bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convolutional neural network-based vocal cord tumor classification technique for home-based self-prescreening purpose
Authors: Kim Gun Ho , Hwang Young Jun , Lee Hongje , Sung Eui-Suk , Nam Kyoung Won 
Published: August 2023

Abstract
Background
In this study, we proposed a deep learning technique that can simultaneously detect suspicious positions of benign vocal cord tumors in laparoscopic images and classify the types of tumors into cysts, granulomas, leukoplakia, nodules and polyps. This technique is useful for simplified home-based self-prescreening purposes to detect the generation of tumors around the vocal cord early in the benign stage.

Results
We implemented four convolutional neural network (CNN) models (two Mask R-CNNs, Yolo V4, and a single-shot detector) that were trained, validated and tested using 2183 laryngoscopic images. The experimental results demonstrated that among the four applied models, Yolo V4 showed the highest F1-score for all tumor types (0.7664, cyst; 0.9875, granuloma; 0.8214, leukoplakia; 0.8119, nodule; and 0.8271, polyp). The model with the lowest false-negative rate was different for each tumor type (Yolo V4 for cysts/granulomas and Mask R-CNN for leukoplakia/nodules/polyps). In addition, the embedded-operated Yolo V4 model showed an approximately equivalent F1-score (0.8529) to that of the computer-operated Yolo-4 model (0.8683).

Conclusions
Based on these results, we conclude that the proposed deep-learning-based home screening techniques have the potential to aid in the early detection of tumors around the vocal cord and can improve the long-term survival of patients with vocal cord tumors.
Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy
Authors: Wan Junlai , He Zhiyi , Peng Renpeng , Wu Xiaopei , Zhu Ziqing , Cui Jiarui , Hao Xiaoxia , Chen Anmin , Zhang Jiaming , Cheng Peng 
Published: August 2023

AbstractOsteoarthritis (OA) is a common degenerative joint disease urgently needing effective treatments. Bone marrow mesenchymal stromal cell-derived exosomes (Exo) are considered good drug carriers whereas they have limitations such as fast clearance and low retention. This study aimed to overcome the limitations of Exo in drug delivery using multiple strategies. Novel photocrosslinking spherical gelatin methacryloyl hydrogel (GelMA)-encapsulated cartilage affinity WYRGRL (W) peptide-modified engineered Exo were developed for OA treatment and the performance of the engineered Exo (W-Exo@GelMA) loaded with a small inhibitor LRRK2-IN-1 (W-Exo-L@GelMA) was investigated in vitro and in vivo. The W-Exo-L@GelMA showed an effective targeting effect on chondrocytes and a pronounced action on suppressing catabolism and promoting anabolism in vitro. Moreover, W-Exo-L@GelMA remarkably inhibited OA-related inflammation and immune gene expression, rescuing the IL-1β-induced transcriptomic responses. With enhanced retention in the joint, W-Exo-L@GelMA demonstrated superior anti-OA activity and cartilage repair ability in the OA murine model. The therapeutic effect was validated in the cultured human OA cartilage. In conclusion, photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered Exo exhibit notable potential in OA therapy. Engineering Exo by a series of strategies enhanced the targeting ability and retention and cartilage-targeting and Exo-mediated drug delivery may offer a novel strategy for OA treatment.Clinical trial registration: Not applciable.
Graphical Abstract
Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery
Authors: Zhao Tianqi , Zhou Mingwei , Wu Ronghui , Wang Huaxin , Zouboulis Christos C. , Zhu Mingji , Lee Myongsoo 
Published: August 2023

Abstract
Background
In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy.
Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D).

Results
Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation.

Conclusion
Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders.

Graphical Abstract
Evaluation of Internet-based pharmaceutical care effect on young and middle-aged patients with hypertension by the principal component analysis and the Markov cohort during COVID-19 pandemic
Authors: Li Xinmei , Xu Wenxiu , Mo Xiaofeng , Wu Fan , Qu Minghong , Ye Junxian , Wu Wenxing , Li Haizhi , Li Te 
Published: August 2023

Abstract
Background
Pharmaceutical care has the potential to improve hypertension control rates in young and middle-aged patients. Due the COVID-19 epidemic, standard intervention methods may not be applicable. We propose establishing an internet-based pharmaceutical care (IPC) route to improve blood pressure control in young and middle-aged patients with hypertension. An evaluation method based on Principal Component Analysis (PCA) and Orthogonal Partial Least-Discriminant Analysis (OPLS-DA) was established to evaluate the effect of the IPC method.

Methods
1) Internet-based Pharmaceutical care (IPC) was provided by pharmacists mainly using Wechat software for one year after enrollment; 2) PCA and OPLS-DA were applied to analyze questionnaire reliability and data variability; 3) Markov cohort was used to evaluate the IPC effect.

Results
Ninety-seven young and middle-aged patients were enrolled. 96 patients received the IPC. 1) The blood pressure control rate increased to 71.88% after IPC in 96 patients. 2) After conducting PCA and OPLS-DA analysis, 10 questions in the questionnaire were significantly improved after the IPC. 3) Markov cohort results showed that patient survival after 28 cycles was 18.62 years and the quality-adjusted life year (QALY) was extended by 5.40 years. The cumulative cost-effectiveness ratio was ¥87.10 per QALY.

Conclusions
The IPC method could significantly improve the blood pressure control rate of patients. The questionnaire analysis method based on PCA and OPLS-DA is an effective method to evaluate the effect of the IPC method. The Markov cohort showed that the IPC had an effect on blood pressure control rate changes. Patients had a strong willingness to pay for IPC.
The FreeD module’s lateral translation timing in the gait robot Lokomat: a manual adaptation is necessary
Authors: Aurich Tabea , van Dellen Florian , Labruyère Rob 
Published: August 2023

Abstract
Background
Pelvic and trunk movements are often restricted in stationary robotic gait trainers. The optional FreeD module of the driven gait orthosis Lokomat offers a combined, guided lateral translation and transverse rotation of the pelvis and may therefore support weight shifting during walking. However, from clinical experience, it seems that the default setting of this timing does not correspond well with the timing of the physiological pelvic movement during the gait cycle. In the software, a manual adaptation of the lateral translation’s timing with respect to the gait cycle is possible. The aim of this study was to investigate if such an offset is indeed present and if a manual adaptation by the therapist can improve the timing towards a more physiological pattern comparable to physiological overground walking.

Methods & Results
Children and adolescents with neurologic gait disorders and a Gross Motor Function Classification System level I-IV completed two different walking conditions (FreeD Default and FreeD Time Offset) in the Lokomat. The medio-lateral center of mass positions were calculated from RGB-Depth video recordings with a marker-less motion capture algorithm. Data of 22 patients (mean age: 12 ± 3 years) were analyzed. Kinematic analyses showed that in the FreeD Default condition, the maximum lateral center of mass excursion occurred too early. In the FreeD Time Offset condition, the manual adaptation by the therapists led to a delay of the maximum center of mass displacement by 8.2% in the first phase of the gait cycle and by 4.9% in the second phase of the gait cycle compared to the FreeD Default condition. The maximum lateral center of mass excursion was closer to that during physiological overground walking in the FreeD Time Offset condition than in the FreeD Default condition.

Conclusion
A manual adaptation of the timing of the FreeD module in the Lokomat shifts pelvis kinematics in a direction of physiological overground walking. We recommend therapists to use this FreeD Time Offset function to adjust the phase of weight shifting for each patient individually to optimize the kinematic walking pattern when a restorative therapy approach is adopted.
Constant ratio between the genomic components of bipartite begomoviruses during infection and transmission
Authors: Xiao Yu-Xin , Li Di , Wu Yi-Jie , Liu Shu-Sheng , Pan Li-Long 
Published: August 2023

AbstractThe genomic components of multipartite viruses are encapsidated in separate virus particles, and the frequencies of genomic components represent one of the key genetic features. Many begomoviruses of economic significance are bipartite, and the details of the association between their genomic components remain largely unexplored. We first analyzed the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of the squash leaf curl China virus (SLCCNV) in plants and found that while the quantities of DNA-A and DNA-B varied significantly during infection, the B/A ratio remained constant. We then found that changes in the B/A ratio in agrobacteria inoculum may significantly alter the B/A ratio in plants at 6 days post inoculation, but the differences disappeared shortly thereafter. We next showed that while the quantities of DNA-A and DNA-B among plants infected by agrobacteria, sap transmission and whitefly-mediated transmission differed significantly, the B/A ratios were similar. Further analysis of gene expression revealed that the ratio of the expression of genes encoded by DNA-A and DNA-B varied significantly during infection. Finally, we monitored the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of another bipartite begomovirus, and a constant B/A ratio was similarly observed. Our findings highlight the maintenance of a constant ratio between the two genomic components of bipartite begomoviruses during infection and transmission, and provide new insights into the biology of begomoviruses.
Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review
Authors: Falkenbach Petra , Raudasoja Aleksi J. , Vernooij Robin W. M. , Mustonen Jussi M. J. , Agarwal Arnav , Aoki Yoshitaka , Blanker Marco H. , Cartwright Rufus , Garcia-Perdomo Herney A. , Kilpeläinen Tuomas P. , Lainiala Olli , Lamberg Tiina , Nevalainen Olli P. O. , Raittio Eero , Richard Patrick O. , Violette Philippe D. , Tikkinen Kari A. O. , Sipilä Raija , Turpeinen Miia , Komulainen Jorma 
Published: August 2023

Abstract
Background
De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research.

Methods
We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool.

Results
We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%).

Conclusion
De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers.

Trial registration
OSF (Open Science Framework):
https://osf.io/ueq32.
MYC up-regulation confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma
Authors: Pitolli Consuelo , Marini Alberto , Guerra Marika , Pieraccioli Marco , Marabitti Veronica , Palluzzi Fernando , Giacò Luciano , Tamburrini Gianpiero , Cecconi Francesco , Nazio Francesca , Sette Claudio , Pagliarini Vittoria 
Published: August 2023

Abstract
Background
Medulloblastoma (MB) is the most common cerebellar malignancy during childhood. Among MB, MYC-amplified Group 3 tumors display the worst prognosis. MYC is an oncogenic transcription factor currently thought to be undruggable. Nevertheless, targeting MYC-dependent processes (i.e. transcription and RNA processing regulation) represents a promising approach.

Methods
We have tested the sensitivity of MYC-driven Group 3 MB cells to a pool of transcription and splicing inhibitors that display a wide spectrum of targets. Among them, we focus on THZ531, an inhibitor of the transcriptional cyclin-dependent kinases (CDK) 12 and 13. High-throughput RNA-sequencing analyses followed by bioinformatics and functional analyses were carried out to elucidate the molecular mechanism(s) underlying the susceptibility of Group 3 MB to CDK12/13 chemical inhibition. Data from International Cancer Genome Consortium (ICGC) and other public databases were mined to evaluate the functional relevance of the cellular pathway/s affected by the treatment with THZ531 in Group 3 MB patients.

Results
We found that pharmacological inhibition of CDK12/13 is highly selective for MYC-high Group 3 MB cells with respect to MYC-low MB cells. We identified a subset of genes enriched in functional terms related to the DNA damage response (DDR) that are up-regulated in Group 3 MB and repressed by CDK12/13 inhibition. Accordingly, MYC- and CDK12/13-dependent higher expression of DDR genes in Group 3 MB cells limits the toxic effects of endogenous DNA lesions in these cells. More importantly, chemical inhibition of CDK12/13 impaired the DDR and induced irreparable DNA damage exclusively in MYC-high Group 3 MB cells. The augmented sensitivity of MYC-high MB cells to CDK12/13 inhibition relies on the higher elongation rate of the RNA polymerase II in DDR genes. Lastly, combined treatments with THZ531 and DNA damage-inducing agents synergically suppressed viability of MYC-high Group 3 MB cells.

Conclusions
Our study demonstrates that CDK12/13 activity represents an exploitable vulnerability in MYC-high Group 3 MB and may pave the ground for new therapeutic approaches for this high-risk brain tumor.
Role of luteinizing hormone urinary levels in the diagnostic and therapeutic management of female central precocious puberty
Authors: Brambilla Ilaria , Guarracino Carmen , Pistone Carmelo , Klersy Catherine , Licari Amelia , Marseglia Gian Luigi , Tondina Enrico 
Published: August 2023

Abstract
Background
Diagnosing central precocious puberty (CPP) requires an integrated approach based on clinical, biochemical and instrumental data. The diagnostic gold standard is represented by GnRH (gonadotropin-releasing hormone) stimulation test. Some undoubted limitations of this procedure led the international scientific community to look for cheaper and less invasive alternative diagnostic methods, such as luteinizing hormone urinary levels (uLH) measurement. This study aims to define the reliability of urinary LH levels as a biomarker of pubertal development, both concerning the initial diagnostic management and the monitoring of patients with central precocious puberty undergoing therapy with GnRH analogues. Furthermore, the study plans to detect the potential association between LH peak serum (pLH) and urinary LH in patients undergoing diagnostic tests with GnRH and to identify a possible cut-off of uLH that may be suggestive of ensued successful hormonal stimulation.

Methods
The study includes 130 female patients with suspected precocious puberty or in follow-up during suppressive therapy. After the collection of the informed consent, the patients underwent clinical evaluation, auxological assessment, and hormone assays (basal levels of LH, FSH, and oestradiol; GnRH stimulating test in patients with suspected precocious puberty; urinary LH assay on the first-morning urine sample, collected after waking up).

Results
Two uLH cut-off values have been identified: the first of 0.25 UI/L [C.I. 95% 0.23–0.27], able to distinguish between pubertal and pre-pubertal patients, the second of 0.45 UI/L [C.I. 95% 0,20 − 0,70] suggestive of occurred hormonal stimulation in patients with diagnosis of CPP at GnRH test. All 30 patients with CPP in follow-up during suppressive therapy presented uLH values ≤ 0.45 IU/L (pU < 0.05), and uLH collected in prepubertal group control.

Conclusions
uLH assays on the first morning urine specimen could be considered a low-cost and minimally invasive tool for precocious puberty diagnosing and monitoring, making possible to be easily performed even by a general pediatrician. Thus, this could help referring only selected patients to pediatric endocrinologists. After an appropriate validation, this approach could reasonably reduce hospital attendance and costs of performing more invasive procedures, with a more significant emotional impact on the pediatric patient.
RETRACTED ARTICLE: Features optimization selection in hidden layers of deep learning based on graph clustering
Authors: Gao Hefei , Yuan Yifei , Wang Wei 
Published: August 2023

AbstractAs it is widely known, big data can comprehensively describe the inherent laws governing various phenomena. However, the effective and efficient analysis of available data has become a major challenge in the fields of artificial intelligence, machine learning, data mining, and others. Deep learning, with its powerful learning ability and effective data-processing methods, has been extensively researched and applied in numerous academic domains. Nevertheless, the data obtained during the deep learning process often exhibits feature homogenization, resulting in highly redundant features in the hidden layers, which, in turn, affects the learning process. Therefore, this paper proposes an algorithm based on graph clustering to optimize the features of hidden layer units, with the aim of eliminating redundancy and improving learner generation.
Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study
Authors: Oudijn M. S. , Linders J. T. W. , Lok A. , Schuurman P. R. , van den Munckhof P. , van Elburg A. A. , van Wingen G. A. , Mocking R. J. T. , Denys D. 
Published: August 2023

Abstract
Background
Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiology of AN.

Methods
We performed functional MRI on four AN patients that participated in a pilot study on the efficacy, safety, and functional effects of DBS targeted at the ventral limb of the capsula interna (vALIC). The patients and six gender-matched healthy controls (HC) were investigated at three different time points. We used an adapted version of the monetary incentive delay task to probe generic reward processing in patients and controls, and a food-specific task in patients only.

Results
At baseline, no significant differences for reward anticipation were found between AN and HC. Significant group (AN and HC) by time (pre- and post-DBS) interactions were found in the right precuneus, right putamen, right ventral and medial orbitofrontal cortex (mOFC). No significant interactions were found in the food viewing task, neither between the conditions high-calorie and low-calorie food images nor between the different time points. This could possibly be due to the small sample size and the lack of a control group.

Conclusion
The results showed a difference in the response of reward-related brain areas post-DBS. This supports the hypotheses that the reward circuitry is involved in the pathogenesis of AN and that DBS affects responsivity of reward-related brain areas.
Trial registration Registered in the Netherlands Trial Register (https://www.trialregister.nl/trial/3322): NL3322 (NTR3469).
Governance of artificial intelligence applications in a business audit via a fusion fuzzy multiple rule-based decision-making model
Authors: Hu Kuang-Hua , Chen Fu-Hsiang , Hsu Ming-Fu , Tzeng Gwo-Hshiung 
Published: August 2023

AbstractA broad range of companies around the world has welcomed artificial intelligence (AI) technology in daily practices because it provides decision-makers with comprehensive and intuitive messages about their operations and assists them in formulating appropriate strategies without any hysteresis. This research identifies the essential components of AI applications under an internal audit framework and provides an appropriate direction of strategies, which relate to setting up a priority on alternatives with multiple dimensions/criteria involvement that need to further consider the interconnected and intertwined relationships among them so as to reach a suitable judgment. To obtain this goal and inspired by a model ensemble, we introduce an innovative fuzzy multiple rule-based decision making framework that integrates soft computing, fuzzy set theory, and a multi-attribute decision making algorithm. The results display that the order of priority in improvement—(A) AI application strategy, (B) AI governance, (D) the human factor, and (C) data infrastructure and data quality—is based on the magnitude of their impact. This dynamically enhances the implementation of an AI-driven internal audit framework as well as responds to the strong rise of the big data environment.