bluuebunny/crossref_metadata_2025 huggingface dataset:
A spacer-based approach for localized Joule heating in membrane distillation
Authors: Ahmed Farah Ejaz , Ibrahim Yazan , Hilal Nidal
Published: May 2024

Membrane distillation (MD) is a versatile low-temperature separation process used for desalinating saline solutions with high salt rejection rates. Its current drawbacks include low flux and high energy demand. This study presents localized electrically induced heating using ceramic-coated metallic spacers to improve MD performance. We coated Ni-Cr spacers with MgO via electrolytic deposition and calcination, optimizing for a crack-free protective surface. Smaller wire diameter Ni-Cr exhibited superior heating. When a periodic current of 0.2 A cm−2 was applied, permeate flux increased by 15% although energy consumption only increased by 4%. Continuous supply of high-grade electrical energy added no further performance improvement as compared to periodic application. Our work highlights a spacer-based approach for localized Joule heating in MD systems without compromising membrane structure, while exploring coating systems to protect conductive spacers and optimizing schemes for electrically controlled performance.
Accessing elusive σ-type cyclopropenium cation equivalents through redox gold catalysis
Authors: Li Xiangdong , Wodrich Matthew D. , Waser Jérôme
Published: May 2024

Cyclopropenes are the smallest unsaturated carbocycles. Removing one substituent from cyclopropenes leads to cyclopropenium cations (C3+ systems, CPCs). Stable aromatic π-type CPCs were discovered by Breslow in 1957 by removing a substituent on the aliphatic position. In contrast, σ-type CPCs—formally accessed by removing one substituent on the alkene—are unstable and relatively unexplored. Here we introduce electrophilic cyclopropenyl-gold(III) species as equivalents of σ-type CPCs, which can then react with terminal alkynes and vinylboronic acids. With catalyst loadings as low as 2 mol%, the synthesis of highly functionalized alkynyl- or alkenyl-cyclopropenes proceeded under mild conditions. A class of hypervalent iodine reagents—the cyclopropenyl benziodoxoles (CpBXs)—enabled the direct oxidation of gold(I) to gold(III) with concomitant transfer of a cyclopropenyl group. This protocol was general, tolerant to numerous functional groups and could be used for the late-stage modification of complex natural products, bioactive molecules and pharmaceuticals.
Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation
Authors: Zinter Matt S. , Dvorak Christopher C. , Mayday Madeline Y. , Reyes Gustavo , Simon Miriam R. , Pearce Emma M. , Kim Hanna , Shaw Peter J. , Rowan Courtney M. , Auletta Jeffrey J. , Martin Paul L. , Godder Kamar , Duncan Christine N. , Lalefar Nahal R. , Kreml Erin M. , Hume Janet R. , Abdel-Azim Hisham , Hurley Caitlin , Cuvelier Geoffrey D. E. , Keating Amy K. , Qayed Muna , Killinger James S. , Fitzgerald Julie C. , Hanna Rabi , Mahadeo Kris M. , Quigg Troy C. , Satwani Prakash , Castillo Paul , Gertz Shira J. , Moore Theodore B. , Hanisch Benjamin , Abdel-Mageed Aly , Phelan Rachel , Davis Dereck B. , Hudspeth Michelle P. , Yanik Greg A. , Pulsipher Michael A. , Sulaiman Imran , Segal Leopoldo N. , Versluys Birgitta A. , Lindemans Caroline A. , Boelens Jaap J. , DeRisi Joseph L. ,   the Pediatric Transplantation and Cell Therapy Consortium
Published: May 2024

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children’s hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung–immune system–microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.
Simulated Sea Surface Salinity Data from a 1/48° Ocean Model
Authors: Bingham Frederick M. , Fournier Séverine , Brodnitz Susannah , Hayashi Akiko , Kuusela Mikael , Westbrook Elizabeth , Ulfsax Carlin Karly M. , González-Haro Cristina , González-Gambau Verónica
Published: May 2024

To study the validation process for sea surface salinity (SSS) we have generated one year (November 2011- October 2012) of simulated satellite and in situ “ground truth” data. This was done using the ECCO (Estimating the Circulation and Climate of the Oceans) 1/48° simulation, the highest resolution global ocean model currently available. The ground tracks of three satellites, Aquarius, SMAP (Soil Moisture Active Passive) and SMOS (Soil Moisture and Ocean Salinity) were extracted and used to sample the model with a gaussian weighting similar to that of the spaceborne sensor ground footprint. This produced simulated level 2 (L2) data. Simulated level 3 (L3) data were then produced by averaging L2 data onto a regular grid. The model was sampled to produce simulated Argo and tropical mooring SSS datasets. The Argo data were combined into a simulated gridded monthly 1° Argo product. The simulated data produced from this effort have been used to study sampling errors, matchups, subfootprint variability and the validation process for SSS at L2 and L3.
About feasibility of SpaceX's human exploration Mars mission scenario with Starship
Authors: Maiwald Volker , Bauerfeind Mika , Fälker Svenja , Westphal Bjarne , Bach Christian
Published: May 2024

After decades where human spaceflight missions have been reserved to low Earth orbit, recent years have seen mission proposals and even implemented plans, e.g. with the mission Artemis I, for returning to the lunar surface. SpaceX has published over various media (e.g., its official website, conference presentations, user manual) conceptual information for its reusable Starship to enable human exploration missions to the Martian surface by the end of the decade. The technological and human challenges associated with these plans are daunting. Such a mission at that distance would require excellent system reliability and in-situ-resource utilization on a grand scale, e.g. to produce propellant. The plans contain little details however and have not yet been reviewed concerning their feasibility. In this paper we show significant technological gaps in these plans. Based on estimates and extrapolated data, a mass model as needed to fulfill SpaceX’s plans could not be reproduced and the subsequent trajectory optimization showed that the current plans do not yield a return flight opportunity, due to a too large system mass. Furthermore, significant gaps exist in relevant technologies, e.g. power supply for the Martian surface. It is unlikely that these gaps can be closed until the end of the decade. We recommend several remedies, e.g. stronger international participation to distribute technology development and thus improve feasibility. Overall, with the limited information published by SpaceX about its system and mission scenario and extrapolation from us to fill information gaps, we were not able to find a feasible Mars mission scenario using Starship, even when assuming optimal conditions such as 100% recovery rate of crew consumables during flight.
Seroprevalence of Treponema pallidum infection in Brazilian indigenous people: a cross-sectional study
Authors: Barbosa Marcelo S. , Queiroz Júlio Henrique F. S. , Schnaufer Erica C. S. , Silva Gerlaine D. , Marques Michele F. R. , Ferreira Tiago S. , de Souza Gleyce H. A. , Gonçalves Crhistinne C. M. , Marchioro Silvana B. , Simionatto Simone
Published: May 2024

Indigenous communities in Brazil have a complex epidemiological profile, which increases their chances of contracting sexually transmitted diseases. However, limited data is available on Treponema pallidum infections in this population. We investigated the seroprevalence and risk factors associated with T. pallidum infection in an indigenous population of Dourados, Mato Grosso do Sul. Blood samples were collected from September 2017 to March 2020, and the participants were interviewed to obtain comprehensive data on demography and sexual behavior. Serological tests were performed to detect T. pallidum infection. Besides conducting descriptive analysis, we performed Chi-squared tests and determined the bivariate odds ratio. The data were also analyzed using logistic regression. Among the 2190 invited individuals, 1927 (88%) were included in this study. The seroprevalence of T. pallidum infection was 2.91%. The results of a multivariate analysis showed that individuals who were 30–39 years old, with up to 4 years of school education, living in households without piped water, with a history of genital lesions, multiple sexual partners, and having a history of STIs had the highest seroprevalence of T. pallidum. This study showed that behavioral, social, and economic factors play an important role in the transmission of T. pallidum within the indigenous population. Thus, targeted intervention, including imparting education in the native language, mass testing initiatives, and implementing public policies to improve socioeconomic indicators, is needed to reduce the cases of syphilis in this community.
Effects of propofol, ketamine-propofol mixture in pediatric dental patients undergoing intravenous sedation: a clinical study
Authors: Isık Gizem , Alpay Nilgun , Daglioglu Gülcin , Ciftci Volkan
Published: May 2024

This study aimed to evaluate the clinical effects, complications (peri- and postoperative), depth of sedation, recovery times, and changes in anxiety levels in paediatric dental patients receiving intravenous sedation with propofol and ketamine–propofol mixtures. This prospective clinical study included 69 healthy children (ASA 1) aged 3–7 years. The patients were assigned randomly to propofol group (n = 23), which received propofol; 1:3 ketofol group (n = 23), which received 1:3 ketofol; or 1:4 ketofol group (n = 23), which received 1:4 ketofol. The bispectral index (BIS) and Ramsay Sedation Scale (RSS) score were recorded at intervals of 5 min to measure the depth of sedation, and vital signs were evaluated. Peri- and postoperative complications and recovery times were recorded. Anxiety levels were also evaluated using the Facial Image Scale (FIS) and changes in saliva cortisol levels (SCLs) before and after the intravenous sedation procedure. The Kruskal‒Wallis test and Wilcoxon signed-rank test were used to determine pre- and posttreatment parameters. Dunn’s test for post hoc analysis was used to determine the differences among groups. Children’s pre- and posttreatment anxiety levels did not differ significantly according to FIS scores, and increases in SCLs were detected in 1:3 ketofol and 1:4 ketofol groups after dental treatment was completed. Compared with those in the other groups, the BIS values of the patients in 1:4 ketofol indicated a slightly lower depth of sedation. The recovery time of the patients in 1:3 ketofol was longer than that of patients in propofol and 1:4 ketofol. The incidence of postoperative complications (agitation, hypersalivation, nausea/vomiting, and diplopia) did not differ among the groups. Ketamine–propofol combinations provided effective sedation similar to that of propofol infusion without any serious complications during dental treatment performed under intravenous sedation. The ketofol infusion increased the anxiety level of paediatric dental patients to a greater extent than the propofol infusion.
Improved differentiation of cavernous malformation and acute intraparenchymal hemorrhage on CT using an AI algorithm
Authors: Kim Jung Youn , Choi Hye Jeong , Kim Sang Heum , Ju Hwangseon
Published: May 2024

This study aimed to evaluate the utility of an artificial intelligence (AI) algorithm in differentiating between cerebral cavernous malformation (CCM) and acute intraparenchymal hemorrhage (AIH) on brain computed tomography (CT). A retrospective, multireader, randomized study was conducted to validate the performance of an AI algorithm in differentiating AIH from CCM on brain CT. CT images of CM and AIH (< 3 cm) were identified from the database. Six blinded reviewers, including two neuroradiologists, two radiology residents, and two emergency department physicians, evaluated CT images from 288 patients (CCM, n = 173; AIH, n = 115) with and without AI assistance, comparing diagnostic performance. Brain CT interpretation with AI assistance resulted in significantly higher diagnostic accuracy than without (86.92% vs. 79.86%, p < 0.001). Radiology residents and emergency department physicians showed significantly improved accuracy of CT interpretation with AI assistance than without (84.21% vs. 75.35%, 80.73% vs. 72.57%; respectively, p < 0.05). Neuroradiologists showed a trend of higher accuracy with AI assistance in the interpretation but lacked statistical significance (95.83% vs. 91.67%, p = 0.56). The use of an AI algorithm can enhance the differentiation of AIH from CCM in brain CT interpretation, particularly for nonexperts in neuroradiology.
Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment
Authors: Orrego Miguel A. , Szczesniak Michal W. , Vasquez Carlos M. , Verastegui Manuela R. , Bustos Javier A. , Garcia Hector H. , Nash Theodore E. ,   Cysticercosis Working Group in Peru, Garcia Hector H. , Gilman Robert H. , Gonzalez Armando E. , Verastegui Manuela , Zimic Mirko , Bustos Javier , O’Neal Seth E. , Rodriguez Silvia , Gonzalez Isidro , Saavedra Herbert , Sanchez Sofia , Martinez Manuel , Santivañez Saul , Mayta Holger , Castillo Yesenia , Pajuelo Monica , Arroyo Gianfranco , Chile Nancy , Toribio Luz , Orrego Miguel A. , Lopez Maria T. , Gomez Luis , Gavidia Cesar M. , Vargas-Calla Ana , Gonzales Eloy , Moyano Luz M. , Gamboa Ricardo , Muro Claudio , Vichez Percy , Handali Sukwan , Noh John , Nash Theodore E. , Friedland Jon
Published: May 2024

Subarachnoid neurocysticercosis (SANCC) is caused by an abnormally transformed form of the metacestode or larval form of the tapeworm Taenia solium. In contrast to vesicular parenchymal and ventricular located cysts that contain a viable scolex and are anlage of the adult tapeworm, the subarachnoid cyst proliferates to form aberrant membranous cystic masses within the subarachnoid spaces that cause mass effects and acute and chronic arachnoiditis. How subarachnoid cyst proliferates and interacts with the human host is poorly understood, but parasite stem cells (germinative cells) likely participate. RNA-seq analysis of the subarachnoid cyst bladder wall compared to the bladder wall and scolex of the vesicular cyst revealed that the subarachnoid form exhibits activation of signaling pathways that promote proliferation and increased lipid metabolism. These adaptions allow growth in a nutrient-limited cerebral spinal fluid. In addition, we identified therapeutic drug targets that would inhibit growth of the parasite, potentially increase effectiveness of treatment, and shorten its duration.
Analysis of player speed and angle toward the ball in soccer
Authors: Novillo Álvaro , Cordón-Carmona Antonio , García-Aliaga Abraham , Roman Ignacio Refoyo , del Campo Roberto López , Resta Ricardo , Buldú Javier M.
Published: May 2024

The study analyzes how the magnitude and angle of the speed of soccer players change according to the distance to the ball and the phases of the game, namely the defensive and attacking phases. We observed how the role played in the team (goalkeeper, defender, midfielder, or forward) strongly determines the speed pattern of players. As a general trend, the speed’s modulus is incremented as their position is closer to the ball, however, it is slightly decreased when arriving at it. Next, we studied how the angle of the speed with the direction to the ball is related to the distance to the ball and the game phases. We observed that, during the defensive phase, goalkeepers are the players that run more parallel to the ball, while forwards are the ones running more directly to the ball position. Importantly, this behavior changes dramatically during the attacking phase. Finally, we show how the proposed methodology can be used to analyze the speed-angle patterns of specific players to understand better how they move on the pitch according to the distance to the ball.
A combinatorial MRI sequence-based radiomics model for preoperative prediction of microsatellite instability status in rectal cancer
Authors: Xing Xiaowei , Li Dongxue , Peng Jiaxuan , Shu Zhenyu , Zhang Yang , Song Qiaowei
Published: May 2024

This study aimed to develop an optimal radiomics model for preoperatively predicting microsatellite instability (MSI) in patients with rectal cancer (RC) based on multiparametric magnetic resonance imaging. The retrospective study included 308 RC patients who did not receive preoperative antitumor therapy, among whom 51 had MSI. Radiomics features were extracted and dimensionally reduced from T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and T1-weighted contrast enhanced (T1CE) images for each patient, and the features of each sequence were combined. Multifactor logistic regression was used to screen the optimal feature set for each combination. Different machine learning methods were applied to construct predictive MSI status models. Relative standard deviation values were determined to evaluate model performance and select the optimal model. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses were performed to evaluate model performance. The model constructed using the k-nearest neighbor (KNN) method combined with T2WI and T1CE images performed best. The area under the curve values for prediction of MSI with this model were 0.849 (0.804–0.887), with a sensitivity of 0.784 and specificity of 0.805. The Delong test showed no significant difference in diagnostic efficacy between the KNN-derived model and the traditional logistic regression model constructed using T1WI + DWI + T1CE and T2WI + T1WI + DWI + T1CE data (P > 0.05) and the diagnostic efficiency of the KNN-derived model was slightly better than that of the traditional model. From ROC curve analysis, the KNN-derived model significantly distinguished patients at low- and high-risk of MSI with the optimal threshold of 0.2, supporting the clinical applicability of the model. The model constructed using the KNN method can be applied to noninvasively predict MSI status in RC patients before surgery based on radiomics features from T2WI and T1CE images. Thus, this method may provide a convenient and practical tool for formulating treatment strategies and optimizing individual clinical decision-making for patients with RC.
Seasonal variability of lesions distribution in acute ischemic stroke: A retrospective study
Authors: Sun Xiao , Xia Xiaoshuang , Xue Juanjuan , Gu Yumeng , Chen Zhuangzhuang , Liu Peilin , Wang Fuyin , Zhou Xiao , Liu Jiaming , Wang Lin , Li Xin
Published: May 2024

Seasonal variability could have an impact on the incidence and outcome of stroke. However, little is known about the correlation between seasonal variability and location of acute cerebral infarction. This study aimed to explore the relationship between onset season and the lesions distribution of acute ischemic stroke (AIS). We retrospectively analysis data from 1488 AIS patients admitted to the Second Hospital of Tianjin Medical University from 2018 to 2022. All subjects completed head magnetic resonance imaging examination (MRI) and were divided into four groups according to the onset seasons. The lesions distribution of AIS was evaluated for anterior/posterior/double circulation infarction (DCI), unilateral/bilateral infarctions, and single/multiple cerebral infarctions based on MRI. Logistic regression models were employed to assess the association of season with lesions distribution of AIS. Subgroup analysis was performed in different stroke subtypes. Of 1488 patients, 387 (26.0%) AIS occurred in spring, 425 (28.6%) in summer, 331 (22.2%) in autumn and 345 (23.2%) in winter. Multivariate logistic regression demonstrated that the winter group had 2.15 times (95% CI:1.44–3.21) risk of multiple infarctions, 2.69 times (95% CI:1.80–4.02) of bilateral infarctions and 1.54 times (95% CI:1.05–2.26) of DCI compared with summer group, respectively. Subgroup analysis showed an increased risk of multiple (p < 0.01) or bilateral infarctions (p < 0.01) in small-artery occlusion (SAO) subtype, and higher risk of bilateral infarctions (p < 0.01) or DCI (p < 0.05) in large artery atherosclerosis (LAA) subtype during winter. No significant associations of season with lesions distribution in cardioembolism subtype. Our study highlighted a prominent seasonal variability in the lesions distribution of AIS, particularly in LAA and SAO subtypes. The findings could help to formulating meteorological risk warning strategies for different subtypes.
Heavy metal poisoning caused by Chinese folk remedies in psoriasis patients: a retrospective analysis
Authors: Xue Changjiang , Du Xuqin , Zhu Xiaoli , Wu Na , Ye Qiao
Published: May 2024

Psoriasis, characterized as a chronic relapsing disease with a protracted course, often drives patients to seek relief through Chinese folk remedies (CFR). Nonetheless, the complex compositions of these remedies frequently result in unintended adverse effects, notably various types of heavy metal poisoning. Our study involved an exhaustive collection and analysis of clinical data from psoriasis patients who developed heavy metal poisoning due to CFR usage, admitted to Beijing Chao-Yang Hospital from January 2011 to October 2023. Our analysis identified 44 cases of mercury poisoning, 17 of lead poisoning, 21 of arsenic poisoning, and 4 instances of mixed heavy metal poisoning. The folk remedies used ranged from fumigation and inhalation to skin application and oral administration. Distinct pathogenic characteristics were observed in each poisoning type. After treatment with metal chelating agents, all patients experienced a reduction in heavy metal levels in their bodies, accompanied by varying degrees of symptom alleviation. This study underscores the vital necessity of opting for formal, medically approved treatments for psoriasis, thereby avoiding the hazardous consequences of unregulated folk remedies that may lead to severe heavy metal poisoning.
Tactile memory impairments in younger and older adults
Authors: Lange Lilith-Sophie , Chrysidou Anastasia , Liu Peng , Kuehn Esther
Published: May 2024

Human tactile memory allows us to remember and retrieve the multitude of somatosensory experiences we undergo in everyday life. An unsolved question is how tactile memory mechanisms change with increasing age. We here use the ability to remember fine-grained tactile patterns passively presented to the fingertip to investigate age-related changes in tactile memory performance. In experiment 1, we varied the degree of similarity between one learned and several new tactile patterns to test on age-related changes in the “uniqueness” of a stored tactile memory trace. In experiment 2, we varied the degree of stimulus completeness of both known and new tactile patterns to test on age-related changes in the weighting between known and novel tactile information. Results reveal that older adults show only weak impairments in both precision and bias of tactile memories, however, they show specific deficits in reaching peak performance > 85% in both experiments. In addition, both younger and older adults show a pattern completion bias for touch, indicating a higher weighting of known compared to new information. These results allow us to develop new models on how younger and older adults store and recall tactile experiences of the past, and how this influences their everyday behavior.
Convolutional MLP orthogonal fusion of multiscale features for visual place recognition
Authors: Gan Wenjian , Zhou Yang , Hu Xiaofei , Zhao Luying , Huang Gaoshuang , Zhang Chenglong
Published: May 2024

Visual place recognition (VPR) involves obtaining robust image descriptors to cope with differences in camera viewpoints and drastic external environment changes. Utilizing multiscale features improves the robustness of image descriptors; however, existing methods neither exploit the multiscale features generated during feature extraction nor consider the feature redundancy problem when fusing multiscale information when image descriptors are enhanced. We propose a novel encoding strategy—convolutional multilayer perceptron orthogonal fusion of multiscale features (ConvMLP-OFMS)—for VPR. A ConvMLP is used to obtain robust and generalized global image descriptors and the multiscale features generated during feature extraction are used to enhance the global descriptors to cope with changes in the environment and viewpoints. Additionally, an attention mechanism is used to eliminate noise and redundant information. Compared to traditional methods that use tensor splicing for feature fusion, we introduced matrix orthogonal decomposition to eliminate redundant information. Experiments demonstrated that the proposed architecture outperformed NetVLAD, CosPlace, ConvAP, and other methods. On the Pittsburgh and MSLS datasets, which contained significant viewpoint and illumination variations, our method achieved 92.5% and 86.5% Recall@1, respectively. We also achieved good performances—80.6% and 43.2%—on the SPED and NordLand datasets, respectively, which have more extreme illumination and appearance variations.
Utilizing machine learning to predict post-treatment outcomes in chronic non-specific neck pain patients undergoing cervical extension traction
Authors: Moustafa Ibrahim M. , Ozsahin Dilber Uzun , Mustapha Mubarak Taiwo , Ahbouch Amal , Oakley Paul A. , Harrison Deed E.
Published: May 2024

This study explored the application of machine learning in predicting post-treatment outcomes for chronic neck pain patients undergoing a multimodal program featuring cervical extension traction (CET). Pre-treatment demographic and clinical variables were used to develop predictive models capable of anticipating modifications in cervical lordotic angle (CLA), pain and disability of 570 patients treated between 2014 and 2020. Linear regression models used pre-treatment variables of age, body mass index, CLA, anterior head translation, disability index, pain score, treatment frequency, duration and compliance. These models used the sci-kit-learn machine learning library within Python for implementing linear regression algorithms. The linear regression models demonstrated high precision and accuracy, and effectively explained 30–55% of the variability in post-treatment outcomes, the highest for the CLA. This pioneering study integrates machine learning into spinal rehabilitation. The developed models offer valuable information to customize interventions, set realistic expectations, and optimize treatment strategies based on individual patient characteristics as treated conservatively with rehabilitation programs using CET as part of multimodal care.
Balanced opioid-free anesthesia with lidocaine and esketamine versus balanced anesthesia with sufentanil for gynecological endoscopic surgery: a randomized controlled trial
Authors: Hu Yang , Zhang Qing-yun , Qin Guan-chao , Zhu Guo-hong , Long Xiang , Xu Jin-fei , Gong Yuan
Published: May 2024

In this randomized controlled trial, 74 patients scheduled for gynecological laparoscopic surgery (American Society of Anesthesiologists grade I/II) were enrolled and randomly divided into two study groups: (i) Group C (control), received sufentanil (0.3 μg/kg) and saline, followed by sufentanil (0.1 μg/kg∙h) and saline; and (ii) Group F (OFA), received esketamine (0.15 mg/kg) and lidocaine (2 mg/kg), followed by esketamine (0.1 mg/kg∙h) and lidocaine (1.5 mg/kg∙h). The primary outcome was the 48-h time-weighted average (TWA) of postoperative pain scores. Secondary outcomes included time to extubation, adverse effects, and postoperative sedation score, pain scores at different time points, analgesic consumption at 48 h, and gastrointestinal functional recovery. The 48-h TWAs of pain scores were 1.32 (0.78) (95% CI 1.06–1.58) and 1.09 (0.70) (95% CI 0.87–1.33) for Groups F and C, respectively. The estimated difference between Groups F and C was − 0.23 (95% CI − 0.58 − 0.12; P = 0.195). No differences were found in any of the secondary outcomes and no severe adverse effects were observed in either group. Balanced OFA with lidocaine and esketamine achieved similar effects to balanced anesthesia with sufentanil in patients undergoing elective gynecological laparoscopic surgery, without severe adverse effects.

Clinical Trial Registration: ChiCTR2300067951, www.chictr.org.cn 01 February, 2023.
Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer
Authors: Dankó Benedek , Hess Julia , Unger Kristian , Samaga Daniel , Walz Christoph , Walch Axel , Sun Na , Baumeister Philipp , Zeng Peter Y. F. , Walter Franziska , Marschner Sebastian , Späth Richard , Gires Olivier , Herkommer Timm , Dazeh Ramin , Matos Thaina , Kreutzer Lisa , Matschke Johann , Eul Katharina , Klauschen Frederick , Pflugradt Ulrike , Canis Martin , Ganswindt Ute , Mymryk Joe S. , Wollenberg Barbara , Nichols Anthony C. , Belka Claus , Zitzelsberger Horst , Lauber Kirsten , Selmansberger Martin
Published: May 2024

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.
Acquired resistance to immunotherapy and chemoradiation in MYC amplified head and neck cancer
Authors: Cyberski Thomas F. , Singh Alka , Korzinkin Michael , Mishra Vasudha , Pun Frank , Shen Le , Wing Claudia , Cheng Xiangying , Baird Brandon , Miao Yuxuan , Elkabets Moshe , Kochanny Sara , Guo Wenji , Dyer Emma , Pearson Alexander T. , Juloori Aditya , Lingen Mark , Cole Grayson , Zhavoronkov Alex , Agrawal Nishant , Izumchenko Evgeny , Rosenberg Ari J.
Published: May 2024

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient’s tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.
Evaluation of stenoses using AI video models applied to coronary angiography
Authors: Labrecque Langlais Élodie , Corbin Denis , Tastet Olivier , Hayek Ahmad , Doolub Gemina , Mrad Sebastián , Tardif Jean-Claude , Tanguay Jean-François , Marquis-Gravel Guillaume , Tison Geoffrey H. , Kadoury Samuel , Le William , Gallo Richard , Lesage Frederic , Avram Robert
Published: May 2024

The coronary angiogram is the gold standard for evaluating the severity of coronary artery disease stenoses. Presently, the assessment is conducted visually by cardiologists, a method that lacks standardization. This study introduces DeepCoro, a ground-breaking AI-driven pipeline that integrates advanced vessel tracking and a video-based Swin3D model that was trained and validated on a dataset comprised of 182,418 coronary angiography videos spanning 5 years. DeepCoro achieved a notable precision of 71.89% in identifying coronary artery segments and demonstrated a mean absolute error of 20.15% (95% CI: 19.88–20.40) and a classification AUROC of 0.8294 (95% CI: 0.8215–0.8373) in stenosis percentage prediction compared to traditional cardiologist assessments. When compared to two expert interventional cardiologists, DeepCoro achieved lower variability than the clinical reports (19.09%; 95% CI: 18.55–19.58 vs 21.00%; 95% CI: 20.20–21.76, respectively). In addition, DeepCoro can be fine-tuned to a different modality type. When fine-tuned on quantitative coronary angiography assessments, DeepCoro attained an even lower mean absolute error of 7.75% (95% CI: 7.37–8.07), underscoring the reduced variability inherent to this method. This study establishes DeepCoro as an innovative video-based, adaptable tool in coronary artery disease analysis, significantly enhancing the precision and reliability of stenosis assessment.
Association of physical activity pattern and risk of Parkinson’s disease
Authors: Lin Fabin , Lin Yixiang , Chen Lina , Huang Tingting , Lin Tianxin , He Jiarui , Lu Xiaoyang , Chen Xiaochun , Wang Yingqing , Ye Qinyong , Cai Guoen
Published: May 2024

Increasing evidence suggests an association between exercise duration and Parkinson’s disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson’s risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson’s risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson’s disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson’s risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson’s disease. In a multifactorial Cox model, using the World Health Organization–recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43–0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34–0.57; P < 0.001) exhibited a lower risk of developing Parkinson’s disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56–1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson’s risk.
The gluconeogenesis enzyme PCK2 has a non-enzymatic role in proteostasis in endothelial cells
Authors: de Zeeuw Pauline , Treps Lucas , García-Caballero Melissa , Harjes Ulrike , Kalucka Joanna , De Legher Carla , Brepoels Katleen , Peeters Kristel , Vinckier Stefan , Souffreau Joris , Bouché Ann , Taverna Federico , Dehairs Jonas , Talebi Ali , Ghesquière Bart , Swinnen Johan , Schoonjans Luc , Eelen Guy , Dewerchin Mieke , Carmeliet Peter
Published: May 2024

Endothelial cells (ECs) are highly glycolytic, but whether they generate glycolytic intermediates via gluconeogenesis (GNG) in glucose-deprived conditions remains unknown. Here, we report that glucose-deprived ECs upregulate the GNG enzyme PCK2 and rely on a PCK2-dependent truncated GNG, whereby lactate and glutamine are used for the synthesis of lower glycolytic intermediates that enter the serine and glycerophospholipid biosynthesis pathways, which can play key roles in redox homeostasis and phospholipid synthesis, respectively. Unexpectedly, however, even in normal glucose conditions, and independent of its enzymatic activity, PCK2 silencing perturbs proteostasis, beyond its traditional GNG role. Indeed, PCK2-silenced ECs have an impaired unfolded protein response, leading to accumulation of misfolded proteins, which due to defective proteasomes and impaired autophagy, results in the accumulation of protein aggregates in lysosomes and EC demise. Ultimately, loss of PCK2 in ECs impaired vessel sprouting. This study identifies a role for PCK2 in proteostasis beyond GNG.
Activation of Nrf2/HO-1 signaling pathway exacerbates cholestatic liver injury
Authors: Wang Yi , Fu Xiaolong , Zeng Li , Hu Yan , Gao Rongyang , Xian Siting , Liao Songjie , Huang Jianxiang , Yang Yonggang , Liu Jilong , Jin Hai , Klaunig James , Lu Yuanfu , Zhou Shaoyu
Published: May 2024

Nuclear factor erythroid 2-related factor-2 (Nrf2) antioxidant signaling is involved in liver protection, but this generalization overlooks conflicting studies indicating that Nrf2 effects are not necessarily hepatoprotective. The role of Nrf2/heme oxygenase-1 (HO-1) in cholestatic liver injury (CLI) remains poorly defined. Here, we report that Nrf2/HO-1 activation exacerbates liver injury rather than exerting a protective effect in CLI. Inhibiting HO-1 or ameliorating bilirubin transport alleviates liver injury in CLI models. Nrf2 knockout confers hepatoprotection in CLI mice, whereas in non-CLI mice, Nrf2 knockout aggravates liver damage. In the CLI setting, oxidative stress activates Nrf2/HO-1, leads to bilirubin accumulation, and impairs mitochondrial function. High levels of bilirubin reciprocally upregulate the activation of Nrf2 and HO-1, while antioxidant and mitochondrial-targeted SOD2 overexpression attenuate bilirubin toxicity. The expression of Nrf2 and HO-1 is elevated in serum of patients with CLI. These results reveal an unrecognized function of Nrf2 signaling in exacerbating liver injury in cholestatic disease.
CaV1.3 channel clusters characterized by live-cell and isolated plasma membrane nanoscopy
Authors: Schwenzer Niko , Teiwes Nikolas K. , Kohl Tobias , Pohl Celine , Giller Michelle J. , Lehnart Stephan E. , Steinem Claudia
Published: May 2024

A key player of excitable cells in the heart and brain is the L-type calcium channel CaV1.3. In the heart, it is required for voltage-dependent Ca2+-signaling, i.e., for controlling and modulating atrial cardiomyocyte excitation-contraction coupling. The clustering of CaV1.3 in functionally relevant channel multimers has not been addressed due to a lack of stoichiometric labeling combined with high-resolution imaging. Here, we developed a HaloTag-labeling strategy to visualize and quantify CaV1.3 clusters using STED nanoscopy to address the questions of cluster size and intra-cluster channel density. Channel clusters were identified in the plasma membrane of transfected live HEK293 cells as well as in giant plasma membrane vesicles derived from these cells that were spread on modified glass support to obtain supported plasma membrane bilayers (SPMBs). A small fraction of the channel clusters was colocalized with early and recycling endosomes at the membranes. STED nanoscopy in conjunction with live-cell and SPMB imaging enabled us to quantify CaV1.3 cluster sizes and their molecular density revealing significantly lower channel densities than expected for dense channel packing. CaV1.3 channel cluster size and molecular density were increased in SPMBs after treatment of the cells with the sympathomimetic compound isoprenaline, suggesting a regulated channel cluster condensation mechanism.
Pan-cancer discovery of somatic mutations from RNA sequencing data
Authors: Tang Gongyu , Liu Xinyi , Cho Minsu , Li Yuanxiang , Tran Dan-Ho , Wang Xiaowei
Published: May 2024

Identification of somatic mutations (SMs) is essential for characterizing cancer genomes. While DNA-seq is the prevalent method for identifying SMs, RNA-seq provides an alternative strategy to discover tumor mutations in the transcribed genome. Here, we have developed a machine learning based pipeline to discover SMs based on RNA-seq data (designated as RNA-SMs). Subsequently, we have conducted a pan-cancer analysis to systematically identify RNA-SMs from over 8,000 tumors in The Cancer Genome Atlas (TCGA). In this way, we have identified over 105,000 novel SMs that had not been reported in previous TCGA studies. These novel SMs have significant clinical implications in designing targeted therapy for improved patient outcomes. Further, we have combined the SMs identified by both RNA-seq and DNA-seq analyses to depict an updated mutational landscape across 32 cancer types. This new online SM atlas, OncoDB (https://oncodb.org), offers a more complete view of gene mutations that underline the development and progression of various cancers.
The role of elasticity on adhesion and clustering of neurons on soft surfaces
Authors: Marinaro Giovanni , Bruno Luigi , Pirillo Noemi , Coluccio Maria Laura , Nanni Marina , Malara Natalia , Battista Edmondo , Bruno Giulia , De Angelis Francesco , Cancedda Laura , Di Mascolo Daniele , Gentile Francesco
Published: May 2024

The question of whether material stiffness enhances cell adhesion and clustering is still open to debate. Results from the literature are seemingly contradictory, with some reports illustrating that adhesion increases with surface stiffness and others suggesting that the performance of a system of cells is curbed by high values of elasticity. To address the role of elasticity as a regulator in neuronal cell adhesion and clustering, we investigated the topological characteristics of networks of neurons on polydimethylsiloxane (PDMS) surfaces - with values of elasticity (E) varying in the 0.55–2.65 MPa range. Results illustrate that, as elasticity increases, the number of neurons adhering on the surface decreases. Notably, the small-world coefficient – a topological measure of networks – also decreases. Numerical simulations and functional multi-calcium imaging experiments further indicated that the activity of neuronal cells on soft surfaces improves for decreasing E. Experimental findings are supported by a mathematical model, that explains adhesion and clustering of cells on soft materials as a function of few parameters - including the Young’s modulus and roughness of the material. Overall, results indicate that – in the considered elasticity interval – increasing the compliance of a material improves adhesion, improves clustering, and enhances communication of neurons.
Anxiety, depression and distress outcomes from the Health4Life intervention for adolescent mental health: a cluster-randomized controlled trial
Authors: Smout S. , Champion K. E. , O’Dean S. , Teesson M. , Gardner L. A. , Newton N. C.
Published: May 2024

Mental disorders are a leading cause of disease burden worldwide. As onset typically occurs in adolescence, prevention during this period is critical. The Health4Life-school-based multiple health behavior change (MHBC) intervention targets six lifestyle risk factors: diet, sleep, physical activity, screentime, alcohol use and smoking. Health4Life has been evaluated in a cluster-randomized controlled trial in 71 Australian schools (6,639 grade seven students). This study presents intervention effects on secondary outcomes of depressive, anxiety and psychological distress symptoms. Generalized linear mixed-effect analyses of data from baseline, post-intervention (7 weeks), 12 months and 24 months showed that the Health4Life intervention was no more effective than an active control in reducing depressive, anxiety or psychological distress symptoms at a 24 or 12 month follow-up; however, there were short-term benefits for psychological distress and depressive symptoms immediately post-intervention. This study offers new evidence that multiple health behavior change interventions may improve adolescent mental health, but future research should explore methods to address anxiety and sustain effects over the longer term. A priori ANZCTR trial registration: ACTRN12619000431123.
Application of nanopore sequencing for accurate identification of bioaerosol-derived bacterial colonies
Authors: Marshall Austin , Fuller Daniel T. , Dougall Paul , Kumaragama Kavindra , Dhaniyala Suresh , Sur Shantanu
Published: May 2024

Nanopore sequencing can be advantageous over Sanger method for the identification of bioaerosol-derived bacterial colonies using 16S reads, enabling accurate detection of individual bacterial components with higher taxonomic resolution.
π–π stacking small molecules enable high performance perovskite solar cells
Authors: He Aoxi , Wang Meng , Gong Xiaoli , Tang Peng , Wu Lili , Hao Xia , Wang Wenwu , Xia Gengpei , Jiang Yu , Zhang Jingquan
Published: May 2024

By introducing bromobenzoic acid (BAC) into the perovskite precursor solution, the micro-strain in the perovskite film was effectively relieved. This additive improved the PCE to 24.02% ultimately.