bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Himplant® for correction of residual deformity following prior treatment of peyronie’s disease: a case series
Authors: Levine Laurence A. , Desouky Elsayed , Elist James J. , Moon Daniel , Wilson Steven K.
Published: February 2024

Over the years, numerous non-surgical and surgical treatment options have been explored for Peyronie’s disease. Current options may result in incomplete correction of the deformity, which can be bothersome to the patient. This is a two-center case series of three patients who had previously undergone treatment for Peyronie’s disease. Patient 1 underwent plication with extratunical grafting. Patient 2 underwent a series of Xiaflex® injections and then subsequent surgical plication for residual curvature. Patient 3 underwent a series of Xiaflex® injections. The Himplant® subcutaneous silicone penile prosthesis was placed in a standardized manner through a scrotal incision in all cases to mask residual penile deformities and enhance penile girth after Peyronie’s disease treatment. Patients were contacted and asked 18 questions regarding satisfaction and erectile function with the responses recorded. This pilot study presents findings of high patient satisfaction, increases in flaccid penile length and girth, and an acceptable profile of adverse events following Himplant® placement. Based on our limited experience, we would consider offering Himplant® implantation when residual curvature is <40° and the penile indentation does not cause instability/buckling during penetrative sexual activity. Further research and larger studies are warranted to validate these findings and assess long-term outcomes and patient-reported satisfaction.
Efficient bosonic nonlinear phase gates
Authors: Park Kimin , Filip Radim
Published: February 2024

Continuous-variable (CV) quantum information processing harnesses versatile experimental tools that leverage the power of infinite-dimensional oscillators controlled by a single qubit. Increasingly available elementary Rabi gates have been proposed as a resource for implementing universal CV gates, but the requirement of many weak, non-commuting gates is a bottleneck in scaling up such an approach. In this study, we propose a resource-efficient technique using Fourier expansion to implement arbitrary non-linear phase gates in a single oscillator. This method reduces the number of sequentially required gates exponentially. These gates represented by cubic, quartic, and other arbitrary nonlinear potentials have applications in CV quantum information processing with infinite-dimensional oscillators controlled by a single qubit. Our method outperforms previous approaches and enables the experimental realization of a wide range of applications, including the development of bosonic quantum sensors, simulations, and computation using trapped ions and superconducting circuits.
Research on highway rain monitoring based on rain monitoring coefficient
Authors: Wang Xingyu , Feng Haixia , Wang Na , Zhu Maoxin , Ning Erwei , Li Jian
Published: February 2024

The real-time and accurate monitoring of severe weather is the key to reducing traffic accidents on highways. Currently, rainy day monitoring based on video images focuses on removing the impact of rain. This article aims to build a monitoring model for rainy days and rainfall intensity to achieve precise monitoring of rainy days on highways. This paper introduces an algorithm that combines the frequency domain and spatial domain, thresholding, and morphology. It incorporates high-pass filtering, full-domain value segmentation, the OTSU method (the maximum inter-class difference method), mask processing, and morphological opening for denoising. The algorithm is designed to build the rain coefficient model Prain coefficient and determine the intensity of rainfall based on the value of Prain coefficient. To validate the model, data from sunny, cloudy, and rainy days in different sections and time periods of the Jinan Bypass G2001 line were used. The aim is to raise awareness about driving safety on highways. The main findings are: the rain coefficient model Prain coefficient can accurately identify cloudy and rainy days and assess the intensity of rainfall. This method is not only suitable for highways but also for ordinary road sections. The model's accuracy has been verified, and the algorithm in this study has the highest accuracy. This research is crucial for road traffic safety, particularly during bad weather such as rain.
Valproic acid exposure affects social visual lateralization and asymmetric gene expression in zebrafish larvae
Authors: Messina Andrea , Sovrano Valeria Anna , Baratti Greta , Musa Alessia , Gobbo Alessandra , Adiletta Alice , Sgadò Paola
Published: February 2024

Cerebral asymmetry is critical for typical brain function and development; at the same time, altered brain lateralization seems to be associated with neuropsychiatric disorders. Zebrafish are increasingly emerging as model species to study brain lateralization, using asymmetric development of the habenula, a phylogenetically old brain structure associated with social and emotional processing, to investigate the relationship between brain asymmetry and social behavior. We exposed 5-h post-fertilization zebrafish embryos to valproic acid (VPA), a compound used to model the core signs of ASD in many vertebrate species, and assessed social interaction, visual lateralization and gene expression in the thalamus and the telencephalon. VPA-exposed zebrafish exhibit social deficits and a deconstruction of social visual laterality to the mirror. We also observe changes in the asymmetric expression of the epithalamic marker leftover and in the size of the dorsolateral part of the habenula in adult zebrafish. Our data indicate that VPA exposure neutralizes the animals’ visual field bias, with a complete loss of the left-eye use bias in front of their own mirror image, and alters brain asymmetric gene expression and morphology, opening new perspectives to investigate brain lateralization and its link to atypical social cognitive development.
Motivation levels and white matter microstructure in children living with HIV
Authors: Wedderburn Catherine J. , Sevenoaks Tatum , Fouche Jean-Paul , Phillips Nicole J. , Lawn Stephen D. , Stein Dan J. , Hoare Jacqueline
Published: February 2024

Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children’s Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6–16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p < 0.05). On multiple regression, associations with the anterior limb of the internal capsule, a subcortical white matter region, remained significant after adjusting for potential confounders. These findings suggest that reduced motivation may be an important neurobehavioural symptom in CLWH and may reflect changes in white matter microstructure of frontostriatal brain regions.
A novel low light object detection method based on the YOLOv5 fusion feature enhancement
Authors: Peng Daxin , Ding Wei , Zhen Tong
Published: February 2024

Low-light object detection is an important research area in computer vision, but it is also a difficult issue. This research offers a low-light target detection network, NLE-YOLO, based on YOLOV5, to address the issues of insufficient illumination and noise interference experienced by target detection tasks in low-light environments. The network initially preprocesses the input image with an improvement technique before suppressing high-frequency noise and enhancing essential information with C2fLEFEM, a unique feature extraction module. We also created a multi-scale feature extraction module, AMC2fLEFEM, and an attention mechanism receptive field module, AMRFB, which are utilized to extract features of multiple scales and enhance the receptive field. The C2fLEFEM module, in particular, merges the LEF and FEM modules on top of the C2f module. The LEF module employs a low-frequency filter to remove high-frequency noise; the FEM module employs dual inputs to fuse low-frequency enhanced and original features; and the C2f module employs a gradient retention method to minimize information loss. The AMC2fLEFEM module combines the SimAM attention mechanism and uses the pixel relationship to obtain features of different receptive fields, adapt to brightness changes, capture the difference between the target and the background, improve the network's feature extraction capability, and effectively reduce the impact of noise. The AMRFB module employs atrous convolution to enlarge the receptive field, maintain global information, and adjust to targets of various scales. Finally, for low-light settings, we replaced the original YOLOv5 detection head with a decoupled head. The Exdark dataset experiments show that our method outperforms previous methods in terms of detection accuracy and performance.
Deep neural networks for crack detection inside structures
Authors: Moreh Fatahlla , Lyu Hao , Rizvi Zarghaam Haider , Wuttke Frank
Published: February 2024

Crack detection is a long-standing topic in structural health monitoring. Conventional damage detection techniques rely on intensive, time-consuming, resource-intensive intervention. The current trend of crack detection emphasizes using deep neural networks to build an automated pipeline from measured signals to damaged areas. This work focuses on the seismic-wave-based technique of crack detection for plate structures. Previous work proposed an encoder–decoder network to extract crack-related wave patterns from measured wave signals and predict crack existence on the plate. We extend previous work with extensive experiments on different network components and a data preprocessing strategy. The proposed methods are tested on an expanded crack detection dataset. We found that a robust backbone network, such as Densely Connected Convolutional Network (DenseNet) can effectively extract the features characterizing cracks of wave signals, and by using the reference wave field for normalization, the accuracy of detecting small cracks can be further improved.
Complex changes in serum protein levels in COVID-19 convalescents
Authors: Pushalkar Smruti , Wu Shaohuan , Maity Shuvadeep , Pressler Matthew , Rendleman Justin , Vitrinel Burcu , Jeffery Lauren , Abdelhadi Ryah , Chen Mechi , Ross Ted , Carlock Michael , Choi Hyungwon , Vogel Christine
Published: February 2024

The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst COVID-19 convalescents compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some alterations opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1S, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst COVID-19 convalescents. We speculate that some of these shifts might originate from a transient decrease in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and proteins related to cholesterol metabolism.
Utilization of aquatic biomass as biosorbent for sustainable production of high surface area, nano- microporous, for removing two dyes from wastewater
Authors: Abdallah Maha Ahmed Mohamed , Alprol Ahmed E.
Published: February 2024

The majority of environmental researchers are becoming increasingly concerned with the manufacture of inexpensive adsorbents for the detoxification of industrial effluents. To address one of the significant and well-known pollution issues with certain drains that act as hotspots and contribute to coastal pollution in Alexandria, this study aims to develop an economical, ecologically friendly sorbent. This study assessed the efficacy of a biomass-coated magnetic composite and a magnetic active adsorbent for the removal of two dyes from an industrially contaminated sewer using a wetland plant (Phragmites australis). Using magnetic biosorbent, the biosorption of Xylenol orange and Congo red ions from polluted drain discharge in Abu Qir Bay was evaluated in the current study. Using scanning electron microscopy imaging and Fourier transform infra-red analysis; the surface function and morphology of the nano-biosorbent were examined. At room temperature, the effects of initial dye concentration, pH, contact time, and nano-biosorbent concentration have all been investigated. The greatest percentages that nano-biosorbent can remove from Congo red and Xylenol orange are 97% and 47%, respectively. The removal of the initial Congo red concentration varied from 42 to 97%, while the removal of the initial Xylenol orange concentration varied from 30 to 47%. The adsorption capacity was shown to be strongly pH-dependent; capacity dose as pH value increased, with pH 10 being the ideal pH for Congo red and pH 6 being the ideal pH value for Xylenol orange. The adsorption capacity for Congo red varied between 0.96 and 3.36 and the adsorption capacity for Xylenol orange varied between 0.18 and 17.58. The removal capacity decreased from 3.36 to 0.96 mg/g when the biosorbent dosage was increased from 0.05 to 0.5 g/L for Congo red, in case of Xylenol orange, the removal capacity increased from 0.18 to 17.58 mg/g when the biosorbent dosage was increased from 0.05 to 0.5 g/L. The removal capacity of Congo red increases quickly with time and varied from 1.66 to 1.88 of contact time; while the removal capacity of Xylenol orange varied between 3.08 and 4.62 of contact time. For the dyes under study, kinetics and adsorption equilibrium were examined. Within 180 min, the equilibrium was attained because to the quick adsorption process. For Congo red and Xylenol orange, the highest adsorption capacities were 3.36 and 17.58 mg g−1, respectively. The equilibrium data were assessed using a number of isotherm models, including Langmuir, Freundlich, BET, and Tempkin, while the kinetic data were examined using a variety of kinetic models, including pseudo-first- and pseudo-second-order equations. The pseudo-second-order equation provides the greatest accuracy for the kinetic data and Langmuir model is the closest fit for the equilibrium data.
13C MRI of hyperpolarized pyruvate at 120 µT
Authors: Kempf Nicolas , Körber Rainer , Plaumann Markus , Pravdivtsev Andrey N. , Engelmann Jörn , Boldt Johannes , Scheffler Klaus , Theis Thomas , Buckenmaier Kai
Published: February 2024

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth’s magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth’s magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years.
The underlying molecular mechanism of ciliated epithelium dysfunction and TGF-β signaling in children with congenital pulmonary airway malformations
Authors: Zhang Gang , Lou Lei , Shen Linghui , Zeng Huiyi , Cai Chun , Wu Rongde , Liu Dandan
Published: February 2024

The aim of this study was to investigate the variation in gene expression in the complete transcripts of Congenitalpulmonary airwaymalformation (CPAM) of the lung using Next Generation Sequencing (NGS) technology. There were 20 cases involving children with CPAM were used for selection of study sample. NGS was used to establish RNA-Seq libraries for the two groups of samples separately, and both groups were conducted to differential expression analysis and Gene Ontology (GO) functional enrichment analysis. The pathways of the differential genes were analyzed to find the enriched target pathways. A total of 592 genes were expressed with significant differences (CPAM vs. normal tissue, P < 0.05). GO functional analysis of DEGs indicated that abnormal ciliary function played a role in the development of CPAM. Subsequently, analysis of these genes pathways showed the TGF-β signaling pathway was significantly enriched. Finally, the results of immunohistochemical analysis of some DEGs showed that a significant reduction in the expression of SMAD6, a gene related to the TGF-β signaling pathway, led to abnormal activation of the pathway. TGF-β signaling pathway involved in the evolution of the disease obtained by DEGs enrichment pathway analysis. SMAD6, a gene involved in this pathway, might be a potential biomarker for the diagnosis and treatment of CPAM.
GIS-based non-grain cultivated land susceptibility prediction using data mining methods
Authors: Hao Qili , Zhang Tingyu , Cheng Xiaohui , He Peng , Zhu Xiankui , Chen Yao
Published: February 2024

The purpose of the present study is to predict and draw up non-grain cultivated land (NCL) susceptibility map based on optimized Extreme Gradient Boosting (XGBoost) model using the Particle Swarm Optimization (PSO) metaheuristic algorithm. In order to, a total of 184 NCL areas were identified based on historical records, and a total of 16 NCL susceptibility conditioning factors (NCLSCFs) were considered, based on both a systematic literature survey and local environmental conditions. The results showed that the XGBoost model optimized by PSO performed well in comparison to other machine learning algorithms; the values of sensitivity, specificity, PPV, NPV, and AUC are 0.93, 0.89, 0.88, 0.93, and 0.96, respectively. Slope, rainfall, fault density, distance from fault and drainage density are most important variables. According to the results of this study, the use of meta-innovative algorithms such as PSO can greatly enhance the ability of machine learning models.
Correlation of MRI quantitative perfusion parameters with EGFR, VEGF and EGFR gene mutations in non-small cell cancer
Authors: Zou Mingyue , Zhang Bingqian , Shi Lei , Mao Haijia , Huang Yanan , Zhao Zhenhua
Published: February 2024

To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans, Kep, Ve, Vp, Fp) were obtained by Omni Kinetics software. Immunohistochemistry staining was used in the detection of the expression of VEGF and EGFR protein, and the mutation of EGFR gene was detected by PCR. Corresponding statistical test was performed to compare the parameters and protein expression between squamous cell carcinoma (SCC) and adenocarcinoma (AC), as well as EGFR mutations and wild-type. Correlation analysis was used to evaluate the correlation between parameters with the expression of VEGF and EGFR protein. Fp (skewness, kurtosis, energy) were statistically significant between SCC and AC, and the area under the ROC curve were 0.733, 0.700 and 0.675, respectively. The expression of VEGF in AC was higher than in SCC. Fp (skewness, kurtosis, energy) were negatively correlated with VEGF (r =  − 0.527, − 0.428, − 0.342); Ktrans (Q50) was positively correlated with VEGF (r = 0.32); Kep (energy), Ktrans (skewness, kurtosis) were positively correlated with EGFR (r = 0.622, r = 0.375, 0.358), some histogram parameters of Kep, Ktrans (uniformity, entropy) and Ve (kurtosis) were negatively correlated with EGFR (r =  − 0.312 to − 0.644). Some perfusion histogram parameters were statistically significant between EGFR mutations and wild-type, they were higher in wild-type than mutated (P < 0.05). Quantitative perfusion histogram parameters of DCE-MRI have a certain value in the differential diagnosis of NSCLC, which have the potential to non-invasively evaluate the expression of cell signaling pathway-related protein.
The disparate impacts of college admissions policies on Asian American applicants
Authors: Grossman Joshua , Tomkins Sabina , Page Lindsay , Goel Sharad
Published: February 2024

There is debate over whether Asian American students face additional barriers, relative to white students, when applying to selective colleges. Here we present the results from analyzing 685,709 applications submitted over five application cycles to 11 highly selective colleges (the “Ivy-11”). We estimate that Asian American applicants had 28% lower odds of ultimately attending an Ivy-11 school than white applicants with similar academic and extracurricular qualifications. The gap was particularly pronounced for students of South Asian descent (49% lower odds). Given the high yield rates and competitive financial aid policies of the schools we consider, the disparity in attendance rates is likely driven, at least in part, by admissions decisions. In particular, we offer evidence that this pattern stems from two factors. First, many selective colleges give preference to the children of alumni in admissions. We find that white applicants were substantially more likely to have such legacy status than Asian applicants. Second, we identify geographic disparities potentially reflective of admissions policies that disadvantage students from certain regions of the United States. We hope these results inform discussions on equity in higher education.
Neurocognitive responses to spatial design behaviors and tools among interior architecture students: a pilot study
Authors: Şekerci Yaren , Kahraman Mehmet Uğur , Özturan Özgü , Çelik Ertuğrul , Ayan Sevgi Şengül
Published: February 2024

The impact of emotions on human behavior is substantial, and the ability to recognize people's feelings has a wide range of practical applications including education. Here, the methods and tools of education are being calibrated according to the data gained over electroencephalogram (EEG) signals. The issue of which design tools would be ideal in the future of interior architecture education, is an uncertain field. It is important to measure the students’ emotional states while using manual and digital design tools to determine the different impacts. Brain-computer interfaces have made it possible to monitor emotional states in a way that is both convenient and economical. In the research of emotion recognition, EEG signals have been employed, and the resulting literature explains basic emotions as well as complicated scenarios that are created from the combination of numerous basic emotions. The objective of this study is to investigate the emotional states and degrees of attachment experienced by interior architecture students while engaging in their design processes. This includes examining the use of 2D or 3D tools, whether manual or digital, and identifying any changes in design tool usage and behaviors that may be influenced by different teaching techniques. Accordingly, the hierarchical clustering which is a technique used in data analysis to group objects into a hierarchical structure of clusters based on their similarities has been conducted.
Non-coding RNA-related FCGBP downregulation in head and neck squamous cell carcinoma: a novel biomarker for predicting paclitaxel resistance and immunosuppressive microenvironment
Authors: Ding Qin , Lin Fengjie , Huang Zongwei , Li Ying , Cai Sunqin , Chen Xin , Liu Hui , Qiu Sufang
Published: February 2024

In head and neck squamous cell carcinoma (HNSC), chemoresistance is a major reason for poor prognosis. Nevertheless, there is a lack of validated biomarkers to screen for patients for categorical chemotherapy. Fc gamma binding protein (FCGBP) is a mucus protein associated with mucosal epithelial cells and has immunological functions that protect against tumors and metastasis. However, the effect of FCGBP on HNSC is unclear. In pan-cancer tissues, the expression of FCGBP and the survival status of patients were analyzed using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Correlation analysis and Cox regression analysis were conducted to confirm the relationship and survival outcome. Bioinformatics analysis was utilized to predict the probable upstream non-coding RNA. FCGBP functioned as a potential tumor suppressor gene in HNSC. Notably, FCGBP expression was negatively correlated with enriched tumor-infiltrating macrophages and paclitaxel resistance. Cox regression with gene, clinical, and immune factors showed that FCGBP was a risk factor acting in an independent manner. In HNSC, the utmost possibly upstream non-coding RNA-related pathway of FCGBP was also discovered to be the PART1/AC007728.2/LINC00885/hsa-miR-877-5p/FCGBP axis. According to the present study, non-coding RNA-related low levels of FCGBP are a prognostic indicator and are linked to an HNSC-related immunosuppressive state.
Assessing peptic ulcer risk with the HAMPROW score in the general Chinese population
Authors: Wang Binli , Yu Weitao , Zhang Zheyu , Jin Weili , Chen Haojun , Wang Linfeng , Xu Min , Hou Chaoqun , Qian Zhiquan , Qiu Ziyue , Zhang Sheng
Published: February 2024

The timely identification of individuals at high risk for peptic ulcers (PUs) is vital in preventing gastrointestinal bleeding after antiplatelet therapy. This study was designed to determine PU risk factors and develop a risk assessment model for PU detection in the general Chinese population. In a prospective dataset, clinical data from individuals undergoing gastroscopic evaluation between April 2019 and May 2022 were recorded. PUs were defined as mucosal defects exceeding 5 mm confirmed via gastroscopy. Participants were categorized into development (April 2019 to April 2021) and validation (May 2021 to May 2022) sets based on chronological order. LASSO-derived logistic regression analysis was employed to create a score, which was further validated via temporal validation. A total of 902 patients were ultimately enrolled, 204 (22.6%) of whom had PUs based on endoscopic findings. In the development cohort (n = 631), seven independent risk factors emerged: male sex (OR = 2.35, P = 0.002), white blood cell (WBC) count (OR = 1.16, P = 0.010), red blood cell (RBC) count (OR = 0.49, P < 0.001), globulin level (OR = 0.92, P = 0.004), albumin level (OR = 0.94, P = 0.020), pepsinogen I (PGI) level (OR = 1.01, P < 0.001), and positive Helicobacter pylori (HP) antibody (OR = 2.50, P < 0.001). Using these factors, a nomogram (HAMPROW score [hazard ratio (HP) antibody, albumin, male, PGI, RBC, globulin, and WBC]) was developed for individual PU prediction. The ability of the HAMPROW score to predict survival was confirmed with AUCs of 0.854 (95% CI 0.816–0.891) and 0.833 (95% CI 0.771–0.895) in the development and validation sets, respectively. In conclusion, the HAMPROW score can be used to screen for PUs effectively in the general Chinese population, facilitating personalized early detection of high risk of gastrointestinal bleeding before antiplatelet therapy.
Lightweight active back exosuit reduces muscular effort during an hour-long order picking task
Authors: Chung Jinwon , Quirk D. Adam , Applegate Megan , Rouleau Michael , Degenhardt Nathalie , Galiana Ignacio , Dalton Diane , Awad Louis N. , Walsh Conor J.
Published: February 2024

Occupational back exoskeletons and exosuits aim to reduce low back injuries in the workplace. For these technologies to be adopted, it is important that they provide biomechanical benefits to the wearer and do not disrupt job performance. To address this challenge, here we developed a lightweight, soft, active back exosuit that can autonomously control virtual impedance to apply differing assistance during lowering and lifting. In usability tests, participants rated the exosuit as easy to learn and use and reported feeling confident while wearing it. In an experiment involving an hour-long order picking task we demonstrated that the exosuit reduced peak and median muscle activations in the back by 18% and 20%, respectively. Despite the complexity of the movements required, such as walking, bending, and navigating around obstacles while lifting boxes from under a rack, our controller demonstrated impressive robustness with only 14 mistriggers out of 9600 lifts (0.1%). The results of this research suggest that active exosuit technology has the potential to be a highly usable solution to aid warehouse workers in real-world settings.
NINJ1 induces plasma membrane rupture and release of damage-associated molecular pattern molecules during ferroptosis
Authors: Ramos Saray , Hartenian Ella , Santos José Carlos , Walch Philipp , Broz Petr
Published: February 2024

Ferroptosis is a regulated form of necrotic cell death caused by iron-dependent accumulation of oxidized phospholipids in cellular membranes, culminating in plasma membrane rupture (PMR) and cell lysis. PMR is also a hallmark of other types of programmed necrosis, such as pyroptosis and necroptosis, where it is initiated by dedicated pore-forming cell death-executing factors. However, whether ferroptosis-associated PMR is also actively executed by proteins or driven by osmotic pressure remains unknown. Here, we investigate a potential ferroptosis role of ninjurin-1 (NINJ1), a recently identified executor of pyroptosis-associated PMR. We report that NINJ1 oligomerizes during ferroptosis, and that Ninj1-deficiency protects macrophages and fibroblasts from ferroptosis-associated PMR. Mechanistically, we find that NINJ1 is dispensable for the initial steps of ferroptosis, such as lipid peroxidation, channel-mediated calcium influx, and cell swelling. In contrast, NINJ1 is required for early loss of plasma membrane integrity, which precedes complete PMR. Furthermore, NINJ1 mediates the release of cytosolic proteins and danger-associated molecular pattern (DAMP) molecules from ferroptotic cells, suggesting that targeting NINJ1 could be a therapeutic option to reduce ferroptosis-associated inflammation.
New precision medicine avenues to the prevention of Alzheimer’s disease from insights into the structure and function of γ-secretases
Authors: De Strooper Bart , Karran Eric
Published: February 2024

Two phase-III clinical trials with anti-amyloid peptide antibodies have met their primary goal, i.e. slowing of Alzheimer’s disease (AD) progression. However, antibody therapy may not be the optimal therapeutic modality for AD prevention, as we will discuss in the context of the earlier small molecules described as “γ-secretase modulators” (GSM). We review here the structure, function, and pathobiology of γ-secretases, with a focus on how mutations in presenilin genes result in early-onset AD. Significant progress has been made in generating compounds that act in a manner opposite to pathogenic presenilin mutations: they stabilize the proteinase-substrate complex, thereby increasing the processivity of substrate cleavage and altering the size spectrum of Aβ peptides produced. We propose the term “γ-secretase allosteric stabilizers” (GSAS) to distinguish these compounds from the rather heterogenous class of GSM. The GSAS represent, in theory, a precision medicine approach to the prevention of amyloid deposition, as they specifically target a discrete aspect in a complex cell biological signalling mechanism that initiates the pathological processes leading to Alzheimer’s disease.
TORC1 is an essential regulator of nutrient-controlled proliferation and differentiation in Leishmania
Authors: Myburgh Elmarie , Geoghegan Vincent , Alves-Ferreira Eliza VC , Nievas Y Romina , Grewal Jaspreet S , Brown Elaine , McLuskey Karen , Mottram Jeremy C
Published: February 2024

Leishmania parasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite’s developmental changes remain elusive. Here, we report that Leishmania TORC1 is a key environmental sensor for parasite proliferation and differentiation in the sand fly-stage promastigotes and for replication of mammalian-stage amastigotes. We show that Leishmania RPTOR1, interacts with TOR1 and LST8, and identify new parasite-specific proteins that interact in this complex. We investigate TORC1 function by conditional deletion of RPTOR1, where under nutrient-rich conditions RPTOR1 depletion results in decreased protein synthesis and growth, G1 cell cycle arrest and premature differentiation from proliferative promastigotes to non-dividing mammalian-infective metacyclic forms. These parasites are unable to respond to nutrients to differentiate into proliferative retroleptomonads, which are required for their blood-meal induced amplification in sand flies and enhanced mammalian infectivity. We additionally show that RPTOR1−/− metacyclic promastigotes develop into amastigotes but do not proliferate in the mammalian host to cause pathology. RPTOR1-dependent TORC1 functionality represents a critical mechanism for driving parasite growth and proliferation.
Synchronizers of Circadian Rhythms
Authors: Tahara Yu , Shibata Shigenobu
Published: February 2024

The adjustment of internal clocks by using external environmental cues, such as light, food, and physical activity, is an important function in the circadian clock system for maintaining an appropriate clock time. This function is referred to as “entrainment.” In this chapter, the entrainment systems in the central and peripheral clocks are introduced with their molecular mechanisms. The interaction between the synchronizers and physiological functions is also explained in each section to understand the importance of the timing of each synchronizer.
The Respiratory System
Authors: Bartman Colleen M. , Prakash Y. S.
Published: February 2024

Rhythms in lung function and time-of-day-dependent exacerbation in disease symptoms have been noted dating back to the 5th century. Today, we recognize the 24-hour variation in normal lung function and how these fluctuations are associated with the circadian component of lung pathophysiology. Diseases of the airway such as allergic asthma, COPD, pulmonary fibrosis, pneumonia and sepsis, and lung cancer all have documented correlations with circadian rhythm and the peripheral molecular clock. Additionally, chronic exposure to particulate matter and other pollutants can induce alterations in clock genes/proteins, and disruption of the circadian system increases susceptibility to poor outcomes following insult to the airway. Investigations into targets of the molecular clock have shed light on chronotherapeutics that can be used to optimize therapeutic approaches in the clinic or leverage endogenous circadian networks to enhance efficacy of currently available treatments.
Chronobiology and the Kidney
Authors: Knapp Martin S.
Published: February 2024

The kidney plays a critical role in maintaining a stable internal environment by balancing output and intake, circadian variations in the contents of intracellular and extracellular fluids, the levels of some pharmaceuticals and total body water volume. Variations in the quantities of daytime and night-time urine were recorded in early observations of humans and later studied in manipulated light/dark environments, in clinical disorders and in laboratory animals. Circadian variations in the transfer of substances from the gastrointestinal tract and in metabolism influence the volume and content of urine. The nephron tubules are responsible for transferring solutes and water, modifying glomerular filtrate as it transits through them. In both health and many disorders, changes are necessary to balance intake and output, and circadian variations result from the influence of clock genes. Exogenous changes from an erect to supine position, during sleep and due to extrinsic events may modify intrinsic circadian rhythms, as can illness. Renal transplantation can change day-to-night variability. The circadian timing of medication can modify renal responses. Benefits, toxicity and side effects may change with the timing of administration of medication. A “best” circadian timing for medications prescribed for renal conditions and times of administration that result in modified side effects are often found.
Clock Proteins and Circadian Rhythms in Immunity
Authors: Curtis Annie M. , Knapp Martin S.
Published: February 2024

The circadian clock influences many, if not all, aspects of immunity. Variations across daily time scales have been observed in immune cell migration, differentiation and effector function, including cytokine/chemokine production, phagocytosis, antigen presentation, lymphocyte proliferation and the allergic response. Circadian clock disruption caused by environmental or genetic means often results in immune system dysfunction. These circadian influences on immunity are mediated through systemic autonomic and hormonal variations, in coordination with intrinsic clocks residing in immune cells and structural cells of the microenvironment. Several inflammatory conditions such as bronchial asthma and rheumatoid arthritis show circadian variations in symptomatology. Other inflammatory conditions, such as cardiovascular disease and responses to organ and cell transplantation also display daily rhythmicity and enhanced severity with circadian disruption. In this chapter, we will address the many types of circadian rhythms present in immunity, shedding light on the underlying molecular mechanisms that operate within cells of the innate and adaptive immune system. We will address how circadian molecular changes within immune cells are linked with immune cell fate and function. Finally, we will briefly discuss the impact of the immune clock on human health and disease and discuss how we can harness the inherent rhythmicity in our immune system to modify pharmacological responses.
The Haematopoietic System
Authors: Laerum Ole D.
Published: February 2024

Circadian variations are present in all aspects of haematopoiesis, including the different cell lineages and stages of development, from stem and progenitor cells to mature leukocytes and erythrocytes. In humans, the circadian variations of cell proliferation in different cell types show covariation, whereby haematopoiesis occurs in synchronized waves. The highest activity is seen in the middle of the day, while the minimum is observed during the night. In nocturnal animals, such as mice and rats, haematopoiesis undergoes similar variations, with a maximum during the active phase. There is also evidence for seasonal variations, although they are not as well-characterized as the circadian variations. The clock genes are present and are actively transcribed in all hematopoietic cells. However, there are great variations in terms of their functions and their importance in individual cell types. Altogether, they create enormous complexity through cellular interactions and regulatory mechanisms, influenced both by the circulation of the nervous system, including signals from the central master clock, as well as by local cellular functions. The clock genes and their proteins modify other regulatory signals and cell functions, mainly mediated by chemokines.
Circadian Aspects of Skeletal Muscle Biology
Authors: Delezie Julien , Lamia Katja
Published: February 2024

Metabolic flexibility is critical to survival for all species. Mammalian metabolism undergoes numerous predictable daily fluctuations, alternating between preferential utilization of carbohydrates and lipids. These variations are partly driven by the circadian clock, an evolutionarily conserved time-keeping molecular mechanism that is present in virtually all cells of the body. In this chapter, we first provide an overview of the mammalian circadian clock and its influence on the skeletal muscle transcriptome. Next, we present key studies demonstrating the involvement of the circadian clock in muscle growth and regeneration, highlighting various transcription factors and pathways directly impacted by clock proteins. We also discuss the relevance of the muscle-intrinsic clock to the regulation of energy homeostasis, outlining the diverse and multifaceted ways through which glucose, lipid, and mitochondrial metabolism are regulated on a daily basis within muscle cells. We conclude with a discussion of the relationships between timed exercise, food, and circadian aspects of muscle biology, with some directions for future studies.
Circadian Clocks in Ageing
Authors: Zhu Pei , Peek Clara B.
Published: February 2024

Human life expectancy has increased dramatically over the past two centuries, owing to advances in modern medicine, nutrition and hygiene. However, molecular mechanisms controlling ageing and lifespan have only recently started to emerge. Ageing coincides with changes in a multitude of physiological processes, including circadian rhythms and sleep. Conversely, recent discoveries have revealed the role of circadian rhythm disruption in the progression and acceleration of ageing. Thus, understanding the interconnection between circadian decline and ageing, as well as the consequences of circadian misalignment, is key to uncovering potential therapeutic approaches to target age-related pathologies. Here, we present an overview of the role of circadian clocks in ageing and age-related processes.
Chronotherapeutic Approaches
Authors: Gubin Denis
Published: February 2024

The chapter provides a comprehensive review of current approaches to personalized chronodiagnosis and chronotherapy. We discuss circadian clock drug targets that aim to affect cellular clock machinery, circadian mechanisms of pharmacokinetics/pharmacodynamics, and chronotherapeutic approaches aimed at increasing treatment efficacy and minimizing its side effects. We explore how chronotherapy can combat acquired and compensatory drug resistance. Non-pharmacological interventions for clock preservation and enhancement are also overviewed, including light treatment, melatonin, sleep scheduling, time-restricted feeding, physical activity, and exercise.
Chronobiological Study Designs
Authors: Weinert Dietmar , Gubin Denis
Published: February 2024

The chapter describes experimental designs for various chronobiological studies aimed at basic research and clinical trials, with an emphasis on circadian rhythms. In the first part, various methods of data collection, particularly longitudinal and transverse sampling and their relative merits, are discussed. Thereafter, specific methods and their constraints for monitoring marker rhythms are presented. Variables that are most effective in characterizing the endogenous pacemaker and those of clinical relevance are discussed. Besides melatonin and core body temperature rhythms, which are widely accepted as the gold standard for representing the circadian clock, rhythms of cortisol concentration, physical activity, sleep parameters and chronotypes are considered. The relevance of stable rhythms with appropriate internal and external phase relationships for health and wellbeing, as well as adverse effects of certain rhythm alterations are discussed. The last part describes two experimental designs that allow separating endogenous and exogenous components of biological rhythms, the constant routine and the forced desynchronization protocols.
A non-peptide-based fluorescent probe capable of sensitively visualizing asparagine endopeptidase
Authors: Li Kang , Hou Yanxian , Han Jinliang , Lv Chengyuan , Liu Wenkai , Du Jianjun , Sun Wen , Fan Jiangli , Peng Xiaojun
Published: February 2024

A sensitive and facilely synthesized fluorescent probe, QMC11, was designed for visualizing AEP.
Computational screening for prediction of co-crystals: method comparison and experimental validation
Authors: Molajafari Fateme , Li Tianrui , Abbasichaleshtori Mehrnaz , Hajian Z. D. Moein , Cozzolino Anthony F. , Fandrick Daniel R. , Howe Joshua D.
Published: February 2024

COSMO-RS and machine learning-based models can reduce the cost of screening and identifying crystal coformers, facilitating discovery of new cocrystals.
Proton transport in oxalate compounds of iron(iii) containing (alkyl)ammonium cations: the influence of the density of hydrogen bonds on conductivity
Authors: Lozančić Ana , Burazer Sanja , Renka Sanja , Molčanov Krešimir , Molčanov Lidija , Jurić Marijana
Published: February 2024

The proton conductivity of novel mononuclear and 1D oxalate-based compounds of iron(iii) containing (alkyl)ammonium cations was investigated: the discrete compound shows remarkable humidity sensing properties and very high proton conductivity.
Flux growth and characterization of gallium-rare earth borates
Authors: Maltsev Victor V. , Koporulina Elizaveta V. , Volkova Elena A. , Mitina Diana D. , Jiliaeva Anna I. , Kosorukov Vladimir L. , Afanasev Alexey E. , Naprasnikov Daniil A.
Published: February 2024

YGa3(BO3)4 single crystals were grown from a K2Mo3O10-based flux, and also RGa3(BO3)4 (R = Y, Pr–Yb) spontaneous crystals (RGB) were obtained by a high-temperature flux growth technique from a complex R2O3–Bi2O3–B2O3–Ga2O3 solvent.
Rational control of the typical surface defects of hybrid perovskite using tetrahexylammonium iodide
Authors: Wang Ben , Yao Shunwei , Hu Wenjing , Peng Lin , Shi Tingting , Wang Yanan , Chen Jing , Liu Xiaolin , Lin Jia
Published: February 2024

This study shows an in-depth understanding of the influence of defects on the electronic properties of the surface of FAPbI3, as well as the passivation mechanism of tetrahexylammonium iodide on the surface typical defects of perovskite.
Intracellular microbial rhodopsin-based optogenetics to control metabolism and cell signaling
Authors: Vlasova Anastasiia D. , Bukhalovich Siarhei M. , Bagaeva Diana F. , Polyakova Aleksandra P. , Ilyinsky Nikolay S. , Nesterov Semen V. , Tsybrov Fedor M. , Bogorodskiy Andrey O. , Zinovev Egor V. , Mikhailov Anatolii E. , Vlasov Alexey V. , Kuklin Alexander I. , Borshchevskiy Valentin I. , Bamberg Ernst , Uversky Vladimir N. , Gordeliy Valentin I.
Published: February 2024

Organelle optogenetics is an approach to control cell physiology by targeted expression of microbial rhodopsins in membranes of subcellular organelles.