bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analysis of WDR12 as a potential prognostic and immunological biomarker in multiple human tumors
Authors: Eid Refaat A. , Eldeen Muhammad Alaa , Soltan Mohamed A. , Al-Shraim Mubarak , Aldehri Majed , Alqahtani Leena S. , Alsharif Ghadi , Albogami Sarah , Jafri Ibrahim , Fayad Eman , Park Moon Nyeo , Bibi Shabana , Behairy Mohammed Y. , Kim Bonglee , Zaki Mohamed Samir A. 
Published: January 2023

Background: Mammalian WD-repeat protein 12 (WDR12), a family member of proteins containing repeats of tryptophan-aspartic acid (WD), is a potential homolog of yeast Ytm1p and consists of seven repeats of WD.Aim of the study: This study aims to investigate the potential oncogenic effects of WDR12 in various human malignancies throughout a pan-cancer analysis that has been carried out to examine the various patterns in which this gene is expressed and behaves in tumor tissues.Methods: Herein, we used The Cancer Genome Atlas (TCGA) and various computational tools to explore expression profiles, prognostic relevance, genetic mutations, immune cell infiltration, as well as the functional characteristics of WDR12 in multiple human cancers.Results: We found that WDR12 was inconsistently expressed in various cancers and that variations in WDR12 expression predicted survival consequences for cancer patients. Furthermore, we observed a significant correlation between WDR12 gene mutation levels and the prognosis of some tumors. Furthermore, significant correlations were found between WDR12 expression patterns and cancer-associated fibroblast (CAF) infiltration, myeloid-derived suppressor cells (MDSCs), tumor mutation burden, microsatellite instability and immunoregulators. Ultimately, pathway enrichment analysis revealed that WDR12-related pathways are involved in carcinogenesis.Conclusions: The findings of our study are stisfactory, demonstrating that WDR12 could serve as a promising reliable prognostic biomarker, as well as a therapeutic target for novel cancer therapeutic approaches.
Addressing disparities in pharmacogenomics through rural and underserved workforce education
Authors: Brown Jacob T. , McGonagle Erin , Seifert Randall , Speedie Marilyn , Jacobson Pamala A. 
Published: January 2023

Introduction: While pharmacogenomic (PGx) testing is routine in urban healthcare institutions or academic health centers with access to existing expertise, uptake in medically-underserved areas is lagging. The primary objective of this workforce education program is to extend access to didactic, case-based and clinical PGx training for pharmacists serving rural Minnesota and populations experiencing health disparities in Minnesota.Methods: A PGx workforce training program funded through the Minnesota Department of Health was offered through the University of Minnesota College of Pharmacy (COP) to pharmacists working in rural and/or underserved areas in the state of Minnesota. Learning activities included a 16-week, asynchronous PGx didactic course covering PGx topics, a 15-min recorded presentation, an in-person PGx case-based workshop, and a live international PGx Conference hosted by the University of Minnesota COP and attendance at our PGx Extension of Community Health Outcomes (ECHO).Results: Twenty-nine pharmacists applied for the initial year of the program, with 12 (41%) being accepted. Four (33%) practiced in a hospital setting, four (33%) in retail pharmacy, two (17%) in managed care, and two (17%) in other areas. The majority had not implemented a PGx program as part of their practice, although nearly all responded definitely or probably yes when asked if they expected their organization to increase its use of PGx testing services over the next three years. All participants either strongly or somewhat agreed that this program helped them identify how and where to access clinical PGx guidelines and literature and improved their ability to read and interpret PGx test results. Eight participants (67%) strongly or somewhat agreed that they expected to increase the number of PGx consultations in their practice, while ten (83%) strongly or somewhat agreed they would be able to apply what they learned in this program to their practice in the next six months to a year.Discussion: This novel PGx training program focused exclusively on pharmacists in rural and/or underserved areas with a delivery method that could be accomplished conveniently and remotely. Although most participants’ organizations had yet to implement PGx testing routinely, most anticipated this to change in the next few years.
Mas-related G protein-coupled receptor MRGPRX2 in human basophils: Expression and functional studies
Authors: Toscano Alessandro , Elst Jessy , Van Gasse Athina L. , Beyens Michiel , van der Poorten Marie-Line , Bridts Chris H. , Mertens Christel , Van Houdt Michel , Hagendorens Margo M. , Van Remoortel Samuel , Timmermans Jean-Pierre , Ebo Didier G. , Sabato Vito 
Published: January 2023

BackgroundOccupancy of MRGPRX2 heralds a new era in our understandings of immediate drug hypersensitivity reactions (IDHRs), but a constitutive expression of this receptor by basophils is debated.ObjectiveTo explore the expression and functionality of MRGPRX2 in and on basophils.MethodsBasophils from patients with birch pollen allergy, IDHRs to moxifloxacin, and healthy controls were studied in different conditions, that is, in rest, after stimulation with anti-IgE, recombinant major birch pollen allergen (rBet v 1), moxifloxacin, fMLP, substance P (SP), or other potential basophil secretagogues. In a separate set of experiments, basophils were studied after purification and resuspension in different media.ResultsResting whole blood basophils barely express MRGPRX2 on their surface and are unresponsive to SP or moxifloxacin. However, surface MRGPRX2 is quickly upregulated upon incubation with anti-IgE or fMLP. Pre-stimulation with anti-IgE can induce a synergic effect on basophil degranulation in IgE-responsive subjects after incubation with SP or moxifloxacin, provided that basophils have been obtained from patients who experienced an IDHR to moxifloxacin. Cell purification can trigger a “spontaneous” and functional upregulation of MRGPRX2 on basophils, not seen in whole blood cells, and its surface density can be influenced by distinct culture media.ConclusionBasophils barely express MRGPRX2 in resting conditions. However, the receptor can be quickly upregulated after stimulation with anti-IgE, fMLP, or after purification, making cells responsive to MRGPRX2 occupation. We anticipate that such “conditioned” basophils constitute a model to explore MRGPRX2 agonism or antagonism, including IDHRs originating from the occupation of this receptor.
Diagnosis and segmentation effect of the ME-NBI-based deep learning model on gastric neoplasms in patients with suspected superficial lesions - a multicenter study
Authors: Liu Leheng , Dong Zhixia , Cheng Jinnian , Bu Xiongzhu , Qiu Kaili , Yang Chuan , Wang Jing , Niu Wenlu , Wu Xiaowan , Xu Jingxian , Mao Tiancheng , Lu Lungen , Wan Xinjian , Zhou Hui 
Published: January 2023

BackgroundEndoscopically visible gastric neoplastic lesions (GNLs), including early gastric cancer and intraepithelial neoplasia, should be accurately diagnosed and promptly treated. However, a high rate of missed diagnosis of GNLs contributes to the potential risk of the progression of gastric cancer. The aim of this study was to develop a deep learning-based computer-aided diagnosis (CAD) system for the diagnosis and segmentation of GNLs under magnifying endoscopy with narrow-band imaging (ME-NBI) in patients with suspected superficial lesions.MethodsME-NBI images of patients with GNLs in two centers were retrospectively analysed. Two convolutional neural network (CNN) modules were developed and trained on these images. CNN1 was trained to diagnose GNLs, and CNN2 was trained for segmentation. An additional internal test set and an external test set from another center were used to evaluate the diagnosis and segmentation performance.ResultsCNN1 showed a diagnostic performance with an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 90.8%, 92.5%, 89.0%, 89.4% and 92.2%, respectively, and an area under the curve (AUC) of 0.928 in the internal test set. With CNN1 assistance, all endoscopists had a higher accuracy than for an independent diagnosis. The average intersection over union (IOU) between CNN2 and the ground truth was 0.5837, with a precision, recall and the Dice coefficient of 0.776, 0.983 and 0.867, respectively.ConclusionsThis CAD system can be used as an auxiliary tool to diagnose and segment GNLs, assisting endoscopists in more accurately diagnosing GNLs and delineating their extent to improve the positive rate of lesion biopsy and ensure the integrity of endoscopic resection.
Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas
Authors: Dong Jiawei , Wang Fang , Gao Xin , Zhao Hongtao , Zhang Jiheng , Wang Nan , Liu Zhihui , Yan Xiuwei , Jin Jiaqi , Ba Yixu , Ma Shuai , Du Jianyang , Ji Hang , Hu Shaoshan 
Published: January 2023

BackgroundCancer-associated fibroblasts (CAFs) are vital components of prominent cellular components in lower-grade gliomas (LGGs) that contribute to LGGs’ progression, treatment resistance, and immunosuppression. Epigenetic modification and immunity have significant implications for tumorigenesis and development.MethodsWe combined aberrant methylation and CAFs abundances to build a prognostic model and the impact on the biological properties of LGGs. Grouping based on the median CAFs abundances score of samples in the TCGA-LGGs dataset, differentially expressed genes and aberrantly methylated genes were combined for subsequent analysis.ResultsWe identified five differentially methylated and expressed genes (LAT32, SWAP70, GSAP, EMP3, and SLC2A10) and established a prognostic gene signature validated in the CGGA-LGGs dataset. Immunohistochemistry (IHC) and in vitro tests were performed to verify these expressions. The high-risk group increased in tumor-promoting immune cells and tumor mutational burden. Notably, risk stratification had different ICB sensitivities in LGGs, and there were also significant sensitivity differences for temozolomide and the other three novel chemotherapeutic agents.ConclusionOur study reveals characteristics of CAFs in LGGs, refines the direct link between epigenetics and tumor stroma, and might provide clinical implications for guiding tailored anti-CAFs therapy in combination with immunotherapy for LGGs patients.
Evaluating the effects of two different kinesiology taping techniques on shoulder pain and function in patients with hypermobile Ehlers-Danlos syndrome
Authors: Tudini Frank , Levine David , Healy Michael , Jordon Max , Chui Kevin 
Published: January 2023

BackgroundEhlers-Danlos Syndrome (EDS) is a group of inherited connective tissue disorders which predominantly affects women and has a prevalence as high as 1 in 5,000 individuals. Hypermobile EDS (hEDS) is the most common subtype of EDS and is characterized by multi-joint pain, particularly in large joints such as the shoulder. Physical therapy is often utilized to address the pain, physical impairments, and functional loss in patients with EDS. Kinesiology Tape (KT) is an intervention commonly used by physical therapists for treating shoulder pain and dysfunction. Studies related to the effectiveness of KT in patients with shoulder pain is equivocal and there are a lack of studies specifically studying the effects of KT in an EDS population.PurposeThe purpose of this study was to assess the efficacy and short-term effects of two different KT techniques on shoulder pain and function in individuals with hEDS and shoulder pain.MethodsParticipants were recruited from EDS support groups in the New England area of the United States; were diagnosed with hEDS by their physician; and had shoulder pain. Baseline demographic information was obtained for each participant followed by completion of 4 patient reported outcome (PRO) measures: the Upper Extremity Functional Index, QuickDASH (Disabilities of the Arm, Shoulder, &amp; Hand), Shoulder Pain and Disability Index, and the Western Ontario Shoulder Instability Index. Current pain level, average pain over the past 24 h, and worst pain over the past 24 h were recorded using the numeric pain rating scale (NPRS). Subjects were randomly assigned to receive either an experimental shoulder KT procedure or a control shoulder taping. Immediately after taping, the NPRS was reassessed. Subjects then returned 48 h later to repeat the NPRS and PRO measures.ResultsThere was no significant difference between the experimental and control tape groups for any outcome measure. There was a significant improvement from pre-taping to 48-hours post taping for each of the 4 PRO measures with large effect sizes (p &lt; 0.001; ƞp2 = .517–.719). Likewise, average, and worst pain over the last 24 h significantly improved with large effect sizes over the same period (p = 0.005; ƞp2 = .225 and p &lt; 0.001; ƞp2 = .382, respectively). Current NPRS levels significantly improved from pre-tape to immediately post-tape (p = .023, ƞp2 = .131) and was maintained through the 48-hour follow up, although no further improvement was seen.ConclusionKT is an inexpensive and relatively safe intervention that is easy to apply and can offer temporary improvements in pain and function for patients with EDS and shoulder pain.
Safety and efficacy of minimally invasive percutaneous nephrolithotomy for infantile nephrolithiasis. Single centre experience from Pakistan
Authors: Ahmad Tariq , Minallah Nasrum , Khaliq Nida , Rashid Hania , Syed Misbah , Almuradi Moath Ahmad Abdullah 
Published: January 2023

ObjectiveTo assess the efficacy and safety of mini-percutaneous nephrolithotomy (PCNL) for small renal stones 1–2 cm in size in infants less than one year.Material and MethodsThis descriptive case series was conducted in the department of pediatric urology Institute of Kidney Diseases Peshawar, Pakistan, from March 2019 to March 2022. All the patients underwent mini-PCNL in prone position under GA with 14 Fr access sheath and 10 Fr nephroscope. Stone clearance was assessed by non-contrast CT KUB at 30th postoperative day. Patients with no residual fragments on the non-contrast CT KUB were defined as stone-free. Patients with residual fragments of any size were defined as procedure failure. Safety was determined in terms of intra and postoperative complications.ResultsA total of 51 infants were included in the study. The mean age of patients was 9.6 + 1.8 (5–12 month). The mean stone size was 15.8 + 2.7 (10–21) mm in length and 12.3 + 2.2 (8–17) mm in width. PCNL mean operative time was 51.6 ± 7.1 (40–70) minutes. Complete stone clearance at one month was observed in 46 (90.2%) patients. Residual fragments were seen in 5(9.8%) patients with a mean size of 1.6 + 0.4 (0.9–2.0) mm. None of the patients required any additional procedure for clearance of stones. In 7 (13.7%) patients, some post-operative complications were observe, all were grade I complications, including fever in 5(9.8%) and transient hematuria in 2(3.9%) patients.ConclusionMini-PCNL is a safe and effective treatment for renal stones in infants measuring 1–2 cm with high SFR and an acceptable complication rate.
Population pharmacokinetic analysis of TQ-B3203 following intravenous administration of TQ-B3203 liposome injection in Chinese patients with advanced solid tumors
Authors: Li Xiaoqing , Bo Yunhai , Yin Han , Liu Xiaohong , Li Xu , Yang Fen 
Published: January 2023

Background: TQ-B3203 is a novel topoisomerase I inhibitor currently in development for the treatment of advanced solid tumors. Great differences in pharmacokinetic characteristics were found among individuals according to the phase I clinical trial following intravenous administration of TQ-B3203 liposome injection (TLI) in Chinese patients with advanced solid tumors. Thus, it is significant to establish a population pharmacokinetic model to find the key factors and recognize their effect on pharmacokinetic parameters in order to guide individualized administration.Methods: Non-linear mixed effect models were developed using the plasma concentrations obtained from the phase I clinical trial by implementing the Phoenix NLME program. Covariates that may be related to pharmacokinetics were screened using stepwise methods. The final model was validated by goodness-of-fit plots, visual predictive check, non-parametric bootstrap and a test of normalized prediction distribution errors.Results: A three-compartment model with first-order elimination was selected as the best structural model to describe TQ-B3203 disposition adequately. Direct bilirubin (DBIL) and body mass index (BMI) were the two most influential factors on clearance, while lean body weight (LBW) was considered to affect the apparent distribution volume of the central compartment. The population estimations of clearance and central volume were typical at 3.97 L/h and 4.81 L, respectively. Model-based simulations indicated that LBW had a great impact on Cmax, BMI exerted a considerable influence on AUC0-t, and the significance of DBIL on both AUC0-t and Cmax was similarly excellent.Conclusion: The first robust population pharmacokinetic model of TQ-B3203 was successfully generated following intravenous administration of TLI in Chinese patients with advanced solid tumors. BMI, LBW and DBIL were significant covariates that affected the pharmacokinetics of TQ-B3203. This model could provide references for the dose regimen in the future study of TLI.
Contribution of muscle stiffness of the triceps surae to passive ankle joint stiffness in young and older adults
Authors: Hirata Kosuke , Akagi Ryota 
Published: January 2023

This study aimed to investigate whether triceps surae muscle stiffness is associated with passive ankle joint stiffness in 40 young (21–24 years) and older (62–83 years) males. Using ultrasound shear wave elastography, the shear modulus of each muscle of the triceps surae (the medial [MG], lateral gastrocnemius [LG], and soleus [Sol]) was assessed as muscle stiffness at the ankle neutral position (NP) and 15-degree dorsiflexed position (DF15) with the knee fully extended. Passive ankle joint stiffness at the NP and DF15 was calculated as the gradient of the angle–torque relationship at each joint angle during passive ankle dorsiflexion at 1°∙s−1 controlled by using an isokinetic dynamometer. Passive ankle joint stiffness was normalized by the body mass. There was no correlation between the absolute ankle joint stiffness and muscle shear modulus of triceps surae in the young and older groups at the NP (r ≤ 0.349, p ≥ 0.138). Significant positive correlations between absolute ankle joint stiffness and muscle shear modulus at DF15 were observed for MG and Sol in the young group (r ≥ 0.451, p ≤ 0.044) but not in the older group. The normalized ankle joint stiffness at the NP was significantly positively correlated with the LG shear modulus in young participants and with the MG and LG shear modulus in older participants (r ≥ 0.466 and p ≤ 0.039). There were significant positive correlations between the normalized ankle joint stiffness and the muscle shear modulus of the triceps surae at DF15 in young and older participants (r ≥ 0.464 and p ≤ 0.040), except for the MG shear modulus in older participants (r = 0.419 and p = 0.066). These results suggest that the material properties of the entire triceps surae, even Sol, which is the most compliant muscle among the triceps surae, affect passive ankle joint stiffness, especially when the triceps surae is lengthened and body size is considered.
Aortic systolic and pulse pressure invasively and non-invasively obtained: Comparative analysis of recording techniques, arterial sites of measurement, waveform analysis algorithms and calibration methods
Authors: Bia Daniel , Zócalo Yanina , Sánchez Ramiro , Lev Gustavo , Mendiz Oscar , Pessana Franco , Ramirez Agustín , Cabrera-Fischer Edmundo I. 
Published: January 2023

Background: The non-invasive estimation of aortic systolic (aoSBP) and pulse pressure (aoPP) is achieved by a great variety of devices, which differ markedly in the: 1) principles of recording (applied technology), 2) arterial recording site, 3) model and mathematical analysis applied to signals, and/or 4) calibration scheme. The most reliable non-invasive procedure to obtain aoSBP and aoPP is not well established.Aim: To evaluate the agreement between aoSBP and aoPP values invasively and non-invasively obtained using different: 1) recording techniques (tonometry, oscilometry/plethysmography, ultrasound), 2) recording sites [radial, brachial (BA) and carotid artery (CCA)], 3) waveform analysis algorithms (e.g., direct analysis of the CCA pulse waveform vs. peripheral waveform analysis using general transfer functions, N-point moving average filters, etc.), 4) calibration schemes (systolic-diastolic calibration vs. methods using BA diastolic and mean blood pressure (bMBP); the latter calculated using different equations vs. measured directly by oscillometry, and 5) different equations to estimate bMBP (i.e., using a form factor of 33% (“033”), 41.2% (“0412”) or 33% corrected for heart rate (“033HR”).Methods: The invasive aortic (aoBP) and brachial pressure (bBP) (catheterization), and the non-invasive aoBP and bBP were simultaneously obtained in 34 subjects. Non-invasive aoBP levels were obtained using different techniques, analysis methods, recording sites, and calibration schemes.Results: 1) Overall, non-invasive approaches yielded lower aoSBP and aoPP levels than those recorded invasively. 2) aoSBP and aoPP determinations based on CCA recordings, followed by BA recordings, were those that yielded values closest to those recorded invasively. 3) The “033HR” and “0412” calibration schemes ensured the lowest mean error, and the “033” method determined aoBP levels furthest from those recorded invasively. 4) Most of the non-invasive approaches considered overestimated and underestimated aoSBP at low (i.e., 80 mmHg) and high (i.e., 180 mmHg) invasive aoSBP values, respectively. 5) The higher the invasively measured aoPP, the higher the level of underestimation provided by the non-invasive methods.Conclusion: The recording method and site, the mathematical method/model used to quantify aoSBP and aoPP, and to calibrate waveforms, are essential when estimating aoBP. Our study strongly emphasizes the need for methodological transparency and consensus for the non-invasive aoBP assessment.