bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia
Authors: Jiang Yi , Xiao Xueshan , Sun Wenmin , Wang Yingwei , Li Shiqiang , Jia Xiaoyun , Wang Panfeng , Hejtmancik J. Fielding , Zhang Qingjiong 
Published: January 2024

Abstract
Backgrounds
Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort.

Methods
A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded. Variants were detected by exome sequencing and then analyzed through multiple-step bioinformatic and co-segregation analysis and finally confirmed by Sanger sequencing. Genetic findings were correlated with associated clinical data for analysis.

Results
Among the 75 probands with a mean age of 6.21 ± 4.70 years at the presentation, myopic fundus of C1 and C2 was observed in 73 (97.3%) probands. Surprisingly, specific peripheral changes were identified in 63 eyes involving 36 (48.0%) probands after extensive examination, including peripheral retinal avascular zone (74.6%, 47/63 eyes), neovascularization (54.0%), fluorescein leakage (31.7%), peripheral pigmentary changes (31.7%), and others. Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage.

Conclusions
Genetic defects were identified in about one-fourth of simplex uHM patients in which significant consequences may be hidden under a classic myopic fundus in up to half. To our knowledge, this is the first systematic genetic study on simplex uHM to date. In addition to routine care of strabismus and amblyopia, careful examination of the peripheral retina and genetic screening is warranted for patients with uHM in order to identify signs of risk for retinal detachment and other complications and provide meaningful genetic counseling.
Oxyresveratrol attenuates bone resorption by inhibiting the mitogen-activated protein kinase pathway in ovariectomized rats
Authors: Lee Yea-Jin , Ahn Jin-Chul , Oh Chung-Hun 
Published: January 2024

Abstract
Background
Bone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model.

Methods
Mouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT.

Results
The polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP).

Conclusion
Oxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells.
Automatic 3D cell segmentation of fruit parenchyma tissue from X-ray micro CT images using deep learning
Authors: Van Doorselaer Leen , Verboven Pieter , Nicolai Bart 
Published: January 2024

AbstractBackgroundHigh quality 3D information of the microscopic plant tissue morphology—the spatial organization of cells and intercellular spaces in tissues—helps in understanding physiological processes in a wide variety of plants and tissues. X-ray micro-CT is a valuable tool that is becoming increasingly available in plant research to obtain 3D microstructural information of the intercellular pore space and individual pore sizes and shapes of tissues. However, individual cell morphology is difficult to retrieve from micro-CT as cells cannot be segmented properly due to negligible density differences at cell-to-cell interfaces. To address this, deep learning-based models were trained and tested to segment individual cells using X-ray micro-CT images of parenchyma tissue samples from apple and pear fruit with different cell and porosity characteristics.ResultsThe best segmentation model achieved an Aggregated Jaccard Index (AJI) of 0.86 and 0.73 for apple and pear tissue, respectively, which is an improvement over the current benchmark method that achieved AJIs of 0.73 and 0.67. Furthermore, the neural network was able to detect other plant tissue structures such as vascular bundles and stone cell clusters (brachysclereids), of which the latter were shown to strongly influence the spatial organization of pear cells. Based on the AJIs, apple tissue was found to be easier to segment, as the porosity and specific surface area of the pore space are higher and lower, respectively, compared to pear tissue. Moreover, samples with lower pore network connectivity, proved very difficult to segment.ConclusionsThe proposed method can be used to automatically quantify 3D cell morphology of plant tissue from micro-CT instead of opting for laborious manual annotations or less accurate segmentation approaches. In case fruit tissue porosity or pore network connectivity is too low or the specific surface area of the pore space too high, native X-ray micro-CT is unable to provide proper marker points of cell outlines, and one should rely on more elaborate contrast-enhancing scan protocols.
The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial
Authors: Kawahara Naoki , Kawaguchi Ryuji , Yamamoto Konosuke , Nishikawa Kyohei , Matsuoka Motoki , Maehana Tomoka , Fukui Yosuke , Yamanaka Shoichiro , Sugimoto Sumire , Iwai Kana , Yamada Yuki , Kurakami Hiroyuki , Hirata Takumi , Takashima Ryuzo , Suzuki Shota , Asada Kiyoshi , Kasahara Masato , Kimura Fuminori 
Published: January 2024

Abstract
Background
Uterine leiomyomas are common for reproductive-aged women and affect women’s quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i.e., to reduce blood loss or surgical duration). Recently, relugolix (40 mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However, long-term administration should not be permitted liable to for climacteric disorder or osteoporosis, and evidence is lacking on the actual efficacy and extent of adverse effects of the every-other-day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety (i.e., reduction of adverse effects) by every-other-day administration after 2 months of everyday administration compared to daily administration throughout the duration.

Methods
A minimization adaptive randomized control trial (RCT) will be conducted. Patients (over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every-other-day administration for 16 weeks after 8 weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume reduction, and the secondary endpoints are the reduction of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration.

Discussion
This study aims to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects while maintaining the effect of leiomyoma reduction.

Trial registration
Japan Registry of Clinical Trials jRCTs051230078. Registered on 26 July 2023.
Efficacy of ultrasound-guided erector spinae plane block on analgesia and quality of recovery after minimally invasive direct coronary artery bypass surgery: protocol for a randomized controlled trial
Authors: Xin Ling , Wang Lu , Feng Yi 
Published: January 2024

Abstract
Background
Minimally invasive direct coronary artery bypass (MIDCAB) surgery offers an effective option for coronary artery disease (CAD) patients with the avoidance of median sternotomy and fast postoperative recovery. However, MIDCAB is still associated with significant postoperative pain which may lead to delayed recovery. The erector spinae plane block (ESPB) is a superficial fascial plane block. There have not been randomized controlled trials evaluating the effects of ESPB on analgesia and patient recovery following MIDCAB surgery. We therefore designed a double-blind prospective randomized placebo-controlled trial, aiming to prove the hypothesis that ESPB reduces postoperative pain scores in patients undergoing MIDCAB surgery.

Methods
The study protocol has been reviewed and approved by the Ethical Review Committee of Peking University People’s Hospital. Sixty adult patients of either sex scheduled for MIDCAB surgery under general anesthesia (GA) will be included. Patients will be randomly allocated to receive either a preoperative single-shot ESPB with 30 mL of ropivacaine 0.5% (ESPB group) or normal saline 0.9% (control group). The primary outcomes are the difference between the two groups in numeric rating scale (NRS) scores at rest at different time points (6, 12, 18, 24, 48 h) after surgery. The secondary outcomes include NRS scores on deep inspiration within 48 h, postoperative hydromorphone consumption, and quality of patient recovery at 24 h and 48 h, using the Quality of Recovery-15 (QoR-15) scale. The other outcomes include intraoperative fentanyl requirements, the need for additional postoperative rescue analgesics, time to tracheal extubation and chest tube removal after surgery, incidence of postoperative nausea and vomiting (PONV) and postoperative cognitive dysfunction (POCD), intensive care unit (ICU) length of stay (LOS), hospital discharge time, and 30-day mortality. Adverse events will be also evaluated.

Discussion
This is a novel randomized controlled study evaluating a preoperative ultrasound-guided single-shot unilateral ESPB on analgesia and quality of patient recovery in MIDCAB surgery. The results of this study will characterize the degree of acute postoperative pain and clinical outcomes following MIDCAB. Our study may help optimizing analgesia regimen selection and improving patient comfort in this specific population.

Trial registration
The study was prospectively registered with the Chinese Clinical Trial Registry (trial identifier: ChiCTR2100052810). Date of registration: November 5, 2021.
Gut microbiome for predicting immune checkpoint blockade-associated adverse events
Authors: Hu Muni , Lin Xiaolin , Sun Tiantian , Shao Xiaoyan , Huang Xiaowen , Du Weiwei , Guo Mengzhe , Zhu Xiaoqiang , Zhou Yilu , Tong Tianying , Guo Fangfang , Han Ting , Wu Xiuqi , Shi Yi , Xiao Xiuying , Zhang Youwei , Hong Jie , Chen Haoyan 
Published: January 2024

AbstractBackgroundThe impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.MethodsWe performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms.ResultsWe identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymesmenHandmenC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group.ConclusionsOur study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.
Metabolomics analysis of serum and urine in type 1 diabetes patients with different time in range derived from continuous glucose monitoring
Authors: Ma Liyuan , Liu Jieying , Deng Mingqun , Zhou Liyuan , Zhang Qian , Xiao Xinhua 
Published: January 2024

Abstract
Background
Time in range (TIR), as an important glycemic variability (GV) index, is clearly associated with disease complications in type 1 diabetes (T1D). Metabolic dysregulation is also involved in the risks of T1D complications. However, the relationship between metabolites and TIR remains poorly understood. We used metabolomics to investigate metabolic profile changes in T1D patients with different TIR.

Methods
This study included 85 T1D patients and 81 healthy controls. GV indices, including TIR, were collected from continuous glucose monitoring system. The patients were compared within two subgroups: TIR-L (TIR < 50%, n = 21) and TIR-H (TIR > 70%, n = 14). To screen for differentially abundant metabolites and metabolic pathways, serum and urine samples were obtained for untargeted metabolomics by ultra-performance liquid chromatography‒mass spectrometry. Correlation analysis was conducted with GV metrics and screened biomarkers.

Results
Metabolites were significantly altered in T1D and subgroups. Compared with healthy controls, T1D patients had higher serum levels of 5-hydroxy-L-tryptophan, 5-methoxyindoleacetate, 4-(2-aminophenyl)-2,4-dioxobutanoate, and 4-pyridoxic acid and higher urine levels of thromboxane B3 but lower urine levels of hypoxanthine. Compared with TIR-H group, The TIR-L subgroup had lower serum levels of 5-hydroxy-L-tryptophan and mevalonolactone and lower urine levels of thromboxane B3 and phenylbutyrylglutamine. Dysregulation of pathways, such as tryptophan, vitamin B6 and purine metabolism, may be involved in the mechanism of diabetic complications related to glycemic homeostasis. Mevalonolactone, hypoxanthine and phenylbutyrylglutamine showed close correlation with TIR.

Conclusions
We identified altered metabolic profiles in T1D individuals with different TIR. These findings provide new insights and merit further exploration of the underlying molecular pathways relating to diabetic complications.
2024 UPDATE: the Brazilian Diabetes Society position on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) in people with prediabetes or type 2 diabetes
Authors: Godoy-Matos Amélio F. , Valério Cynthia Melissa , Silva Júnior Wellington S. , de Araujo-Neto João Marcello , Bertoluci Marcello Casaccia 
Published: January 2024

Abstract
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease affecting 30% of the world’s population and is often associated with metabolic disorders such as metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease. This review is an update of the Brazilian Diabetes Society (Sociedade Brasileira de Diabetes [SBD]) evidence-based guideline for the management of MASLD in clinical practice.

Methods
The methodology was published previously and was defined by the internal institutional steering committee. The SBD Metabolic Syndrome and Prediabetes Department drafted the manuscript, selecting key clinical questions for a narrative review using MEDLINE via PubMed with the MeSH terms [diabetes] and [fatty liver]. The best available evidence was reviewed, including randomized clinical trials (RCTs), meta-analyses, and high-quality observational studies related to MASLD.

Results and conclusions
The SBD Metabolic Syndrome and Prediabetes Department formulated 9 recommendations for the management of MASLD in people with prediabetes or T2D. Screening for the risk of advanced fibrosis associated with MASLD is recommended in all adults with prediabetes or T2D. Lifestyle modification (LSM) focusing on a reduction in body weight of at least 5% is recommended as the first choice for these patients. In situations where LSMs are insufficient to achieve weight loss, the use of anti-obesity medications is recommended for those with a body mass index (BMI) ≥ 27 kg/m2. Pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RA) monotherapy are the first-line pharmacological treatments for steatohepatitis in people with T2D, and sodium–glucose cotransporter-2 (SGLT2) inhibitors may be considered in this context. The combination of these agents may be considered in the treatment of steatohepatitis and/or fibrosis, and bariatric surgery should be considered in patients with a BMI ≥ 35 kg/m2, in which the combination of LSM and pharmacotherapy has not been shown to be effective in improving MASLD.
Enhancing local recurrence detection in patients with high-grade soft tissue sarcoma: value of short-term Ultrasonography added to post-operative MRI surveillance
Authors: Park Ho Young , Chung Hye Won , Yoon Min A , Chee Choong Guen , Kim Wanlim , Lee Jong-Seok 
Published: January 2024

Abstract
Background
Limited data exist on the optimal postoperative surveillance protocol for high-grade soft tissue sarcoma, particularly regarding the optimal imaging modality and imaging interval for detecting local recurrence. This study aimed to assess the benefit of short-term postoperative ultrasonography (USG) for detecting local recurrence in patients with high-grade soft tissue sarcoma.

Methods
Patients with newly diagnosed high-grade soft tissue sarcoma who underwent surgical resection between January 2010 and June 2020 were included. Short-term USG was added to the follow-up protocol as a surveillance tool alongside routine magnetic resonance imaging (MRI). The primary outcome was the additional detection rate of short-term USG compared with routine MRI surveillance for early local recurrence detection. Subgroup analysis was performed to evaluate factors influencing USG detection rate. The additional detection rate of short-term USG for detection of metastatic lymph nodes was also evaluated. The secondary outcome was the false referral rate of short-term USG.

Results
In total, 198 patients (mean age ± standard deviation: 52.1 ± 15.8 years; 94 women) were included. Local recurrence occurred in 20 patients (10.1%; 20/198). Short-term USG detected local recurrence in advance of routine MRI visits in 7 out of 198 patients, resulting in an additional detection rate of 3.5% (95% CI: 1.7–7.1%). Subgroup analysis showed no significant difference in the short-term USG detection rate based on initial tumor characteristics, and receipt of radiotherapy or chemotherapy. Short-term USG additionally detected five of seven patients with metastatic lymph nodes [2.5% (95% CI, 1.1–5.8%, 5/198)]. The false referral rate of short-term USG was 3.5% (95% CI: 1.7–7.1%; 7/198).

Conclusions
Short-term USG as part of postoperative surveillance for high-grade soft tissue sarcoma can enhance early detection of local tumor recurrence and metastatic lymphadenopathy. Early detection of local tumor recurrence could lead to a prompt surgical resection and aid in local disease control.