bluuebunny/crossref_metadata_2025 huggingface dataset:
Is an image-based eyelid management service safe and effective?
Authors: Gillam Matthew , Younus Osman , Loo Shi-Pei , Connolly Julie , Cauchi Paul , Gregory Marilena , Drummond Suzy , Chadha Vikas
Published: May 2023

Introduction

The COVID-19 pandemic created a requirement for reduced patient contact and reduced capacity in clinics. We previously published results of an Image-Based Eyelid Lesion Management Service (IBELMS) which was found non-inferior to traditional face-to-face clinic at diagnosing lesions and identifying eyelid malignancies. We now present first-year safety and efficacy data from this service.

Methods

Data were collected retrospectively on all patients seen in NHS Greater Glasgow and Clyde eyelid photography clinics from 30th September 2020 to 29th September 2021, including referral source and diagnosis, time to clinic review, treatment and patient outcomes.

Results

808 patients were included in the study. Chalazion was the most common diagnoses recorded (38.4%). There was a statistically significant decrease in mean time from referral to appointment time between the first 4 months and last 4 months of the service (93 days to 22 days, p ≤ 0.0001). 266 (33%) of patients were discharged following photographs, 45 (6%) were discharged for non-attendance and 371 (46%) were booked for a minor procedure. 13 biopsy-confirmed malignant lesions were identified; only 3 had been referred as suspected malignancy. 23 patients out of 330 with at least 6 months follow up (7%) were re-referred within 6 months of treatment or discharge; however, none of them with a missed periocular malignancy.

Discussion

Eyelid photography clinics effectively reduce patient waiting times and maximise clinic capacity. They accurately identify eyelid lesions including malignancies with a low re-referral rate. We propose that an image-based service for eyelid lesions is a safe and effective way of managing such patients.
Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features
Authors: Zhao Weizhu , Jia Yanfei , Sun Guangyu , Yang Haiying , Liu Luguang , Qu Xianlin , Ding Jishuang , Yu Hang , Xu Botao , Zhao Siwei , Xing Ligang , Chai Jie
Published: May 2023

Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.
Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism
Authors: Van Acker Zoë P. , Perdok Anika , Hellemans Ruben , North Katherine , Vorsters Inge , Cappel Cedric , Dehairs Jonas , Swinnen Johannes V. , Sannerud Ragna , Bretou Marine , Damme Markus , Annaert Wim
Published: May 2023

Phospholipase D3 (PLD3) polymorphisms are linked to late-onset Alzheimer’s disease (LOAD). Being a lysosomal 5’-3’ exonuclease, its neuronal substrates remained unknown as well as how a defective lysosomal nucleotide catabolism connects to AD-proteinopathy. We identified mitochondrial DNA (mtDNA) as a major physiological substrate and show its manifest build-up in lysosomes of PLD3-defective cells. mtDNA accretion creates a degradative (proteolytic) bottleneck that presents at the ultrastructural level as a marked abundance of multilamellar bodies, often containing mitochondrial remnants, which correlates with increased PINK1-dependent mitophagy. Lysosomal leakage of mtDNA to the cytosol activates cGAS–STING signaling that upregulates autophagy and induces amyloid precursor C-terminal fragment (APP-CTF) and cholesterol accumulation. STING inhibition largely normalizes APP-CTF levels, whereas an APP knockout in PLD3-deficient backgrounds lowers STING activation and normalizes cholesterol biosynthesis. Collectively, we demonstrate molecular cross-talks through feedforward loops between lysosomal nucleotide turnover, cGAS-STING and APP metabolism that, when dysregulated, result in neuronal endolysosomal demise as observed in LOAD.
Trogocytic molting of T cell microvilli upregulates T cell receptor surface expression and promotes clonal expansion
Authors: Park Jeong-Su , Kim Jun-Hyeong , Soh Won-Chang , Kim Na-Young , Lee Kyung-Sik , Kim Chang-Hyun , Chung Ik-Joo , Lee Sunjae , Kim Hye-Ran , Jun Chang-Duk
Published: May 2023

Although T cell activation is known to involve the internalization of the T cell antigen receptor (TCR), much less is known regarding the release of TCRs following T cell interaction with cognate antigen-presenting cells. In this study, we examine the physiological mechanisms underlying TCR release following T cell activation. We show that T cell activation results in the shedding of TCRs in T cell microvilli, which involves a combined process of trogocytosis and enzymatic vesiculation, leading to the loss of membrane TCRs and microvilli-associated proteins and lipids. Surprisingly, unlike TCR internalization, this event results in the rapid upregulation of surface TCR expression and metabolic reprogramming of cholesterol and fatty acid synthesis to support cell division and survival. These results demonstrate that TCRs are lost through trogocytic ‘molting’ following T cell activation and highlight this mechanism as an important regulator of clonal expansion.
Lithium crystallization at solid interfaces
Authors: Yang Menghao , Liu Yunsheng , Mo Yifei
Published: May 2023

Understanding the electrochemical deposition of metal anodes is critical for high-energy rechargeable batteries, among which solid-state lithium metal batteries have attracted extensive interest. A long-standing open question is how electrochemically deposited lithium-ions at the interfaces with the solid-electrolytes crystalize into lithium metal. Here, using large-scale molecular dynamics simulations, we study and reveal the atomistic pathways and energy barriers of lithium crystallization at the solid interfaces. In contrast to the conventional understanding, lithium crystallization takes multi-step pathways mediated by interfacial lithium atoms with disordered and random-closed-packed configurations as intermediate steps, which give rise to the energy barrier of crystallization. This understanding of multi-step crystallization pathways extends the applicability of Ostwald’s step rule to interfacial atom states, and enables a rational strategy for lower-barrier crystallization by promoting favorable interfacial atom states as intermediate steps through interfacial engineering. Our findings open rationally guided avenues of interfacial engineering for facilitating the crystallization in metal electrodes for solid-state batteries and can be generally applicable for fast crystal growth.
Tunable directional photon scattering from a pair of superconducting qubits
Authors: Redchenko Elena S. , Poshakinskiy Alexander V. , Sett Riya , Žemlička Martin , Poddubny Alexander N. , Fink Johannes M.
Published: May 2023

The ability to control the direction of scattered light is crucial to provide flexibility and scalability for a wide range of on-chip applications, such as integrated photonics, quantum information processing, and nonlinear optics. Tunable directionality can be achieved by applying external magnetic fields that modify optical selection rules, by using nonlinear effects, or interactions with vibrations. However, these approaches are less suitable to control microwave photon propagation inside integrated superconducting quantum devices. Here, we demonstrate on-demand tunable directional scattering based on two periodically modulated transmon qubits coupled to a transmission line at a fixed distance. By changing the relative phase between the modulation tones, we realize unidirectional forward or backward photon scattering. Such an in-situ switchable mirror represents a versatile tool for intra- and inter-chip microwave photonic processors. In the future, a lattice of qubits can be used to realize topological circuits that exhibit strong nonreciprocity or chirality.
Liquid biopsy for brain metastases and leptomeningeal disease in patients with breast cancer
Authors: Morganti Stefania , Parsons Heather A. , Lin Nancy U. , Grinshpun Albert
Published: May 2023

A significant subset of patients with metastatic breast cancer develops brain metastasis. As efficacy of systemic therapies has improved and patients live longer with metastatic breast cancer, the incidence of breast cancer brain metastases has increased. Brain metastases pose a clinical challenge in diagnosis, treatment, and monitoring across all breast cancer subtypes, and better tools are needed. Liquid biopsy, which enables minimally invasive sampling of a patient’s cancer, has the potential to shed light on intra-cranial tumor biology and to improve patient care by enabling therapy tailoring. Here we review current evidence for the clinical validity of liquid biopsy in patients with breast cancer brain metastases, with a focus on circulating tumor cells and circulating tumor DNA.
Untargeted mass spectrometry-based metabolomics approach unveils biochemical changes in compound probiotic fermented milk during fermentation
Authors: Sun Yaru , Guo Shuai , Wu Ting , Zhang Jingwen , Kwok Lai-Yu , Sun Zhihong , Zhang Heping , Wang Jicheng
Published: May 2023

Probiotic functional products have drawn wide attention because of their increasing popularity. However, few studies have analyzed probiotic-specific metabolism in the fermentation process. This study applied UPLC-QE-MS-based metabolomics to track changes in the milk metabolomes in the course of fermentation by two probiotic strains, Lacticaseibacillus paracasei PC-01 and Bifidobacterium adolescentis B8589. We observed substantial changes in the probiotic fermented milk metabolome between 0 and 36 h of fermentation, and the differences between the milk metabolomes at the interim period (36 h and 60 h) and the ripening stage (60 h and 72 h) were less obvious. A number of time point-specific differential metabolites were identified, mainly belonging to organic acids, amino acids, and fatty acids. Nine of the identified differential metabolites are linked to the tricarboxylic acid cycle, glutamate metabolism, and fatty acid metabolism. The contents of pyruvic acid, γ-aminobutyric acid, and capric acid increased at the end of fermentation, which can contribute to the nutritional quality and functional properties of the probiotic fermented milk. This time-course metabolomics study analyzed probiotic-specific fermentative changes in milk, providing detailed information of probiotic metabolism in a milk matrix and the potential beneficial mechanism of probiotic fermented milk.
Flexible solar cells based on foldable silicon wafers with blunted edges
Authors: Liu Wenzhu , Liu Yujing , Yang Ziqiang , Xu Changqing , Li Xiaodong , Huang Shenglei , Shi Jianhua , Du Junling , Han Anjun , Yang Yuhao , Xu Guoning , Yu Jian , Ling Jiajia , Peng Jun , Yu Liping , Ding Bin , Gao Yuan , Jiang Kai , Li Zhenfei , Yang Yanchu , Li Zhaojie , Lan Shihu , Fu Haoxin , Fan Bin , Fu Yanyan , He Wei , Li Fengrong , Song Xin , Zhou Yinuo , Shi Qiang , Wang Guangyuan , Guo Lan , Kang Jingxuan , Yang Xinbo , Li Dongdong , Wang Zhechao , Li Jie , Thoroddsen Sigurdur , Cai Rong , Wei Fuhai , Xing Guoqiang , Xie Yi , Liu Xiaochun , Zhang Liping , Meng Fanying , Di Zengfeng , Liu Zhengxin
Published: May 2023

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1–4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between −70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.
Dynamic optical response of solids following 1-fs-scale photoinjection
Authors: Zimin Dmitry A. , Karpowicz Nicholas , Qasim Muhammad , Weidman Matthew , Krausz Ferenc , Yakovlev Vladislav S.
Published: May 2023

Photoinjection of charge carriers profoundly changes the properties of a solid. This manipulation enables ultrafast measurements, such as electric-field sampling1,2, advanced recently to petahertz frequencies3–7, and the real-time study of many-body physics8–13. Nonlinear photoexcitation by a few-cycle laser pulse can be confined to its strongest half-cycle14–16. Describing the associated subcycle optical response, vital for attosecond-scale optoelectronics, is elusive when studied with traditional pump-probe metrology as the dynamics distort any probing field on the timescale of the carrier, rather than that of the envelope. Here we apply field-resolved optical metrology to these dynamics and report the direct observation of the evolving optical properties of silicon and silica during the first few femtoseconds following a near-1-fs carrier injection. We observe that the Drude–Lorentz response forms within several femtoseconds—a time interval much shorter than the inverse plasma frequency. This is in contrast to previous measurements in the terahertz domain8,9 and central to the quest to speed up electron-based signal processing.
Tree islands enhance biodiversity and functioning in oil palm landscapes
Authors: Zemp Delphine Clara , Guerrero-Ramirez Nathaly , Brambach Fabian , Darras Kevin , Grass Ingo , Potapov Anton , Röll Alexander , Arimond Isabelle , Ballauff Johannes , Behling Hermann , Berkelmann Dirk , Biagioni Siria , Buchori Damayanti , Craven Dylan , Daniel Rolf , Gailing Oliver , Ellsäßer Florian , Fardiansah Riko , Hennings Nina , Irawan Bambang , Khokthong Watit , Krashevska Valentyna , Krause Alena , Kückes Johanna , Li Kevin , Lorenz Hendrik , Maraun Mark , Merk Miryam Sarah , Moura Carina C. M. , Mulyani Yeni A. , Paterno Gustavo B. , Pebrianti Herni Dwinta , Polle Andrea , Prameswari Di Ajeng , Sachsenmaier Lena , Scheu Stefan , Schneider Dominik , Setiajiati Fitta , Setyaningsih Christina Ani , Sundawati Leti , Tscharntke Teja , Wollni Meike , Hölscher Dirk , Kreft Holger
Published: May 2023

In the United Nations Decade on Ecosystem Restoration1, large knowledge gaps persist on how to increase biodiversity and ecosystem functioning in cash crop-dominated tropical landscapes2. Here, we present findings from a large-scale, 5-year ecosystem restoration experiment in an oil palm landscape enriched with 52 tree islands, encompassing assessments of ten indicators of biodiversity and 19 indicators of ecosystem functioning. Overall, indicators of biodiversity and ecosystem functioning, as well as multidiversity and ecosystem multifunctionality, were higher in tree islands compared to conventionally managed oil palm. Larger tree islands led to larger gains in multidiversity through changes in vegetation structure. Furthermore, tree enrichment did not decrease landscape-scale oil palm yield. Our results demonstrate that enriching oil palm-dominated landscapes with tree islands is a promising ecological restoration strategy, yet should not replace the protection of remaining forests.
Programming inactive RNA-binding small molecules into bioactive degraders
Authors: Tong Yuquan , Lee Yeongju , Liu Xiaohui , Childs-Disney Jessica L. , Suresh Blessy M. , Benhamou Raphael I. , Yang Chunying , Li Weimin , Costales Matthew G. , Haniff Hafeez S. , Sievers Sonja , Abegg Daniel , Wegner Tristan , Paulisch Tiffany O. , Lekah Elizabeth , Grefe Maison , Crynen Gogce , Van Meter Montina , Wang Tenghui , Gibaut Quentin M. R. , Cleveland John L. , Adibekian Alexander , Glorius Frank , Waldmann Herbert , Disney Matthew D.
Published: May 2023

Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded RNA structures. Mapping these interaction landscapes across the human transcriptome defined structure–activity relationships. Although RNA-binding compounds that bind to functional sites were expected to elicit a biological response, most identified interactions were predicted to be biologically inert as they bind elsewhere. We reasoned that, for such cases, an alternative strategy to modulate RNA biology is to cleave the target through a ribonuclease-targeting chimera, where an RNA-binding molecule is appended to a heterocycle that binds to and locally activates RNase L1. Overlay of the substrate specificity for RNase L with the binding landscape of small molecules revealed many favourable candidate binders that might be bioactive when converted into degraders. We provide a proof of concept, designing selective degraders for the precursor to the disease-associated microRNA-155 (pre-miR-155), JUN mRNA and MYC mRNA. Thus, small-molecule RNA-targeted degradation can be leveraged to convert strong, yet inactive, binding interactions into potent and specific modulators of RNA function.
Combination of Lactobacillus fermentum NS9 and aronia anthocyanidin extract alleviates sodium iodate-induced retina degeneration
Authors: Xing Yan , Liang Shan , Zhang Limei , Ni He , Zhang Xueqin , Wang Jiancheng , Yang Liu , Song Shuangshuang , Li Hai-Hang , Jia Chenxi , Jin Feng
Published: May 2023

It is important to explore the effective approaches to prevent dry age-related macular degeneration (AMD). In this study, significantly decreased full-field electroretinograms wave amplitudes and disordered retina structures were detected in rat retinas of sodium iodate induced dry AMD model. Six a- and b-wave amplitudes and the antioxidant activities were significantly increased, and the outer nuclear layer thickness was significantly improved in the rat retinas treated with the combination of Lactobacillus fermentum NS9 (LF) and aronia anthocyanidin extract (AAE) compared with the model. The effects were much better than the treatment with AAE alone. The proteomics analysis showed the expressions of α-, β- and γ-crystallins were increased by 3–8 folds in AAE treated alone and by 6–11 folds in AAE + LF treatment compared with the model, which was further confirmed by immuno-blotting analysis. Analysis of gut microbial composition indicated that higher abundance of the genus Parasutterella and species P. excrementihominis was found in the AAE + LF treatment compared with the other groups. The results indicated that the combined treatment of AAE + LF is a potential way to prevent the retina degeneration which is significantly better than the AAE treated alone.
Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study
Authors: Zadi T. , van Dam-Nolen D. H. K. , Aizaz M. , van der Kolk A. G. , Nederkoorn P. J. , Hendrikse J. , Kooi M. E. , van der Lugt A. , Bos D.
Published: May 2023

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58–0.90 respectively OR = 2.24, 95% CI 1.60–3.13).We found significant correlation for change in ECAC volume with diabetes (β = 0.46, 95% CI 0.03–0.89) and baseline ECAC volume (β = 0.81, 95% CI 0.73–0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48–3.16), age (OR = 2.00, 95% CI 1.19–3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20–11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (β = 0.92, 95% CI 1.59–7.02), use of oral hypoglycemic drugs (β = 0.86, 95% CI 0.12–1.59) and baseline ICAC volume (β = 0.71, 95% CI 0.55–0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.
Convolutional neural networks in the qualitative improvement of sweet potato roots
Authors: Clara Gonçalves Fernandes Ana , Ribeiro Valadares Nermy , Henrique Oliveira Rodrigues Clóvis , Aguiar Alves Rayane , Lorena Melucio Guedes Lis , Luiz Mendes Athayde André , Mistico Azevedo Alcinei
Published: May 2023

The objective was to verify whether convolutional neural networks can help sweet potato phenotyping for qualitative traits. We evaluated 16 families of sweet potato half-sibs in a randomized block design with four replications. We obtained the images at the plant level and used the ExpImage package of the R software to reduce the resolution and individualize one root per image. We grouped them according to their classifications regarding shape, peel color, and damage caused by insects. 600 roots of each class were destined for training the networks, while the rest was used to verify the quality of the fit. We used the python language on the Google Colab platform and the Keras library, considering the VGG-16, Inception-v3, ResNet-50, InceptionResNetV2, and EfficientNetB3 architectures. The InceptionResNetV2 architecture stood out with high accuracy in classifying individuals according to shape, insect damage, and peel color. Image analysis associated with deep learning may help develop applications used by rural producers and improve sweet potatoes, reducing subjectivity, labor, time, and financial resources in phenotyping.
Novel cementitious materials with mechanoluminescence for the application of visible stress monitoring and recording
Authors: Zhang Bing , Liu Shiqi , Zhou Zichen , Zeng Ming , Zhang Jianfeng , Tu Dong
Published: May 2023

The development of real-time and accurate visual stress detection is crucial for the field of building engineering. Herein, a new strategy is explored for the development of novel cementitious materials by hierarchical aggregation smart luminescent material and resin-based material. The cementitious material with such layered structure is inherently capable of visualization of stress monitoring and recording by converting the stress to visible light. The specimen fabricated by the novel cementitious material could repetitively emit green visible light under excitation of a mechanical pulse for 10 cycles, suggesting that the cementitious material shows highly reproducible performance. Moreover, the numerical simulations and analysis for the models of stress indicate that the luminescent time is synchronous with the stress and the emission intensity is proportional to the value of stress. To the best of our knowledge, this is the first study that the cementitious material realizes visible stress monitoring and recording, which supplies new insights for exploring modern multi-functional building materials.
Early depressive symptoms and disability accrual in Multiple Sclerosis: a UK MS Register study
Authors: Jacobs Benjamin M. , Daruwalla Cyrus , McKeon Mollie O. , Al-Najjar Raghda , Simcock-Davies Andrea , Tuite-Dalton Katherine , Brown J. William L. , Dobson Ruth , Rodgers Jeff , Middleton Rod
Published: May 2023

Understanding the associations and potential drivers of long-term disability in Multiple Sclerosis (MS) is of clinical and prognostic value. Previous data have suggested a link between depression and disability accrual in MS. We aimed to determine whether depression in early MS predicts subsequent accrual of disability. Using data from the UK MS Register, we identified individuals with and without symptoms of depression and anxiety close to disease onset. We used Cox proportional hazards regression to evaluate whether early depressive or anxiety symptoms predict subsequent physical disability worsening, measured using the Expanded Disability Status Scale (EDSS). We analysed data from 862 people with MS of whom 134 (15.5%) reached an EDSS of ≥ 6.0. Early depressive symptoms were associated with an increased risk of reaching an EDSS of 6.0 (HR 2.42, 95% CI 1.49–3.95, p < 0.001), however this effect dissipated when adjusting for baseline EDSS (HR 1.40, 95% CI 0.84–2.32, p = 0.2). These data suggest that early depressive symptoms in MS are associated with subsequent disability accrual, but are likely the result of disability rather than its cause.
Association between visceral obesity, metformin use, and recurrence risk in early-stage colorectal cancer
Authors: Vedire Yeshwanth Reddy , Mukherjee Sarbajit , Dondapati Sumedha , Yendamuri Sai
Published: May 2023

We sought to investigate the association between visceral obesity with disease recurrence and survival in early-stage colorectal cancer (CRC) patients. We also wanted to examine if such an association, if exists, is influenced by metformin use. Stage I/II CRC adenocarcinoma patients treated surgically were identified. L3 level CT VFI (visceral fat index) was used as a metric of visceral obesity and was calculated as the proportion of total fat area composed of visceral fat. N = 492. 53% were males, 90% were Caucasians, 35% had stage I disease, and 14% used metformin. 20.3% patients developed a recurrence over a median follow-up of 56 months. VFI was associated with both RFS and OS in a multivariate model, but not BMI. The final multivariate model for RFS included an interaction term for VFI and metformin (p = 0.04). Confirming this result, subgroup analysis showed an increasing VFI was associated with a poor RFS (p = 0.002), and OS (p < 0.001) in metformin non-users only and metformin use was associated with a better RFS only in the top VFI tertile (p = 0.01). Visceral obesity, but not BMI, is associated with recurrence risk and poorer survival in stage I/II CRC. Interestingly, this association is influenced by metformin use.
Second-generation supraglottic airway in laparoscopic donor nephrectomy
Authors: Lee Ja Eun , Kim Ha Yeon , Lee Kyo Won , Kim Gaab Soo
Published: May 2023

Supraglottic airway (SGA) may have advantages over endotracheal tube (ETT) regarding laryngospasm, coughing, sore throat, and hemodynamic changes; however, studies on the use of SGA in laparoscopic donor nephrectomy (LDN) are lacking. Here, we aimed to confirm the safety and feasibility of second-generation SGA in LDN and compare them with those of ETT. Enrolled adult donors (aged > 18 years) who underwent LDN between August 2018 and November 2021 were divided into two groups—ETT vs. SGA. Airway pressure, lung compliance, desaturation, and hypercapnia were recorded during surgery. After propensity score matching for baseline characteristics and surgical duration, 82 and 152 donors were included in the ETT and SGA groups, respectively, and their outcomes were compared. The peak airway pressure was lower in the SGA group than in the ETT group 5 min after pneumoperitoneum. Dynamic lung compliance was higher in the SGA group than in the ETT group during surgery. There were no cases of intraoperative desaturation, hypercapnia, or postoperative aspiration pneumonitis. The use of second-generation SGA, a safe alternative to ETT for LDN, resulted in reduced airway resistance and increased lung compliance, which suggests its benefits for airway management in kidney donors.
Memory compensation strategies in everyday life: similarities and differences between younger and older adults
Authors: Radnan Madeleine J. , Nicholson Riley , Brookman Ruth , Harris Celia B.
Published: May 2023

Memory compensation strategies serve an important role in everyday functioning, especially in the face of cognitive decline. Research on the external memory compensation strategies employed by older adults has focused almost entirely on non-digital tools. Less is known about how memory compensation strategies might have changed due to the rapid and widespread uptake of digital technologies. In the current research, 208 younger adults and 114 older adults freely reported what internal or external memory strategy or tool they would use to accomplish 20 different everyday memory tasks. Participants’ responses were coded as involving either internal (e.g. using a mnemonic) or external (e.g. writing a list) strategies, and then underwent further categorisation to classify types of internal and external strategies (e.g. digital or physical tool). Findings indicated that external strategies were much more prevalent than internal strategies for both younger and older adults, and that digital compensation strategies were prevalent for both age groups. There were age differences such that older adults reported more strategies overall, and were less likely to report digital tools, more likely to report physical tools, more likely to report environmental tools, and less likely to report social tools than younger adults. Positive attitudes to technology were associated with digital tool use for older but not younger participants. Findings are discussed in terms of existing theories and approaches to studying memory compensation strategies and cognitive offloading.
A simple model for pink noise from amplitude modulations
Authors: Morikawa Masahiro , Nakamichi Akika
Published: May 2023

We propose a simple model for the origin of pink noise (or 1/f fluctuation) based on the waves with accumulating frequencies. These waves arise spontaneously in a system with synchronization, resonance, and infrared divergence. Many waves with accumulating frequencies can produce signals of arbitrary small frequencies from a system of small size. This beat mechanism can be understood as amplitude modulation. The pink noise can appear after the demodulation process, which produces a variety of pink noise in many fields. The pink noise thus formed from the beat has nothing to do with dissipation or long-time memory. We also suggest new ways of looking at pink noise in earthquakes, solar flares, and stellar activities.
Oncostatin M is a regulator of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast-like cells
Authors: Münz Sina , Feger Martina , Föller Michael
Published: May 2023

Renal phosphate and vitamin D metabolism is under the control of fibroblast growth factor 23 (FGF23), an endocrine and paracrine factor predominantly produced in bone. FGF23 formation is stimulated by active vitamin D, or parathyroid hormone (PTH), which are further regulators of phosphate homeostasis. In renal, inflammatory, and other diseases, plasma FGF23 reflects disease stage and correlates with outcome. Oncostatin M is part of the interleukin-6 (IL-6) family and regulates remodeling and PTH effects in bone as well as cardiac FGF23 production in heart failure via glycoprotein gp130. Here, we studied whether oncostatin M is a regulator of FGF23 in bone cells. Experiments were performed in UMR106 osteoblast-like cells, Fgf23 mRNA was determined by qRT-PCR, FGF23 protein by Western Blotting and ELISA, and oncostatin M receptor and leukemia inhibitory factor (LIF) receptor gene knockout accomplished by siRNA. As a result, oncostatin M dose-dependently up-regulated Fgf23 expression and protein secretion. The oncostatin M effect on FGF23 was mediated by oncostatin M receptor and gp130 and involved, at least in part, STAT3 and MEK1/2. Taken together, oncostatin M is a regulator of FGF23 through oncostatin M receptor, gp130, as well as STAT3 and MEK1/2 in UMR106 osteoblasts.
Multi-level meta-analysis of whether fostering creativity during physical activity interventions increases their impact on cognitive and academic outcomes during childhood
Authors: Vasilopoulos Fotini , Jeffrey Holly , Wu Yanwen , Dumontheil Iroise
Published: May 2023

Neuroplasticity research supports the idea that varied practice and new environments promote cognitive engagement and enhance learning. Expanding on a meta-analysis of the effect of physical activity interventions on cognition and academic outcomes, we reviewed and quantified the impact of task and environmental factors that foster creative physical activity. Interventions were considered as fostering creative physical activity to a greater extent if (1) they were varied, (2) relied less on technical acquisition, instruction or demonstration, (3) involved open spaces, props, or open-ended instructions, and (4) involved interactions with peers. A wide range of physical activities were considered, from dance to aerobic exercise across 92 studies in 5–12-year-old children. Creativity ratings of physical activity interventions were varied but did not associate with greater beneficial effects on executive functions (k = 45), academic achievement (k = 47), or fluid intelligence (k = 8). Studies assessing on-task behaviour (k = 5) tended not to foster creativity, while reversely studies assessing creativity tended to foster creative physical activities (k = 5). As a group, three studies that fostered more creative PA showed a small significant negative summary effect on cognitive flexibility. Considering qualitative differences in the physical activities performed in schools will improve our understanding of their mechanisms of impact. Future research should consider using more varied measures, including more proximal outcomes that involve body movements (e.g., a Simon Says task to measure inhibitory control).
Tracking supercritical geothermal fluid distribution from continuous seismic monitoring
Authors: Andajani Rezkia Dewi , Tsuji Takeshi , Ikeda Tatsunori , Matsumoto Satoshi , Kitamura Keigo , Nishijima Jun
Published: May 2023

Continuous seismic monitoring could play a pivotal role in deep geothermal energy exploration. We monitored seismicity near geothermal production areas of the Kuju volcanic complex with a dense seismic network and automated event detection. Most events were shallow (less than 3 km below sea level) and distributed along a boundary between regions of high and low resistivity and S-wave velocity, interpreted as a lithological boundary or related fracture zone. Deeper events located on top of subvertical conductors may reflect fracturing associated with magmatic fluid intrusion. A correlation may exist between seismicity and heavy rainfall three days prior to increased pore pressure in pre-existing fractures. Our findings support the presence of supercritical geothermal fluids and demonstrate the importance of continuous seismic monitoring in supercritical geothermal energy exploration.
Patterns of the radiation properties for Peano antennas
Authors: Pérez-Moroyoqui René , Rodríguez-Romo Suemi , Ibáñez-Orozco Oscar
Published: May 2023

This paper studies metallic microstrip antennas with air as a substrate in the UHF band, patterned after space-filling, self-avoiding, and self-similar (FASS) Peano curves. Our novel study is based on context-free grammar and genetic programming as computing tools to unravel the role of geometry on both; the Voltage Standing Wave Ratio (VSWR$$<2$$

<
2

) and frequency resonance patterns for Peano antennas. We use in our approach the numeric method of moments (MoM) implemented in Matlab 2021a to solve the corresponding Maxwell equations. Novel equations for the patterns of both features (resonance frequencies and frequencies such that the VSWR$$<2$$

<
2

) are provided as functions of the characteristic length L. Antennas spanning a $$L\times L$$

L
×
L

area ($$L\le 0.1\,m$$

L
≤
0.1

m

), feeding points set at seven places, and three widths of the metallic strip are introduced as instances of our approach. Finally, a Python 3.7 application is constructed to facilitate the extension and use of our results.
Study on strength characteristics and thickening characteristics of classified-fine cemented backfill in gold mine
Authors: Wang Xian-qing , Wan Wen , Yao Zhong-liang , Gao Ru-gao , Lu Zhen-xing , Tang Xiao-yu , Fan Bao-jie
Published: May 2023

For some new mines, the utilization rate of tailings is not satisfactory when using unclassified tailings as backfill aggregate for cemented backfill. At the same time, with the progress of mineral processing technology, the tailings discharged by the concentrator gradually become finer. Therefore, cemented filling with fine-grained tailings as aggregate will become the development direction of filling technology in the future. In this paper, the feasibility of fine particle tailings backfill is studied by taking the particle tailings of-200 mesh as aggregate in Shaling gold mine. The calculation shows that the utilization rate of tailings is increased from 45.1% to 90.3% by using-200 mesh tailings as filling aggregate. The response surface central composite design method (RSM-CCD) was used to study the strength of backfill with alkali-activated cementitious material as binder by taking the mass concentration of backfill slurry and sand-binder ratio as input factors. The results show that the 28-day strength of the backfill with graded fine-grained tailings as filling aggregate can reach 5.41 MPa when the sand-binder ratio is 4, which can fully meet the needs of the mine for the strength of the backfill. The thickening test of-200 mesh fine particle tailings was carried out by static limit concentration test and dynamic thickening test. In the case of adding 35 g/t BASF 6920 non-ionic flocculant, the concentration of 64.74% tail mortar can reach 67.71% after 2 h of static thickening, and the concentration can reach 69.62% after 2 h of static thickening. The feeding speed of thickener should be controlled between 0.4 and 0.59 t/(m2 h). In this case, the underflow concentration of thickener is relatively high, which is 64.92–65.78%, and the solid content of overflow water is less than 164 ppm. The conventional full tailings thickening process was improved by using the design of high-efficiency deep cone thickener and vertical sand silo. The feasibility of fine-grained tailings as filling aggregate was demonstrated by combining the filling ratio test of fine-grained tailings, the data of thickening test and the improved thickening process. The research results can provide reference for other mines to use fine-grained tailings as filling aggregate to design filling system.
Prediction of protein subplastid localization and origin with PlastoGram
Authors: Sidorczuk Katarzyna , Gagat Przemysław , Kała Jakub , Nielsen Henrik , Pietluch Filip , Mackiewicz Paweł , Burdukiewicz Michał
Published: May 2023

Due to their complex history, plastids possess proteins encoded in the nuclear and plastid genome. Moreover, these proteins localize to various subplastid compartments. Since protein localization is associated with its function, prediction of subplastid localization is one of the most important steps in plastid protein annotation, providing insight into their potential function. Therefore, we create a novel manually curated data set of plastid proteins and build an ensemble model for prediction of protein subplastid localization. Moreover, we discuss problems associated with the task, e.g. data set sizes and homology reduction. PlastoGram classifies proteins as nuclear- or plastid-encoded and predicts their localization considering: envelope, stroma, thylakoid membrane or thylakoid lumen; for the latter, the import pathway is also predicted. We also provide an additional function to differentiate nuclear-encoded inner and outer membrane proteins. PlastoGram is available as a web server at https://biogenies.info/PlastoGram and as an R package at https://github.com/BioGenies/PlastoGram. The code used for described analyses is available at https://github.com/BioGenies/PlastoGram-analysis.
Long-term use of denosumab and its association with skeletal-related events and osteonecrosis of the jaw
Authors: Fu Pei-An , Shen Chin-Yao , Yang Shuen‑Ru , Lee Chun-Hui , Chen Hui-Wen , Lai Edward Chia-Cheng , Chung Wei-Pang
Published: May 2023

Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, reduces skeletal-related events (SREs) and is approved for solid tumors with bone metastases. We studied long-term denosumab efficacy and safety because real-world data is scarce. This single-arm, single-center retrospective study included denosumab-treated breast cancer patients with bone metastases. Kaplan–Meier survival curves assessed exposure, SREs, osteonecrosis of the jaw (ONJ), and death. 132 patients were enrolled. The median denosumab exposure was 28.3 months (range 1.0–84.9). In the first year, 11.1% experienced SREs. This increased to 18.6% in the second, 21% in the third, and 35.1% in the fourth year and beyond. The median time to first on-study SRE has not been reached. 10 denosumab users (7.6%) developed ONJ. ONJ incidence was 0.9% in the first year, 6.2% in the second, 13.6% in the third, and 16.2% in subsequent years. The median time to first on-study ONJ has not been reached yet. Seven patients resumed denosumab after careful management of ONJ. Our data suggest that long-term treatment with denosumab may further prevent or postpone SREs at the cost of an increased risk of ONJ. The majority of patients who resumed denosumab did not experience a recurrence of ONJ.
APOE ɛ4, but not polygenic Alzheimer’s disease risk, is related to longitudinal decrease in hippocampal brain activity in non-demented individuals
Authors: Håglin Sofia , Koch Elise , Schäfer Hackenhaar Fernanda , Nyberg Lars , Kauppi Karolina
Published: May 2023

The hippocampus is affected early in Alzheimer’s disease (AD) and altered hippocampal functioning influences normal cognitive aging. Here, we used task-based functional MRI to assess if the APOE ɛ4 allele or a polygenic risk score (PRS) for AD was linked to longitudinal changes in memory-related hippocampal activation in normal aging (baseline age 50–95, n = 292; n = 182 at 4 years follow-up, subsequently non-demented for at least 2 years). Mixed-models were used to predict level and change in hippocampal activation by APOE ɛ4 status and PRS based on gene variants previously linked to AD at p ≤ 1, p < 0.05, or p < 5e−8 (excluding APOE). APOE ɛ4 and PRSp<5e−8 significantly predicted AD risk in a larger sample from the same study population (n = 1542), while PRSp≤1 predicted memory decline. APOE ɛ4 was linked to decreased hippocampal activation over time, with the most prominent effect in the posterior hippocampi, while PRS was unrelated to hippocampal activation at all p-thresholds. These results suggests a link for APOE ɛ4, but not for AD genetics in general, on functional changes of the hippocampi in normal aging.
Multimodal imaging of laser-induced choroidal neovascularization in pigmented rabbits
Authors: Nguyen Van Phuc , Henry Jessica , Zhe Josh , Hu Justin , Wang Xueding , Paulus Yannis M.
Published: May 2023

This study aimed to demonstrate longitudinal multimodal imaging of laser photocoagulation-induced choroidal neovascularization (CNV) in pigmented rabbits. Six Dutch Belted pigmented rabbits were treated with 12 laser lesions in each eye at a power of 300 mW with an aerial diameter spot size of 500 μm and pulse duration of 100 ms. CNV progression was monitored over a period of 4 months using different imaging techniques including color fundus photography, fluorescein angiography (FA), photoacoustic microscopy (PAM), and optical coherence tomography (OCT). All treated eyes developed CNV with a success rate of 100%. The margin and morphology of CNV were detected and rendered in three dimensions using PAM and OCT. The CNV was further distinguished from the surrounding melanin and choroidal vessels using FDA-approved indocyanine green dye-enhanced PAM imaging. By obtaining PAM at 700 nm, the location and density of CNV were identified, and the induced PA signal increased up to 59 times. Immunohistochemistry with smooth muscle alpha-actin (αSMA) antibody confirmed the development of CNV. Laser photocoagulation demonstrates a great method to create CNV in pigmented rabbits. The CNV was stable for up to 4 months, and the CNV area was measured from FA images similar to PAM and OCT results. In addition, this study demonstrates that contrast agent-enhanced PAM imaging allows for precise visualization and evaluation of the formation of new blood vessels in a clinically-relevant animal model of CNV. This laser-induced CNV model can provide a unique technique for longitudinal studies of CNV pathogenesis that can be imaged with multimodal imaging.
Coronavirus spike protein-specific antibodies indicate frequent infections and reinfections in infancy and among BNT162b2-vaccinated healthcare workers
Authors: Kolehmainen Pekka , Huttunen Moona , Iakubovskaia Alina , Maljanen Sari , Tauriainen Sisko , Yatkin Emrah , Pasternack Arja , Naves Rauno , Toivonen Laura , Tähtinen Paula A. , Ivaska Lauri , Lempainen Johanna , Peltola Ville , Waris Matti , Kakkola Laura , Ritvos Olli , Julkunen Ilkka
Published: May 2023

The prevalence of seasonal human coronavirus (HCoV) infections in early childhood and adults has not been well analyzed in longitudinal serological studies. Here we analyzed the changes in HCoV (229E, HKU1, NL63, OC43, MERS, and SARS-CoV-2) spike-specific antibody levels in follow-up serum specimens of 140 children at the age of 1, 2, and 3 years, and of 113 healthcare workers vaccinated for Covid-19 with BNT162b2-vaccine. IgG antibody levels against six recombinant HCoV spike subunit 1 (S1) proteins were measured by enzyme immunoassay. We show that by the age of three years the cumulative seropositivity for seasonal HCoVs increased to 38–81% depending on virus type. BNT162b2 vaccinations increased anti-SARS-CoV-2 S1 antibodies, but no increase in seasonal coronavirus antibodies associated with vaccinations. In healthcare workers (HCWs), during a 1-year follow-up, diagnostic antibody rises were seen in 5, 4 and 14% of the cases against 229E, NL63 and OC43 viruses, respectively, correlating well with the circulating HCoVs. In 6% of the HCWs, a diagnostic antibody rise was seen against S1 of HKU1, however, these rises coincided with anti-OC43 S1 antibody rises. Rabbit and guinea pig immune sera against HCoV S1 proteins indicated immunological cross-reactivity within alpha-CoV (229E and NL63) and beta-CoV (HKU1 and OC43) genera.