bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical applications and perspectives of circulating tumor DNA in gastric cancer
Authors: Li Jing-Han , Zhang Dan-Ying , Zhu Ji-Min , Dong Ling 
Published: January 2024

AbstractGastric cancer remains a leading cause of cancer-related death worldwide, largely due to inadequate screening methods, late diagnosis, and limited treatment options. Liquid biopsy has emerged as a promising non-invasive approach for cancer screening and prognosis by detecting circulating tumor components like circulating tumor DNA (ctDNA) in the blood. Numerous gastric cancer-specific ctDNA biomarkers have now been identified. CtDNA analysis provides insight into genetic and epigenetic alterations in tumors, holding promise for predicting treatment response and prognosis in gastric cancer patients. This review summarizes current research on ctDNA biology and detection technologies, while highlighting clinical applications of ctDNA for gastric cancer diagnosis, prognosis, and guiding treatment decisions. Current challenges and future perspectives for ctDNA analysis are also discussed.
Adoptive cell transfer therapy with ex vivo primed peripheral lymphocytes in combination with anti-PDL1 therapy effectively inhibits triple-negative breast cancer growth and metastasis
Authors: Gammelgaard Odd L. , Terp Mikkel G. , Kirkin Alexei F. , Johansen Simone , Traynor Sofie , Vever Henriette , Guldberg Per , Kodahl Annette R. , Gjerstorff Morten F. , Ditzel Henrik J. 
Published: January 2024

Abstract
Background
Adoptive cell transfer cancer immunotherapy holds promise for treating disseminated disease, yet generating sufficient numbers of lymphocytes with anti-cancer activity against diverse specificities remains a major challenge. We recently developed a novel procedure (ALECSAT) for selecting, expanding and maturating polyclonal lymphocytes from peripheral blood with the capacity to target malignant cells.

Methods
Immunodeficient mice were challenged with triple-negative breast cancer cell lines or patient-derived xenografts (PDX) and treated with allogeneic or autologous ALECSAT cells with and without anti-PDL1 therapy to assess the capacity of ALECSAT cells to inhibit primary tumor growth and metastasis.

Results
ALECSAT mono therapy inhibited metastasis, but did not inhibit primary tumor growth or prolong survival of tumor-bearing mice. In contrast, combined ALECSAT and anti-PDL1 therapy significantly inhibited primary tumor growth, nearly completely blocked metastasis, and prolonged survival of tumor-bearing mice.

Conclusions
Combined ALECSAT and anti-PDL1 therapy results in favorable anti-cancer responses in both cell line-derived xenograft and autologous PDX models of advanced triple-negative breast cancer.
N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation
Authors: Li Han , Lin Run , Zhang Yanna , Zhu Yanni , Huang Shuting , Lan Jing , Lu Nian , Xie Chuanmiao , He Shanyang , Zhang Weijing 
Published: January 2024

Abstract
Background
Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear.

Methods
Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH.

Results
circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model.

Conclusions
Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.
Proteomic profile of tepary bean seed storage proteins in germination with low water potential
Authors: Padilla-Chacón Daniel , Campos-Patiño Laura , Peña-Valdivia Cecilia B. , García-Esteva Antonio , Jiménez-Galindo José Cruz , Pizeno-García Jorge Luis 
Published: January 2024

Abstract
Background
Tepary bean (Phaseolus acutifolius A. Gray) is one of the five species domesticated from the genus Phaseolus with genetic resistance to biotic and abiotic stress. To understand the mechanisms underlying drought responses in seed storage proteins germinated on water and polyethylene glycol (PEG-6000) at -0.49 MPa, we used a proteomics approach to identify potential molecular target proteins associated with the low water potential stress response.

Methods
Storage proteins from cotyledons of Tepary bean seeds germinated at 24, 48 and 72 h on water and PEG-6000 at -0.49 MPa were analyzed by one-dimensional electrophoresis (DE) with 2-DE analysis and shotgun mass spectrometry. Using computational database searching and bioinformatics analyses, we performed Gene Ontology (GO) and protein interactome (functional protein association network) String analyses.

Results
Comparative analysis showed that the effect of PEG-6000 on root growth was parallel to that on germination. Based on the SDS‒PAGE protein banding patterns and 2-DE analysis, ten differentially abundant seed storage proteins showed changes in storage proteins, principally in the phaseolin and lectin fractions. We found many proteins that are recognized as drought stress-responsive proteins, and several of them are predicted to be intrinsically related to abiotic stress. The shotgun analysis searched against UniProt’s legume database, and Gene Ontology (GO) analysis indicated that most of the seed proteins were cytosolic, with catalytic activity and associated with carbohydrate metabolism. The protein‒protein interaction networks from functional enrichment analysis showed that phytohemagglutinin interacts with proteins associated with the degradation of storage proteins in the cotyledons of common bean during germination.

Conclusion
These findings suggest that Tepary bean seed proteins provide valuable information with the potential to be used in genetic improvement and are part of the drought stress response, making our approach a potentially useful strategy for discovering novel drought-responsive proteins in other plant models.
People Who Inject Drugs in Mozambique: We need to normalize HIV treatment and care services in specialized community centers for people who inject drugs!
Authors: Semá Baltazar Cynthia , Ribeiro Banze Auria , Seleme Jessica , Boothe Makini 
Published: January 2024

AbstractGlobally, People Who Inject Drugs (PWID) have limited healthcare, treatment, and prevention services, and they frequently experience stigma and negative attitudes toward healthcare providers when accessing services. Mozambique, with a general population HIV prevalence of 12.5%, has one of the highest rates in the world, and the PWID population has the highest HIV prevalence among key populations, estimated at nearly 50%. Less than half of HIV positives who inject drugs are linked to HIV treatment and are retained in care. One of the main reasons is that HIV treatment is mainly provided in a public health facility and PWID delayed accessing healthcare since they anticipated mistreatment from multiple levels of healthcare providers. To improve the health outcomes in this group, we need to treat them where they feel comfortable and respected. In this commentary, we outline the importance of innovative approaches to enhance the management of HIV-positive PWID. As a country gets close to controlling the HIV epidemic, refocusing and targeting responses to the highest-risk groups becomes even more essential for shaping more effective HIV interventions and achieving epidemic control.
PLOD3 facilitated T cell activation in the colorectal tumor microenvironment and liver metastasis by the TNF-α/ NF-κB pathway
Authors: Ding Min , Wang Cheng , Hu Junhong , She Junjun , Shi Ruoyu , Liu Yixuan , Sun Qi , Xu Haojun , Zhou Guoren , Wu Wenlan , Xia Hongping 
Published: January 2024

Abstract
Background
Colorectal cancer (CRC) has been the third most prevalent cancer worldwide. Liver metastasis is the critical factor for the poor prognosis of CRC. Here, we investigated the expression and role of PLOD3 in CRC.

Methods
Different liver metastasis models were established by injecting PLOD3 stable knockdown or overexpression CT26 or MC38 mouse CRC cells into the spleen of mice to verify the tumorigenicity and metastasis ability in vivo.

Results
We identified PLOD3 is significantly overexpressed in liver metastasis samples of CRC. High expression of PLOD3 was significantly associated with poor survival of CRC patients. The knockdown of PLOD3 exhibited remarkable inhibition of proliferation, migration, and invasion in CRC cells, while the opposite results could be found in different PLOD3-overexpressed CRC cells. Stable knockdown of PLOD3 also significantly inhibited liver metastasis of CRC cells in different xenografts models, while stable overexpression of PLOD3 promotes liver metastasis and tumor progression. Further studies showed that PLOD3 facilitated the T cell activation in the tumor microenvironment and affected the TNF-α/ NF-κB pathway.

Conclusions
This study revealed the essential biological functions of PLOD3 in colon cancer progression and metastasis, suggesting that PLOD3 is a promising translational medicine target and bioengineering targeting PLOD3 overcomes CRC liver metastasis.

Graphical Abstract
Effect of residual volume after surgery of the discoid lateral meniscus on tibiofemoral joint biomechanics: a finite element analysis
Authors: Shen Xin , Lu Meifeng , Liu Muzi , Xie Ronghui , Gong Shiguo , Yang Chunjing , Sun Guicai 
Published: January 2024

Abstract
Background
The purpose of this study was to investigate the influence of different residual meniscus volume on the biomechanics of tibiofemoral joint after discoid lateral meniscus (DLM) surgery by finite element analysis.

Methods
A knee joint model was established based on CT and MRI imaging data. The DLM model was divided into five regions according to conventional meniscectomy, with volumes of 15%, 15%, 15%, 15%, 15%, and 40% for each region. Additionally, the DLM model was divided into anterior and posterior parts to obtain ten regions. The DLM was resected according to the design scheme, and together with the intact discoid meniscus, a total of 15 models were obtained. Finite element analysis was conducted to assess shear and pressure trends on the knee joint.

Results
The study observed significant changes in peak shear stress and compressive stress in the lateral meniscus and lateral femur cartilage. As the meniscus volume decreased, there was an increase in these stresses. Specifically, when the meniscus volume reduced to 40%, there was a sharp increase in shear stress (302%) and compressive stress (152%) on the meniscus, as well as shear stress (195%) and compressive stress (157%) on the lateral femur cartilage. Furthermore, the model grouping results showed that preserving a higher frontal volume in the meniscus model provided better biomechanical advantages.

Conclusion
The use of finite element analysis has demonstrated that preserving more than 55% of the meniscus volume is necessary to prevent a significant increase in joint stress, which can potentially lead to joint degeneration. Additionally, it is crucial to preserve the front volume of the DLM in order to achieve improved knee biomechanical outcomes.
Establishment of a risk prediction model for residual low back pain in thoracolumbar osteoporotic vertebral compression fractures after percutaneous kyphoplasty
Authors: Tu Weiqiao , Niu Yanping , Su Peng , Liu Di , Lin Fanguo , Sun Yongming 
Published: January 2024

Abstract
Objective
This study aims to identify potential independent risk factors for residual low back pain (LBP) in patients with thoracolumbar osteoporotic vertebral compression fractures (OVCFs) following percutaneous kyphoplasty (PKP) treatment. Additionally, we aim to develop a nomogram that can accurately predict the occurrence of residual LBP.

Methods
We conducted a retrospective review of the medical records of thoracolumbar OVCFs patients who underwent PKP treatment at our hospital between July 2021 and December 2022. Residual LBP was defined as the presence of moderate or greater pain (VAS score ≥ 4) in the low back one day after surgery, and patients were divided into two groups: the LBP group and the non-LBP group. These patients were then randomly allocated to either a training or a validation set in the ratio of 7:3. To identify potential risk factors for residual LBP, we employed lasso regression for multivariate analysis, and from this, we constructed a nomogram. Subsequently, the predictive accuracy and practical clinical application of the nomogram were evaluated through a receiver operating characteristic (ROC) curve, a calibration curve, and a decision curve analysis (DCA).

Results
Our predictive model revealed that five variables—posterior fascial oedema, intravertebral vacuum cleft, time from fracture to surgery, sarcopenia, and interspinous ligament degeneration—were correlated with the presence of residual LBP. In the training set, the area under the ROC was 0.844 (95% CI 0.772–0.917), and in the validation set, it was 0.842 (95% CI 0.744–0.940), indicating that the model demonstrated strong discriminative performance. Furthermore, the predictions closely matched actual observations in both the training and validation sets. The decision curve analysis (DCA) curve suggested that the model provides a substantial net clinical benefit.

Conclusions
We have created a novel numerical model capable of accurately predicting the potential risk factors associated with the occurrence of residual LBP following PKP in thoracolumbar OVCFs patients. This model serves as a valuable tool for guiding specific clinical decisions for patients with OVCFs.
Renal injuries in conflict zones: a 6-year study of traumatic cases in Afghanistan
Authors: Ząbkowski Tomasz , Brzozowski Robert , Durma Adam Daniel 
Published: January 2024

Abstract
Purpose
During hostilities, gunshot wounds are the most common cause of penetrating injuries. In 8–10% of abdominal injuries kidneys are involved. The treatment method include surgical or conservative treatment (fluids + blood components).

Methods
Of 1266 combat trauma cases treated during 6 to 14 rotation of the Polish Military Contingent in Afghanistan, we extracted a subgroup of 44 kidney injuries. Corelation of trauma mechanism, PATI score, treatment methods, and outcomes was evaluated.

Results
Out of the 41 renal injuries, 20 considered left, 18 right, and 3 both kidneys. There were no statistical significancy in injury lateralization (p = 0.669), and no differences regarding side of a trauma and quantity of blood component used for the treatment (p = 0.246). Nephrectomy was performed on 17 patients (13 left vs. 4 right). A significant correlation between PATI score and the need for a nephrectomy (p = 0.027) was confirmed. Penetrating trauma recquired higher number of blood components comparing to blunt trauma (p < 0.001). The renal salvage rate was in study group was 61.36%. The overall survival (OS) rate was 90.25% − 4 patients died due to trauma.

Conclusions
The damage side does not result in a statistically significant increase in the need for blood transfusions or differences in the PATI score. The mechanism of trauma does, however, affect the number of blood components required for treatment, particularly in cases of penetrating trauma. With the introduction of proper treatment, the overall survival rate exceeds 90%, even when opting for conservative treatment.
Effects of the COVID-19 pandemic on youth mental health: a cross-sectional study on eating disorder patients and their unaffected siblings
Authors: Meneguzzo Paolo , Ajello Alessio , Consolati Mauro Domenico , Ceccato Enrico , Vita Antonio , Sala Alessandra , Santonastaso Paolo 
Published: January 2024

Abstract
Background
Adolescence has emerged as a particularly vulnerable phase during the COVID-19 pandemic, with eating disorders (EDs) representing a prominent psychopathological challenge linked to the restrictions imposed by the pandemic. Emerging evidence suggests that not only individuals with EDs but also their healthy siblings (HS) may experience unique psychological effects in this context. However, the existing literature on this topic remains limited. This study seeks to examine and compare the effects of the pandemic on adolescents and adults, with a specific focus on the impact of containment measures, disruptions in daily routines, and alterations in life trajectories, for both individuals with EDs and their HS.

Methods
We enrolled 273 individuals, including those diagnosed with EDs and their HS. Among the participants, 120 were under the age of 19. Multiple self-report questionnaires were administered to assess the psychological impact of 1 year of the COVID-19 pandemic. These assessments covered a range of psychological constructs, including posttraumatic symptoms, general psychopathology, and eating-related concerns.

Results
Notably, adolescent patients with EDs demonstrated the highest psychopathological scores within our sample. They were the sole subgroup to surpass clinical cutoffs, exhibiting more pronounced issues concerning eating-related concerns and general psychological well-being. Our findings also shed light on the unique experiences of HS during the pandemic.

Conclusion
Our findings highlight the specific psychological burden endured by adolescents with EDs throughout the COVID-19 pandemic, emphasizing the vulnerability of this demographic. Moreover, the experiences of HS, often overlooked in the literature, warrant increased attention in future health programs and interventions.
The effects of higher versus lower protein delivery in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials with trial sequential analysis
Authors: Lee Zheng-Yii , Dresen Ellen , Lew Charles Chin Han , Bels Julia , Hill Aileen , Hasan M. Shahnaz , Ke Lu , van Zanten Arthur , van de Poll Marcel C. G. , Heyland Daren K. , Stoppe Christian 
Published: January 2024

Abstract
Background
A recent large multicentre trial found no difference in clinical outcomes but identified a possibility of increased mortality rates in patients with acute kidney injury (AKI) receiving higher protein. These alarming findings highlighted the urgent need to conduct an updated systematic review and meta-analysis to inform clinical practice.

Methods
From personal files, citation searching, and three databases searched up to 29-5-2023, we included randomized controlled trials (RCTs) of adult critically ill patients that compared higher vs lower protein delivery with similar energy delivery between groups and reported clinical and/or patient-centred outcomes. We conducted random-effect meta-analyses and subsequently trial sequential analyses (TSA) to control for type-1 and type-2 errors. The main subgroup analysis investigated studies with and without combined early physical rehabilitation intervention. A subgroup analysis of AKI vs no/not known AKI was also conducted.

Results
Twenty-three RCTs (n = 3303) with protein delivery of 1.49 ± 0.48 vs 0.92 ± 0.30 g/kg/d were included. Higher protein delivery was not associated with overall mortality (risk ratio [RR]: 0.99, 95% confidence interval [CI] 0.88–1.11; I2 = 0%; 21 studies; low certainty) and other clinical outcomes. In 2 small studies, higher protein combined with early physical rehabilitation showed a trend towards improved self-reported quality-of-life physical function measurements at day-90 (standardized mean difference 0.40, 95% CI − 0.04 to 0.84; I2 = 30%). In the AKI subgroup, higher protein delivery significantly increased mortality (RR 1.42, 95% CI 1.11–1.82; I2 = 0%; 3 studies; confirmed by TSA with high certainty, and the number needed to harm is 7). Higher protein delivery also significantly increased serum urea (mean difference 2.31 mmol/L, 95% CI 1.64–2.97; I2 = 0%; 7 studies).

Conclusion
Higher, compared with lower protein delivery, does not appear to affect clinical outcomes in general critically ill patients but may increase mortality rates in patients with AKI. Further investigation of the combined early physical rehabilitation intervention in non-AKI patients is warranted.

Prospero ID
CRD42023441059.
Synthesis and cytotoxic activity evaluation of novel imidazopyridine carbohydrazide derivatives
Authors: Firouzi Maryam , Haghighijoo Zahra , Eskandari Masoomeh , Mohabbati Maryam , Miri Ramin , Jamei Mohammad Hasan , Poustforoosh Alireza , Nazari Somayeh , Firuzi Omidreza , Khoshneviszadeh Mehdi , Edraki Najmeh 
Published: January 2024

AbstractTwo series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group (11a-e). In vitro cytotoxicity screening was carried out using MTT assay against three human cancer cells including breast cancer (MCF-7), colon cancer (HT-29), and leukemia (K562) cell lines as well as a non-cancer cell line (Vero). Compound 7d bearing 4-bromophenyl pendant from aryl hydrazone series exhibited the highest cytotoxic potential with IC50values of 22.6 µM and 13.4 µM against MCF-7 and HT-29 cells, respectively, while it was not toxic towards non-cancer cells up to the concentration of 100 µM. Cell cycle analysis revealed that 7d increased the number of MCF-7 cells in the G0/G1 phase and also induced apoptosis in these cells as revealed by Hoechst 33,258 staining. The molecular mechanism contributing to the anti-proliferative effect of the most potent compound was investigated in silico using Super Pred software and introduced PDGFRA as a plausible target for 7d. Molecular docking and molecular dynamic studies demonstrated Lys627 and Asp836 as key residues interacting with the active compound. Overall, 7d could serve as a suitable candidate for further modifications as a lead anticancer structure.