bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of lncRNA LINC00943 in lung squamous cell carcinoma and its relationship with tumor progression
Authors: Zhao Zhenshan , Li Haiyang , Li Jing , Rong Yao , Zhao Lidong , Hao Menghui , Tian Faming 
Published: April 2024

Abstract
Background
Molecular biology has been applied to the diagnosis, prognosis and treatment of various diseases, and long noncoding RNA LINC00943 (lncRNA LINC00943; LINC00943) plays an important role in a variety of cancers. Therefore, this study explored the prognostic role of LINC00943 in lung squamous cell carcinoma (LUSC) and understood its impact on the development of LUSC.

Methods
There are 89 LUSC patients were involved in current assay. By detecting the expression of LINC00943 and miR-196b-5p in tissues and cells, LINC00943 and its correlation with the characteristics of clinical data were analyzed. The biological function of LINC00943 was studied by Transwell migration and invasion assays. In addition, Pearson correlation coefficient and luciferase activity experiments were chosen to characterize the relationship between LINC00943 and miR-196b-5p and explore the mechanism of LINC00943.

Results
Compared with normal controls, LINC00943 expression in LUSC tissues and cells was significantly reduced, miR-196b-5p was markedly increased, there was a negative correlation between LINC00943 and miR-196b-5p. According to the in vitro cell experiments, migration and invasion of LUSC cells were suppressed by overexpression of LINC00943. Besides, LINC00943 was demonstrated to have prognostic power and targeting miR-196b-5p was involved in the progression of LUSC.

Conclusions
Overexpression of LINC00943 was molecular sponge for miR-196b-5p that controlled the deterioration of LUSC, which had great potential as a prognostic biomarker for LUSC.
Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer
Authors: Zhang Wenxin , Chen Lu , Liu Jiafeng , Chen Bicui , Shi Huanying , Chen Haifei , Qi Huijie , Wu Zimei , Mao Xiang , Wang Xinhai , Huang Yuxin , Li Jiyifan , Yu Zheng , Zhong Mingkang , Wang Tianxiao , Li Qunyi 
Published: April 2024

Abstract
Background
The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood.

Methods
In this study, patients from the cancer genome altas (TCGA) COAD/READ cohorts were used to investigate the biological mechanism driving ATG7 development. Several assays were conducted including the colony formation, cell viability, qRT-PCR, western blot, immunofluorescence, flow cytometry, ELISA, immunohistochemistry staining and in vivo tumorigenicity tests.

Results
We found that ATG7 plays a crucial role in MSI-H CRC. Its knockdown decreased tumor growth and caused an infiltration of CD8+ T effector cells in vivo. ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Meanwhile, ATG7 inhibition also suppressed cholesterol accumulation and augmentation of anti-tumor immune responses. Combining ATG7 inhibition and statins improved the therapeutic benefit of anti-PD-1 in MSI-H CRC. Importantly, CRC patients with high expression of both ATG7 and recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) experienced worse prognosis compared to those with low ATG7 and HMGCR expression.

Conclusions
Inhibition of ATG7 leads to upregulation of MHC-I expression, augments immune response and suppresses cholesterol accumulation. These findings demonstrate that ATG7 inhibition has therapeutic potential and application of statins can increase the sensitivity to immune checkpoint inhibitors.
Acute compartment syndrome and fasciotomy after a viper bite in Italy: a case report
Authors: Sassoè-Pognetto Marco , Cavalcante Riccardo , Paonessa Matteo 
Published: April 2024

Abstract
Background
Bites caused by European vipers are rare medical emergencies but can occasionally cause life-threatening complications. Viper venom causes local symptoms, which can be accompanied by systemic manifestations in severe cases. The local effects of snakebites include edema and, more rarely, necrosis and compartment syndrome. The consequences of envenomation are often more pronounced in children due to their smaller body size.

Case presentation
We present the case of a 6-year-old girl who experienced multiple viper bites in the lower limb in northwest Italy. The girl received supportive care but progressed to develop compartment syndrome that required emergency fasciotomy. The patient’s condition improved promptly after surgical decompression and administration of antivenom, but full recovery required prolonged hospitalization and rehabilitation.

Conclusions
This case highlights the importance of obtaining a timely assessment of the severity of viper envenomation without delaying the administration of antivenom in most serious cases. The presence of multiple bite marks on the patient is one factor that may help to predict the clinical severity of snakebites and anticipate symptom progression.
Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis
Authors: Gatti Milo , Cojutti Pier Giorgio , Pea Federico 
Published: April 2024

Abstract
Background
To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets.

Methods
Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs. conservative PK/PD targets on clinical efficacy of beta-lactams. Independent predictive factors of failure in attaining aggressive PK/PD targets were also assessed. Aggressive PK/PD target was considered a100%fT>4xMIC, and clinical cure rate was selected as primary outcome. Meta-analysis was performed by pooling odds ratios (ORs) extrapolated from studies providing adjustment for confounders using a random-effects model with inverse variance method.

Results
A total of 20,364 articles were screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 aggressive vs. 2640 conservative PK/PD target). Attaining aggressive PK/PD target was significantly associated with higher clinical cure rate (OR 1.69; 95% CI 1.15–2.49) and lower risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01–0.29). Male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint emerged as significant independent predictors of failure in attaining aggressive PK/PD targets, whereas prolonged/continuous infusion administration of beta-lactams resulted as protective factor. The risk of bias was moderate in 19 studies and severe in the other 2.

Conclusions
Attaining aggressive beta-lactams PK/PD targets provided significant clinical benefits in critical patients. Our analysis could be useful to stratify patients at high-risk of failure in attaining aggressive PK/PD targets.
3D printing vs traditional workflow for the fabrication of mandibular implant overdentures: study protocol for a mixed-methods cross-over RCT
Authors: Jafarpour Dana , El-Amier Nesma , Feine Jocelyne , Bedos Christophe , Abi-Nader Samer , Esfandiari Shahrokh , Shuster Tibor , Zimmermann Elizabeth , de Souza Raphael 
Published: April 2024

Abstract
Background
Complete tooth loss is a significant global oral health issue, particularly impacting older individuals with lower socioeconomic status. Computer-assisted technologies enhance oral healthcare access by the elderly. Despite promising in vitro reports on digital denture materials, evidence from randomized clinical trials (RCTs) is lacking to verify their performance. This cross-over RCT will investigate whether 3D-printed implant-retained mandibular overdentures (IMO) are more satisfactory for edentulous seniors than those made through traditional methods.

Methods/design
We will recruit 26 completely edentulous participants (any sex/gender) based on the following eligibility criteria: age ≥ 60 years, no tooth extraction in the past 12 months, two implants in the lower jaw, and need for new dentures in both jaws. Each participant will receive two denture pairs, either manufactured by 3D printing or traditionally, to be worn in a random order. A timeline of 3 months with each denture pair will be considered for outcome assessment (total: 6 months). Patient satisfaction with dentures will be measured by the McGill Denture Satisfaction Questionnaire. We will evaluate other patient-reported outcomes (including oral health-related quality of life) as well as clinician-assessed quality and cost. At the end of the trial, participants will choose which denture pair they wish to keep and interviewed about their experiences with the 3D-printed IMO. The quantitative and qualitative data will be incorporated through an explanatory mixed-methods strategy. A final quantitative assessment will happen after 12 months with the preferred IMO to assess the long-term performance and maintenance needs.

Discussion
This mixed-methods RCT will explore patient experiences with 3D-printed IMOs, aiming to assess the potential for altering clinical practice and dental public health policies. Our results will inform policies by showing whether 3D printing offers comparable outcomes at lower costs, facilitating greater access to oral care for the elderly.

Trial registration
ClinicalTrials.gov, NCT06155630, Registered on 04 December 2023. https://classic.clinicaltrials.gov/ct2/show/NCT06155630
Enhancing insulin sensitivity in type 2 diabetes mellitus using apelin-loaded small extracellular vesicles from Wharton’s jelly-derived mesenchymal stem cells: a novel therapeutic approach
Authors: Cui Jing , Wang Mingkun , Zhang Wenhong , Sun Jiachen , Zhang Yan , Zhao Li , Hong Zhibo , Li Dongtao , Huang Yi Xiong , Zhang Ningkun , Chen Yu 
Published: April 2024

Abstract
Background
Type 2 diabetes mellitus (T2DM), characterized by β-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin.

Methods
WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation.

Results
Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic β-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs.

Conclusion
Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs.
Arterial embolization in the treatment of multiple renal and hepatic hamartomas with spontaneous hemorrhage and 2-year follow-up: a case report
Authors: Zhang Jianhua , Zhen Tao , Jian Hongmei , Yang Jinlan , Zhang Ni 
Published: April 2024

Abstract
Background
Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening.

Case presentation
This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature

Conclusions
the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.
Non-invasive quantification of 18F-florbetaben with total-body EXPLORER PET
Authors: Holy Emily Nicole , Li Elizabeth , Bhattarai Anjan , Fletcher Evan , Alfaro Evelyn R. , Harvey Danielle J. , Spencer Benjamin A. , Cherry Simon R. , DeCarli Charles S. , Fan Audrey P. 
Published: April 2024

Abstract
Background
Kinetic modeling of 18F-florbetaben provides important quantification of brain amyloid deposition in research and clinical settings but its use is limited by the requirement of arterial blood data for quantitative PET. The total-body EXPLORER PET scanner supports the dynamic acquisition of a full human body simultaneously and permits noninvasive image-derived input functions (IDIFs) as an alternative to arterial blood sampling. This study quantified brain amyloid burden with kinetic modeling, leveraging dynamic 18F-florbetaben PET in aorta IDIFs and the brain in an elderly cohort.

Methods
18F-florbetaben dynamic PET imaging was performed on the EXPLORER system with tracer injection (300 MBq) in 3 individuals with Alzheimer’s disease (AD), 3 with mild cognitive impairment, and 9 healthy controls. Image-derived input functions were extracted from the descending aorta with manual regions of interest based on the first 30 s after injection. Dynamic time-activity curves (TACs) for 110 min were fitted to the two-tissue compartment model (2TCM) using population-based metabolite corrected IDIFs to calculate total and specific distribution volumes (VT, Vs) in key brain regions with early amyloid accumulation. Non-displaceable binding potential ($$ {BP}_{ND})$$ was also calculated from the multi-reference tissue model (MRTM).

Results
Amyloid-positive (AD) patients showed the highest VT and VS in anterior cingulate, posterior cingulate, and precuneus, consistent with $$ {BP}_{ND}$$ analysis. $$ {BP}_{ND} $$and VT from kinetic models were correlated (r² = 0.46, P < 2$$ {e}^{-16})$$ with a stronger positive correlation observed in amyloid-positive participants, indicating reliable model fits with the IDIFs. VT from 2TCM was highly correlated ($$ {r}^{2}$$= 0.65, P < 2$$ {e}^{-16}$$) with Logan graphical VT estimation.

Conclusion
Non-invasive quantification of amyloid binding from total-body 18F-florbetaben PET data is feasible using aorta IDIFs with high agreement between kinetic distribution volume parameters compared to $$ {BP}_{ND} $$in amyloid-positive and amyloid-negative older individuals.
Patterns and trends of medicinal poisoning substances: a population-based cohort study of injuries in 0–11 year old children from 1998–2018
Authors: Tyrrell Edward G , Orton Elizabeth , Tata Laila J , Kendrick Denise 
Published: April 2024

Abstract
Background
There have been sharp increases in antidepressant and opioid prescriptions over the last 10 years, as well as increased over-the-counter medicine availability. However, the impact on childhood medicinal poisonings rates, particularly by socioeconomic deprivation is unclear. This study reports population level medicinal poisoning substance patterns in England among children aged 0–11 years, helping inform safety advice and poisoning prevention interventions.

Methods
An open cohort study of 1,489,620 0–11 year olds was conducted from 1998 to 2018, using the Clinical Practice Research Datalink, to examine inpatient hospital admissions for poisoning. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substance groups by age, sex, socio-economic deprivation and year.

Results
3,685 medicinal poisoning hospital admissions were identified. The most common substances were paracetamol (33.2%), dependence/withdrawal risk drugs (DWRD - antidepressants, opioids, gabapentinoids, benzodiazepines) (13.5%) and other over-the-counter (OTC) analgesics/anti-common cold drugs (13.0%). Over the study period DWRD poisonings decreased 33% (aIRR 0.67, 95%CI 0.50–0.90 comparing 2013/14-2017/18 to 1998/99-2002/03), while paracetamol poisonings increased 43% (aIRR 1.43, 95%CI 1.20–1.70 for the same periods), with no change in incidence rates for other OTC drugs (aIRR 0.82, 95% CI 0.60–1.12) or all medications combined (aIRR 0.97, 95%CI 0.88–1.07). A gradient in poisonings by area-level socioeconomic deprivation was shown for all medications (aIRR 1.32, 95%CI 1.18–1.47 for most deprived compared to least deprived quintile), and DWRDs (aIRR 2.03, 95%CI 1.42–2.88 for 4th most deprived quintile and aIRR 1.88, 95%CI 1.32–2.66 for 5th most deprived quintile, compared to least deprived quintile), but not for paracetamol or other OTC drug poisonings.

Conclusions
Poisonings from DWRDs decreased by 33%, while paracetamol poisonings increased by 43% during the study period. There was a gradient by area-level socioeconomic deprivation in prescribed medication poisonings, including drugs with withdrawal/dependence risk, but not OTC medication poisonings. Households in more socioeconomically deprived areas have the potential to benefit most from measures to improve safe storage of medicines and are likely to require targeted interventions providing education and safety equipment. In addition, universal promotion of the safe storage of OTC and prescribed medicines must be provided by prescribers, community pharmacies and other outlets of such medication.
Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence
Authors: Liu Yuanhui , Peng Bi , Chen Ziqi , Shen Yimin , Zhang Jingmin , Yuan Xianglin 
Published: April 2024

AbstractChemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.
Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients
Authors: Ho Minh , Nguyen Huynh-Nga , Van Hoang Minh , Bui Tien Thuy Thi , Vu Bao-Quoc , Dinh Truc Huong Thi , Vo Hoa Thi My , Blaydon Diana C. , Eldirany Sherif A. , Bunick Christopher G. , Bui Chi-Bao 
Published: April 2024

Abstract
Background
Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI.

Results
This case–control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing.

Conclusions
Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.