timothy E. , Gonzenbach Virgilio , Gur Ruben C. , Gur Raquel E. , Vandekar Simon , Detre John A. , Linn Kristin A. , Alexander‐Bloch Aaron , Satterthwaite Theodore D. , Shinohara Russell T.
Published: June 2022

When individual subjects are imaged with multiple modalities, biological information is present not only within each modality, but also between modalities – that is, in how modalities covary at the voxel level. Previous studies have shown that local covariance structures between modalities, or intermodal coupling (IMCo), can be summarized for two modalities, and that two‐modality IMCo reveals otherwise undiscovered patterns in neurodevelopment and certain diseases. However, previous IMCo methods are based on the slopes of local weighted linear regression lines, which are inherently asymmetric and limited to the two‐modality setting. Here, we present a generalization of IMCo estimation which uses local covariance decompositions to define a symmetric, voxel‐wise coupling coefficient that is valid for two or more modalities. We use this method to study coupling between cerebral blood flow, amplitude of low frequency fluctuations, and local connectivity in 803 subjects ages 8 through 22. We demonstrate that coupling is spatially heterogeneous, varies with respect to age and sex in neurodevelopment, and reveals patterns that are not present in individual modalities. As availability of multi‐modal data continues to increase, principal‐component‐based IMCo (pIMCo) offers a powerful approach for summarizing relationships between multiple aspects of brain structure and function. An R package for estimating pIMCo is available at: https://github.com/hufengling/pIMCo.
DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine
Authors: Fatemi Nayeralsadat , Tierling Sascha , Es Hamidreza Aboulkheyr , Varkiani Maryam , Mojarad Ehsan Nazemalhosseini , Aghdaei Hamid Asadzadeh , Walter Jörn , Totonchi Mehdi
Published: June 2022

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide that is attributed to gradual long‐term accumulation of both genetic and epigenetic changes. To reduce the mortality rate of CRC and to improve treatment efficacy, it will be important to develop accurate noninvasive diagnostic tests for screening, acute and personalized diagnosis. Epigenetic changes such as DNA methylation play an important role in the development and progression of CRC. Over the last decade, a panel of DNA methylation markers has been reported showing a high accuracy and reproducibility in various semi‐invasive or noninvasive biosamples. Research to obtain comprehensive panels of markers allowing a highly sensitive and differentiating diagnosis of CRC is ongoing. Moreover, the epigenetic alterations for cancer therapy, as a precision medicine strategy will increase their therapeutic potential over time. Here, we discuss the current state of DNA methylation‐based biomarkers and their impact on CRC diagnosis. We emphasize the need to further identify and stratify methylation‐biomarkers and to develop robust and effective detection methods that are applicable for a routine clinical setting of CRC diagnostics particularly at the early stage of the disease.
Enhancing the optical response and biosensing capabilities of bioinspired peptide micro‐waveguides exploiting chromatic aberration
Authors: Tiwari Roshan , Roy Sauvik , Mondal Sahabaj , Ghosh Nirmalya , Haldar Debasish , Banerjee Ayan
Published: June 2022

Bioinspired peptide waveguides of mesoscopic length scales have established a new paradigm in photonics with possible applications in precision bioimaging, sensing, and diagnostics. Here, we improve the efficiency of coupling various constituent colors of a white light source into single self‐assembled microtube‐shaped passive peptide waveguides by employing chromatic aberration. Thus, we use a chromatically aberrated microscope objective lens to couple light into peptide waveguides. Using both numerical simulation and experiments, we show that the waveguide response displays higher quality factor, wavelength selectivity, and axial coupling range compared to a chromatically corrected standard plan‐fluoritic objective lens. We also demonstrate absorption and refractive index‐based sensing by studying the changes in the optical responses of the peptide tubes in the presence of a wide concentration range of the absorptive Congo red, and the nonabsorptive Coumarin dyes. The former understandably display a much higher response than the latter due to the low finesse of the waveguides. We obtain a detection limit of around 10 nM for Congo red, and 10 mM for Coumarin. Our study opens up possibilities for deploying such peptide microtubes for various biosensing applications utilizing spectral and waveguide characteristics.
Circ‐POLR3A accelerates TGF‐β2‐induced promotion in cell viability, migration, and invasion of lens epithelial cells via miR‐31/TXNIP signaling cascade
Authors: Wang Huajun , Zheng Guangying , Sun Miaomiao , Chi Yingjie
Published: June 2022

Posterior capsular opacification (PCO) is the major complication after cataract surgery and can result in secondary vision loss. Circular RNAs (circRNAs) are reported to play critical regulatory roles in multiple cell biological processes. The most common working mechanism of circRNAs is by acting as microRNA sponges. Here, we analyzed the role and mechanism of circRNA RNA polymerase III subunit A (POLR3A) in PCO. Cell viability was analyzed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Cell motility was assessed by transwell and wound healing assays. Dual‐luciferase reporter and RNA‐pull‐down assays were performed to verify the interaction between microRNA‐31 (miR‐31) and circ‐POLR3A or thioredoxin interacting protein (TXNIP). PCO cell model was established by treating SRA01/04 cells with transforming growth factor‐β2 (TGF‐β2). We found that TGF‐β2 enhanced SRA01/04 cell viability, migration, and invasion abilities. Circ‐POLR3A expression was upregulated in PCO tissues and TGF‐β2‐induced SRA01/04 cells. TGF‐β2 promoted the viability and motility of SRA01/04 cells largely by upregulating circ‐POLR3A. Circ‐POLR3A negatively regulated the miR‐31 level by directly interacting with it. Circ‐POLR3A absence‐induced influences in TGF‐β2‐induced SRA01/04 cells were partly reversed by silencing miR‐31. miR‐31 is directly bound to the 3′‐untranslated region of TXNIP. TXNIP overexpression largely attenuated miR‐31 overexpression‐mediated effects in TGF‐β2‐induced SRA01/04 cells. Circ‐POLR3A could elevate the protein expression of TXNIP by sponging miR‐31. Exosomes were involved in mediating the delivery of circ‐POLR3A in SRA01/04 cells. In conclusion, circ‐POLR3A contributed to TGF‐β2‐induced promotion of cell viability, migration, and invasion of SRA01/04 cells by targeting miR‐31/TXNIP axis.
A Randomized, Controlled Study to Assess Biomarkers of Exposure in Adult Smokers Switching to Oral Nicotine Products
Authors: Edmiston Jeffery , Liu Jianmin , Wang Jingzhu , Sarkar Mohamadi
Published: June 2022

This open‐label, randomized, controlled, in‐clinic, 6‐parallel‐group study evaluated changes in biomarkers of exposure (BoEs) to select harmful and potentially harmful constituents in adult smokers (N = 213) not planning to quit smoking. Adult smokers were randomized to continue smoking (CS), reduce smoking by 50% and dual use oral tobacco‐derived nicotine (OTDN) products (VERVE chews/discs), stop smoking and exclusively use discs or chews, or stop using all tobacco products (NT). The primary objective compared 24‐hour urinary total 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL; a biomarker for the carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone) in dual and exclusive use of discs and chews to continue smoking and NT on day 7. NNAL levels on day 7 were significantly lower (P < .05) among dual and exclusive users of discs/chews compared to continue smoking; median percent reductions were ≈30% and ≈73%, respectively. NNAL levels were not significantly different between those who used discs/chews and the NT group. Many of the additional secondary biomarkers of exposure were significantly lower in dual users (10/19) and exclusive users of discs/chews (17/19) compared to the continue smoking group. Overall, reductions in secondary biomarkers of exposure were greater in exclusive users than dual users. The 24‐hour urinary nicotine equivalents were significantly lower (P < .05) among exclusive users of discs/chews compared to continue smoking. The discs/chews appeared to be well tolerated. These results demonstrate that while switching completely to discs/chews substantially reduces exposure to select harmful and potentially harmful constituents, dual use with 50% reduction in cigarette consumption also reduces exposure. oral tobacco‐derived nicotine products like discs/chews may present a harm reduction opportunity for adult smokers, particularly those not intending to quit smoking.
Clinical application of ultra‐high frequency ultrasound: Discovering a new imaging frontier
Authors: Fogante Marco , Carboni Nicola , Argalia Giulio
Published: June 2022

The ultra‐high frequency ultrasound (UHFUS) is characterized by the use of probes between 30 and 100 MHz. This technology has recently been introduced in clinical practice and represents an opportunity for the diagnosis of numerous pathologies. The high spatial resolution of UHFUS, up to 30 μ in pixel size, allows to study the pathological modifications and to guide microsurgery treatments in anatomical body structures not evaluable by conventional HFUS. The aim of this work is to provide a review of the literature on the current clinical applications of UHFUS and to discuss its added role in different clinical settings.
IL-17A produced by invariant natural killer T cells and CD3+CD56+αGalcer-CD1d tetramer– T cells promote liver fibrosis in patients with primary biliary cholangitis
Authors: Jia Hongyu , Chen Jianing , Zhang Xujun , Bi Kefan , Zhou Hetong , Liu Tianxing , Xu Jia , Diao Hongyan
Published: June 2022

Primary biliary cholangitis (PBC) is characterized as interlobular bile duct injury and fibrosis, which results from the loss of tolerance to self-antigens. However, the exact pathologic mechanism leading to injury and fibrosis in PBC patients is not fully understood. Therefore, in this study, we examined the role of the T cell subsets in PBC patients and healthy controls (HCs). A higher number of invariant Natual killer T (iNKT) cells as well as CD3+CD56+ αGalcer-CD1d tetramer– T cells were found in patients with PBC compared with HCs. Moreover, these 2 T subpopulations produced significantly higher levels of Interleukin (IL)-17A in PBC patients than those in in HCs, which has also been positively correlated with the disease severity. Furthermore, the level of IL-17A produced by these 2 subpopulations was increased after stimulation of the autoantibodies in patients with PBC. Also, the elevated IL-17A levels promoted the PBC-related fibrosis, thus presenting a change in frequencies and functions of these cell phenotypes in the deterioration of the duct damage-related fibrosis. This study clarified PBC patients’ distinct T subpopulations characteristics, providing evidence-based diagnostic and therapies for these patients. The correlation between unclassical T subsets and IL-17A may provide a novel target for the immunotherapy of PBC.
The SELENOT mimetic PSELT promotes nerve regeneration by increasing axonal myelination in a facial nerve injury model in female rats
Authors: Pothion Hugo , Lihrmann Isabelle , Duclos Celia , Riou Gaëtan , Cartier Dorthe , Boukhzar Loubna , Lefranc Benjamin , Leprince Jérôme , Guérout Nicolas , Marie Jean‐Paul , Anouar Youssef
Published: June 2022

Peripheral nerve injury (PNI) is frequent and many patients suffer lifelong disabilities in severe cases. Although the peripheral nervous system is able to regenerate, its potential is limited. In this study, we tested in a nerve regeneration model in rat the potential beneficial effect of a short mimetic peptide, named PSELT, which derives from SELENOT, an essential thioredoxin‐like selenoprotein endowed with neuroprotective and antioxidant activities. For this purpose, the right facial nerve of female Long–Evans rats was axotomized then bridged with a free femoral vein interposition graft. PSELT (1 μM) was injected into the vein immediately and 48 h after the injury, and the effects observed were compared to those found after an end‐to‐end suture used as a gold standard treatment. Whisking behavior, electrophysiological potential, and histological analyses were performed 3 months after injury to determine the effects of these treatments. These analyses revealed that PSELT‐treated animals exhibit a better motor recovery in terms of protraction amplitude and velocity of vibrissae compared to control and end‐sutured nerve animal groups. Moreover, administration of PSELT following injury enhanced muscle innervation, axonal elongation, and myelination of newly formed nerve fibers. Altogether, these results indicate that a PSELT‐based treatment is sufficient to enhance facial nerve myelination and regeneration and could represent a new therapeutic tool to treat PNI.
Investigation of the effects of antimicrobial and anti‐biofilm peptide IDR1018 and chitosan nanoparticles on ciprofloxacin‐resistant Escherichia coli
Authors: Haji Hossein Tabrizi Aida , Habibi Mehri , Foroohi Fatemeh , Mohammadian Taher , Asadi Karam Mohammad Reza
Published: June 2022

Peptide IDR1018 and chitosan nanoparticles (CNs) showed antimicrobial and anti‐biofilm activity against bacteria. In this study, the antimicrobial effects of peptide IDR1018 and CNs were evaluated on 50 clinical isolates of uropathogenic Escherichia coli (UPEC) resistant to ciprofloxacin. Ion gelation method was applied for CNs synthesis. Scanning electron microscope (SEM) and dynamic light scattering (DLS) were utilized to evaluate the nanoparticles. Antimicrobial and synergistic activity of peptide IDR1018 and CNs with ciprofloxacin were evaluated by microtiter broth dilution method. The checkerboard test was used to investigate the antimicrobial effects of IDR1018 and CNS in combination with ciprofloxacin. Anti‐biofilm effect of ciprofloxacin, peptide IDR1018, and CNs was evaluated using crystal violet method. Fourteen (28%), 21 (42%), and 15 (30%) of clinical isolates produced strong, moderate, and weak biofilm, respectively. The CNs were spherical and uniform under electron microscopy with an average diameter of 246 nm. The minimum inhibitory concentration (MIC) values were 16–128, 20–40, and 375–750 (µg/ml) for ciprofloxacin, peptide IDR1018, and CNs, respectively. Fractional inhibitory concentration (FIC) analysis indicated a synergistic effect of ciprofloxacin in combination with peptide IDR1018, but in combination with CNs, this antibiotic showed an additive effect. Our results revealed that peptide IDR1018 and CNs have antimicrobial properties on UPEC isolates. Biofilm inhibition and biofilm eradication of clinical isolate were shown by peptide IDR1018 and CNs in a concentration‐dependent manner. The antimicrobial agents alone and in combination decreased the number of viable bacteria in the biofilms. Therefore, these components seem to be a treating approach against biofilm‐forming UPEC isolates.
Development of a microecologic product from Lactobacillus rhamnosus based on silica
Authors: Wu Wanqin , Liu Guanwen , Li Huixin , Yang Rongrong , Ai Chongyang , Pang Bing , Jiang Chunmei , Shi Junling
Published: June 2022

Background

Probiotics are primarily made into microecologic products for use in the food and feed industries. The freeze‐drying technique is widely used in their preparation to maintain their high level of bioactivity. This causes high costs in terms of the energy and time needed. In this study, we developed a method to produce a highly active microecologic product from Lactobacillus rhamnosus using heating and silica.

Results

A microecologic product was made successfully from L. rhamnosus using the whole bacterial culture broth, without waste, and using food‐grade silica (4.5 mL g−1) to absorb water before drying at 37 °C for 8 h. The activity of L. rhamnosus cells was increased significantly by adding water extracts of green tea to the culture medium. The viable amount of L. rhamnosus in the obtained microecologic product was 9.80 × 1010 cfu g−1 with a survival rate of 224.67% in simulated gastric juice for 3 h and 68.2% in simulated intestinal juice for 3 h. The microecologic product treated an intestinal infection by multi‐drug‐resistant Staphylococcus aureus in mice very efficiently.

Conclusion

The study developed an economic, eco‐friendly, and efficient method for preparing highly active microecologic agents using heating and without waste. © 2022 Society of Chemical Industry.
Effects of moisture content on the enolization products formation in glucose–proline Maillard reaction models
Authors: Li He , Yang Fu‐Han , Zhang Wen‐Chao , Zhang Zhi‐Jun , Yu Shu‐Juan
Published: June 2022

BACKGROUND

2,3‐Dihydro‐3,5‐dihydroxy‐6‐methyl‐4(H)‐pyran‐4‐one (DDMP) and 5‐hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d‐glucose and l‐proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times.

RESULTS

DDMP was predominantly generated in dry or low water‐content heating models along with n increased 1‐deoxyglucosone (1‐DG) generation via 2,3‐enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1‐DG, and DDMP due to a change in the reaction mechanism from 2,3‐enolization to 1,2‐enolization, which facilitated 3‐deoxyglucosone (3‐DG) and HMF formation.

CONCLUSION

Increased moisture content in glucose–proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3‐enolization to 1,2‐enolization to generate more 3‐DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2‐enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry.
Long noncoding RNA TFAP2A‐AS1 promotes oral squamous cell carcinoma cell growth and movement via competitively binding miR‐1297 and regulating TFAP2A expression
Authors: Yang Kaicheng , Niu Yunfeng , Cui Zifeng , Jin Linyu , Peng Shixiong , Dong Zhiming
Published: June 2022

Oral squamous cell carcinoma (OSCC) is an aggressive and common malignancy in the head and neck, characterized by poor prognosis and high incidence. This study aimed to investigate the role of long noncoding RNA TFAP2A‐AS1 in OSCC. The competing endogenous RNA network of TFAP2A‐AS1 was constructed by bioinformatics analysis. The expressions of miR‐1297, TFAP2A‐AS1, and TFAP2A were measured by quantitative reverse transcription‐polymerase chain reaction. The correlations of TFAP2A‐AS1, miR‐1297, and TFAP2A with clinicopathological characteristics of OSCC were assessed. RNA immunoprecipitation and dual‐luciferase reporter assay were used to identify the target of miR‐1297. Cell proliferation was measured by colony formation assay and [3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium] assay. Transwell assay and wound healing assay were performed to assess cell movement. TFAP2A‐AS1 and TFAP2A were upregulated in OSCC and their expression levels were positively correlated. The levels of TFAP2A‐AS1, miR‐1297, and TFAP2A were also associated with lymphatic metastasis and the tumor‐node‐metastasis (TNM) stage of OSCC patients. TFAP2A‐AS1 acted as a miR‐1297 sponge. OSCC cell growth and movement were inhibited by miR‐1297. Changes in the miR‐1297 expression abolished the effects of TFAP2A‐AS1 on OSCC cells. Additionally, TFAP2A was a target of miR‐1297. TFAP2A promoted OSCC cell growth and migration/invasion, indicating that TFAP2A mediated the effects of TFAP2A‐AS1 and miR‐1297. TFAP2A‐AS1 exerts an oncogenic effect in OSCC via the TFAP2A‐AS1/miR‐1297/TFAP2A axis, which may provide new targets and strategies for OSCC treatments
The impacts of subsidy strategies and recycling modes on the closed‐loop supply chain
Authors: Song Hongzhen , Zhang Jiantong , Li Junchang
Published: June 2022

This paper explored the effect of government subsidies and recycling modes on a four‐echelon closed‐loop supply chain (CLSC) including a government, a manufacturer, a retailer, and a third‐party recycler. The government directly subsidizes remanufacturing activities, recycling activities, or consumption activities with social welfare maximization objective. Meanwhile, the used products can be recycled by the retail, the third party, or both. We developed nine Stackelberg game models and derived the optimal decision and the equilibrium revenue of all members. Then, the optimal subsidy intensity, retail price, and wholesale price under different scenarios were compared theoretically. Finally, we analyzed the sensitivity of all stakeholders' optimal decisions and revenue to important parameters. Some novel and meaningful conclusions were established: (a) Government directly subsidy for remanufacturing has the same effect as subsidy for recycling; (b) it is better for the government directly subside manufacturing when two recyclers participate under the uncertainty of manufacturing cost or potential market; (c) all members should intervene the recycling cost coefficient, the costs saved of remanufacturing unit used product, and the price elasticity coefficient; (d) it is a conservative and effective strategy for the government to directly subside consumption activities.
A pilot study on oral cyclosporine A in association with fulguration for the treatment of interstitial cystitis with Hunner's lesions
Authors: Brière Raphaëlle , Bouchard Frédérique , Ismail Salima , Gareau Labelle Annie‐Kim , Tu Le Mai
Published: June 2022

Aims

To evaluate the efficacy and safety of lesion fulguration in combination with cyclosporine A (CyA) as a maintenance therapy in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner's lesion (HL).

Methods

Retrospective observational study of refractory patients with HL treated with daily 1.5 mg/kg or less of oral CyA following lesion fulguration. Pain severity, subjective improvement, urinary symptoms, and adverse events were used to assess long‐term treatment efficiency and safety.

Results

Among the 22 patients, median follow‐up under CyA was 27 months. Patients reported sustained significant reduction compared to pretreatment in pain (0/10 vs. 8/10; p < 0.001), urinary frequency per 24 h (9.5 vs. 20.8; p < 0.001), and nocturia (2.3 vs. 7.6; p < 0.001). Subjective improvement rate (SIR) and patient global impression of improvement were of 90% and 1 (“very much better”), respectively, including four patients who considered themselves cured (SIR: 100%). Three patients needed an additional procedure due to pain relapse. Minor increase in creatinine was observed and three patients developed or worsened their arterial hypertension. CyA dosage was decreased to 1.2 mg/kg or less for long‐term relief (n = 8), creatinine increase (n = 5), and neutropenia (n = 1) with subsequent improvement in renal function without symptom deterioration.

Conclusions

Oral CyA seems to allow a sustained long‐term relief following HL fulguration by alleviating pain, decreasing urinary symptoms, and procuring great subjective improvement. The daily low dose of 1.5 mg/kg or less appears to have limited adverse events while preventing repeated procedures. Larger trials are warranted.
Characteristic periglacial topography: Multi‐scale hypsometric analysis of cryoplanated uplands in eastern Beringia
Authors: Queen Clayton W. , Nelson Frederick E.
Published: June 2022

General geomorphometry is concerned with the geometric form of the continuous land surface and can be useful for identifying topographic “signatures.” Hypsometry has found numerous applications in several subfields of geomorphology, but has not been used extensively in published periglacial work. Hypsometric analysis was applied in this study to several unglaciated and glaciated locales in Alaska's Yukon‐Tanana Upland and Indian River Upland physiographic sections, extensive areas of eastern Beringia in which cryoplanation landforms are ubiquitous. Never‐glaciated terrain in this region has a hypsometric signature distinctly different from that of glaciated areas within sample areas ranging in size from 0.25 to 100 km2. Cryoplanated terrain exhibits a distinctive convex‐upward hypsometric signature, a reflection of a greater proportion of the reference solid (land mass) remaining intact than in typical mature fluvial or glaciated terrain. Because the elevational position of cryoplanation terraces is slightly below and parallel with snowline position it is, in effect, climatically determined from above, and localized planar surfaces develop near that level. Comparison with terrain in the southwestern USA demonstrates that substantial differences also exist between the hypsometry of upland periglacial terrain in eastern Beringia and that of inselbergs and pediments in warm‐desert geomorphic landscapes, casting doubt on a suggestion that cryoplanation terraces and cryopediments in high‐latitude mountains could be inherited from past intervals of subtropical desert conditions We conclude that characteristic periglacial erosional topography exists in unglaciated areas of Beringia and can be detected and described quantitatively through objective methods.
Perspectives on biotechnology: Public and corporate narratives in the GM archives
Authors: Holmes Matthew
Published: June 2022

Societal Impact Statement

The contentious debate over genetically modified (GM) crops in Britain has entered a new era following Brexit and the development of gene editing. At the same time, the events of the 1980s and 1990s are now entering historical archives, including the GM Archive at the Science Museum in London. This article explores how fears of unnaturalness and arguments from historical continuity informed the British GM controversy. It also analyses the limitations of these modern archives. The concerns surrounding the naturalness and continuity of biotechnology have recently been resurrected following suggestions that gene editing will be employed in plant breeding.

This research examines the introduction of genetically modified (GM) crops to Britain, including the backlash from environmentalist groups and the public that led to a de facto government moratorium on their commercialisation in 1998.

Harnessing archival materials from the Science Museum's GM Archive, this paper shows that GM was viewed as an alien or unnatural technology in Britain, while campaigns from Monsanto and scientific supporters of GM attempted to show how recombinant DNA technology was simply the latest step in a long history of plant breeding.

By moving outside the archive, it becomes clear that the creation of this narrative from continuity was a standard industry strategy. Appeals to the history of plant breeding was a strategy adopted by Monsanto well before the British GM controversy, while twentieth‐century food scares had already undermined public trust in government and industry.

Public concern over the naturalness of biotechnology remains. Meanwhile, contemporary advocates of gene editing have begun to make similar arguments to those deployed in the 1990s, highlighting the similarity of gene editing to natural variation and selection.
Mechanically Modulated Ferromagnetism and Critical Properties of Flexible Perovskite SrRuO3 Thin Film
Authors: Wang Jing , Fan Jiyu , Liu Fengguang , Zu Lin , Ma Chunlan , Zhang Lei , Rahman Azizur , Wang Caixia , Qian Fengjiao , Hu Dazhi , Zhu Yan , Yang Hao
Published: June 2022

In an effort to explore new electronic devices with multiple functionalities, there are numerous studies of depositing perovskite oxides on flexible substrates to replace rigid silicon‐based wafer in device applications. In this study, the growth of pseudocubic SrRuO single‐crystal thin film on a transparent and flexible muscovite is established. The experimental results confirm that the Curie temperature T
C and the magnetic properties can be effectively tuned via the mechanical strain due to the facilitation of flexible substrate. It is found that the tensile strain increases while the compressive strain decreases the spontaneous magnetization for the thin film suffering the same ±0.24% strain. Based on the study of critical behavior, the critical exponents β
 = 0.543(19) and γ
 = 1.262(1) with the critical temperature T
C = 159.04(5) K and T
C = 159.10 K, respectively, are obtained by the modified Arrott plot. The set of critical exponents matches well with Widom scaling relation and the scaling equation, indicating these critical exponents are intrinsic for SrRuO3 thin films. Moreover, it is achieved that the SrRuO3 thin films exhibit a long‐range interaction coupled with 3D‐Heisenberg type.
Free N‐heterocyclic carbenes from Brønsted acidic ionic liquids: Direct detection by electrospray ionization mass spectrometry
Authors: Salvitti Chiara , Pepi Federico , Managò Marta , Bortolami Martina , Michenzi Cinzia , Chiarotto Isabella , Troiani Anna , de Petris Giulia
Published: June 2022

Rationale

The occurrence of N‐heterocyclic carbenes in imidazolium‐based ionic liquids has long been discussed, but no spectroscopic evidence has been reported yet due to their transient nature. The insertion of an ionizable acid group into the cation scaffold of an ionic liquid which acts as a charge tag allows for the direct detection of free carbenes by mass spectrometry.

Methods

Three different Brønsted acidic ionic liquids were synthesized: 1‐methyl‐3‐carboxymethylimidazolium chloride (MAICl), 1‐methyl‐3‐carboxymethylimidazolium acetate (MAIAc) and the corresponding 2‐(3‐methyl‐1H‐imidazol‐3‐ium‐1‐yl)acetate zwitterion (MAI − H). The speciation of these compounds was then analysed by electrospray ionization ion‐trap mass spectrometry in the negative ion mode.

Results

The C2‐H deprotonation of the imidazolium cation leading to the formation of the corresponding carbene is highly affected by the basic properties of the counter‐anion. In the case of MAICl and MAI − H ionic liquids, no charged species corresponding to the free N‐heterocyclic carbene was detected. On the contrary, in the presence of a sufficiently basic anion, such as acetate of MAIAc ionic liquid, an intense signal related to the free carbenic species was observed without the addition of an external base.

Conclusions

In situ formation of free N‐heterocyclic carbenes from Brønsted acidic ionic liquids was demonstrated, highlighting the crucial role of anion basicity in promoting the C2‐H proton abstraction from imidazolium cations with a carboxylic side chain.
Rapid and flexible online desalting using Nafion‐coated melamine sponge for mass spectrometry analysis
Authors: Li Chong , DeVor Amanda , Wang Jing , Valentine Stephen J. , Li Peng
Published: June 2022

Rationale

The performance of mass spectrometry (MS) analysis is often affected by the presence of salt ions. To achieve optimal MS detection results, desalting is necessary for samples with high salt concentrations. We report a rapid, low‐cost and flexible online desalting method using Nafion‐coated sponge. This method is easy to perform and can be implemented to a wide range of customized fluidic systems.

Methods

Nafion‐coated melamine sponge was fabricated by soaking a glass tube containing a melamine sponge in Nafion solution and then drying overnight. The online desalting workflow is comprised of three major parts: (1) Syringe pump, which provides a continuous flow for the online fluid system; (2) Nafion sponge in a glass tube, where the online desalting of sample solution happens; (3) Capillary Vibrating Sharp‐Edge Spray Ionization (cVSSI), which is an ionization technique to ionize the desalted analytes.

Results

Effective online desalting of a 10 mM NaCl solution was demonstrated for a wide range of molecules including small molecules, peptides, DNAs, and proteins using a flow rate of 10 μL/min. By incorporating multiple pieces of the Nafion‐coated sponge, effective desalting for ubiquitin and cytochrome c (Cyt‐c) from physiological buffers, including phosphate‐buffered saline (PBS) and tris‐buffered saline (TBS), were also achieved. For molecules that are sensitive to low pH conditions after desalting, a R‐SO3NH4‐type Nafion‐coated sponge was fabricated. Desalting of ubiquitin, oligosaccharide, and DNA oligomers from 10 mM NaCl or 10 mM KCl solutions was demonstrated.

Conclusions

Flexible, low‐cost, and efficient online desalting was achieved by the Nafion‐coated sponge. A variety of molecules ranging from small molecules, peptides, proteins to oligosaccharides and DNAs can be desalted for MS analysis. The desalting by Nafion sponge has great potential for desalting applications that require customized fluidic design and rapid analysis.
Addiction, present‐bias, and self‐restraint
Authors: Jin Lawrence , Kang Minwook
Published: June 2022

We study the economic rationale for people to engage in self‐restraint. Specifically, we show that when a good is addictive and harmful, forward‐looking present‐biased consumers have an incentive to restrict their current consumption—below the level at which marginal utility of consumption equals marginal cost—in order to curb their future consumption of the harmful good. If the incentive is sufficiently strong, then present bias may encourage consumers to consume less of the addictive bad today. Finally, we show that a self‐restraint incentive can coexist with a sin tax on the addictive bad.
Changes in epigenetic features in legumes under abiotic stresses
Authors: Yung Wai‐Shing , Huang Cheng , Li Man‐Wah , Lam Hon‐Ming
Published: June 2022

Legume crops are rich in nutritional value for human and livestock consumption. With global climate change, developing stress‐resilient crops is crucial for ensuring global food security. Because of their nitrogen‐fixing ability, legumes are also important for sustainable agriculture. Various abiotic stresses, such as salt, drought, and elevated temperatures, are known to adversely affect legume production. The responses of plants to abiotic stresses involve complicated cellular processes including stress hormone signaling, metabolic adjustments, and transcriptional regulations. Epigenetic mechanisms play a key role in regulating gene expressions at both transcriptional and posttranscriptional levels. Increasing evidence suggests the importance of epigenetic regulations of abiotic stress responses in legumes, and recent investigations have extended the scope to the epigenomic level using next‐generation sequencing technologies. In this review, the current knowledge on the involvement of epigenetic features, including DNA methylation, histone modification, and noncoding RNAs, in abiotic stress responses in legumes is summarized and discussed. Since most of the available information focuses on a single aspect of these epigenetic features, integrative analyses involving omics data in multiple layers are needed for a better understanding of the dynamic chromatin statuses and their roles in transcriptional regulation. The inheritability of epigenetic modifications should also be assessed in future studies for their applications in improving stress tolerance in legumes through the stable epigenetic optimization of gene expressions.
Cost‐effectiveness of dementia training for caregivers in caregiver‐patient dyads: A randomized controlled study
Authors: Birkenhäger‐Gillesse Elizabeth G. , Achterberg Wilco P. , Janus Sarah I.M. , Zuidema Sytse U. , van den Hout Wilbert B.
Published: June 2022

Introduction

We evaluated the cost‐effectiveness of the “More at Home with Dementia” intervention, a multicomponent training program for co‐residing caregivers of people with dementia (PwDs).

Methods

We performed a two‐armed randomized controlled trial with an intervention and a control group. Participants were community‐dwelling caregivers living with a person with dementia (59 randomized to intervention and 50 to control arm). The training program lasted 5 days and took place in a holiday accommodation. Quality‐adjusted life‐years (QALYs) were calculated using the EuroQol‐5 Dimensions 3 Levels (EQ‐5D‐3L) for caregivers and PwDs. Costs for informal and formal social care, as well as health care, were collected at four times over a 6‐month period from baseline. Information on nursing home admission or death was collected for 2 years after baseline.

Results

QALYs for caregivers and PwDs added together were 0.12 higher in the intervention group compared with the control group (P = .11). After 1 year, there tended to be fewer nursing home admissions in the intervention group, but this difference was lost by 2 years (P = .19). The cost of the intervention was estimated at €1000 (USD 1090) per dyad. Compared with the control group, the intervention group used other health care and formal social care significantly less for a year after baseline (P = .02 and .001, respectively). The estimated decrease in total costs was €10,437 (P = .07), with an estimated 96% probability that the intervention was cost‐effective vs usual care.

Discussion

The multicomponent “More at Home with Dementia” training program is effective and appears to save costs compared with usual care. Savings appear to be achieved by delaying nursing home admissions and by reducing the use of other care resources. Further research is also needed to clarify if this intervention is effective for caregivers who do not live with a PwD, such as adult children, and for the caregivers of patients with other debilitating chronic diseases. At the same time, effort is advised to implement caregiver training in standard care programs.
Spinal epidural and synovial lipomatosis in a 3‐year‐old Eurasian dog receiving sustained steroid therapy
Authors: Signoret Marion , Gros Lucile , Dumont Renaud , Dally Claire , Le Boedec Kevin , Cauzinille Laurent
Published: June 2022

This report describes a spinal cord epidural and synovial lipomatosis in a 3‐year‐old neutered male Eurasian dog. This dog presented for ambulatory paraparesis and was previously treated with immunosuppressive dosages of prednisolone for 2 years. Computed tomography (CT) myelography and magnetic resonnance imaging (MRI) images identified dorsal compression of the thoraco‐lumbar spinal cord by hypertrophic epidural fat. Histological examination identified extensive well‐differentiated mature adipose tissue in the subepithelial area of the tarsal synovium. Prednisolone is a reported predisposing factor in humans with lipomatosis.
Correction To: Emergence and Ephemerality of Humour During Live Coverage of Large-Scale eSports Events
Authors: Felczak Mateusz
Published: June 2022

The chapter “Emergence and Ephemerality of Humour During Live Coverage of Large-Scale eSports Events” was previously published non-open access.
Reasons Why Crime and Safety in Rural Areas Matter
Authors: Ceccato Vania , Abraham Jonatan
Published: June 2022

This chapter starts by listing 20 reasons why crime and safety in rural areas is a subject worth examining in its own right. We present reasons from common misconceptions of crime in rural areas to illustrations of how globalization and climate change link to crime and safety in areas on the rural-urban continuum, as well as how all these are associated with rural development and sustainability.
Introduction
Authors: Swan Jerry , Nivel Eric , Kant Neel , Hedges Jules , Atkinson Timothy , Steunebrink Bas
Published: June 2022

The rise of civilization is synonymous with the creation of tools that extend the intellectual and physical reach of human beings [133]. The pinnacle of such endeavours is to replicate the flexible reasoning capacity of human intelligence within a machine, making it capable of performing useful work on command, despite the complexity and adversity of the real world. In order to achieve such Artificial Intelligence (AI), a new approach is required: traditional symbolic AI has long been known to be too rigid to model complex and noisy phenomena and the sample-driven approach of Deep Learning cannot scale to the long-tailed distributions of the real world. In this book, we describe a new approach for building a situated system that reflects upon its own reasoning and is capable of making decisions in light of its limited knowledge and resources. This reflective reasoning process addresses the vital safety issues that inevitably accompany open-ended reasoning: the system must perform its mission within a specifiable operational envelope.
Challenges for Deep Learning
Authors: Swan Jerry , Nivel Eric , Kant Neel , Hedges Jules , Atkinson Timothy , Steunebrink Bas
Published: June 2022

Deep learning (DL) has emerged as the dominant branch of machine learning, becoming the state of the art for machine intelligence in various domains. As discussed in the previous chapter, this has led some researchers to believe that deep learning could hypothetically scale to achieve general intelligence. However, there is increasing consensus (e.g. [57, 210, 230]) that the techniques do not scale as well as was anticipated to harder problems. In particular, deep learning methods find their strength in automatically synthesizing distributed quantitative features from data. These features are useful insofar as they enable mostly reliable classification and regression, and in some limited cases also few- or zero-shot transfer to related tasks. However, it is increasingly questionable whether deep learning methods are appropriate for autonomous roles in environments that are not strongly constrained. While there are still countless use-cases for narrow artificial intelligence, many of the truly transformative use-cases can only be realized by general intelligence
A Compositional Framework
Authors: Swan Jerry , Nivel Eric , Kant Neel , Hedges Jules , Atkinson Timothy , Steunebrink Bas
Published: June 2022

The system architecture presented in Chapter controls (i.e., sustains and constrains) the invocation of the inference methods introduced in Chapter. In this chapter, we describe the methods of higher level inference in more detail.
The ultra-high-energy neutrino-nucleon cross section: measurement forecasts for an era of cosmic EeV-neutrino discovery
Authors: Valera Víctor B. , Bustamante Mauricio , Glaser Christian
Published: June 2022

Abstract

Neutrino interactions with protons and neutrons probe their deep structure and may reveal new physics. The higher the neutrino energy, the sharper the probe. So far, the neutrino-nucleon (νN) cross section is known across neutrino energies from a few hundred MeV to a few PeV. Soon, ultra-high-energy (UHE) cosmic neutrinos, with energies above 100 PeV, could take us farther. So far, they have evaded discovery, but upcoming UHE neutrino telescopes endeavor to find them. We present the first detailed measurement forecasts of the UHEνNcross section, geared to IceCube-Gen2, one of the leading detectors under planning. We use state-of-the-art ingredients in every stage of our forecasts: in the UHE neutrino flux predictions, the neutrino propagation inside Earth, the emission of neutrino-induced radio signals in the detector, their propagation and detection, and the treatment of backgrounds. After 10 years, if at least a few tens of UHE neutrino-induced events are detected, IceCube-Gen2 could measure theνNcross section at center-of-mass energies of$$ \sqrt{s} $$s≈10–100 TeV for the first time, with a precision comparable to that of its theory prediction.
Spin impurities, Wilson lines and semiclassics
Authors: Cuomo Gabriel , Komargodski Zohar , Mezei Márk , Raviv-Moshe Avia
Published: June 2022

Abstract

We consider line defects with large quantum numbers in conformal field theories. First, we consider spin impurities, both for a free scalar triplet and in the Wilson-Fisher O(3) model. For the free scalar triplet, we find a rich phase diagram that includes a perturbative fixed point, a new nonperturbative fixed point, and runaway regimes. To obtain these results, we develop a new semiclassical approach. For the Wilson-Fisher model, we propose an alternative description, which becomes weakly coupled in the large spin limit. This allows us to chart the phase diagram and obtain numerous rigorous predictions for large spin impurities in 2 + 1 dimensional magnets. Finally, we also study 1/2-BPS Wilson lines in large representations of the gauge group in rank-1 $$ \mathcal{N} $$
N
= 2 superconformal field theories. We contrast the results with the qualitative behavior of large spin impurities in magnets.
The muon g − 2 anomaly confronts new physics in e± and μ± final states scattering
Authors: Darmé Luc , di Cortona Giovanni Grilli , Nardi Enrico
Published: June 2022

Abstract

The 4.2σ discrepancy between the standard model prediction for the muon anomalous magnetic moment aμ and the experimental result is accompanied by other anomalies. A crucial input for the prediction is the hadronic vacuum polarization $$ {a}_{\mu}^{\mathrm{HVP}} $$

a
μ
HVP

inferred from σhad = σ(e+e−→ hadrons) data. However, the two most accurate determinations of σhad from KLOE and BaBar disagree by almost 3 σ. Additionally, the combined data-driven result disagrees with the most precise lattice determination of $$ {a}_{\mu}^{\mathrm{HVP}} $$

a
μ
HVP

by 2.1 σ. We show that all these discrepancies could be accounted for by a new boson produced resonantly around the KLOE centre of mass energy and decaying promptly yielding e+e− and μ+μ− pairs in the final states. This gives rise to three different effects: (i) the additional e+e− events will affect the KLOE luminosity determination based on measurements of the Bhabha cross section, and in turn the inferred value of σhad; (ii) the additional μ+μ− events will affect the determination of σhad via the (luminosity independent) measurement of the ratio of π+π−γ versus μ+μ−γ events; (iii) loops involving the new boson would contribute directly to the prediction for aμ. We discuss in detail this possibility, and we present a simple model that can reconcile the KLOE and BaBar results for σhad, the data-driven and the lattice determinations of $$ {a}_{\mu}^{\mathrm{HVP}} $$

a
μ
HVP

, the predicted and measured values of aμ, while complying with all phenomenological constraints.