bluuebunny/crossref_metadata_2025 huggingface dataset:
NINJ1 is activated by cell swelling to regulate plasma membrane permeabilization during regulated necrosis
Authors: Dondelinger Yves , Priem Dario , Huyghe Jon , Delanghe Tom , Vandenabeele Peter , Bertrand Mathieu J. M.
Published: November 2023

Plasma membrane permeabilization (PMP) is a defining feature of regulated necrosis. It allows the extracellular release of damage-associated molecular patterns (DAMPs) that trigger sterile inflammation. The pore forming molecules MLKL and GSDMs drive PMP in necroptosis and pyroptosis, respectively, but the process of PMP remains unclear in many other forms of regulated necrosis. Here, we identified NINJ1 as a crucial regulator of PMP and consequent DAMP release during ferroptosis, parthanatos, H2O2-induced necrosis and secondary necrosis. Importantly, the membrane-permeabilizing function of NINJ1 takes place after the metabolic death of the cells and is independent of the pore-forming molecules MLKL, GSDMD and GSDME. During ferroptosis, NINJ1 acts downstream of lipid peroxidation, which suggested a role for reactive oxygen species (ROS) in NINJ1 activation. Reactive oxygen species were however neither sufficient nor required to trigger NINJ1-dependent PMP. Instead, we found that NINJ1 oligomerization is induced by the swelling of the cell and that its permeabilizing potential still requires an addition, and yet to be discovered, activation mechanism.
Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway
Authors: Li Hong-Ying , Wei Ting-Ting , Zhuang Miao , Tan Cheng-Ye , Xie Tian-Hua , Cai Jiping , Yao Yong , Zhu Lingpeng
Published: November 2023

Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.
Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature
Authors: Ong Ariel Yuhan , Kiire Christine A. , Frise Charlotte , Bakr Yasmin , de Silva Samantha R.
Published: November 2023

Introduction

Anti-vascular endothelial growth factor (anti-VEGF) agents may occasionally need to be considered for sight-threatening macular pathology in pregnant and breastfeeding women. This is controversial due to the dearth of data on systemic side effects for mother and child. We aimed to expand the evidence base to inform management.

Methods

Retrospective case series of pregnant and breastfeeding women treated with intravitreal anti-VEGF injections at Oxford Eye Hospital between January 2015 and December 2022. In addition, we conducted a systematic review and combined eligible cases in a narrative synthesis.

Results

We treated six pregnant women with anti-VEGF for diabetic macular oedema(DMO) (n = 5) or choroidal neovascularisation (CNV) (n = 1). Four received ranibizumab whilst two (not known to be pregnant) received aflibercept. Patients known to be pregnant underwent counselling by an obstetric physician. Five pregnancies resulted in live births. Combining our cases with those previously published, treatment of 41 pregnant women (42 pregnancies) are reported. Indications for treatment included CNV (n = 28/41,68%), DMO (n = 7/41,17%) and proliferative diabetic retinopathy (n = 6/41,15%). Bevacizumab (n = 22/41,54%) and ranibizumab (n = 17/41,41%) were given more frequently than aflibercept (n = 2/41,5%). Many (n = 16/41,40%) were unaware of their pregnancy when treated. Most pregnancies resulted in live births (n = 34/42,81%). First trimester miscarriages (n = 5/42,12%) and stillbirths (n = 3/42,7%) mostly occurred in women with significant risk factors.

Conclusion

Intravitreal anti-VEGF injections may not necessarily compromise obstetric outcomes, although clear associations cannot be drawn due to small numbers and confounders from high rates of first trimester miscarriages in general and inherently high-risk pregnancies. It may be worth considering routinely investigating pregnancy and breastfeeding status in women of childbearing age prior to each injection, as part of anti-VEGF treatment protocols.
Effect of Bergmeister papilla on disc parameters in spectral domain optical coherence tomography
Authors: Chun Yeoun Sook , Moon Nam Ju , Kim Ungsoo Samuel , Yeo Joon Hyung , Jeong Jae Hoon
Published: November 2023

Objectives

To investigate the morphological characteristics of Bergmeister papilla (BMP), a persistent hyaloid remnant tissue, and its effects on the measurements and repeatability of spectral-domain optical coherence tomography (OCT).

Subjects/Methods

The subjects of this prospective cross-sectional study including 83 patients with BMP and 76 unaffected individuals, all had open-angle structures. Images, including a 5-line raster and three consecutive optic disc cube scans centred on the optic disc, were acquired using the Cirrus high-definition OCT. BMP’s structural characteristics were classified based on the raster scan images, and repeatability of acquiring optic nerve head and retinal nerve fibre layer parameters acquisition was analysed by calculating the test-retest standard deviation (Sw), coefficient of variance (CV), and intraclass correlation coefficient.

Results

BMPs (n = 83) were categorised into lifting edge (LE) type (63.9%, n = 53), which partially covers the edge of the optic nerve head, and covering disc (CD) type (36.1%, n = 30), which completely covers the cupping area like a cap. The average cup-to-disc ratio (0.58 ± 0.21), vertical cup-to-disc ratio (0.55 ± 0.21), and cup volume (0.22 ± 0.22) of the CD type were lower than those of the LE type (0.66 ± 0.13, 0.64 ± 0.13, and 0.4 ± 0.27, respectively; all P < 0.05). Tolerability indices for repeatability of cup volume (Sw = 0.40 and CV = 0.36) and inferonasal (4 o’clock) retinal nerve fibre layer (Sw = 0.27 and CV = 0.25) in LE-type BMPs exceeded the cut-off value (0.22) and demonstrated stronger correlation with BMP location than that of the controls.

Conclusion

Caution should be exercised when interpreting OCT findings in eyes with BMP, as BMP can introduce a pitfall in OCT imaging.
Perioperative outcomes of penile prosthesis implantation in Germany: results from the GRAND study
Authors: Pyrgidis Nikolaos , Schulz Gerald B. , Chaloupka Michael , Volz Yannic , Pfitzinger Paulo L. , Rodler Severin , Berg Elena , Weinhold Philipp , Jokisch Friedrich , Stief Christian G. , Becker Armin J. , Marcon Julian
Published: November 2023

We aimed to assess the recommended annual hospital volume for inflatable penile prosthesis implantation (PPI) and to provide evidence on perioperative outcomes of semi-rigid and inflatable PPI in Germany. We used the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021 and report the largest study to date with 7,222 patients. 6,818 (94.4%) patients underwent inflatable and 404 (5.6%) semi-rigid PPI. Inflatable PPI was significantly associated with shorter length of hospital stay (difference of 2.2 days, 95%CI: 1.6–2.7, p < 0.001), lower odds of perioperative urinary tract infections (5.5% versus 9.2%; OR: 0.58, 95%CI: 0.41–0.84, p = 0.003) and surgical wound infections (1% versus 2.5%; OR: 0.42, 95%CI: 0.22–0.88, p = 0.012) compared to semi-rigid PPI. Overall, 4255 (62.4%) inflatable PPIs were undertaken in low- ( < 20 PPI/year) and 2563 (37.6%) in high-volume ( ≥ 20 PPI/year) centers. High-volume centers were significantly associated with shorter length of hospital stay (difference of 1.4 days, 95%CI: 1.2–1.7, p < 0.001) compared to low-volume centers. Our findings suggest that inflatable PPI leads to a shorter length of hospital stay and lower rates of perioperative urinary tract and surgical wound infections compared to semi-rigid PPI. Patients undergoing surgery in high-volume centers for inflatable PPI are discharged earlier from the hospital.
Genome-wide CRISPR off-target prediction and optimization using RNA-DNA interaction fingerprints
Authors: Chen Qinchang , Chuai Guohui , Zhang Haihang , Tang Jin , Duan Liwen , Guan Huan , Li Wenhui , Li Wannian , Wen Jiaying , Zuo Erwei , Zhang Qing , Liu Qi
Published: November 2023

The powerful CRISPR genome editing system is hindered by its off-target effects, and existing computational tools achieved limited performance in genome-wide off-target prediction due to the lack of deep understanding of the CRISPR molecular mechanism. In this study, we propose to incorporate molecular dynamics (MD) simulations in the computational analysis of CRISPR system, and present CRISOT, an integrated tool suite containing four related modules, i.e., CRISOT-FP, CRISOT-Score, CRISOT-Spec, CRISORT-Opti for RNA-DNA molecular interaction fingerprint generation, genome-wide CRISPR off-target prediction, sgRNA specificity evaluation and sgRNA optimization of Cas9 system respectively. Our comprehensive computational and experimental tests reveal that CRISOT outperforms existing tools with extensive in silico validations and proof-of-concept experimental validations. In addition, CRISOT shows potential in accurately predicting off-target effects of the base editors and prime editors, indicating that the derived RNA-DNA molecular interaction fingerprint captures the underlying mechanisms of RNA-DNA interaction among distinct CRISPR systems. Collectively, CRISOT provides an efficient and generalizable framework for genome-wide CRISPR off-target prediction, evaluation and sgRNA optimization for improved targeting specificity in CRISPR genome editing.
Defect-driven nanostructuring of low-nuclearity Pt-Mo ensembles for continuous gas-phase formic acid dehydrogenation
Authors: Guo Luyao , Zhuge Kaixuan , Yan Siyang , Wang Shiyi , Zhao Jia , Wang Saisai , Qiao Panzhe , Liu Jiaxu , Mou Xiaoling , Zhu Hejun , Zhao Ziang , Yan Li , Lin Ronghe , Ding Yunjie
Published: November 2023

Supported metal clusters comprising of well-tailored low-nuclearity heteroatoms have great potentials in catalysis owing to the maximized exposure of active sites and metal synergy. However, atomically precise design of these architectures is still challenging for the lack of practical approaches. Here, we report a defect-driven nanostructuring strategy through combining defect engineering of nitrogen-doped carbons and sequential metal depositions to prepare a series of Pt and Mo ensembles ranging from single atoms to sub-nanoclusters. When applied in continuous gas-phase decomposition of formic acid, the low-nuclearity ensembles with unique Pt3Mo1N3 configuration deliver high-purity hydrogen at full conversion with unexpected high activity of 0.62 molHCOOH molPt−1 s−1 and remarkable stability, significantly outperforming the previously reported catalysts. The remarkable performance is rationalized by a joint operando dual-beam Fourier transformed infrared spectroscopy and density functional theory modeling study, pointing to the Pt-Mo synergy in creating a new reaction path for consecutive HCOOH dissociations.
Activation and substrate specificity of the human P4-ATPase ATP8B1
Authors: Dieudonné Thibaud , Kümmerer Felix , Laursen Michelle Juknaviciute , Stock Charlott , Flygaard Rasmus Kock , Khalid Syma , Lenoir Guillaume , Lyons Joseph A. , Lindorff-Larsen Kresten , Nissen Poul
Published: November 2023

Asymmetric distribution of phospholipids in eukaryotic membranes is essential for cell integrity, signaling pathways, and vesicular trafficking. P4-ATPases, also known as flippases, participate in creating and maintaining this asymmetry through active transport of phospholipids from the exoplasmic to the cytosolic leaflet. Here, we present a total of nine cryo-electron microscopy structures of the human flippase ATP8B1-CDC50A complex at 2.4 to 3.1 Å overall resolution, along with functional and computational studies, addressing the autophosphorylation steps from ATP, substrate recognition and occlusion, as well as a phosphoinositide binding site. We find that the P4-ATPase transport site is occupied by water upon phosphorylation from ATP. Additionally, we identify two different autoinhibited states, a closed and an outward-open conformation. Furthermore, we identify and characterize the PI(3,4,5)P3 binding site of ATP8B1 in an electropositive pocket between transmembrane segments 5, 7, 8, and 10. Our study also highlights the structural basis of a broad lipid specificity of ATP8B1 and adds phosphatidylinositol as a transport substrate for ATP8B1. We report a critical role of the sn-2 ester bond of glycerophospholipids in substrate recognition by ATP8B1 through conserved S403. These findings provide fundamental insights into ATP8B1 catalytic cycle and regulation, and substrate recognition in P4-ATPases.
A toxin-antidote system contributes to interspecific reproductive isolation in rice
Authors: You Shimin , Zhao Zhigang , Yu Xiaowen , Zhu Shanshan , Wang Jian , Lei Dekun , Zhou Jiawu , Li Jing , Chen Haiyuan , Xiao Yanjia , Chen Weiwei , Wang Qiming , Lu Jiayu , Chen Keyi , Zhou Chunlei , Zhang Xin , Cheng Zhijun , Guo Xiuping , Ren Yulong , Zheng Xiaoming , Liu Shijia , Liu Xi , Tian Yunlu , Jiang Ling , Tao Dayun , Wu Chuanyin , Wan Jianmin
Published: November 2023

Breakdown of reproductive isolation facilitates flow of useful trait genes into crop plants from their wild relatives. Hybrid sterility, a major form of reproductive isolation exists between cultivated rice (Oryza sativa) and wild rice (O. meridionalis, Mer). Here, we report the cloning of qHMS1, a quantitative trait locus controlling hybrid male sterility between these two species. Like qHMS7, another locus we cloned previously, qHMS1 encodes a toxin-antidote system, but differs in the encoded proteins, their evolutionary origin, and action time point during pollen development. In plants heterozygous at qHMS1, ~ 50% of pollens carrying qHMS1-D (an allele from cultivated rice) are selectively killed. In plants heterozygous at both qHMS1 and qHMS7, ~ 75% pollens without co-presence of qHMS1-Mer and qHMS7-D are selectively killed, indicating that the antidotes function in a toxin-dependent manner. Our results indicate that different toxin-antidote systems provide stacked reproductive isolation for maintaining species identity and shed light on breakdown of hybrid male sterility.
LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation
Authors: Liu Lihui , Liu Ziyang , Liu Qinghua , Wu Wei , Lin Peng , Liu Xing , Zhang Yuechuan , Wang Dongpeng , Prager Briana C. , Gimple Ryan C. , Yu Jichuan , Zhao Weixi , Wu Qiulian , Zhang Wei , Wu Erzhong , Chen Xiaomin , Luo Jianjun , Rich Jeremy N. , Xie Qi , Jiang Tao , Chen Runsheng
Published: November 2023

Glioblastoma (GBM) ranks among the most lethal of human cancers, containing glioma stem cells (GSCs) that display therapeutic resistance. Here, we report that the lncRNA INHEG is highly expressed in GSCs compared to differentiated glioma cells (DGCs) and promotes GSC self-renewal and tumorigenicity through control of rRNA 2’-O-methylation. INHEG induces the interaction between SUMO2 E3 ligase TAF15 and NOP58, a core component of snoRNP that guides rRNA methylation, to regulate NOP58 sumoylation and accelerate the C/D box snoRNP assembly. INHEG activation enhances rRNA 2’-O-methylation, thereby increasing the expression of oncogenic proteins including EGFR, IGF1R, CDK6 and PDGFRB in glioma cells. Taken together, this study identifies a lncRNA that connects snoRNP-guided rRNA 2’-O-methylation to upregulated protein translation in GSCs, supporting an axis for potential therapeutic targeting of gliomas.
scReadSim: a single-cell RNA-seq and ATAC-seq read simulator
Authors: Yan Guanao , Song Dongyuan , Li Jingyi Jessica
Published: November 2023

Benchmarking single-cell RNA-seq (scRNA-seq) and single-cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq) computational tools demands simulators to generate realistic sequencing reads. However, none of the few read simulators aim to mimic real data. To fill this gap, we introduce scReadSim, a single-cell RNA-seq and ATAC-seq read simulator that allows user-specified ground truths and generates synthetic sequencing reads (in a FASTQ or BAM file) by mimicking real data. At both read-sequence and read-count levels, scReadSim mimics real scRNA-seq and scATAC-seq data. Moreover, scReadSim provides ground truths, including unique molecular identifier (UMI) counts for scRNA-seq and open chromatin regions for scATAC-seq. In particular, scReadSim allows users to design cell-type-specific ground-truth open chromatin regions for scATAC-seq data generation. In benchmark applications of scReadSim, we show that UMI-tools achieves the top accuracy in scRNA-seq UMI deduplication, and HMMRATAC and MACS3 achieve the top performance in scATAC-seq peak calling.
Key role of eg* band broadening in nickel-based oxyhydroxides on coupled oxygen evolution mechanism
Authors: Zhong Haoyin , Zhang Qi , Yu Junchen , Zhang Xin , Wu Chao , An Hang , Ma Yifan , Wang Hao , Zhang Jun , Zhang Yong-Wei , Diao Caozheng , Yu Zhi Gen , Xi Shibo , Wang Xiaopeng , Xue Junmin
Published: November 2023

A coupled oxygen evolution mechanism (COM) during oxygen evolution reaction (OER) has been reported in nickel oxyhydroxides (NiOOH)-based materials by realizing eg* band (3d electron states with eg symmetry) broadening and light irradiation. However, the link between the eg* band broadening extent and COM-based OER activities remains unclear. Here, Ni1-xFexOOH (x = 0, 0.05, 0,2) are prepared to investigate the underlying mechanism governing COM-based activities. It is revealed that in low potential region, realizing stronger eg* band broadening could facilitate the *OH deprotonation. Meanwhile, in high potential region where the photon utilization is the rate-determining step, a stronger eg* band broadening would widen the non-overlapping region between dz2 and a1g* orbitals, thereby enhancing photon utilization efficiency. Consequently, a stronger eg* band broadening could effectuate more efficient OER activities. Moreover, we demonstrate the universality of this concept by extending it to reconstruction-derived X-NiOOH (X = NiS2, NiSe2, Ni4P5) with varying extent of eg* band broadening. Such an understanding of the COM would provide valuable guidance for the future development of highly efficient OER electrocatalysts.
Regulation of species metabolism in synthetic community systems by environmental pH oscillations
Authors: Li Shubin , Zhao Yingming , Wu Shuqi , Zhang Xiangxiang , Yang Boyu , Tian Liangfei , Han Xiaojun
Published: November 2023

Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B (Saccharomyces cerevisiae), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO2. In addition, a three-species community is constructed with species A′ (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD+ and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A′; G6P then enters species C to promote the metabolic reaction that converts NAD+ to NADH. The location of species A′ and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA′B, CBA′, and A′CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.
c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
Authors: Li Shuyu , Liu Qinmeng , Duan Chongyi , Li Jialin , Sun Hengxi , Xu Lei , Yang Qiao , Wang Yao , Shen Xihui , Zhang Lei
Published: November 2023

Cyclic di-GMP (c-di-GMP) is a second messenger that transduces extracellular stimuli into cellular responses and regulates various biological processes in bacteria. H-NS is a global regulatory protein that represses expression of many genes, but how H-NS activity is modulated by environmental signals remains largely unclear. Here, we show that high intracellular c-di-GMP levels, induced by environmental cues, relieve H-NS-mediated transcriptional silencing inSalmonella entericaserovar Typhimurium. We find that c-di-GMP binds to the H-NS protein to inhibit its binding to DNA, thus derepressing genes silenced by H-NS. However, c-di-GMP is unable to displace H-NS from DNA. In addition, a K107A mutation in H-NS abolishes response to c-di-GMP but leaves its DNA binding activity unaffected in vivo. Our results thus suggest a mechanism by which H-NS acts as an environment-sensing regulator in Gram-negative bacteria.
Metaproteogenomic analysis of saliva samples from Parkinson’s disease patients with cognitive impairment
Authors: Arıkan Muzaffer , Demir Tuğçe Kahraman , Yıldız Zeynep , Nalbantoğlu Özkan Ufuk , Korkmaz Nur Damla , Yılmaz Nesrin H. , Şen Aysu , Özcan Mutlu , Muth Thilo , Hanoğlu Lütfü , Yıldırım Süleyman
Published: November 2023

Cognitive impairment (CI) is very common in patients with Parkinson’s Disease (PD) and progressively develops on a spectrum from mild cognitive impairment (PD-MCI) to full dementia (PDD). Identification of PD patients at risk of developing cognitive decline, therefore, is unmet need in the clinic to manage the disease. Previous studies reported that oral microbiota of PD patients was altered even at early stages and poor oral hygiene is associated with dementia. However, data from single modalities are often unable to explain complex chronic diseases in the brain and cannot reliably predict the risk of disease progression. Here, we performed integrative metaproteogenomic characterization of salivary microbiota and tested the hypothesis that biological molecules of saliva and saliva microbiota dynamically shift in association with the progression of cognitive decline and harbor discriminatory key signatures across the spectrum of CI in PD. We recruited a cohort of 115 participants in a multi-center study and employed multi-omics factor analysis (MOFA) to integrate amplicon sequencing and metaproteomic analysis to identify signature taxa and proteins in saliva. Our baseline analyses revealed contrasting interplay between the genus Neisseria and Lactobacillus and Ligilactobacillus genera across the spectrum of CI. The group specific signature profiles enabled us to identify bacterial genera and protein groups associated with CI stages in PD. Our study describes compositional dynamics of saliva across the spectrum of CI in PD and paves the way for developing non-invasive biomarker strategies to predict the risk of CI progression in PD.
No graph state is preparable in quantum networks with bipartite sources and no classical communication
Authors: Makuta Owidiusz , Ligthart Laurens T. , Augusiak Remigiusz
Published: November 2023

In research concerning quantum networks, it is often assumed that the parties can classically communicate with each other. However, classical communication might introduce a substantial delay to the network, especially if it is large. As the latency of a network is one of its most important characteristics, it is interesting to consider quantum networks in which parties cannot communicate classically and ask what limitations this assumption imposes on the possibility of preparing multipartite states in such networks. We show that graph states of an arbitrary prime local dimension known for their numerous applications in quantum information cannot be generated in a quantum network in which parties are connected via sources of bipartite quantum states and the classical communication is replaced by some pre-shared classical correlations. We then generalise our result to arbitrary quantum states that are sufficiently close to graph states.
An integrated model for pre- and post-harvest aflatoxin contamination in maize
Authors: Stutt Richard O.J.H. , Castle Matthew D. , Markwell Peter , Baker Robert , Gilligan Christopher A.
Published: November 2023

Aflatoxin contamination caused by colonization of maize by Aspergillus flavus continues to pose a major human and livestock health hazard in the food chain. Increasing attention has been focused on the development of models to predict risk and to identify effective intervention strategies. Most risk prediction models have focused on elucidating weather and site variables on the pre-harvest dynamics of A. flavus growth and aflatoxin production. However fungal growth and toxin accumulation continue to occur after harvest, especially in countries where storage conditions are limited by logistical and cost constraints. In this paper, building on previous work, we introduce and test an integrated meteorology-driven epidemiological model that covers the entire supply chain from planting to delivery. We parameterise the model using approximate Bayesian computation with monthly time-series data over six years for contamination levels of aflatoxin in daily shipments received from up to three sourcing regions at a high-volume maize processing plant in South Central India. The time series for aflatoxin levels from the parameterised model successfully replicated the overall profile, scale and variance of the historical aflatoxin datasets used for fitting and validation. We use the model to illustrate the dynamics of A. flavus growth and aflatoxin production during the pre- and post-harvest phases in different sourcing regions, in short-term predictions to inform decision making about sourcing supplies and to compare intervention strategies to reduce the risks of aflatoxin contamination.
Photos and rendered images of LEGO bricks
Authors: Boiński Tomasz Maria
Published: November 2023

The paper describes a collection of datasets containing both LEGO brick renders and real photos. The datasets contain around 155,000 photos and nearly 1,500,000 renders. The renders aim to simulate real-life photos of LEGO bricks allowing faster creation of extensive datasets. The datasets are publicly available via the Gdansk University of Technology “Most Wiedzy” institutional repository. The source files of all tools used during the creation of the dataset were made publicly available via GitHub repositories. The images, both photos and the renders were annotated with the unique brick ID and category from the official LEGO catalog. The proposed datasets are stored in easy-to-read formats and are labeled via directory structure allowing easy manipulation and conversion of metadata to other formats.
In silico investigation on interaction of small Ag6 nano-particle cluster with tyramine neurotransmitter
Authors: Chakroborty Subhendu , Shakerzadeh E. , Yadav T. , Mishra Nilima Priyadarsini , Barik Arundhati , Upadhyay Versha , Abhilasha  , Soren Siba , Malviya Jitendra , Panda Amiya Ranjan , Uniyal Kartik , Kumar Narendra , Wagadre Shradha , Pandey F. P.
Published: November 2023

The interaction of tyramine neurotransmitter with silver nano-particle (Ag6) cluster is explored in terms of the molecular structure, electronic properties and NBO analysis of tyramine-AgNPs bio-molecular conjugate. The adsorption mechanism of tyramine onto the Ag6 cluster has been investigated through computing of the electronic and geometrical properties in addition to the adsorption energies in various possible configurations. The magnitude of adsorption energy corresponding to the most favorable tyramine-Ag6 bio-molecular conjugate has been computed to be − 14.36 kcal/mol in the gas phase, which infers a good adsorption of tyramine with AgNPs cluster suggesting the practical applications of tyramine-AgNPs bio-molecular conjugates in bio-sensing, drug delivery, bio-imaging and other applications. Different electronic properties such as the energy gap of HOMO–LUMO, Fermi level and work function have been investigated in detail. Moreover, the effect of aqueous media on adsorption energy and electronic properties of the most favorable tyramine-AgNPs bio-molecular conjugate is investigated in order to understand the impact of the real biological situation.
Modelling droplet size distribution in inline electrostatic coalescers for improved crude oil processing
Authors: Kooti Ghazal , Dabir Bahram , Taherdangkoo Reza , Butscher Christoph
Published: November 2023

Water-in-oil emulsions pose significant challenges in the petroleum and chemical industrial processes, necessitating the coalescence enhancement of dispersed water droplets in emulsified oils. This study develops a mathematical model to predict the evolution of water droplet size distribution in inline electrostatic coalescers (IEC) as a promising means to improve the water separation efficiency of current oil processing systems. The proposed model utilizes the population balance modelling approach to effectively simulate the dynamic and complex processes of coalescence and breakage of droplets in crude oil which directly influence the separation efficiency of the process. The method of classes as an effective mathematical technique is selected to solve the population balance equation (PBE). The accuracy of the model and considered assumptions agree well with experimental data collected from the literature. The results demonstrate the model's ability to accurately simulate droplet coalescence and breakage in emulsified oil while predicting droplet size distribution and water removal efficiency. The electric field strength, residence time, and fluid flow rate significantly influence the coalescence of droplets. At 4 kV and 5 m3/h after 4 s the mean diameter of droplets (D50) and separation efficiency reach the maximum of 94.3% and 432 µm, respectively. The model enables the optimization of operational conditions, resulting in increased performance and reliability of oil-processing systems while reducing the energy consumption and use of chemical demulsifiers. Additionally, utilization of the device in optimized conditions significantly reduces the size and weight of downstream separation equipment, which is particularly advantageous for heavy oils and offshore fields.
Construction of an anoikis-associated lncRNA-miRNA-mRNA network reveals the prognostic role of β-elemene in non-small cell lung cancer
Authors: Tan Kai , Zhang Changhui , He Zuomei , Zeng Puhua
Published: November 2023

β-Elemene is the main active ingredient in Curcumae Rhizoma that exerts antitumour effects. Anoikis affects tumour development through various biological pathways in non-small cell lung cancer (NSCLC), but the regulation between β-elemene and anoikis remains to be explored. First, we explored the molecular expression patterns of anoikis-associated genes (AAGs) using consensus clustering and characterized the impact of AAGs on patient prognosis, clinical characteristics, and genomic instability. In addition, we revealed that AAG regulatory genes have rich interactions with β-elemene targets, and established a lncRNA-miRNA-mRNA network to explain the effect of β-elemene on anoikis. Finally, to reveal the prognostic effect of their correlation, the prognostic scoring model and clinical nomogram of β-elemene and anoikis were successfully established by least absolute shrinkage and selection operator (LASSO) and random forest algorithms. This prognostic scoring model containing noncoding RNA (ncRNA) can indicate the immunotherapy and mutational landscape, providing a novel theoretical basis and direction for the study of the antitumour mechanism of β-elemene in NSCLC patients.
Novel role of folate (vitamin B9) released by fermenting bacteria under Human Intestine like environment
Authors: Nara Sharda , Parasher Gulshan , Malhotra Bansi Dhar , Rawat Manmeet
Published: November 2023

The anaerobic region of the gastrointestinal (GI) tract has been replicated in the anaerobic chamber of a microbial fuel cell (MFC). Electroactive biomolecules released by the facultative anaerobes (Providencia rettgeri) under anoxic conditions have been studied for their potential role for redox balance. MALDI study reveals the presence of vitamin B9 (folate), 6-methylpterin, para-aminobenzoic acid (PABA) and pteroic acid called pterin pool. ATR-FTIR studies further confirm the presence of the aromatic ring and side chains of folate, 6-methylpterin and PABA groups. The photoluminescence spectra of the pool exhibit the maximum emission at 420, 425, 440, and 445 nm when excited by 310, 325, 350, and 365 nm wavelengths (day 20 sample) highlighting the presence of tunable bands. The cyclic voltammetric studies indicate the active participation of pterin pool molecules in the transfer of electrons with redox potentials at − 0.2 V and − 0.4 V for p-aminobenzoate and pterin groups, respectively. In addition, it is observed that under prolonged conditions of continuous oxidative stress (> 20 days), quinonoid tetrahydrofolate is formed, leading to temporary storage of charge. The results of the present study may potentially be useful in designing effective therapeutic strategies for the management of various GI diseases by promoting or blocking folate receptors.
Shoulder reduction on the scene: current practice and outcome of the Bavarian Mountain Rescue Service—a prospective observational study
Authors: Woyke Simon , Pawlak Johannes , Cappello Tomas Dal , Schultheiss Georg , Mayer Herbert , Witt Ulrike , Strapazzon Giacomo , Brugger Hermann , Jacob Matthias
Published: November 2023

Out-of-hospital reduction of shoulder dislocations using the Campell method is recommended by the International Commission for Alpine Rescue and applied in the Bavarian Mountain Rescue Service (Bergwacht Bayern, BWB) protocols. This prospective observational study includes patients out-of-hospital with suspected shoulder dislocation and treated and evacuated by the BWB. Data were systematically collected using three questionnaires: one completed on-site by the rescuer, the second in hospital by the physician and the third within 28 (8–143) days after the accident by the patient. The suspected diagnosis of shoulder dislocation was confirmed in hospital in 37 (84%) of 44 cases. Concomitant injuries in other body regions were found in eight (16%) of 49 cases and were associated with incorrect diagnosis (p = 0.002). Younger age (p = 0.043) and first shoulder dislocation event (p = 0.038) were associated with a higher success rate for reduction attempts. Out-of-hospital reduction of shoulder dislocations leads to significant pain relief and no poorer long-term outcome. Signs that are associated with successful out-of-hospital reduction (younger age and first event), but also those that are associated with incorrect diagnosis (concomitant injuries) should be considered before trying to reduce shoulder dislocation on site. The considerable rate of incorrect first diagnosis on site should give rise to an intensive discussion around teaching and training for this intervention.

Trial registration: This study is registered with the German Registry for Clinical Trials (DRKS00023377).
Humoral immunogenicity assessment after receiving three types of SARS-CoV-2 vaccine
Authors: Najafi Niloofar , Soleimanjahi Hoorieh , Moghaddam-Banaem Lida , Raoufy Mohammad Reza , Shahali Shadab , Kazemnejad Anoshirvan , Nasiri Zeynab
Published: November 2023

Several vaccines have been developed against SARS-CoV-2 and subsequently approved by national/international regulators. Detecting specific antibodies after vaccination enables us to evaluate the vaccine’s effectiveness. We conducted a prospective longitudinal study among members of Tarbiat Modares University of Tehran, Iran, from 4 September 2021 until 29 December 2021. We aimed to compare the humoral immunogenicity of 3 vaccine types. Participants consisted of 462 adults. Anti-SARS-CoV-2 receptor-binding domain [RBD] IgG titer was compared in 3 groups, each vaccinated by available vaccines in Iran at the time: Oxford/AstraZeneca, COVIran Barekat, and Sinopharm. The median IgG titer was: 91.2, 105.6, 224.0 BAU/ml for Sinopharm, COVIran Barekat and Oxford/AstraZeneca respectively after the first dose; 195.2, 192.0, 337.6 BAU/ml after the second one. We also analyzed the frequency of antibody presence in each vaccine group, in the same order the results were 59.0%, 62.6% and 89.4% after the first dose and 92.1%,89.5% and 98.9% after the second. The comparison of results demonstrated that AstraZeneca vaccine is a superior candidate vaccine for COVID-19 vaccination out of the three. Our data also demonstrated statistically significant higher antibody titer among recipients with an infection history.
Thrombospondin1 antagonist peptide treatment attenuates obesity-associated chronic inflammation and metabolic disorders in a diet-induced obese mouse model
Authors: Zhou Qi , Gwag Taesik , Wang Shuxia
Published: November 2023

Thrombospondin1 (TSP1) is a multifunctional matricellular protein. Previously, we demonstrated that TSP1 plays a pivotal role in obesity-related inflammation and insulin resistance (IR) by modulating macrophage accumulation and activation in adipose tissue. Moreover, in our in vitro studies, a CD36-derived peptide, functioning as a TSP1 antagonist, effectively inhibited TSP1-induced proinflammatory macrophage activation. However, whether this CD36 peptide can inhibit obesity-induced inflammation and IR in vivo is unknown and determined in this study in a high fat diet-induced obese mouse model (DIO). CD36 peptide or control peptide was intraperitoneally administered into the established obese mice triweekly for 6 weeks. We found that CD36 peptide treatment didn’t affect obesity or weight gain but significantly reduced proinflammatory cytokine production systemically and in visceral fat tissue. Adipose tissue exhibited fewer crown-like structures and reduced macrophage infiltration. CD36 peptide treatment also attenuated the proinflammatory phenotype of bone marrow derived macrophages from obese mice. Furthermore, CD36 peptide treatment improved glucose tolerance and insulin sensitivity, and mitigated obesity-related fatty liver disease and kidney damage. Collectively, this study suggests that the CD36 peptide, as a TSP1 antagonist, shows promise as a novel therapeutic approach for managing obesity-related metabolic disorders.
International survey on complications of religious fasting after metabolic and bariatric surgery
Authors: Kermansaravi Mohammad , Husain Farah A. , Bashir Ahmad , Valizadeh Rohollah , Abbas Syed Imran , Abouzeid Tarek , Amini Masoud , Davarpanah Jazi Amir Hossein , Elfawal Mohamad Hayssam , Gado Waleed , Gee Tikfu , Habeeb Tamer A. A. M. , Al Hadhrami Bader , Inam Atif , Vaziri Nader Moein , Mokhber Somayyeh , Al-momani Hazem , Omerov Taryel , Pazouki Abdolreza , Rezapanah Alireza , Rezvani Masoud , Sadat Mansouri Majid , Sewefy Alaa M. , Taskin Halit Eren , Yunus Tahir , Kassir Radwan , Nimeri Abdelrahman
Published: November 2023

Religious fasting in Ramadan the 9th month of the lunar year is one of five pillars in Islam and is practiced for a full month every year. There may be risks with fasting in patients with a history of metabolic/bariatric surgery (MBS). There is little published evidence on the possible complications during fasting and needs stronger recommendations and guidance to minimize them. An international survey was sent to surgeons to study the types of complications occurring during religious fasting in patients with history of MBS to evaluate the risk factors to manage and prepare more evidence-based recommendations. In total, 21 centers from 11 countries participated in this survey and reported a total of 132 patients with complications occurring during religious fasting after MBS. The mean age of patients with complications was 36.65 ± 3.48 years and mean BMI was 43.12 ± 6.86 kg/m2. Mean timing of complication occurring during fasting after MBS was 14.18 months. The most common complications were upper GI (gastrointestinal) symptoms including [gastroesophageal reflux disease (GERD), abdominal pain, and dyspepsia], marginal ulcers and dumping syndrome in 24% (32/132), 8.3% (11/132) and 23% (31/132) patients respectively. Surgical management was necessary in 4.5% of patients presenting with complications (6/132) patients due to perforated marginal or peptic ulcer in Single Anastomosis Duodenoileostomy with Sleeve gastrectomy (SADI-S), one anastomosis gastric bypass (OAGB) and sleeve gastrectomy (SG), obstruction at Jejunojenostomy after Roux-en-Y gastric bypass (RYGB) (1/6) and acute cholecystitis (1/6). Patients after MBS should be advised about the risks while fasting including abdominal pain, dehydration, and peptic ulcer disease exacerbation, and a thorough review of their medications is warranted to minimize complications.
Registration in the supine position improve the accuracy of cup placement in total hip arthroplasty using a portable navigation system
Authors: Naito Yohei , Hasegawa Masahiro , Tone Shine , Wakabayashi Hiroki , Sudo Akihiro
Published: November 2023

Portable navigation systems have been developed for use in total hip arthroplasty (THA) in recent years. Although intraoperative registration in the lateral decubitus position or the supine position is need to create the three-dimensional coordinate system, it is not clear which position is appropriate. The purpose of this study was to assess the accuracy of cup placement in primary THA in the lateral decubitus position using an image-free handheld navigation device with registration in the lateral decubitus or the supine position, and clarify which position is appropriate. This retrospective study included 129 consecutive cementless THAs performed using an image-free handheld navigation device in the lateral decubitus position. Registration in the first 68 hips was performed in the lateral decubitus position and the last 61 hips was performed in the supine position. Postoperative cup radiographic inclination and radiographic anteversion were assessed, and the accuracy was compared between the two groups. The mean absolute errors of the postoperative measured inclination and anteversion from the target angles were 3.9° ± 2.2° and 4.8° ± 3.5° in the lateral group and 2.9° ± 2.7° and 3.2° ± 2.7° in the supine group (p < 0.05). The percentage of cups inside Lewinnek’s safe zone was 94% in the lateral group and 95% in the supine group (ns). The mean absolute values of navigation error in inclination and anteversion were 3.1° ± 2.1° and 4.2° ± 2.8° in the lateral group and 2.3° ± 2.0° and 3.1° ± 2.4° in the supine group (p < 0.05 and p < 0.05). Registration in the supine position improved the accuracy of cup insertion compared with the lateral decubitus position in THA using an image-free handheld navigation device in the lateral decubitus position.
Incidental detection of FGFR3 fusion via liquid biopsy leading to earlier diagnosis of urothelial carcinoma
Authors: Huang Quillan , Mitsiades Irene , Dowst Heidi , Zarrin-Khameh Neda , Noor Attiya Batool , Castro Patricia , Scheurer Michael E. , Godoy Guilherme , Mims Martha P. , Mitsiades Nicholas
Published: November 2023

The rising utilization of circulating tumor DNA (ctDNA) assays in Precision Oncology may incidentally detect genetic material from secondary sources. It is important that such findings are recognized and properly leveraged for both diagnosis and monitoring of response to treatment. Here, we report a patient in whom serial cell-free DNA (cfDNA) monitoring for his known prostate adenocarcinoma uncovered the emergence of an unexpected FGFR3-TACC3 gene fusion, a BRCA1 frameshift mutation, and other molecular abnormalities. Due to the rarity of FGFR3 fusions in prostate cancer, a workup for a second primary cancer was performed, leading to the diagnosis of an otherwise-asymptomatic urothelial carcinoma (UC). Once UC-directed treatment was initiated, the presence of these genetic abnormalities in cfDNA allowed for disease monitoring and early detection of resistance, well before radiographic progression. These findings also uncovered opportunities for targeted therapies against FGFR and BRCA1. Overall, this report highlights the multifaceted utility of longitudinal ctDNA monitoring in early cancer diagnosis, disease prognostication, therapeutic target identification, monitoring of treatment response, and early detection of emergence of resistance.
The oncogenic fusion protein TAZ::CAMTA1 promotes genomic instability and senescence through hypertranscription
Authors: Neil Emily , Paredes Roberto , Pooley Oscar , Rubin Brian , Kouskoff Valerie
Published: November 2023

TAZ::CAMTA1 is a fusion protein found in over 90% of Epithelioid Hemangioendothelioma (EHE), a rare vascular sarcoma with an unpredictable disease course. To date, how TAZ::CAMTA1 initiates tumour formation remains unexplained. To study the oncogenic mechanism leading to EHE initiation, we developed a model system whereby TAZ::CAMTA1 expression is induced by doxycycline in primary endothelial cells. Using this model, we establish that upon TAZ::CAMTA1 expression endothelial cells rapidly enter a hypertranscription state, triggering considerable DNA damage. As a result, TC-expressing cells become trapped in S phase. Additionally, TAZ::CAMTA1-expressing endothelial cells have impaired homologous recombination, as shown by reduced BRCA1 and RAD51 foci formation. Consequently, the DNA damage remains unrepaired and TAZ::CAMTA1-expressing cells enter senescence. Knockout ofCdkn2a, the most common secondary mutation found in EHE, allows senescence bypass and uncontrolled growth. Together, this provides a mechanistic explanation for the clinical course of EHE and offers novel insight into therapeutic options.