bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous and Oral Whole Body Ketone Dosimetry, Biodistribution, Metabolite Correction and Kinetics Studied by (R)-[1-11C]ß-Hydroxybutyrate ([11C]OHB) PET in Healthy Humans
Authors: Luong Thien Vinh , Nielsen Erik Nguyen , Falborg Lise , Kjærulff Mette Louise Gram , Tolbod Lars Poulsen , Søndergaard Esben , Møller Niels , Munk Ole Lajord , Gormsen Lars Christian 
Published: April 2023

Abstract
Background: Ketones are increasingly recognized as an important and possibly oxygen sparing source of energy in vital organs such as the heart, the brain and the kidneys. Drug treatments, dietary regimens and oral ketone drinks designed to deliver ketones for organ and tissue energy production have therefore gained popularity. However, whether ingested ketones are taken up by various extra-cerebral tissues and to what extent is still largely unexplored. It was therefore the aim of this study to use positron emission tomography (PET) to explore the whole body dosimetry, biodistribution and kinetics of the ketone tracer (R)-[1-11C]b-hydroxybutyrate ([11C]OHB).
Six healthy subjects (3 women and 3 men) underwent dynamic PET studies after both intravenous (90 minutes) and oral (120 minutes) administration of [11C]OHB. Dosimetry estimates of [11C]OHB was calculated using OLINDA/EXM software, biodistribution was assessed visually and [11C]OHB tissue kinetics were obtained using an arterial input function and tissue time-activity curves.
Results: Radiation dosimetry yielded effective doses of 3.28 Sv/MBq (intravenous administration) and 12.51 Sv/MBq (oral administration). Intravenous administration of [11C]OHB resulted in avid radiotracer uptake in the heart, liver, and kidneys, whereas lesser uptake was observed in the salivary glands, pancreas, skeletal muscle and red marrow. Only minimal uptake was noted in the brain. Oral ingestion of the tracer resulted in rapid radiotracer appearance in the blood and radiotracer uptake in the heart, liver and kidneys. In general, [11C]OHB tissue kinetics after intravenous administration were best described by a reversible 2-tissue compartmental model.
Conclusion: The PET radiotracer [11C]OHB is highly suitable for imaging ketone uptake in all physiologically relevant tissues. It is therefore a safe and non-invasive imaging tool to investigate organ and tissue ketone metabolism in both patients and healthy subjects.
Trial registration: Clinical trials, NCT0523812, Registered February 10th 2022, https://clinicaltrials.gov/ct2/show/NCT05232812?cond=NCT05232812&draw=2&rank=1.
Comparison of the safety and efficiency of flexible ureteroscopy with the different hanged water heights in a kidney model
Authors: Jiang Shuangjian , Bai Baohua , Zhang Junlong , Zeng Qinsong , Mo Chengqiang , Wu Rongpei 
Published: April 2023

Abstract
Objective To develop an in vitro model of the renal pelvis to compare intrarenal pressure(IRP) and irrigation flow at various suspended water heights during flexible ureteroscopy (fURS).Methods A 100 mL saline bag was used to simulate the renal pelvis. The fURS sheath was connected to the bag and the ureteric access sheath (UAS) was positioned at the junction of the ureteropelvic region. Central venous pressure tubing was connected to monitor the pressure in the renal pelvis under different conditions. Two different sheath sizes (12Fr and 14Fr) were tested with fURS sizes of 7.5, 8.5, and 9.5Fr, respectively. The perfusion method was gravity based, and the hanging water heights were set at 60, 90, 120, 150, and 180 cm. A separate manual pumping group was also measured.Results In the group using a 12Fr sheath, the use of a 9.5Fr flexible ureteroscope without accessories resulted in a minimum gravity perfusion pressure of 8.4 cmH2O and a maximum pressure of 17.5cmH2O. However, manually administering perfusion in the pelvis produced pressures exceeding 60cmH2O. When the fURS was employed with a 200um laser fiber within the same sheath size, the minimum pressure of gravity perfusion decreased to 6.4cmH2O, and the maximum pressure was 10.5cmH2O. The IRP reached 48cmH2O while hand pumping. In the 14Fr sheath group, while using a 9.5Fr fURS, minimum and maximum gravity perfusion pressures were 2.5cmH2O and 6.0cmH2O, respectively. In contrast, manual perfusion resulted in a pressure of 17cmH2O. For the 12Fr sheath group using a 7.5Fr fURS, the minimum pressure of gravity perfusion was 5.4cmH2O, the maximum was 8.2H2O, and renal pelvic pressure during manual perfusion was 25.5cmH2O.Conclusion It is safe and efficient to hang the water at different heights during the operation of the disposable ureteroscopy to maintain low and safe IRP when using a UAS.
Biocoordination reactions in copper(II) ions and phosphocholine systems including pyrimidine nucleosides and nucleotides
Authors: Gabryel-Skrodzka Malwina , Nowak Martyna , Grajewski Jakub , Jastrząb Renata 
Published: April 2023

Abstract
The complexation reactions of phosphocholine and pyrimidine nucleosides as well as nucleotides with copper(II) ions were studied in the water system. Using potentiometric methods and computer calculations, the stability constants of the species were determined. Using spectroscopic methods such as UV-vis, EPR, 13C NMR, 31P NMR, FT-IR and CD, the coordination mode was established for complexes created in pH range 2.5 - 11.0. These studies will lead to a better understanding the role of copper(II) ions in living organisms and explain the interactions between them and the studied bioligands. The differences and similarities between nucleosides and nucleotides in the studied systems were also described, which testify to the significant influence of phosphate groups on the processes of metal ion complexation and interactions between ligands.
Identification of novel phytochemicals from Hibiscus rosa sinensis flower as a prospective inhibitor targeting the 3CLpro enzyme of SARS-CoV-2 using computational approaches.
Authors: Das Subhadeep , Satapathy Sagarika , Acharya Diptikanta , Sahu Sushil Kumar 
Published: April 2023

Abstract
Hibiscus rosa sinensis has an infinite resource of phytochemicals and has emerged as a solution for different health-related issues such as anti-diabetic, anti-microbial and wound healing activity as proved in past clinical studies. Focusing on the current situation, an incessant increase in daily COVID-19 cases and the struggle to discover effective treatment measures for SARS-CoV-2 had led to a global health catastrophe. Upsurge in COVID-19 cases had revealed a pattern characterised as a first, second, third wave and beyond. This cycle of new SARS-CoV-2 variant transmission needed to be terminated by selecting a favourable effective target, and the 3CL protease enzyme (3CLpro or Mpro) of SARS-CoV-2 acts as a possible target. The objective of this study is to investigate the phytochemicals identified in Hibiscus rosa sinensis flowers for their potential anti-SARS-CoV-2 properties virtually, targeting the 3CLpro or Mpro, which regulates viral pathogenesis. The present research protocol includes molecular docking of 34 phytochemicals identified from the Hibiscus rosa sinensis flower and targeted against the active site of the 3CLpro enzyme. Computational analysis revealed that the top 3 ligands: cyanidin-3-sophoroside-5-glucoside (-10.9 kcal/mol), 1,2-benzenedicarboxylic acid isodecyl octyl ester (-10.1 kcal/mol) and rutin (-9.3 kcal/mol) had better binding affinity as compared to the control inhibitor remdesivir (-8 kcal/mol). Further investigation in terms of ligand-protein interaction, physiochemical, ADMET and drug-likeness parameters showed that cyanidin-3-sophoroside-5-glucoside possessed promising properties and could act as a potentially effective drug candidate. However, our study needs to be supported by in vitro and in vivo evaluations to determine the precise mechanism of inhibitory action.
“It’s important to foster open discussion about the topic”: Development, Implementation, and Evaluation of an Ethics of Abortion Independent Learning Module for Second Year Medical Students
Authors: McCarty Catherine A , Hutto Sarah L , Shaw Aubie K 
Published: April 2023

Abstract
Purpose
Despite the frequency of abortions, one-third of medical schools in the US and Canada did not include coverage of that topic, according to a survey conducted in 2002–2005. The purpose of this project was to develop, implement, and evaluate a module for second year medical students related to the ethics of abortion.
Methods
The module was designed as Independent Learning Time (ILT). The stated purpose was for students to consider some of the recent debate in the ethics literature related to conscientious objection and abortion and how personal views may influence future practice. The ILT included readings and Power Points to view. Students were asked to write a one-page refection on one of three writing prompts.
Results
The most commonly selected writing prompt was on personal values in relation to abortion (56.5%), followed by information about nearest provider of reproductive services to their rural preceptor site (34.7%), followed by conscientious objection (23.3%). We received many positive comments about the ILT, such as: “First, I would like to acknowledge my gratitude for this assignment and its subject. I believe it is very important that future physicians learn the entirety of women’s reproductive health care, including abortion and contraception, but unfortunately this is not always the case in medical training”.
Conclusions
There has been an extremely positive response to the ILT. With the exception of the prompt specific to our regional campus mission that includes rural preceptorships during the preclinical years, this module could be implementable at other medical schools.
Treatment of tuberculosis-associated vertebral compression with percutaneous vertebroplasty (PVP) relieves pain and prevents kyphosis
Authors: Fan Yu , Zhou Xi , Li Wing Fai , Yue Zeyang , Liu Shuzhong , Liu Yong 
Published: April 2023

Abstract
Background Patients with suspected tuberculosis of the spine often present with back pain and/or neurological symptoms due to underlying compression fractures. Needle biopsy is frequently needed for confirmatory diagnosis. An additional surgical procedure may be required to stabilize the spine and prevent complications.Methods T0 retrospectively reviewed medical records of 44 patients with suspected spinal tuberculosis from 2013–2017 who underwent bone biopsy for diagnosis and simultaneous PVP for stabilization of the spine. A follow-up telephone interview was conducted to evaluate the effect of treatment including the degree of post-surgical pain, presence of neurological symptoms, and kyphosis.Results At the time of follow-up, 18 patients achieved complete remission, 6 patients underwent a second surgery and 1 patient had no change in the clinical course. Secondary systemic infection after PVP is not reported and the results suggest PVP is not an absolute contraindication in the patients with suspected spinal tuberculosis. PVP has demonstrated a significant improvement in pain one-day post-op and at the time of follow-up (from NRS 6.64 to NRS 1.33 and 0.64, respectively). Neurological symptoms (from 16–4%) and kyphosis (from 32–8%) also improved with PVP treatment.Conclusion PVP is a feasible and effective technique for treating compression fractures due to spinal tuberculosis. It augments the fractured vertebrae, improves pain relief and prevents kyphosis. It does not help spread the infection and should not be regarded as a contraindication for infectious disease, particularly in the context of tuberculosis.
HIF-1α promotes osteogenic regeneration of titanium implants by coupling angiogenesis and osteogenesis via HIF-1α/VEGF/AKT/mTOR signaling pathway
Authors: Song Shuang , Zhang Guanhua , Chen Xutao , Zheng Jian , Liu Xiangdong , Wang Yiqing , Chen Zijun , Wang Yuxi , Song Yingliang , Zhou Qin 
Published: April 2023

Abstract
Background: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) could directly increase cancellous bone formation and was playing an essential role in bone modeling and remodeling. However, whether an increase of HIF-1α in ADSCs promoted osteogenic differentiation and bone formation was not known.
Results: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression cDNA were established to investigate the proliferation, migration, adhesion, and osteogenic capacity in ADSCs, and angiogenic ability in HUVEC. Overexpression of HIF-1α could promote cell proliferation, migration, adhesive and osteogenic capacity of ADSCs and angiogenic ability of HUVEC. Western blotting showed that the protein levels of osteogenesis-related factors were upregulated when overexpression of HIF-1α. Furthermore, the influence of up-regulating HIF-1α in ADSCs sheets on osseointegration had evaluated using the SD rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The over-expression of HIF-1α in ADSCs enhanced osteogenic differentiation and osseointegration around implants. Whereas transfecting HIF-1α-silenced ADSCs attenuated the osteogenic and angiogenic capacity. Finally, to explore the mechanism underlying HIF-1α promoted osteogenesis and angiogenesis, Western blotting was measured to analyze the VEGF/AKT/mTOR signaling pathway.
Conclusions: These data first demonstrated that up-regulation of HIF-1α in ADSCs significantly improved the osteogenic capacity and peri-implant bone formation via VEGF/AKT/mTOR signaling pathway. Our findings revealed that HIF-1α exerts a critical effect on promoting osseointegration by improving osteogenesis and angiogenesis via VEGF/AKT/mTOR signaling pathway, and hence offered the considerable therapeutic potential for modifying stem cells to enhance osseointegration.
Sparse Dropout: a dropout layer specialized for attention mechanism
Authors: Liu Peng , Deng Guowei , Zhao Shuai , Shi Yanli , Liu Xiaoli 
Published: April 2023

Abstract
Recently, the Transformer-architecture-based model takes an absolute predominance in natural language processing. Attention is a critical component of the Transformer. Attention allows the model to focus on different parts of the input sequence selectively. Dropout regularization is widely adopted and plays an active role by decoupling the hidden units in the model, preventing dependency on only several hidden units and finally making the model over-fitting. Though powerful and effective, the randomness introduced in attention may cause substantial information loss because of its completely random nature. In this paper, we present a simple but effective method named Sparse Dropout dedicated, which no longer randomly sets some values of attention scores to 0. A manually designated threshold super-parameter called $\alpha$ was introduced in Sparse Dropout. All scores lower than this threshold will be set to 0 to suppress unwanted randomness and help the model to pay more attention to high attention scores parts of sequences. We verify our method on three mainstream tasks, including Chinese Named Entity Recognition, Text Summarization, and Text Classification. We achieve apparent improvements on the condition that we only substitute the Dropout layer during attention scores calculation with our Sparse Dropout. It demonstrates that our Sparse Dropout is effective and universal for all attention mechanisms entailed deep learning models with an elegant form.
Exploring the key genes associated with breast cancer radiotherapy sensitivity based on the stromal-immune score and analysis of the WGCNA and ceRNA network
Authors: Sun Xiaoyue , Wu Chihua , Zhang Shengwei , Zhao Xinchen , Wang Xiaoshan 
Published: April 2023

Abstract

Background: Breast cancer is a highly malignant disease worldwide. Among the numerous treatment options for breast cancer, radiotherapy is one of the commonly used treatments, while there is currently no sufficient molecular biomarkers to predict prognosis and guide its application. The tumor microenvironment (TME) is an important factor affecting tumor biological function, and changes in its composition are equally relevant to tumor progression and prognosis during radiotherapy.
Methods: Here, we performed bioinformatic analyses using data obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to screen for molecular biomarkers related to TME that may influence radiotherapy sensitivity. By combining immune scores and stromal scores calculated as well as performing weighted co-expression network analysis (WGCNA), we identified key modules and hub genes to construct competing endogenous RNA (ceRNA) networks. Then, key pathways and genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
Results: Genes of the PI3K-AKT pathway in the blue module were significantly enriched. Among hub genes in the blue module, we further found that the expression levels of COL1A1, COL1A2, COL6A3, THBS2 and PDGFRB were negatively associated with radiotherapy sensitivity.
Conclusion: These findings may provide new insights into the mechanisms of radiotherapy sensitivity in breast cancer patients, offering hope for the discovery of new therapeutic targets.
A Consensus-based ADMM Approach to Parallelize Large-Scale Minimum-Lap-Time Problems
Authors: Bartali Lorenzo , Grabovic Eugeniu , Gabiccini Marco 
Published: April 2023

Abstract
Minimum-Lap-Time Planning (MLTP) problems, which entail finding optimal trajectories for race cars on racetracks, have received significant attention in the recent literature. They are commonly addressed as optimal control problems (OCP) and are numerically discretized using direct collocation methods. Subsequently, they are solved as nonlinear programs (NLP). The conventional approach to solving MLTP problems is serial, whereby the resulting NLP is solved all at once. However, for problems characterized by a large number of variables, distributed optimization algorithms, such as the Alternating Direction Method of Multipliers (ADMM), may represent a viable option, especially when multi-core CPU architectures are available. This study presents a consensus-based ADMM approach tailored to solving MLTP problems through a distributed optimization algorithm. The algorithm partitions the problem into smaller sub-problems based on different sectors of a track, distributing them among multiple processors. ADMM is then used to ensure consensus among the distributed computational processes. The paper also outlines specific strategies leveraging domain knowledge to improve the convergence of the distributed algorithm.The ADMM approach is validated against the serial approach, and numerical results are presented for both single-lap and multi-lap scenarios. In both cases, the ADMM approach proves superior for problem dimensions of 70k+ variables compared to serial methods. In planning scenarios with complex vehicle models on long track horizons, i.e., for problems with 1M+ variables, the efficiency gain of the ADMM approach is substantial, and it becomes the only viable option to maintain computational times within acceptable limits.
Clonidine stimulates force of contraction via histamine H2 receptors in the human atrium
Authors: Neumann Joachim , Pockes Steffen , Humphrys Laura J. , Mönnich Denise , Forster Lisa , Kirchhefer Uwe , Hofmann Britt , Gergs Ulrich 
Published: April 2023

Abstract
Introduction: Clonidine has various clinical effects mediated by agonism of α1- or α2-adrenoceptors and the blocking of HCN-channels. It is unknown whether clonidine can also stimulate human cardiac histamine H2 receptors (hH2R).
Methods: We used isolated electrically stimulated left and spontaneously beating right atrial preparations from mice overexpressing the h H2R specifically in the heart (H2-TG), and spontaneously beating right atrial preparations of guinea pigs for comparison. Moreover, we studied isolated electrically stimulated muscle strips from the human right atrium.
Results: Clonidine (1, 3, 10 µM) increased force of contraction in isolated left atrial preparations from H2-TG mice. In contrast, clonidine reduced the spontaneous beating rate in right atrial preparations from H2-TG. Clonidine raised the beating rate in guinea pig right atrial preparations. Clonidine failed to increase the force of contraction but reduced beating rate in wild type litter mate mice (WT). In WT, histamine failed to increase the force of contraction in left atrial preparations and beating rate in right atrial preparations. Clonidine (10 µM) increased the force of contraction in isolated human right atrial preparations. These effects in the human atrium were attenuated by cimetidine (10 µM). Clonidine increased the beating rate of the isolated spontaneously beating guinea pig right atrium and acted as a H2R partial agonist. Furthermore, clonidine showed binding to the guinea pig H2R (100 µM) using HEK cells in a recombinant expression system (pKi < 4.5) but not to the human H2R.
Conclusions: These data suggest that clonidine can activate cardiac human histamine H2 receptors.
Eribulin represses effector T cell differentiation and enhances T cell-mediated anti-tumor activity to triple negative breast cancer cells through the facilitation of CD8+ T cell proliferation
Authors: Shimizu Tadafumi , Oba Takaaki , Oshi Masanori , Ito Ken-ichi 
Published: April 2023

Abstract
Purpose Chemotherapeutic agents exert immunomodulatory effects on triple-negative breast cancer (TNBC) cells and immune cells. Eribulin favorably affects the immunological status of patients with breast cancer. However, the effects of eribulin on the immune cells remain unexplored. The aim of this study was to investigate the effects of eribulin on immune cells.Methods Peripheral blood mononuclear cells (PBMCs) from healthy donors and mouse splenocytes were stimulated with anti-CD3 and anti-CD28 antibodies. The effects of eribulin and paclitaxel on cell proliferation and differentiation status were analyzed using flow cytometry. RNA sequencing was performed to assess alterations in gene expression in CD8+ T cells following eribulin and paclitaxel treatment. Using TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157), the anti-tumor activity of CD3/CD28-stimulated T cells combined with eribulin or paclitaxel was evaluated.Results Eribulin did not affect CD3/CD28-stimulated PBMCs proliferation. However, eribulin significantly decreased the CD4/CD8 ratio in T cells, indicating that eribulin facilitates CD8+ T cell proliferation. Furthermore, eribulin significantly increased the frequency of less differentiated CD45RA+, CCR7+, and TCF1+ subsets of CD8+ T cells. RNA sequencing revealed that eribulin enhanced the expression of gene sets related to cell proliferation and immune responses. Moreover, eribulin augmented the antitumor effects of CD3/CD28-stimulated T cells against TNBC cells. These results were not observed in experiments using paclitaxel.Conclusions Eribulin promoted CD8+ T cell proliferation, repressed effector T cell differentiation, and harnessed T cell-mediated antitumor effects. These mechanisms may be one of the cues that eribulin can improve the immunological status of tumor-bearing hosts.