bluuebunny/crossref_metadata_2025 huggingface dataset:
Release kinetics of growth factors loaded into β-TCP ceramics in an in vitro model
Authors: Waldmann Marco , Bohner Marc , Baghnavi Anna , Riedel Bianca , Seidenstuecker Michael
Published: September 2024

Introduction

β-TCP ceramics are bone replacement materials that have recently been tested as a drug delivery system that can potentially be applied to endogenous substances like growth factors found in blood platelets to facilitate positive attributes.

Methods

In this work, we used flow chamber loading to load β-TCP dowels with blood suspensions of platelet-rich plasma (PRP), platelet-poor plasma (PPP), or buffy coat (BC) character. PRP and BC platelet counts were adjusted to the same level by dilution. Concentrations of TGF-β1, PDGF-AB, and IGF-1 from dowel-surrounding culture medium were subsequently determined using ELISA over 5 days. The influence of alginate was additionally tested to modify the release.

Results

Concentrations of TGF-β1 and PDGF-AB increased and conclusively showed a release from platelets in PRP and BC compared to PPP. The alginate coating reduced the PDGF-AB release but did not reduce TGF-β1 and instead even increased TGF-β1 in the BC samples. IGF-1 concentrations were highest in PPP, suggesting circulating levels rather than platelet release as the driving factor. Alginate samples tended to have lower IGF-1 concentrations, but the difference was not shown to be significant.

Discussion

The release of growth factors from different blood suspensions was successfully demonstrated for β-TCP as a drug delivery system with release patterns that correspond to PRP activation after Ca2+-triggered activation. The release pattern was partially modified by alginate coating.
Regulation of p53 by the mitotic surveillance/stopwatch pathway: implications in neurodevelopment and cancer
Authors: Stracker Travis H.
Published: September 2024

The transcription factor p53 (encoded by TP53) plays diverse roles in human development and disease. While best known for its role in tumor suppression, p53 signaling also influences mammalian development by triggering cell fate decisions in response to a wide variety of stresses. After over 4 decades of study, a new pathway that triggers p53 activation in response to mitotic delays was recently identified. Termed the mitotic surveillance or mitotic stopwatch pathway, the USP28 and 53BP1 proteins activate p53 in response to delayed mitotic progression to control cell fate and promote genomic stability. In this Minireview, I discuss its identification, potential roles in neurodevelopmental disorders and cancer, as well as explore outstanding questions about its function, regulation and potential use as a biomarker for anti-mitotic therapies.
Association of monocyte-lymphocyte ratio and myocardial infarction in the U.S. population with diabetes
Authors: Wu Yue , Xiang Hong-Ju , Yuan Min
Published: September 2024

Background and objective

The monocyte-to-lymphocyte ratio (MLR) has emerged as a novel inflammatory biomarker; however, its relationship with myocardial infarction (MI) in diabetic populations remains unclear. This study aimed to elucidate the association between MLR and MI prevalence in this unique population.

Methods

This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES), 2015-2018. MLR was utilized as both a continuous and categorical factor to examine its correlation with MI in individuals diagnosed with DM. Subgroup and sensitivity analyses were also performed.

Results

In this study, 1,295 individuals with DM were enrolled, among whom 148 (11.4%) were diagnosed with MI. Patients with MI showed a greater MLR. Using a smoothed curve-fitting analysis, a linear relationship was observed between MLR and MI (pfor non−linearity = 0.27). Multivariate logistic regression analysis showed that MLR * 10 was positively correlated with the risk of MI (OR = 1.14, 95% CI 1.01∼1.29, p = 0.041). Compared with the lowest quartile, the OR for Q2, Q3, and Q4 were 2.13 (95% CI: 1.01∼4.47), 2.95 (95% CI: 1.45∼6.00), and 2.74 (95% CI: 1.32∼5.69), respectively. Subgroup analyses showed no significant interaction for MLR in any subgroup (all P > 0.05). The receiver operating characteristic (ROC) curve indicated that the area under the curve (AUCs) of MLR for predicting MI was 0.661 (95% CI: 0.617–0.706; P < 0.05).

Conclusions

Our study demonstrated that MLR is significantly correlated with MI in patients with DM.
Stereotactic arrhythmia radioablation (STAR) opens a new era in the treatment of arrhythmias?
Authors: Zhang Shuang , Hu Lin , Tang Hanze , Liao Liyi , Li Xuping
Published: September 2024

Tachyarrhythmias are common cardiovascular emergencies encountered in clinical practice. Among these, atrial fibrillation (AF) and ventricular tachycardia (VT) pose significant hazards due to their prevalence and severity. Initially, non-invasive pharmacological antiarrhythmic interventions were the primary treatment modality; however, due to their limited control rates and side effects, invasive therapies have been introduced in recent years. These include catheter ablation, alcohol ablation, cardiac implantable electronic devices, and heart transplantation. Nonetheless, for some patients, invasive treatments do not offer a definitive cure for arrhythmias and carry the risk of recurrence, especially with AF and VT, where the relapse rates are high and the treatment for VT is correlated with the type of tachycardia present. Currently, novel non-invasive treatment methods are emerging, with stereotactic radioablation therapy becoming an effective alternative for the management of refractory tachyarrhythmias. This review provides an overview of the application background of Stereotactic Arrhythmia Radioablation (STAR) therapy and promising results from its use in animal models and clinical applications.
Clinical outcomes of three follitropin alfa preparations for ovarian stimulation using an oral micronized progesterone-primed protocol in an oocyte donation program
Authors: Cruz María , Howles Colin M.
Published: September 2024

Introduction

This large multicenter study aimed to evaluate clinical outcomes using three follitropin alfa preparations within a progestin-primed ovarian stimulation (PPOS) protocol, while identifying contributing factors to cycle success.

Methods

A retrospective, anonymized cohort analysis was conducted on donor-recipient cycles from 12 clinics during 2019 to 2021. 7389 oocyte donors underwent ovarian stimulation (OS) with three follitropin alfa preparations (Ovaleap® [n=3231], Bemfola® [n=3542], Gonal-F® [n=616]) were included. Stimulation began on cycle days 2 or 3 with daily administration of 150-225 IU follitropin alfa. 10 mg medroxyprogesterone acetate (MPA) was administered daily until GnRH agonist trigger using a single dose of 0.2mg GnRH agonist for final follicular maturation. Statistical analysis included ANOVA, Chi-squared, and logistic regression.

Results

Whilst there were some differences in patient and stimulation characteristics, including donor age and number of retrieved oocytes, clinical variables did not significantly differ among the three study groups. Linear regression revealed donor age [0.986 (0.974-0.999)] and number of mature oocytes [1.027 (1.007-1.047)] significantly impacted ongoing pregnancy rates, while the type of follitropin alfa [1.048 (0.956-1.149)] used did not. No significant differences were observed in the cumulative live birth rate (CLBR) among oocytes obtained from stimulation with Bemfola (64.9%), Gonal-F (64.1%) and Ovaleap (66.1%), p= 0.385.

Discussion

This study demonstrated comparable clinical outcomes and CLBR between biosimilars and the reference product of follitropin alfa within PPOS protocols, hence they are interchangeable in a real-world patient setting.
Allogeneic mesenchymal stromal cell therapy in kidney transplantation: should repeated human leukocyte antigen mismatches be avoided?
Authors: Bezstarosti Suzanne , Erpicum Pauline , Maggipinto Gianni , Dreyer Geertje J. , Reinders Marlies E. J. , Meziyerh Soufian , Roelen Dave L. , De Fijter Johan W. , Kers Jesper , Weekers Laurent , Beguin Yves , Jouret François , Heidt Sebastiaan
Published: September 2024

Mesenchymal stromal cells (MSCs) have immunomodulatory properties and are therefore considered promising tools in kidney transplantation. Although most studies have been conducted with autologous MSCs, using allogeneic MSCs as an off-the-shelf product is more feasible in clinical settings. However, allogeneic MSCs could potentially induce an immune response, which might eventually be directed towards the kidney allograft because of shared human leukocyte antigen (HLA) epitope mismatches between the kidney and MSC donor. In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation. While the Neptune Study from Leiden University Medical Center specifically selected MSC to avoid repeated HLA antigen mismatches between kidney and MSC donors, the study from the University of Liège did not perform specific MSC selection. The comparative analyses of amino acid mismatches between these cohorts showed that MSC selection to avoid repeated HLA mismatches at the split antigen level was not sufficient to prevent repeated mismatches at the amino acid level. However, repeated amino acid mismatches were not associated with the occurrence of donor-specific antibodies (DSAs). Thus, the clinical relevance of repeated amino acid mismatches seems to be limited with regard to the risk of DSA formation. Since DSA formation was limited (3 of 20 patients) in this study, larger studies are required to investigate the relevance of preventing repeated HLA mismatches in allogeneic MSC therapy in kidney transplantation.
Accelerated calciprotein crystallization time (T50) is correlated with impaired lung diffusion capacity in systemic sclerosis
Authors: Geroldinger-Simic Marija , Sohail Azmat , Razazian Mehdi , Krennmayr Beatrice , Pernsteiner Victoria , Putz Thomas , Lackner Helmut K. , Pasch Andreas , Sepp Norbert , Alesutan Ioana , Voelkl Jakob
Published: September 2024

Background

Systemic sclerosis (SSc) is a complex auto-immune disease characterized by vascular damage, inflammation, fibrosis and calcinosis, where pulmonary involvement is the leading cause of mortality. Calciprotein particles (CPPs) are increasingly formed upon disbalance of the physiological mineral buffering system and induce pro-inflammatory effects. This exploratory study investigated whether functional indicators of the endogenous mineral buffering system are dysregulated in SSc and linked to disease activity.

Methods

T50 (calciprotein crystallization test or serum calcification propensity) and hydrodynamic radius of secondary CPPs (CPP2) were determined in serum samples from 78 SSc patients and 44 controls without SSc, and were associated with disease activity markers of SSc.

Results

T50 was reduced and CPP2 radius was increased in SSc patients as compared to controls, indicating a deranged mineral buffering system. This was accompanied by slightly higher serum phosphate and PTH levels in SSc patients, while iFGF23 was not significantly modified. Longitudinally, all parameters remained unchanged over time in SSc patients, only iFGF23 increased. While the modified Rodnan skin score showed some inconsistent correlations with mineral buffering indicators, their association was not independent of other factors. However, lower T50 was significantly correlated to reduced lung diffusion capacity and this association remained significant in a multivariate linear regression model.

Conclusion

This study provides indications for a disturbed mineral buffering system in SSc. Increased serum calcification propensity (lower T50) is correlated with impaired lung diffusion capacity, suggesting a possible role of deranged mineral buffering in disease progression. Further studies are required to confirm these observations in larger cohorts and to investigate a putative functional relevance.
Multiscale micromechanics modeling of viscoelastic natural plant fibers
Authors: Li Jie , Wang Jian , Wang Miao , Tie Jinxin , Gao Xuefeng , Wu Yujie , Song Jinhua , Xia Chen
Published: September 2024

Natural plant fibers are hierarchical structures with multi-level microstructures. With advances in composite material science, these fibers have been widely used in various polymer products. Therefore, it is crucial to quantitatively understand the relationship between their microstructures and mechanical behavior. This paper utilizes the Mori-Tanaka micromechanics model, viscoelasticity theory, and Zakian’s inversion method to study the impact of plant fiber microstructure on the viscoelastic behavior of multiscale structures. At the microscopic scale, the macromolecular polymer (matrix) and cellulose (fiber) are first homogenized. The second homogenization involves the cell wall microstructure, and the third homogenization considers the porosity of the cell wall and lumen to predict the effective modulus of fiber bundles. By applying the principle of elastic-viscoelastic correspondence, the viscoelastic mechanical parameters of plant fibers are calculated. The study examines the effects of cellulose crystallinity and lumen porosity on the structural stiffness and viscoelastic properties of fibers, identifying these factors as key influences on the mechanical behavior of plant fibers. Given their significant economic potential, the feasibility of using tobacco plant fibers as bio-based materials is also explored.
Association of outdoor artificial light at night with myopia among Chinese adolescents: a representative cross-sectional study
Authors: Liu Ting , Tan Weixing , Fu Youjuan , Cheng Beijing , Tian Hua , Liu Can , Wang Zhixiang , Zhang Yanting , Guan Suzhen , Liu Zhihong
Published: September 2024

Background

The association between the rapid increase in myopia among adolescents and the amount of outdoor artificial light at night (ALAN) remains unclear. The aim of this study was to investigate the association between outdoor ALAN and myopia in adolescents.

Methods

Stratified cluster random sampling was used to obtain a sample of 33,160 students (age range: 9–18 years; mean: 13.51 years) with complete data from 120 primary and secondary schools across the Ningxia region in China in 2021. Myopia was defined as a spherical equivalent (SE) ≤−0.5 diopters (D) in at least one eye, determined by automated refractometers without cycloplegia. Outdoor ALAN data were obtained from satellite data and the two-year average outdoor ALAN exposure for each participant was determined by matching it to their school address (home addresses were not available). The association between ALAN and myopia was assessed using multiple logistic regression models and restricted cubic spline (RCS) regression. Stratified analyses were performed by age, sex, residence, school level, and outdoor exercise time.

Results

The myopia group had higher outdoor ALAN levels than the non-myopia group [median (interquartile spacing): 14.44 (3.88–26.56) vs. 6.95 (1.21–21.74) nanoWatts/cm2/sr]. After adjusting for covariates identified through stepwise regression, it was observed that the prevalence of myopia increased by 4% for every 10-unit change [95% confidence interval (CI): 1.02–1.07]. Compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratio (OR) of myopia was 1.20 (95% CI: 1.08–1.34) in the fourth quantile. RCS further showed a positive nonlinear relationship between outdoor ALAN exposure and myopia (p for nonlinear <0.001). Stronger effects were not found in subgroup analyses.

Conclusion

Outdoor ALAN exposure is positively and nonlinearly associated with the prevalence of myopia in adolescents. Controlling outdoor light pollution may constitute a potential strategy to reduce the incidence of myopia in adolescents.
Fast reconstruction of milling temperature field based on CNN-GRU machine learning models
Authors: Ma Fengyuan , Wang Haoyu , E Mingfeng , Sha Zhongjin , Wang Xingshu , Cui Yunxian , Yin Junwei
Published: September 2024

With the development of intelligent manufacturing technology, robots have become more widespread in the field of milling processing. When milling difficult-to-machine alloy materials, the localized high temperature and large temperature gradient at the front face of the tool lead to shortened tool life and poor machining quality. The existing temperature field reconstruction methods have many assumptions, large arithmetic volume and long solution time. In this paper, an inverse heat conduction problem solution model based on Gated Convolutional Recurrent Neural Network (CNN-GRU) is proposed for reconstructing the temperature field of the tool during milling. In order to ensure the speed and accuracy of the reconstruction, we propose to utilize the inverse heat conduction problem solution model constructed by knowledge distillation (KD) and compression acceleration, which achieves a significant reduction of the training time with a small loss of optimality and ensures the accuracy and efficiency of the prediction model. With different levels of random noise added to the model input data, CNN-GRU + KD is noise-resistant and still shows good robustness and stability under noisy data. The temperature field reconstruction of the milling tool is carried out for three different working conditions, and the curve fitting excellence under the three conditions is 0.97 at the highest, and the root mean square error is 1.43°C at the minimum, respectively, and the experimental results show that the model is feasible and effective in carrying out the temperature field reconstruction of the milling tool and is of great significance in improving the accuracy of the milling machining robot.
Multi-task learning for predicting quality-of-life and independence in activities of daily living after stroke: a proof-of-concept study
Authors: Nguyen Thi Nguyet Que , García-Rudolph Alejandro , Saurí Joan , Kelleher John D.
Published: September 2024

A health-related (HR) profile is a set of multiple health-related items recording the status of the patient at different follow-up times post-stroke. In order to support clinicians in designing rehabilitation treatment programs, we propose a novel multi-task learning (MTL) strategy for predicting post-stroke patient HR profiles. The HR profile in this study is measured by the Barthel index (BI) assessment or by the EQ-5D-3L questionnaire. Three datasets are used in this work and for each dataset six neural network architectures are developed and tested. Results indicate that an MTL architecture combining a pre-trained network for all tasks with a concatenation strategy conditioned by a task grouping method is a promising approach for predicting the HR profile of a patient with stroke at different phases of the patient journey. These models obtained a mean F1-score of 0.434 (standard deviation 0.022, confidence interval at 95% [0.428, 0.44]) calculated across all the items when predicting BI at 3 months after stroke (MaS), 0.388 (standard deviation 0.029, confidence interval at 95% [0.38, 0.397]) when predicting EQ-5D-3L at 6MaS, and 0.462 (standard deviation 0.029, confidence interval at 95% [0.454, 0.47]) when predicting the EQ-5D-3L at 18MaS. Furthermore, our MTL architecture outperforms the reference single-task learning models and the classic MTL of all tasks in 8 out of 10 tasks when predicting BI at 3MaS and has better prediction performance than the reference models on all tasks when predicting EQ-5D-3L at 6 and 18MaS. The models we present in this paper are the first models to predict the components of the BI or the EQ-5D-3L, and our results demonstrate the potential benefits of using MTL in a health context to predict patient profiles.
Multimodal functional imaging and clinical correlates of pain regions in chronic low-back pain patients treated with spinal cord stimulation: a pilot study
Authors: Shamli Oghli Yazan , Ashok Arjun , Glener Steven , Ailes Isaiah , Syed Mashaal , Kang Ki Chang , Naghizadehkashani Sara , Fayed Islam , Mohamed Feroze B. , Talekar Kiran , Krisa Laura , Wu Chengyuan , Matias Caio , Alizadeh Mahdi
Published: September 2024

Objective

Spinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions.

Methods

Multi-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis.

Results

Arterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients.

Conclusion

The present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools.
BRAF/MEK inhibitors use for pediatric gliomas; real world experience from a resource-limited country
Authors: Abu Laban Dima , Alsharif Abeer , Al-Hussaini Maysa , Obeidat Mouness , Maraqa Bayan , Alzoubi Qasem , Musharbash Awni , Jaddoua Saad , Ramlawi Raed , Khaleifeh Kawther , Ibrahimi Ahmad Kh. , Sarhan Nasim , Bouffet Eric , Amayiri Nisreen
Published: September 2024

Introduction

Most pediatric low-grade-gliomas (LGG) and some high-grade-gliomas (HGG) have alterations in the RAS/MAPK pathway. Promising high tumor response rates were achieved using BRAF/MEK inhibitors, however data on their use in low-middle-income-countries (LMICs) are limited.

Methods

We retrospectively reviewed our Jordanian experience of using compassionate BRAF/MEK inhibitors in treating children with gliomas. We reviewed patients’ clinical characteristics, tumor response, and side effects.

Results

Twenty patients (13 males, 7 females) were identified. Median age at diagnosis was 8.3 years (0.3-18.9years). There were fifteen LGGs, three HGGs and two grade-2 pleomorphic xanthoastrocytoma (PXA-2). Fifteen tumors were supratentorial, three posterior fossa/brainstem, one diffuse-glioneuronal tumor (DLGNT) and one spinal. Five tumors were metastatic. Except for one patient with neurofibromatosis, ten patients underwent partial resection and nine had biopsy. All patients, except three, received BRAF/MEK inhibitors after initial standard chemo/radiotherapy. Seven LGGs had BRAF-mutation, six had BRAF-fusion, and two were empirically treated (one neurofibromatosis and one DLGNT). Fourteen LGGs were treated with 1-4 chemotherapy regimens before BRAF/MEK inhibitors’ use; all had partial/stable response on targeted therapy at a median of 1.9 years (0.5-5.4years). Two patients with BRAFv600E-mutated/CDKN2A deleted PXA-2, had progression following resection, and experienced stable/partial response at 9 months of dabrafenib use. Two patients with HGGs had BRAFv600E-mutation, and one had an FGFR-mutation. All three patients with HGG had temporary stable/partial response, two with significant clinical improvement. At a median of 2.7 years (1.3-3.2years), all patients experienced tumor progression, and two died. Eight patients (40%) developed acneiform rash, three (15%) paronychia, and one had significant panniculitis and fatigue. Six patients (30%) needed dose-reduction. Nine patients had temporary drug interruptions [due to side effects (5) and drug shortage (4)]. Two patients who stopped trametinib due to side effects (significant acneiform rash/paronychia and intracranial bleeding) did not experience progression.

Conclusions

Our experience with BRAF/MEK inhibitors’ use was positive achieving response in all LGGs and provided sustained response with good quality of life for patients with HGG. Cost effectiveness analyses and patients’ satisfaction comparisons with chemotherapy are needed to evaluate the routine use of these drugs in LMICs.
Preoperative predictive model for the probability of lymph node metastasis in gastric cancer: a retrospective study
Authors: Teng Fei , Zhu Qian , Zhou Xi-Lang , Shi Yi-Bing , Sun Han
Published: September 2024

Background

Effectively diagnosing lymph node (LN) metastasis (LNM) is crucial in determining the condition of patients with gastric cancer (GC). The present study was devised to develop and validate a preoperative predictive model (PPM) capable of assessing the LNM status of individuals with GC.

Methods

A retrospective analysis of consecutive GC patients from two centers was conducted over the period from January 2021 to December 2023. These patients were utilized to construct a 289-patient training cohort for identifying LNM-related risk factors and developing a PPM, as well as a 90-patient testing cohort used for PPM validation.

Results

Of the GC patients included in the training cohort, 67 (23.2%) and 222 (76.8%) were respectively LNM negative and positive. Risk factors independently related to LNM status included cT3 invasion (P = 0.001), CT-reported LN (+) (P = 0.044), and CA199 value (P = 0.030). LNM risk scores were established with the following formula: score = -2.382 + 0.694×CT-reported LN status (+: 1; -: 0)+2.497×invasion depth (cT1: 0; cT2: 1; cT3: 2)+0.032×CA199 value. The area under the curve (AUC) values for PPM and CT-reported LN status were 0.753 and 0.609, respectively, with a significant difference between them (P < 0.001). When clinical data from the testing cohort was included in the PPM, the AUC values for the PPM and CT-reported LN status were 0.756 and 0.568 (P < 0.001).

Conclusions

The established PPM may be an effective technique for predicting the LNM status of patients preoperatively. This model can better diagnose LNM than CT-reported LN status alone, this model is better able to diagnose LNM.
The efficacy of curcumin/Qing Dai combination in children with active ulcerative colitis: a multicenter retrospective cohort study
Authors: Nachum Nurit Loberman , Salomon Nir , Yerushalmy-Feler Anat , Weintraub Yael , Yogev Dotan , Granot Maya , Haberman Yael , Ben-Horin Shomron , Weiss Batia
Published: September 2024

Background

Curcumin and Qing Dai (QD) are herbal extracts that recently showed efficacy in treating inflammatory bowel disease (IBD). Since 2016, a combination of curcumin with QD (CurQD) has been employed in our center for management of active ulcerative colitis (UC).

Objectives

We report the effectiveness and safety of CurQD therapy in children with mild-moderate UC or IBD-unclassified (IBD-U).

Design

A multicenter retrospective study.

Methods

Children aged ≤OP18 years who were treated with CurQD during 2017–2021 were included. Disease activity measures were Pediatric UC Activity Index (PUCAI), and fecal calprotectin (FC). The primary outcome was a decrease in PUCAI by ≥10 points, FC normalization (≤100 µg/gr when baseline ≥300 µg/gr) or a ≥ 50% decrease in FC.

Results

Of 30 patients (60% males, mean age 14 ± 3.9 years), 15 (50%), 13 (43%), and 2 (7%) had pancolitis, left-sided colitis and proctitis, respectively. The daily medication dose was 0.5–3 gm QD with 1–4 gm curcumin. Concomitant treatment at induction was corticosteroids (19%), biologics (28%) and 5-aminosalicylic acid (40%). The mean duration of induction was 11.6 weeks [95% confidence interval (CI) 10.2–13.1, range 8–16]. PUCAI decreased from a mean of 31.3 (95% CI 26.6–36.0, range 5–60) to 10.9 (95% CI 7.6–14.4, range 5–35) (n = 26, p < 0.001). FC response and normalization occurred in 11/12 and 7/12 patients, respectively. The median decline in FC was from 749 µg/gm [interquartile range (IQR) 566–1000] to 39 µg/gm (IQR 12–132) (n = 15, p = 0.04). During follow-up (median 8 months, IQR 6–10), 10 patients (33%) flared; five of them regained remission or responded to a treatment change. Of 18 patients treated beyond induction, 12 (67%) achieved clinical response and 10 achieved clinical remission by the end of follow up.

Conclusion

CurQD may be effective and safe as an add-on option to conventional management, for induction and maintenance in children with mild-moderate UC/IBD-U.
Integrating text mining with network models for successful target identification: in vitro validation in MASH-induced liver fibrosis
Authors: Venhorst Jennifer , Hanemaaijer Roeland , Dulos Remon , Caspers Martien P. M. , Toet Karin , Attema Joline , de Ruiter Christa , Kalkman Gino , Rouhani Rankouhi Tanja , de Jong Jelle C. B. C. , Verschuren Lars
Published: September 2024

An in silico target discovery pipeline was developed by including a directional and weighted molecular disease network for metabolic dysfunction-associated steatohepatitis (MASH)-induced liver fibrosis. This approach integrates text mining, network biology, and artificial intelligence/machine learning with clinical transcriptome data for optimal translational power. At the mechanistic level, the critical components influencing disease progression were identified from the disease network using in silico knockouts. The top-ranked genes were then subjected to a target efficacy analysis, following which the top-5 candidate targets were validated in vitro. Three targets, including EP300, were confirmed for their roles in liver fibrosis. EP300 gene-silencing was found to significantly reduce collagen by 37%; compound intervention studies performed in human primary hepatic stellate cells and the hepatic stellate cell line LX-2 showed significant inhibition of collagen to the extent of 81% compared to the TGFβ-stimulated control (1 μM inobrodib in LX-2 cells). The validated in silico pipeline presents a unique approach for the identification of human-disease-mechanism-relevant drug targets. The directionality of the network ensures adherence to physiologically relevant signaling cascades, while the inclusion of clinical data boosts its translational power and ensures identification of the most relevant disease pathways. In silico knockouts thus provide crucial molecular insights for successful target identification.
Notoginsenoside R1, a metabolite from Panax notoginseng (Burkill) F.H.Chen, stimulates insulin secretion through activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway
Authors: Al-Romaiyan Altaf , Barakat Ahmad , Marafie Sulaiman K. , Masocha Willias
Published: September 2024

Background

For ages, botanical medicine has been used in the treatment of diabetes mellitus (DM). Notoginsenoside R1 (NGR1), a Panax notoginseng (Burkill) F.H.Chen metabolite, has been documented to possess antidiabetic action in vivo. However, its precise molecular mechanism of action is not clear.

Objectives

We evaluated NGR1’s effects on blood glucose in vivo and then evaluated in vitro whether NGR1 has effects on insulin secretion and the probable molecular pathways involved in NGR1-induced insulin secretion.

Methods

Diabetes was induced in mice by streptozotocin. Glucose tolerance test was performed before and after NGR1 was administered intraperitoneally to diabetic animals for 4 weeks. Static and perifusion experiments were performed using isolated female BALB/c mouse islets. Preproinsulin (Ins) mRNA expression was measured using q-PCR. Protein expression of PI3K/Akt pathway was assessed using the fully automated Wes™ capillary-based protein electrophoresis.

Results

Treatment of diabetic mice with NGR1 improved their glucose intolerance. In vitro, NGR1 increased insulin secretion in a concentration-dependent manner. NGR1 initiated the secretion of insulin at 2 mM glucose and augmented glucose-stimulated insulin secretion which was sustained throughout NGR1 perifusion. NGR1-induced insulin secretion was not altered by a voltage gated calcium channel blocker or protein kinase A inhibitor. NGR1 did not significantly modulate Ins mRNA expression. However, NGR1 significantly increased the levels of phospho-Akt and phopho-p-85.

Conclusion

In conclusion, this study has shown that NGR1 ameliorates hyperglycemia in diabetic mice. NGR1 has a direct insulin secretagogue activity on mouse islets, stimulates insulin secretion at both basal and postprandial glucose concentrations, and activates PI3K/Akt pathway to induce insulin secretion. These results suggest that NGR1 may provide an alternative therapy to manage DM.
Tea leaf disease and insect identification based on improved MobileNetV3
Authors: Li Yang , Lu Yuheng , Liu Haoyang , Bai Jiahe , Yang Chen , Yuan Haiyan , Li Xin , Xiao Qiang
Published: September 2024

Accurate detection of tea leaf diseases and insects is crucial for their scientific and effective prevention and control, essential for ensuring the quality and yield of tea. Traditional methods for identifying tea leaf diseases and insects primarily rely on professional technicians, which are difficult to apply in various scenarios. This study proposes a recognition method for tea leaf diseases and insects based on improved MobileNetV3. Initially, a dataset containing images of 17 different types of tea leaf diseases and insects was curated, with data augmentation techniques utilized to broaden recognition scenarios. Subsequently, the network structure of MobileNetV3 was enhanced by integrating the CA (coordinate attention) module to improve the perception of location information. Moreover, a fine-tuning transfer learning strategy was employed to optimize model training and accelerate convergence. Experimental results on the constructed dataset reveal that the initial recognition accuracy of MobileNetV3 is 94.45%, with an F1-score of 94.12%. Without transfer learning, the recognition accuracy of MobileNetV3-CA reaches 94.58%, while with transfer learning, it reaches 95.88%. Through comparative experiments, this study compares the improved algorithm with the original MobileNetV3 model and other classical image classification models (ResNet18, AlexNet, VGG16, SqueezeNet, and ShuffleNetV2). The findings show that MobileNetV3-CA based on transfer learning achieves higher accuracy in identifying tea leaf diseases and insects. Finally, a tea diseases and insects identification application was developed based on this model. The model showed strong robustness and could provide a reliable reference for intelligent diagnosis of tea diseases and insects.
Recent advancements in gene therapy for sickle cell disease and β-thalassemia
Authors: Li Lushen , Mandal Pankaj K.
Published: September 2024

β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia, are prevalent monogenic disorders causing abnormal hemoglobin structure or production that affect millions globally. Current available therapies for SCD and β-thalassemia are primarily symptomatic treatments and allogeneic hematopoietic stem cell transplant (HSCT). Allo-HSCT is the only curative treatment, which has limitations. Gene therapy using genetically modified hematopoietic stem cells (HSCs) holds promise to be an effective curative therapy. Recently approved ex vivo genetically modified HSC-based therapeutics (CASGEVY, LYFGENIA, ZYNTEGLO) have shown remarkable and durable therapeutic benefits for SCD and β-Thalassemia. In this review article, we discuss the current genetic approaches and innovative strategies to ensure safe and effective gene therapy for SCD and β-thalassemia and summarize findings from completed and ongoing clinical trials. We also discuss prospects and challenges of in vivo gene editing with CRISPR/Cas technology for SCD and beta-thalassemia that may simplify manufacturing and treatment process. In vivo gene therapy may minimize the risks associated with ex vivo gene therapy and may overcome multiple barriers associated with complex gene therapy products for wider patient access, especially in developing regions of the world where these diseases are highly prevalent.
Managers’ perspectives on their role in implementing fall prevention interventions: a qualitative interview study in Norwegian homecare services
Authors: Linnerud Siv , Bjerk Maria , Olsen Nina Rydland , Taraldsen Kristin , Brovold Therese , Kvæl Linda Aimée Hartford
Published: September 2024

Introduction

The implementation of fall prevention interventions in homecare services is crucial for reducing falls among older adults and effective leadership could determine success. Norwegian homecare services provide home nursing, rehabilitation, and practical assistance, to residents living in private homes or assisted living facilities. This study aims to explore how managers in Norwegian homecare services experience implementation of fall prevention interventions and how they perceive their roles.

Methods

We conducted 14 semi-structured individual interviews with managers from different levels of homecare services in five city districts. The interviews were transcribed verbatim and reflexive thematic analysis was used to analyze the material.

Results

The analysis resulted in three main themes: (1) understanding organizational mechanisms to facilitate new practices, (2) practicing positive leadership behavior to facilitate implementation, and (3) demonstrating persistence to sustain implementation. Our results showed the importance of clear leadership across all levels of the organization and the value of devoting time and utilizing existing systems. Managers described using recognition and positive attitudes to motivate employees in the implementation process. They emphasized listening to and involving employees, providing trust, and being flexible. However, the implementation process could be challenging, highlighting the need for managers to be persistent.

Conclusion

Managers at all levels play an important role in the implementation of fall prevention, but there is a need to define and align their specific roles in the process. Understanding how to use existing systems and influence through positive leadership behavior seem to be vital for success. Recognizing the demanding nature of implementation, managers emphasized the importance of systems for long term support. The study findings may influence how managers in clinical practice engage in the implementation process and inform future researchers about managers’ roles in implementation in homecare services.
Three important roles and chemical properties of glomalin-related soil protein
Authors: Son Yejin , Martínez Carmen Enid , Kao-Kniffin Jenny
Published: September 2024

The consequences of climate change urgently demand the reduction of atmospheric carbon, including by sequestering carbon in soil. The glomalin-related soil proteins (GRSP) of arbuscular mycorrhizal fungi (AMF) are renowned for their soil aggregation and carbon sequestration properties. With their considerable binding abilities, GRSP can also adsorb various cations and sequester heavy metals in soil, thereby assisting in soil fertilization and remediation efforts. However, despite its benefits for soil health and climate change, the mechanisms underlying these traits in the context of soil chemistry remain unexplored. In this review, we focus on three crucial roles of GRSP—long-term carbon sequestration, soil aggregation, and soil remediation and fertility—in the context of the chemical characteristics elucidated by previous research, namely hydrophobicity, amid group glycosylation (N-glycosylation), and metal adsorption. Based on the proposed chemical mechanisms, the current review also offers insight into soil factors that may influence the persistence of GRSP. We conclude by proposing a working model for GRSP, aiming to establish a conceptual platform for future research to examine GRSP in terms of their known or novel chemical and biochemical reactions, thereby improving our understanding of this important group of soil proteins.
Evaluating social network metrics as indicators of tail injury caused by tail biting in growing-finishing pigs (Sus scrofa domesticus)
Authors: St. Charles Kaitlyn M. , VanderWaal Kimberly L. , Anderson Jon E. , Johnston Lee J. , Li Yuzhi Z.
Published: September 2024

Tail biting is a multifactorial behavior that causes welfare and economic challenges in swine production. As of 2024, research exploring the influence of pig social structure on the development of tail biting is limited. The objective of this study was to explore whether social structures of pigs from different litter origins can impact tail biting and, ultimately, tail damage. Pigs (n = 96) were grouped (eight pigs/pen) based on their litter origin: non-littermates (NLM), half-littermates, and littermates (LM). Tail injury scores were assessed twice weekly from 10 to 24 weeks of age, with a maximal tail injury score (MTS) over the study period being used to evaluate victimization by tail biting. Pig behavior was video-recorded at 15, 19, and 23 weeks of age. Association networks based on lying behavior and tail biting interaction networks were evaluated at pen-and pig-levels using social network analysis. Pigs in LM pens experienced higher median MTS compared to pigs in NLM pens (Median = 1.5; Interquartile range = 1–2; p = 0.009). Within association networks, NLM pens had lower degree centralization measures than other pens at both 15 (Estimated marginal mean [EMM] = 0.07; 95% CI = 0.02–0.12; p = 0.003) and 23 weeks (EMM = 0.09; 95% CI = 0.04–0.14; p = 0.01) and pigs in NLM pens had higher weighted degree centrality than those in other pens (EMM = 1.00; 95% CI = 0.90–1.11; p = 0.002), suggesting pigs in NLM pens had more uniform, stronger, and more connections with their pen-mates. In tail biting networks, increased weighted in-degree centrality was associated with increased odds of pigs receiving a more severe MTS (OR = 1.56; 95% CI = 1.08–2.27; p = 0.02). Pigs with increased weighted out-degree centrality tended to have increased odds of receiving a more severe MTS (OR = 1.19; 95% CI = 0.97–1.48; p = 0.09). These preliminary data suggest a potential relationship between social structures and tail biting in growing-finishing pigs.
Management of Kidney Transplant Outpatients With COVID-19: A Single Center Experience
Authors: Matysková Kubišová Michaela , Dusilová Sulková Sylvie , Moučka Petr , Pokorná Anita , Heislerová Marcela , Guňka Igor , Navrátil Pavel , Pacovský Jaroslav , Malá Alena , Šafránek Roman
Published: September 2024

Patients undergoing kidney transplant are at risk of severe COVID-19. Our single-center retrospective analysis evaluated the outcomes of kidney transplant outpatients with COVID-19 who were managed with reduced immunosuppression and treatment with molnupiravir. Between January 2022 and May 2023, we included 93 patients (62 men, average age 56 years), serum creatinine 127 (101–153) µmol/L. Molnupiravir was administered, and immunosuppressive therapy was reduced immediately following the confirmation of SARS-CoV-2 infection by PCR, which was 2 (1–3) days after the onset of symptoms. Only three (3.2%) patients required hospitalization, and one patient died. Acute kidney injury was observed in two patients. During the follow-up period of 19 (15–22) months, there was no significant increase in proteinuria, no acute or new chronic graft rejection, and kidney graft function remained stable; serum creatinine was 124 (106–159) µmol/L post-COVID-19 infection and 128 (101–161) µmol/L at the end of the follow-up period. Our results demonstrate that early initiation of molnupiravir treatment combined with a temporary reduction in immunosuppressive therapy results in favorable clinical outcomes in patients with COVID-19, with preservation of good graft function and no episodes of graft rejection.
Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates
Authors: Längin Matthias , Bender Martin , Schmoeckel Michael , Reichart Bruno
Published: September 2024

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.
Algorethics in Healthcare: Balancing Innovation and Integrity in AI Development
Authors: Lastrucci Andrea , Pirrera Antonia , Lepri Graziano , Giansanti Daniele
Published: September 2024

The rapid advancement of artificial intelligence (AI) technology has catalyzed unprecedented innovation in the healthcare industry, transforming medical practices and patient care. However, this progress brings significant ethical challenges, highlighting the need for a comprehensive exploration of algorethics—the intersection of algorithm design and ethical considerations. This study aimed to conduct a narrative review of reviews in the field of algorethics with specific key questions. The review utilized a standardized checklist for narrative reviews, including the ANDJ Narrative Checklist, to ensure thoroughness and consistency. Searches were performed on PubMed, Scopus, and Google Scholar. The review revealed a growing emphasis on integrating fairness, transparency, and accountability into AI systems, alongside significant progress in ethical AI development. The importance of collaboration between different domains of scientific production, such as social sciences and standardization (like the IEEE), and the development of guidelines is significantly emphasized, with demonstrated direct impact in the health domain. However, gaps persist, particularly in the lack of standardized evaluation methods and the challenges posed by complex sectors like healthcare. The findings underscore the need and importance for robust data governance to prevent biases and highlight the importance of cross-disciplinary collaboration in creating comprehensive ethical frameworks for AI. The field of algorethics has important applications in the health domain, and there is a significant increase in attention, with a focus on addressing issues and seeking both practical and theoretical solutions. Future research should prioritize establishing standardized evaluation practices for AI, fostering interdisciplinary collaboration, developing sector-specific ethical guidelines, exploring AI’s long-term societal impacts, and enhancing ethical training for developers. Continued attention to emerging ethical standards is also crucial for aligning AI technologies with evolving ethical principles.