bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the role of neddylation in tumor microenvironment modulation: common outcome of multiple signaling pathways
Authors: Liu Dequan , Che Xiangyu , Wu Guangzhen 
Published: January 2024

AbstractNeddylation is a post-translational modification process, similar to ubiquitination, that controls several biological processes. Notably, it is often aberrantly activated in neoplasms and plays a critical role in the intricate dynamics of the tumor microenvironment (TME). This regulatory influence of neddylation permeates extensively and profoundly within the TME, affecting the behavior of tumor cells, immune cells, angiogenesis, and the extracellular matrix. Usually, neddylation promotes tumor progression towards increased malignancy. In this review, we highlight the latest understanding of the intricate molecular mechanisms that target neddylation to modulate the TME by affecting various signaling pathways. There is emerging evidence that the targeted disruption of the neddylation modification process, specifically the inhibition of cullin-RING ligases (CRLs) functionality, presents a promising avenue for targeted therapy. MLN4924, a small-molecule inhibitor of the neddylation pathway, precisely targets the neural precursor cell-expressed developmentally downregulated protein 8 activating enzyme (NAE). In recent years, significant advancements have been made in the field of neddylation modification therapy, particularly the integration of MLN4924 with chemotherapy or targeted therapy. This combined approach has demonstrated notable success in the treatment of a variety of hematological and solid tumors. Here, we investigated the inhibitory effects of MLN4924 on neddylation and summarized the current therapeutic outcomes of MLN4924 against various tumors. In conclusion, this review provides a comprehensive, up-to-date, and thorough overview of neddylation modifications, and offers insight into the critical importance of this cellular process in tumorigenesis.
Nanomaterial-encapsulated STING agonists for immune modulation in cancer therapy
Authors: Chen Xi , Xu Zhijie , Li Tongfei , Thakur Abhimanyu , Wen Yu , Zhang Kui , Liu Yuanhong , Liang Qiuju , Liu Wangrui , Qin Jiang-Jiang , Yan Yuanliang 
Published: January 2024

AbstractThe cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.
Chromatographic analysis of natural dyes in mediaeval Islamic paper
Authors: Ebeid Hassan , Di Gianvincenzo Fabiana , Kralj Cigić Irena , Strlič Matija 
Published: January 2024

Abstract
Numerous natural dyes were used to dye mediaeval Islamic paper from the tenth to the nineteenth century, using a variety of techniques. The objective of this research is to develop an analytical method using high performance liquid chromatography with diode array detection (HPLC–DAD) to identify natural dyes in forty historical Islamic paper manuscripts from two collections. In addition, novel information was obtained from original treatises containing recipes for dyeing paper and the chronological use of dyes in dyeing mediaeval Islamic paper between the tenth and seventeenth centuries. The results show that thirty-four of the forty manuscripts examined contained dyes. Six natural dyes were detected, including henna, madder, lac, safflower, turmeric, and weld. This is the first study aimed at developing a method for determining various natural dyes in Islamic paper from a wide historical and geographical range in the mediaeval time and to fill significant gaps in the technical and historical knowledge of papermaking.
Three-dimensional velocity structure models in and around the Kathmandu Valley, Central Nepal
Authors: Koketsu Kazuki , Suzuki Haruhiko , Guo Yujia 
Published: January 2024

AbstractWe analyzed observations of microtremors and seismic ground motion to determine the depths of sedimentary interfaces and basement surface in the Kathmandu Valley. The results of these analyses and a reflection survey were combined to produce a data set of seismic depths for sedimentary interfaces and basement surface in the valley. Moreover, we introduced a data set of gravimetric depths, which had been produced for the basement surface from gravity observations. Because both sets of data differ in accuracy and number, we adopt the Sequential Gaussian Co-Simulation to generate the depth distributions of the sedimentary interfaces and basement surface. This method includes the cokriging approach, wherein the seismic and gravimetric depths are used as primary and secondary data, respectively. A three-dimensional velocity structure model of the Kathmandu Valley was constructed from the obtained depth distributions, which showed that the sedimentation in the valley is mainly related to the Paleo-Kathmandu Lake. Subsequently, we incorporated this model into a previous regional-scale model, and revised the latter to solve the issues of the extension of the underthrusting lithosphere and the S-wave velocity in its adjacent area.
Graphical Abstract
Performance of the double-thin-shell approach for studying nighttime medium-scale traveling ionospheric disturbances using two dense GNSS observation networks in Japan
Authors: Fu Weizheng , Otsuka Yuichi , Shinbori Atsuki , Nishioka Michi , Perwitasari Septi 
Published: January 2024

AbstractElectrodynamic coupling between the ionospheric E and F regions is widely recognized as the underlying mechanism for generating medium-scale traveling ionospheric disturbances (MSTIDs) during nighttime at midlatitudes. Recently, the double-thin-shell approach has proven to be a useful tool for studying the E–F coupling. By using total electron content (TEC) measurements, this approach enables the simultaneous reconstruction of electron density perturbations in both the E and F regions with broad and continuous coverage. However, the current reconstruction performance is limited when using only GPS-TEC measurements from GEONET, a dense network of ground-based Global Navigation Satellite System (GNSS) receivers over Japan. The expansion of available data sources and the integration of multi-GNSS observation data are considered important to enhance the double-thin-shell model. Fortunately, SoftBank Corp., a Japanese telecommunications provider, has recently developed a dense independent GNSS observation network to improve positioning services. In this paper, we analyze the potential of the improved double-thin-shell approach and emphasize the importance of incorporating multi-GNSS observation data from both GEONET and SoftBank networks. The solvability analysis, simulation, and observation results collectively indicate a substantial improvement in the spatiotemporal resolution. Specifically, the longitudinal and latitudinal resolution is improved from 0.15° to 0.1° in the E region, and from 0.5° to 0.3° in the F region. The temporal resolution is also improved from 2 to 1 min. In addition, significant improvements have been achieved in the reconstruction performance, particularly for the E region under complex background conditions. Based on these assessments, we conclude that the incorporation of GEONET and SoftBank GNSS observation data holds significant potential for improving the double-thin-shell model and advancing our understanding of MSTIDs.
Graphical abstract
Enhancing child dietary diversity through cooking demonstration and nutritional education in rural Lao PDR
Authors: Sato Yu , Khamphithoun Somboun , Saiyachak Khamphanavanh , Ando Hisao , Ishizuka Takaaki , Saeki Shinjiro , Miyoshi Miki 
Published: January 2024

Abstract
Background
Efforts to prevent malnutrition in children under five are crucial for both short-term and long-term impact, especially in resource-constrained low- and middle-income countries, where ensuring minimal food diversity remains an urgent challenge. Our organization implemented initiatives to improve dietary diversity among children under five in rural areas of Lao People’s Democratic Republic (Lao PDR).

Methods
We carried out educational and awareness programs directed at caregivers of children aged 6–59 months. These programs were delivered by healthcare professionals and trained community volunteers in specific areas of Xaybouathong District, Khammouane Province. To evaluate the impact of our interventions, we conducted surveys both at the beginning and end of the project. We designated the Individual Dietary Diversity Score IDDS as the objective variable, serving as an indicator of child dietary diversity. Using sociodemographic and economic indicators as explanatory variables, we assessed the impact of the intervention through multivariate analysis with a generalized linear model as well as a bivariate analysis.

Results
The comparison between 210 children at baseline and 205 children at endline revealed a significant increase in IDDS among children aged 6–23 months (from 3.36 to 4.22) and children aged 24–59 months (from 3.29 to 3.83). Multivariate analysis indicated a significant association between the intervention effect (baseline vs. endline) and the village of residence. Furthermore, significant improvements were observed in each food group that constitute IDDS, including vegetables and fruits, eggs, and legumes and nuts.

Conclusions
Even in resource-limited settings, such as rural areas of Lao PDR, it is possible to improve child dietary diversity through educational approaches that encourage the utilization of locally available foods.
The gut-liver axis in hepatobiliary diseases
Authors: Ichikawa Masataka , Okada Haruka , Nakamoto Nobuhiro , Taniki Nobuhito , Chu Po-Sung , Kanai Takanori 
Published: January 2024

AbstractRecent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis.
Early versus late diagnosis of LAMA2 congenital muscular dystrophy: a distinct consequence
Authors: Lin Chien-Heng , Lin Sheng-Shing , Hong Syuan-Yu , Chen Chieh-Ho , Chou I-Ching 
Published: January 2024

Abstract
Background
Laminin subunit alpha 2 (LAMA2)-related muscular dystrophy (LAMA2 MD) is caused by homozygous or compound heterozygous mutations in LAMA2 (OMIM#156225), located on chromosome 6q22.

Case presentation
We describe two patients with LAMA2 MD treated at a Taiwanese hospital. Both presented with gradual hypotonia starting in early infancy. A targeted muscular dystrophy/myopathy panel and whole-exome sequencing were used as diagnostic tools in both patients. In Patient 1, a maternally inherited variant (NM_000426.3:c.7525_7528dupCTCA/ p.Ser2510ThrfsTer3) and a paternally inherited variant (c.112 + 2 T > C) were revealed. In Patient 2, compound heterozygote mutations in LAMA2 were identified: 1) c.1583dupA(p.S529Efs*18) in exon 11, inherited paternally, and 2) c.A6931T:p.K2311X in exon 49, inherited maternally. The discovery of these four mutations enriches the genetic spectrum of LAMA2 MD.

Conclusions
We suggest that comprehensive genetic investigations be performed as early as possible in patients with suspected muscular dystrophy to provide appropriate treatment.
Maternal Serum Polyols and Its Link to Gestational Diabetes Mellitus: A Population-Based Nested Case–Control Study
Authors: Li Xiaoyong , Liu Yu , Qi Yicheng , Wu Yiming , Wang Meng , Gao Jing , Su Qing , Ma Jing , Qin Li 
Published: January 2024

Abstract

Context
Sugar alcohols (also called polyols) are regarded as a “healthy” sugar substitute. One of the possible reasons for their safe use in pregnant women is their natural origin and the presence of polyols in maternal and fetal samples during normal human gestation. But little is known about the association between circulating sugar alcohols levels and maternal metabolic disorders during pregnancy.

Objective
We aimed to detect the concentration of the polyols in participants with and without gestational diabetes mellitus (GDM), and to investigate the association between maternal serum levels of polyols and GDM, as well as newborn outcomes.

Methods
A nested population-based case–control study was conducted in 109 women with and without GDM. Maternal concentrations of serum erythritol, sorbitol, and xylitol in the fasting state were quantified using a time of flight mass spectrometry system.

Result
In women with GDM, serum concentrations of erythritol and sorbitol were higher, but serum concentrations of xylitol were lower than those in women without GDM. Per 1-SD increment of Box–Cox-transformed concentrations of erythritol and sorbitol were associated with the increased odds of GDM by 43% and 155% (95% CI 1.07-1.92 and 95% CI 1.77-3.69), while decreased odds were found for xylitol by 25% (95% CI 0.57-1.00). Additionally, per 1-SD increase of Box–Cox-transformed concentrations of serum sorbitol was associated with a 52% increased odds of large for gestational age newborns controlling for possible confounders (95% CI 1.00-2.30).

Conclusion
Maternal circulating sugar alcohols levels during pregnancy were significantly associated with GDM. These findings provide the potential roles of polyols on maternal metabolic health during pregnancy.
Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis
Authors: Ekrami Elyad , Sari Sinem , Kopac Orkun , Wang Dong , Mascha Edward J. , Stamper Samantha , Esa Wael Ali Sakr , Nair Harsha , Ruetzler Kurt , Turan Alparslan 
Published: January 2024

BACKGROUND:
Cannabis is a widely used illicit drug with effects on different pain pathways. However, interactions between cannabis and postoperative pain are unclear. Cannabis smoking also affects the lungs, but the impact of cannabis use on postoperative pulmonary complications is unknown. We hypothesized that preoperative cannabis use in adults having elective surgery is associated with higher postoperative opioid consumption. Secondarily, we tested the hypothesis that cannabis use is associated with higher pain scores, hypoxemia (oxygen saturation [Spo
2]/fraction of inspired oxygen [Fio
2] ratio), and higher postoperative pulmonary complications compared to nonuse of cannabis.

METHODS:
In this retrospective study, we included adult patients who had elective surgeries at Cleveland Clinic Main Campus between January 2010 and December 2020. The exposure was use of cannabis within 30 days before surgery, and the control group never used cannabis. Patients who had regional anesthesia or chronic pain diagnosis were excluded. The primary outcome was postoperative opioid consumption; 3 secondary outcomes were time-weighted average (TWA) postoperative pain score, TWA Spo
2/Fio
2 ratio, and composite of pulmonary complications after surgery. We assessed the association between cannabis use and opioid consumption during the first 24 postoperative hours using linear regression on log-transformed opioid consumption with a propensity score–based method (inverse probability of treatment weighting [IPTW]) adjusting for confounders. We further adjusted for imbalanced confounding variables after IPTW was applied.

RESULTS:
In total, 1683 of 34,521 patients were identified as cannabis users. Cannabis use was associated with increased opioid consumption, with an adjusted ratio of geometric means (95% confidence interval [CI]) of 1.30 (1.22–1.38; P < .0001) for cannabis users versus nonusers. Secondarily, (1) cannabis use was associated with increased TWA pain score, with a difference in means of 0.57 (95% CI, 0.46–0.67; P < .0001); (2) cannabis use was not associated with TWA Spo
2/Fio
2, with an adjusted difference in means of 0.5 (95% CI, −3.1 to 4.2; P = .76); and (3) cannabis use was not associated with a collapsed composite of pulmonary complications, with estimated odds ratio of 0.90 (95% CI, 0.71–1.13; P = .34).

CONCLUSIONS:
Adult cannabis users undergoing surgeries were found to have significantly higher postoperative opioid consumption and pain scores than nonusers. Cannabis use did not have a clinically meaningful association with hypoxia or composite pulmonary complications.
What Is the Role of a Periarticular Injection for Knee Arthroplasty Patients Receiving a Multimodal Analgesia Regimen Incorporating Adductor Canal and Infiltration Between the Popliteal Artery and Capsule of the Knee Blocks? A Randomized Blinded Placebo-Controlled Noninferiority Trial
Authors: YaDeau Jacques T. , Cushner Fred D. , Westrich Geoffrey , Lauzadis Justas , Kahn Richard L. , Lin Yi , Goytizolo Enrique A. , Mayman David J. , Jules-Elysee Kethy M. , Gbaje Ejiro , Padgett Douglas E. 
Published: January 2024

BACKGROUND:
Optimal analgesic protocols for total knee arthroplasty (TKA) patients remain controversial. Multimodal analgesia is advocated, often including peripheral nerve blocks and/or periarticular injections (PAIs). If 2 blocks (adductor canal block [ACB] plus infiltration between the popliteal artery and capsule of the knee [IPACK]) are used, also performing PAI may not be necessary. This noninferiority trial hypothesized that TKA patients with ACB + IPACK + saline PAI (sham infiltration) would have pain scores that were no worse than those of patients with ACB + IPACK + active PAI with local anesthetic.

METHODS:
A multimodal analgesic protocol of spinal anesthesia, ACB and IPACK blocks, intraoperative ketamine and ketorolac, postoperative ketorolac followed by meloxicam, acetaminophen, duloxetine, and oral opioids was used. Patients undergoing primary unilateral TKA were randomized to receive either active PAI or control PAI. The active PAI included a deep injection, performed before cementation, of bupivacaine 0.25% with epinephrine, 30 mL; morphine; methylprednisolone; cefazolin; with normal saline to bring total volume to 64 mL. A superficial injection of 20 mL bupivacaine, 0.25%, was administered before closure. Control injections were normal saline injected with the same injection technique and volumes. The primary outcome was numeric rating scale pain with ambulation on postoperative day 1. A noninferiority margin of 1.0 was used.

RESULTS:
Ninety-four patients were randomized. NRS pain with ambulation at POD1 in the ACB + IPACK + saline PAI group was not found to be noninferior to that of the ACB + IPACK + active PAI group (difference = 0.3, 95% confidence interval [CI], [−0.9 to 1.5], P = .120). Pain scores at rest did not differ significantly among groups. No significant difference was observed in opioid consumption between groups. Cumulative oral morphine equivalents through postoperative day 2 were 89 ± 40 mg (mean ± standard deviation), saline PAI, vs 73 ± 52, active PAI, P = .1. No significant differences were observed for worst pain, fraction of time in severe pain, pain interference, side-effects (nausea, drowsiness, itching, dizziness), quality of recovery, satisfaction, length of stay, chronic pain, and orthopedic outcomes.

CONCLUSIONS:
For TKA patients given a comprehensive analgesic protocol, use of saline PAI did not demonstrate noninferiority compared to active PAI. Neither the primary nor any secondary outcomes demonstrated superiority for active PAI, however. As we cannot claim either technique to be better or worse, there remains flexibility for use of either technique.
Open Surgical Obliteration of Three Indirect Carotid-Cavernous Fistulas
Authors: Kosarchuk Jacob , Patel Shrey , Dent Walter , Hedges Thomas , Malek Adel , Heilman Carl 
Published: January 2024

BACKGROUND AND IMPORTANCE:
Carotid-cavernous fistulas (CCFs) are abnormal connections between the carotid artery and the cavernous sinus (CS). CCFs are primarily treated by an endovascular route, but there are situations in which a lesion is not amenable to endovascular or transorbital treatment, necessitating a transcranial approach. In this select group of patients, the use of crushed temporalis muscle to pack the CS fistula site was found to be an effective method for treatment of CCFs.

CLINICAL PRESENTATION:
In this case series, we present 3 patients with CCFs in which endovascular treatment was not possible because of occlusion of the petrosal sinuses or stenosis of the superior ophthalmic vein at the superior orbital fissure, rendering the lesion inaccessible by a transvenous or transorbital route. Each patient was treated with a variation of temporalis muscle packing through a skull base triangle; one was treated through the anteromedial triangle, one through the supratrochlear triangle, and the third through the Parkinson triangle. The fistulas were cured in each case.

CONCLUSION:
Cavernous-carotid fistulas that are not amenable to endovascular or transorbital treatment can be successfully treated by packing the CS fistula site with crushed temporalis muscle. To cure these patients' symptoms and enhance their quality of life, it is crucial to weigh the advantages and disadvantages of each therapy option.