bluuebunny/crossref_metadata_2025 huggingface dataset:
Based on whole-exome sequencing to explore the rule of Herceptin and TKI resistance in breast cancer patients
Authors: Guo Liantao , Cheng Hong , Liu Jianhua , Shao Weikang , Luo Lan , Zheng Weijie , Sun Shengrong , Kong Deguang , Chen Chuang
Published: January 2024

Background

Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs).

Methods

There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response.

Results

The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it.

Conclusions

Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.
What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study
Authors: de Diego Cristina , Lasierra Ana Belén , López-Vergara Lucía , Torralba Laura , Ruiz de Gopegui Pablo , Lahoz Raquel , Abadía Claudia , Godino Javier , Cebollada Alberto , Jimeno Beatriz , Bello Carlota , Tejada Antonio , Bello Salvador
Published: January 2024

Background

Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization.

Methods

We prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF.

Results

The COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10–16 of evolution in those who died. Correlations among the other NET markers were lower than expected.

Conclusions

The circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis.
How do the carbon and nitrogen sources affect the synthesis of β-(1,3/1,6)-glucan, its structure and the susceptibility of Candida utilis yeast cells to immunolabelling with β-(1,3)-glucan monoclonal antibodies?
Authors: Bzducha-Wróbel Anna , Farkaš Pavol , Bieliková Sandra , Čížová Alžbeta , Sujkowska-Rybkowska Marzena
Published: January 2024

Background

The need to limit antibiotic therapy due to the spreading resistance of pathogenic microorganisms to these medicinal substances stimulates research on new therapeutic agents, including the treatment and prevention of animal diseases. This is one of the goals of the European Green Deal and the Farm-To-Fork strategy. Yeast biomass with an appropriate composition and exposure of cell wall polysaccharides could constitute a functional feed additive in precision animal nutrition, naturally stimulating the immune system to fight infections.

Results

The results of the research carried out in this study showed that the composition of Candida utilis ATCC 9950 yeast biomass differed depending on growth medium, considering especially the content of β-(1,3/1,6)-glucan, α-glucan, and trehalose. The highest β-(1,3/1,6)-glucan content was observed after cultivation in deproteinated potato juice water (DPJW) as a nitrogen source and glycerol as a carbon source. Isolation of the polysaccharide from yeast biomass confirmed the highest yield of β-(1,3/1,6)-glucan after cultivation in indicated medium. The differences in the susceptibility of β-(1,3)-glucan localized in cells to interaction with specific β-(1,3)-glucan antibody was noted depending on the culture conditions. The polymer in cells from the DPJW supplemented with glycerol and galactose were labelled with monoclonal antibodies with highest intensity, interestingly being less susceptible to such an interaction after cell multiplication in medium with glycerol as carbon source and yeast extract plus peptone as a nitrogen source.

Conclusions

Obtained results confirmed differences in the structure of the β-(1,3/1,6)-glucan polymers considering side-chain length and branching frequency, as well as in quantity of β-(1,3)- and β-(1,6)-chains, however, no visible relationship was observed between the structural characteristics of the isolated polymers and its susceptibility to immunolabeling in whole cells. Presumably, other outer surface components and molecules can mask, shield, protect, or hide epitopes from antibodies. β-(1,3)-Glucan was more intensely recognized by monoclonal antibody in cells with lower trehalose and glycogen content. This suggests the need to cultivate yeast biomass under appropriate conditions to fulfil possible therapeutic functions. However, our in vitro findings should be confirmed in further studies using tissue or animal models.
Tumor-derived small extracellular vesicles in cancer invasion and metastasis: molecular mechanisms, and clinical significance
Authors: Zhang Chi , Qin Chaoying , Dewanjee Saikat , Bhattacharya Hiranmoy , Chakraborty Pratik , Jha Niraj Kumar , Gangopadhyay Moumita , Jha Saurabh Kumar , Liu Qing
Published: January 2024

The production and release of tumor-derived small extracellular vesicles (TDSEVs) from cancerous cells play a pivotal role in the propagation of cancer, through genetic and biological communication with healthy cells. TDSEVs are known to orchestrate the invasion-metastasis cascade via diverse pathways. Regulation of early metastasis processes, pre-metastatic niche formation, immune system regulation, angiogenesis initiation, extracellular matrix (ECM) remodeling, immune modulation, and epithelial-mesenchymal transition (EMT) are among the pathways regulated by TDSEVs. MicroRNAs (miRs) carried within TDSEVs play a pivotal role as a double-edged sword and can either promote metastasis or inhibit cancer progression. TDSEVs can serve as excellent markers for early detection of tumors, and tumor metastases. From a therapeutic point of view, the risk of cancer metastasis may be reduced by limiting the production of TDSEVs from tumor cells. On the other hand, TDSEVs represent a promising approach for in vivo delivery of therapeutic cargo to tumor cells. The present review article discusses the recent developments and the current views of TDSEVs in the field of cancer research and clinical applications.
Cumulative residual cholesterol predicts the risk of cardiovascular disease in the general population aged 45 years and older
Authors: Zhao Mengjie , Xiao Mengli , Tan Qin , Ji Jinjin , Lu Fang
Published: January 2024

Background

Numerous studies have affirmed a robust correlation between residual cholesterol (RC) and the occurrence of cardiovascular disease (CVD). However, the current body of literature fails to adequately address the link between alterations in RC and the occurrence of CVD. Existing studies have focused mainly on individual RC values. Hence, the primary objective of this study is to elucidate the association between the cumulative RC (Cum-RC) and the morbidity of CVD.

Methods

The changes in RC were categorized into a high-level fast-growth group (Class 1) and a low-level slow-growth group (Class 2) by K-means cluster analysis. To investigate the relationship between combined exposure to multiple lipids and CVD risk, a weighted quantile sum (WQS) regression analysis was employed. This analysis involved the calculation of weights for total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which were used to effectively elucidate the RC.

Results

Among the cohort of 5,372 research participants, a considerable proportion of 45.94% consisted of males, with a median age of 58. In the three years of follow-up, 669 participants (12.45%) had CVD. Logistic regression analysis revealed that Class 2 individuals had a significantly reduced risk of developing CVD compared to Class 1. The probability of having CVD increased by 13% for every 1-unit increase in the Cum-RC according to the analysis of continuous variables. The restricted cubic spline (RCS) analysis showed that Cum-RC and CVD risk were linearly related (P for nonlinearity = 0.679). The WQS regression results showed a nonsignificant trend toward an association between the WQS index and CVD incidence but an overall positive trend, with the greatest contribution from TC (weight = 0.652), followed by LDL (weight = 0.348).

Conclusion

Cum-RC was positively and strongly related to CVD risk, suggesting that in addition to focusing on traditional lipid markers, early intervention in patients with increased RC may further reduce the incidence of CVD.
CircNUP50 is a novel therapeutic target that promotes cisplatin resistance in ovarian cancer by modulating p53 ubiquitination
Authors: Zhu Yunshu , Liang Leilei , Zhao Yuxi , Li Jian , Zeng Jia , Yuan Yihang , Li Ning , Wu Lingying
Published: January 2024

Background

Most patients with ovarian cancer (OC) treated with platinum-based chemotherapy have a dismal prognosis owing to drug resistance. However, the regulatory mechanisms of circular RNA (circRNA) and p53 ubiquitination are unknown in platinum-resistant OC. We aimed to identify circRNAs associated with platinum-resistant OC to develop a novel treatment strategy.

Methods

Platinum-resistant circRNAs were screened through circRNA sequencing and validated using quantitative reverse-transcription PCR in OC cells and tissues. The characteristics of circNUP50 were analysed using Sanger sequencing, oligo (dT) primers, ribonuclease R and fluorescence in situ hybridisation assays. Functional experimental studies were performed in vitro and in vivo. The mechanism underlying circNUP50-mediated P53 ubiquitination was investigated through circRNA pull-down analysis and mass spectrometry, luciferase reporters, RNA binding protein immunoprecipitation, immunofluorescence assays, cycloheximide chase assays, and ubiquitination experiments. Finally, a platinum and si-circNUP50 co-delivery nanosystem (Psc@DPP) was constructed to treat platinum-resistant OC in an orthotopic animal model.

Results

We found that circNUP50 contributes to platinum-resistant conditions in OC by promoting cell proliferation, affecting the cell cycle, and reducing apoptosis. The si-circNUP50 mRNA sequencing and circRNA pull-down analysis showed that circNUP50 mediates platinum resistance in OC by binding p53 and UBE2T, accelerating p53 ubiquitination. By contrast, miRNA sequencing and circRNA pull-down experiments indicated that circNUP50 could serve as a sponge for miR-197-3p, thereby upregulating G3BP1 to mediate p53 ubiquitination, promoting OC platinum resistance. Psc@DPP effectively overcame platinum resistance in an OC tumour model and provided a novel idea for treating platinum-resistant OC using si-circNUP50.

Conclusions

This study reveals a novel molecular mechanism by which circNUP50 mediates platinum resistance in OC by modulating p53 ubiquitination and provides new insights for developing effective therapeutic strategies for platinum resistance in OC.

Graphical Abstract
Cell-cell communication characteristics in breast cancer metastasis
Authors: Xu Jingtong , Gao Fangyan , Liu Weici , Guan Xiaoxiang
Published: January 2024

Breast cancer, a highly fatal disease due to its tendency to metastasize, is the most prevalent form of malignant tumors among women worldwide. Numerous studies indicate that breast cancer exhibits a unique predilection for metastasis to specific organs including the bone, liver, lung, and brain. However, different types of, The understanding of the heterogeneity of metastatic breast cancer has notably improved with the recent advances in high-throughput sequencing techniques. Focusing on the modification in the microenvironment of the metastatic organs and the crosstalk between tumor cells and in situ cells, noteworthy research points include the identification of two distinct modes of tumor growth in bone metastases, the influence of type II pneumocyte on lung metastases, the paradoxical role of Kupffer cells in liver metastases, and the breakthrough of the blood-brain barrier (BBB) breach in brain metastases. Overall, this review provides a comprehensive overview of the characteristics of breast cancer metastases, shedding light on the pivotal roles of immune and resident cells in the development of distinct metastatic foci.

Graphical Abstract
Exploring the predictive power of jejunal microbiome composition in clinical and subclinical necrotic enteritis caused by Clostridium perfringens: insights from a broiler chicken model
Authors: Gautam Hemlata , Ayalew Lisanework E. , Shaik Noor Ahmad , Subhasinghe Iresha , Popowich Shelly , Chow-Lockerbie Betty , Dixon Alexa , Ahmed Khawaja Ashfaque , Tikoo Suresh K. , Gomis Susantha
Published: January 2024

Background

Necrotic enteritis (NE) is a severe intestinal infection that affects both humans and poultry. It is caused by the bacterium Clostridium perfringens (CP), but the precise mechanisms underlying the disease pathogenesis remain elusive. This study aims to develop an NE broiler chicken model, explore the impact of the microbiome on NE pathogenesis, and study the virulence of CP isolates with different toxin gene combinations.

Methods

This study established an animal disease model for NE in broiler chickens. The methodology encompassed inducing abrupt protein changes and immunosuppression in the first experiment, and in the second, challenging chickens with CP isolates containing various toxin genes. NE was evaluated through gross and histopathological scoring of the jejunum. Subsequently, jejunal contents were collected from these birds for microbiome analysis via 16S rRNA amplicon sequencing, followed by sequence analysis to investigate microbial diversity and abundance, employing different bioinformatic approaches.

Results

Our findings reveal that CP infection, combined with an abrupt increase in dietary protein concentration and/or infection with the immunosuppressive variant infectious bursal disease virus (vIBDV), predisposed birds to NE development. We observed a significant decrease (p < 0.0001) in the abundance of Lactobacillus and Romboutsia genera in the jejunum, accompanied by a notable increase (p < 0.0001) in Clostridium and Escherichia. Jejunal microbial dysbiosis and severe NE lesions were particularly evident in birds infected with CP isolates containing cpa, netB, tpeL, and cpb2 toxin genes, compared to CP isolates with other toxin gene combinations. Notably, birds that did not develop clinical or subclinical NE following CP infection exhibited a significantly higher (p < 0.0001) level of Romboutsia. These findings shed light on the complex interplay between CP infection, the gut microbiome, and NE pathogenesis in broiler chickens.

Conclusion

Our study establishes that dysbiosis within the jejunal microbiome serves as a reliable biomarker for detecting subclinical and clinical NE in broiler chicken models. Additionally, we identify the potential of the genera Romboutsia and Lactobacillus as promising candidates for probiotic development, offering effective alternatives to antibiotics in NE prevention and control.
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

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

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

Background

High 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.

Results

The 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.

Conclusions

The 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

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

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

Background

The 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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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

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

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

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.
Contrast-enhanced CT radiomics features to preoperatively identify differences between tumor and proximal tumor-adjacent and tumor-distant tissues of resectable esophageal squamous cell carcinoma
Authors: Gao Dan , Tan Bang-guo , Chen Xiao-qian , Zhou Chuanqinyuan , Ou Jing , Guo Wen-wen , Zhou Hai-ying , Li Rui , Zhang Xiao-ming , Chen Tian-wu
Published: January 2024

Background

Esophagectomy is the main treatment for esophageal squamous cell carcinoma (ESCC), and patients with histopathologically negative margins still have a relatively higher recurrence rate. Contrast-enhanced CT (CECT) radiomics might noninvasively obtain potential information about the internal heterogeneity of ESCC and its adjacent tissues. This study aimed to develop CECT radiomics models to preoperatively identify the differences between tumor and proximal tumor-adjacent and tumor-distant tissues in ESCC to potentially reduce tumor recurrence.

Methods

A total of 529 consecutive patients with ESCC from Centers A (n = 447) and B (n = 82) undergoing preoperative CECT were retrospectively enrolled in this study. Radiomics features of the tumor, proximal tumor-adjacent (PTA) and proximal tumor-distant (PTD) tissues were individually extracted by delineating the corresponding region of interest (ROI) on CECT and applying the 3D-Slicer radiomics module. Patients with pairwise tissues (ESCC vs. PTA, ESCC vs. PTD, and PTA vs. PTD) from Center A were randomly assigned to the training cohort (TC, n = 313) and internal validation cohort (IVC, n = 134). Univariate analysis and the least absolute shrinkage and selection operator were used to select the core radiomics features, and logistic regression was performed to develop radiomics models to differentiate individual pairwise tissues in TC, validated in IVC and the external validation cohort (EVC) from Center B. Diagnostic performance was assessed using area under the receiver operating characteristics curve (AUC) and accuracy.

Results

With the chosen 20, 19 and 5 core radiomics features in TC, 3 individual radiomics models were developed, which exhibited excellent ability to differentiate the tumor from PTA tissue (AUC: 0.965; accuracy: 0.965), the tumor from PTD tissue (AUC: 0.991; accuracy: 0.958), and PTA from PTD tissue (AUC: 0.870; accuracy: 0.848), respectively. In IVC and EVC, the models also showed good performance in differentiating the tumor from PTA tissue (AUCs: 0.956 and 0.962; accuracy: 0.956 and 0.937), the tumor from PTD tissue (AUCs: 0.990 and 0.974; accuracy: 0.952 and 0.970), and PTA from PTD tissue (AUCs: 0.806 and 0.786; accuracy: 0.760 and 0.786), respectively.

Conclusion

CECT radiomics models could differentiate the tumor from PTA tissue, the tumor from PTD tissue, and PTA from PTD tissue in ESCC.
Comparison of factors influencing landslide risk near a forest road in Chungju-si, South Korea
Authors: Moon Seong-Woo , Noh Jeongdu , Kim Hyeong-Sin , Kang Seong-Seung , Seo Yong-Seok
Published: January 2024

Background

The study aimed to identify the influential factors required to prepare landslide vulnerability maps and establish disaster prevention measures for mountainous areas with forest roads. The target area is Sancheok-myeon, Chungju-si, where several landslides have occurred in a narrow area of approximately 3 km × 4 km. As the area has the same rainfall and vegetation conditions, the influences of the physico-mechanical characteristics of the soil in accordance with compaction and topographic characteristics could be analyzed precisely.

Methods

Geological surveying, sampling, and laboratory testing assessed landslide risk in the study area, and data including unit weight, specific gravity, porosity, water content, soil depth, friction angle, cohesion, slope angle, profile/plan curvature, TWI were obtained. Preprocessing and screening such as min-max normalization and multicollinearity were conducted for the data in order to eliminate overestimation of each factor’s effectiveness. The influence of each factor was analyzed using logistic regression (LR), structural equation modeling (SEM), extreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM).

Results

All methods showed that soil depth has the greatest impact on landslide occurrence. Friction angle, slope angle, and porosity were also selected as influential factors, although each method ranked them slightly differently. Topographic factors, such as plan curvature, profile curvature, and the topographic wetness index, had minimal influence. This appears to be because landslides near forest roads are more affected by how well compaction was performed during banking than by the concave or convex shape of the slope. This study presents analysis results for an area with the same rainfall and vegetation conditions; therefore, the analysis of the influence of the physico-mechanical characteristics of the soil and topography was more precise than when comparing landslides occurring in different regions. Our results may be helpful in preparing landslide vulnerability maps.
Impact of recapitalisation and dividend payout policies on financial sustainability of rural and community banks in Ghana
Authors: Oduro Richard
Published: January 2024

The study examines the effect of bank recapitalization and dividend policies on the financial sustainability of rural and community banks (RCBs) in Ghana. Data from 135 RCBs from 2011 to 2020 revealed an average financial sustainability index of 0.525 over the past decade, suggesting that RCBs can finance their operations and liabilities without diminishing shareholder value. Recapitalization and dividend payouts positively impact financial sustainability, with well-capitalized, highly pay-out RCBs showing faster improvements in sustainability compared to those with retention policy. This highlights the importance of RCBs bolstering their capital base, even when not mandated by regulators, to enhance financial sustainability. Furthermore, adopting a relaxed pay-out policy can signal operational efficiency and sustainability to shareholders.