bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between the cumulative average triglyceride glucose-body mass index and cardiovascular disease incidence among the middle-aged and older population: a prospective nationwide cohort study in China
Authors: Li Fadong , Wang Yue , Shi Boqun , Sun Shuaifeng , Wang Shen , Pang Shuo , Wu Xiaofan
Published: January 2024

Background

Findings from earlier research have established that insulin resistance (IR) is implicated in atherosclerosis progression, representing a noteworthy risk factor for cardiovascular disease (CVD). Recently, the triglyceride glucose-body mass index (TyG-BMI) has been introduced as a straightforward and robust alternative indicator for early detection of IR. Nevertheless, there is a scarcity of studies that have examined the capability of TyG-BMI for predicting incident CVD. Consequently, the core objective of this study was to determine whether the cumulative average TyG-BMI correlated with CVD incidence.

Methods

All data was sourced from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the cumulative average TyG-BMI, determined by the average of TyG-BMI values for the baseline and follow-up investigations (Wave 1 in 2011, Wave 3 in 2015, respectively). The calculation of TyG-BMI involved a combination of triglyceride, fasting blood glucose, and body mass index. The primary outcome was incident CVD. Logistic regression analyses as well as restricted cubic spline (RCS) regression analyses were performed for examining the association between the cumulative average TyG-BMI and CVD incidence.

Results

In all, 5,418 participants were enrolled in our analysis, with 2,904 (53.6%) being female, and a mean (standard deviation, SD) age of 59.6 (8.8) years. The mean (SD) cumulative average TyG-BMI among all participants was 204.9 (35.7). Totally, during a 4-year follow-up, 543 (10.0%) participants developed CVD. The fully adjusted logistic regression analysis revealed a significant association between the cumulative average TyG-BMI and incident CVD [odds ratio (OR), 95% confidence interval (CI): 1.168, 1.040–1.310, per 1 SD increase]. The RCS regression analysis displayed a positive, linear association of the cumulative average TyG-BMI with CVD incidence (P for overall = 0.038, P for nonlinear = 0.436).

Conclusions

Our study revealed a noteworthy correlation between the cumulative average TyG-BMI and incident CVD among the middle-aged and older population. The cumulative average TyG-BMI emerges as a valuable tool that may enhance the primary prevention and treatment of CVD.
Altering phosphorylation in cancer through PP2A modifiers
Authors: Johnson Hannah , Narayan Satya , Sharma Arun K.
Published: January 2024

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase integral to the regulation of many cellular processes. Due to the deregulation of PP2A in cancer, many of these processes are turned toward promoting tumor progression. Considerable research has been undertaken to discover molecules capable of modulating PP2A activity in cancer. Because PP2A is capable of immense substrate specificity across many cellular processes, the therapeutic targeting of PP2A in cancer can be completed through either enzyme inhibitors or activators. PP2A modulators likewise tend to be effective in drug-resistant cancers and work synergistically with other known cancer therapeutics. In this review, we will discuss the patterns of PP2A deregulation in cancer, and its known downstream signaling pathways important for cancer regulation, along with many activators and inhibitors of PP2A known to inhibit cancer progression.
Role of long non-coding RNAs in metabolic reprogramming of gastrointestinal cancer cells
Authors: Wang Kang , Lu Yan , Li Haibin , Zhang Jun , Ju Yongle , Ouyang Manzhao
Published: January 2024

Metabolic reprogramming, which is recognized as a hallmark of cancer, refers to the phenomenon by which cancer cells change their metabolism to support their increased biosynthetic demands. Tumor cells undergo substantial alterations in metabolic pathways, such as glycolysis, oxidative phosphorylation, pentose phosphate pathway, tricarboxylic acid cycle, fatty acid metabolism, and amino acid metabolism. Latest studies have revealed that long non-coding RNAs (lncRNAs), a group of non-coding RNAs over 200 nucleotides long, mediate metabolic reprogramming in tumor cells by regulating the transcription, translation and post-translational modification of metabolic-related signaling pathways and metabolism-related enzymes through transcriptional, translational, and post-translational modifications of genes. In addition, lncRNAs are closely related to the tumor microenvironment, and they directly or indirectly affect the proliferation and migration of tumor cells, drug resistance and other processes. Here, we review the mechanisms of lncRNA-mediated regulation of glucose, lipid, amino acid metabolism and tumor immunity in gastrointestinal tumors, aiming to provide more information on effective therapeutic targets and drug molecules for gastrointestinal tumors.

Graphical Abstract
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

Gastric 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

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

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

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

Globally, 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

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

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

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

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

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

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

Two 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.
Tosyl-carrageenan/alginate composite adsorbent for removal of Pb2+ ions from aqueous solutions
Authors: Awed Mohamed , Mohamed Riham R. , Kamal Kholod H. , Sabaa Magdy W. , Ali Korany A.
Published: January 2024

The current study effectively designed novel cross-linked tosyl-carrageenan/alginate (Ts-Car/Alg) beads to remove Pb2+ ions from their aqueous solutions. To confirm the structure of the produced matrix, characterization methods such as XRD, SEM, FTIR, and EDX were used. Batch experiments were employed in order to further evaluate the adsorption efficiency of Pb2+ ions. Additionally, various variables, including contact time, solution pH, adsorbent dosage, and initial concentration of Pb2+ ions were investigated using atomic absorption. The results of this study showed that the adsorption equilibrium increased as Pb2+ ions concentration increased at pH = 5.3 after a contact time of 120 min, with 0.3 g of Ts-Car/Alg that having the best adsorption capacity at 74 mg/g. The adsorption progression was further examined using the kinetic and isothermal models. With a correlation coefficient of 0.975, the Freundlich model was thought to better fit Pb2+ ions adsorption from the isotherm investigation. Also, the adsorption kinetics were investigated using a pseudo-second-order model with 1/n ratio of 0.683. This Ts-Car/Alg adsorbent is regarded as an effective candidate to be used for water treatment because the reusability process of produced beads was successfully completed twice, and the adsorbent maintained its ability to remove Pb2+ ions. The prepared Ts-Car/Alg beads are therefore excellent candidates to be used as potent Pb2+ ions adsorbents from their aqueous solutions. The Ts-Car/Alg beads' regeneration and reusability investigation for the removal of heavy metal ions was completed in at least two successful cycles.
Western diet consumption by host vertebrate promotes altered gene expression on Aedes aegypti reducing its lifespan and increasing fertility following blood feeding
Authors: Menezes Alexandre , Peixoto Marilia , Silva Melissa , Costa-Bartuli Emylle , Oliveira Cinara Lima , Walter-Nuno Ana Beatriz , Kistenmacker Nathan da Cruz , Pereira Jessica , Ramos Isabela , Paiva-Silva Gabriela O. , Atella Geórgia C. , Zancan Patricia , Sola-Penna Mauro , Gomes Fabio M.
Published: January 2024

Background

The high prevalence of metabolic syndrome in low- and middle-income countries is linked to an increase in Western diet consumption, characterized by a high intake of processed foods, which impacts the levels of blood sugar and lipids, hormones, and cytokines. Hematophagous insect vectors, such as the yellow fever mosquito Aedes aegypti, rely on blood meals for reproduction and development and are therefore exposed to the components of blood plasma. However, the impact of the alteration of blood composition due to malnutrition and metabolic conditions on mosquito biology remains understudied.

Methods

In this study, we investigated the impact of whole-blood alterations resulting from a Western-type diet on the biology of Ae. aegypti. We kept C57Bl6/J mice on a high-fat, high-sucrose (HFHS) diet for 20 weeks and followed biological parameters, including plasma insulin and lipid levels, insulin tolerance, and weight gain, to validate the development of metabolic syndrome. We further allowed Ae. aegypti mosquitoes to feed on mice and tracked how altered host blood composition modulated parameters of vector capacity.

Results

Our findings identified that HFHS-fed mice resulted in reduced mosquito longevity and increased fecundity upon mosquito feeding, which correlated with alteration in the gene expression profile of nutrient sensing and physiological and metabolic markers as studied up to several days after blood ingestion.

Conclusions

Our study provides new insights into the overall effect of alterations of blood components on mosquito biology and its implications for the transmission of infectious diseases in conditions where the frequency of Western diet-induced metabolic syndromes is becoming more frequent. These findings highlight the importance of addressing metabolic health to further understand the spread of mosquito-borne illnesses in endemic areas.

Graphical Abstract
Sex-based disparities in DNA methylation and gene expression in late-gestation mouse placentas
Authors: Legault Lisa-Marie , Breton-Larrivée Mélanie , Langford-Avelar Alexandra , Lemieux Anthony , McGraw Serge
Published: January 2024

Background

The placenta is vital for fetal development and its contributions to various developmental issues, such as pregnancy complications, fetal growth restriction, and maternal exposure, have been extensively studied in mice. The placenta forms mainly from fetal tissue and therefore has the same biological sex as the fetus it supports. Extensive research has delved into the placenta’s involvement in pregnancy complications and future offspring development, with a notable emphasis on exploring sex-specific disparities. However, despite these investigations, sex-based disparities in epigenetic (e.g., DNA methylation) and transcriptomic features of the late-gestation mouse placenta remain largely unknown.

Methods

We collected male and female mouse placentas at late gestation (E18.5, n = 3/sex) and performed next-generation sequencing to identify genome-wide sex differences in transcription and DNA methylation.

Results

Our comparison between male and female revealed 358 differentially expressed genes (DEGs) on autosomes, which were associated with signaling pathways involved in transmembrane transport and the responses to viruses and external stimuli. X chromosome DEGs (n = 39) were associated with different pathways, including those regulating chromatin modification and small GTPase-mediated signal transduction. Differentially methylated regions (DMRs) were more common on the X chromosomes (n = 3756) than on autosomes (n = 1705). Interestingly, while most X chromosome DMRs had higher DNA methylation levels in female placentas and tended to be included in CpG dinucleotide-rich regions, 73% of autosomal DMRs had higher methylation levels in male placentas and were distant from CpG-rich regions. Several DEGs were correlated with DMRs. A subset of the DMRs present in late-stage placentas were already established in mid-gestation (E10.5) placentas (n = 348 DMRs on X chromosome and 19 DMRs on autosomes), while others were acquired later in placental development.

Conclusion

Our study provides comprehensive lists of DEGs and DMRs between male and female that collectively cause profound differences in the DNA methylation and gene expression profiles of late-gestation mouse placentas. Our results demonstrate the importance of incorporating sex-specific analyses into epigenetic and transcription studies to enhance the accuracy and comprehensiveness of their conclusions and help address the significant knowledge gap regarding how sex differences influence placental function.
WRN loss accelerates abnormal adipocyte metabolism in Werner syndrome
Authors: Tian Yuyao , Lautrup Sofie , Law Patrick Wai Nok , Dinh Ngoc-Duy , Fang Evandro Fei , Chan Wai-Yee
Published: January 2024

Background

Metabolic dysfunction is one of the main symptoms of Werner syndrome (WS); however, the underlying mechanisms remain unclear. Here, we report that loss of WRN accelerates adipogenesis at an early stage both in vitro (stem cells) and in vivo (zebrafish). Moreover, WRN depletion causes a transient upregulation of late-stage of adipocyte-specific genes at an early stage.

Methods

In an in vivo study, we generated wrn−/− mutant zebrafish and performed histological stain and Oil Red O staining to assess the fat metabolism. In an in vitro study, we used RNA-seq and ATAC-seq to profile the transcriptional features and chromatin accessibility in WRN depleted adipocytes. Moreover, we performed ChIP-seq to further study the regulatory mechanisms of metabolic dysfunction in WS.

Results

Our findings show that mechanistically WRN deficiency causes SMARCA5 upregulation. SMARCA5 is crucial in chromatin remodeling and gene regulation. Additionally, rescuing WRN could normalize SMARCA5 expression and adipocyte differentiation. Moreover, we find that nicotinamide riboside (NR) supplementation restores adipocyte metabolism in both stem cells and zebrafish models.

Conclusions

Our findings unravel a new mechanism for the influence of WRN in the early stage of adipogenesis and provide a possible treatment for metabolic dysfunction in WS. These data provide promising insights into potential therapeutics for ageing and ageing-related diseases.
Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis
Authors: Sirotich Emily , Nazaryan Hasmik , Chowdhury Saifur Rahman , Guyatt Gordon , Agarwal Arnav , Leong Russell , Wen Aaron , Xu Emily , Liu Bonnie , Pallapothu Sushmitha , Rathod Preksha , Kwon Henry Y. , Dookie Jared , Shafiee Amirmohammad , Charness Jay , DiRaimo Jennifer , Paynter Dale , Pruitt Barbara , Strachan Gail , Couban Rachel , Ye Zhikang , Arnold Donald M.
Published: January 2024

Background

Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations.

Methods

Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability.

Discussion

Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting.

Systematic review registration

CRD42020161206.
Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis
Authors: Li Jinghui , Ma Yongli , Wen Liang , Zhang Guosheng , Huang Chengzhi , Wang Junjiang , Yao Xueqing
Published: January 2024

Background

Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy.

Methods

A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively.

Results

A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38–2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21–2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47–11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51–11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion.

Conclusion

Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings.

Systematic review registration

PROSPERO CRD42022377564.
Optimal reconstruction methods after distal gastrectomy for gastric cancer: a protocol for a systematic review and network meta-analysis update
Authors: Zhao Zhou , Li Hancong , Pan Xiangcheng , Shen Chaoyong , Mu Mingchun , Yin Xiaonan , Liao Jing , Cai Zhaolun , Zhang Bo
Published: January 2024

Background

Distal gastrectomy (DG) is a commonly used surgical procedure for gastric cancer (GC), with three reconstruction methods available: Billroth I, Billroth II, and Roux-en-Y. In 2018, our team published a systematic review to provide guidance for clinical practice on the optimal reconstruction method after DG for GC. However, since then, new evidence from several randomized controlled trials (RCTs) has emerged, prompting us to conduct an updated systematic review and network meta-analysis to provide the latest comparative estimates of the efficacy and safety of the three reconstruction methods after DG for GC.

Method

This systematic review and network meta-analysis update followed the PRISMA-P guidelines and will include a search of PubMed, Embase, and the Cochrane Library for RCTs comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after DG for patients with GC. Two independent reviewers will screen the titles and abstracts based on predefined eligibility criteria, and two reviewers will assess the full texts of relevant studies. The Bayesian network meta-analysis will evaluate various outcomes, including quality of life after surgery, anastomotic leakage within 30 days after surgery, operation time, intraoperative blood loss, major postoperative complications within 30 days after surgery, incidence and severity of bile reflux, and loss of body weight from baseline.

Ethics and dissemination

The review does not require ethical approval. The findings of the review will be disseminated through publication in an academic journal, presentations at conferences, and various media outlets.

INPLASY registration number

INPLASY2021100060.
Modifying the walk score based on daily social activities: residential neighborhood in Egypt as a case study
Authors: Mohamed Amr N. , El Mokadem Ashraf , Ali Shimaa M. , Badawy Nancy Mahmoud
Published: January 2024

Walkability has been linked to quality of life in many ways. The Walk Score is one of several methodologies aimed at assisting people in evaluating walkability. Despite the validation of this method, the amenity schedule around the day and the occupancy percentage in each amenity are not included in the calculation of the Walk Score, resulting in reduced accuracy. The research aims to improve the Walk Score methodology by inserting the amenity schedule around the day and the occupancy percentage in each amenity in the calculating method of the walk score, as the amenities do not have the same occupancy throughout the day. The research proposes a new method to calculate the Walk Score according to the time and occupancy for each amenity at the residential neighborhood level in Egypt. The research uses Salam New City as a case study to apply the new method to a residential neighborhood using the Urban Modelling Interference (Umi) plugin. Finally, the research proposes the Walk Score Model of Salam New City to calculate the Walk Score around the day. The new Walk Score model helps urban planners improve urban space design and the distribution of amenities.
Blockchain meets machine learning: a survey
Authors: Kayikci Safak , Khoshgoftaar Taghi M.
Published: January 2024

Blockchain and machine learning are two rapidly growing technologies that are increasingly being used in various industries. Blockchain technology provides a secure and transparent method for recording transactions, while machine learning enables data-driven decision-making by analyzing large amounts of data. In recent years, researchers and practitioners have been exploring the potential benefits of combining these two technologies. In this study, we cover the fundamentals of blockchain and machine learning and then discuss their integrated use in finance, medicine, supply chain, and security, including a literature review and their contribution to the field such as increased security, privacy, and decentralization. Blockchain technology enables secure and transparent decentralized record-keeping, while machine learning algorithms can analyze vast amounts of data to derive valuable insights. Together, they have the potential to revolutionize industries by enhancing efficiency through automated and trustworthy processes, enabling data-driven decision-making, and strengthening security measures by reducing vulnerabilities and ensuring the integrity of information. However, there are still some important challenges to be handled prior to the common use of blockchain and machine learning such as security issues, strategic planning, information processing, and scalable workflows. Nevertheless, until the difficulties that have been identified are resolved, their full potential will not be achieved.
Disaggregated effect of construction investments on the Saudi economy: a dynamic computable general equilibrium model of Saudi Arabia
Authors: Ahmed Irfan , Mehrez Khadija , Socci Claudio , Deriu Stefano , Mathkur Naif M. , Casasr Ian P.
Published: January 2024

The role of the construction industry in economic growth has been widely discussed in the extant literature, but existing studies have not investigated the disaggregated impact of construction investments on the production and social sectors. This study examines the disaggregated effect of construction investments on the Saudi economy. The study uses a social accounting matrix of Saudi Arabia and constructs a dynamic computable general equilibrium model. The findings reveal that construction investments significantly boosted GDP and aggregate investments in the first two periods; however, the growth declined in the following three periods. This finding underlines the importance of long-term investments in the construction sector and calls for continuous monitoring and updating of the investment policy for sustainable development. This study also presents the disaggregated impact of investments on the value-added by each sector of the economy. The ranking of sectors exhibits that mining and quarry activities underwent a high increase in value-added, second to construction activities. Other economic activities also experienced growth in value-added and some of them changed their ranks within the five years.
Mobile money innovations, income inequality and gender inclusion in sub-Saharan Africa
Authors: Asongu Simplice A. , Agyemang-Mintah Peter , Nnanna Joseph , Ngoungou Yolande E.
Published: January 2024

This study assesses the role of mobile money innovations on income inequality and gender inclusion in 42 sub-Saharan African countries from 1980 to 2019 using interactive quantile regressions. It finds that, first, income inequality unconditionally reduces the involvement of women in business and politics. Second, mobile money innovations interact with income inequality to have a positive impact on women in business and politics. Third, the net effects of mobile money innovations on gender inclusion through income inequality are consistently negative. Fourth, as the positive conditional or interactive effects and negative net effects are consistent across the conditional distribution of gender inclusion, thresholds at which mobile money innovations can completely dampen the negative effect of income inequality on gender inclusion are provided. Therefore, policymakers should work toward improving conditions for mobile money innovations. They should also be aware that reducing both income inequality and enhancing mobile money innovations simultaneously leads to more inclusive outcomes in terms of gender inclusion.