bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-pyrogenicity and biocompatibility of parylene-coated magnetic bead implants
Authors: Taylor Cameron R. , Nott Joshua K. , Ratnasena Nilmini H. , Cohen Joel M. , Herr Hugh M.
Published: February 2024

Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless communication through human tissue. We recently developed a new strategy, magnetomicrometry, that uses magnetic bead implants as passive communication devices to wirelessly sense muscle tissue lengths. We manufactured clinical-grade magnetic bead implants and verified their biocompatibility via intramuscular implantation, cytotoxicity, sensitization, and intracutaneous irritation testing. In this work, we test the pyrogenicity of the magnetic bead implants via a lagomorph model, and we test the biocompatibility of the magnetic bead implants via a full chemical characterization and toxicological risk assessment. Further, we test the cleaning, sterilization, and dry time of the devices that are used to deploy these magnetic bead implants. We find that the magnetic bead implants are non-pyrogenic and biocompatible, with the insertion device determined to be safe to clean, sterilize, and dry in a healthcare setting. These results provide confidence for the safe use of these magnetic bead implants in humans.
Bichronous scientific writing course for medical faculty during Covid-19: a SWOT analysis experience
Authors: Khojasteh Laleh , Zarifsanaiey Nahid , Karimian Zahra
Published: February 2024

Introduction

Writing and publishing scholarly articles in international peer-reviewed journals can be a challenging undertaking for medical and healthcare professionals in universities, especially in non-English speaking countries. Surprisingly, very few faculty members report receiving guidance on scientific writing. To encourage more faculty engagement in professional development courses aimed at enhancing their writing abilities, we have revamped scientific writing courses to incorporate bichronous (a combination of asynchronous and synchronous) teaching methods.

Methods

After forming a team, we performed a SWOT (strengths, weaknesses, opportunities, and threats) study of the medical faculty’s present programs and proposed alternatives to prior course issues. In this interventional study, fifty-nine eligible medical educators selected by purposeful sampling underwent a two-and-a-half-month bichronous scientific writing course from March to August 2021. The perspectives of the participants were evaluated through a SWOT analysis. The data were collected through online semi-structured interviews, and data collection continued until data saturation was achieved (40 participants). Data were then coded and analyzed based on conventional qualitative content analysis principles.

Results

Our planned blending sequence and e-feedback increased the medical faculty’s drive to learn, self-confidence, and autonomy while improving their writing skills. Poor ICT and network infrastructure hindered course adoption. Due to the course’s time and the faculty’s own online teaching, many battled with computer vision syndrome, self-discipline, and distractions. Our participants struggled with self-discipline and distractions, so setting a daily time limit may help them concentrate.

Discussion

Given the faculty’s demanding professional lives, this designed course provided a learning opportunity for many that would not have been feasible otherwise.
Early-phase insulin secretion during mixed-meal tolerance testing predicts β-cell function and secretory capacity in cystic fibrosis
Authors: Sheikh Saba , Stefanovski Darko , Kilberg Marissa J. , Hadjiliadis Denis , Rubenstein Ronald C. , Rickels Michael R. , Kelly Andrea
Published: February 2024

Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF.

Methods

Secondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin secretory rates (ISR) were derived by parametric deconvolution using 2-compartment model of C-peptide kinetics, and incremental area under the curve (AUC) was calculated for 30, 60 and 180-minutes. GPA: acute insulin (AIR) and C-peptide responses (ACR) were calculated as average post-arginine insulin or C-peptide response minus pre-arginine insulin or C-peptide under fasting (AIRarg and ACRarg), ~230 mg/dL (AIRpot and ACRpot), and ~340 mg/dL (AIRmax and ACRmax) hyperglycemic clamp conditions. Relationships of MMTT to GPA parameters were derived using Pearson’s correlation coefficient. Predicted values were generated for MMTT ISR and compared to GPA parameters using Bland Altman analysis to assess degree of concordance.

Results

85 PwCF (45 female; 75 PI-CF and 10 PS-CF) median (range) age 23 (6-56) years with BMI 23 (13-34) kg/m2, HbA1c 5.5 (3.8-10.2)%, and FEV1%-predicted 88 (26-125) and 4 non-CF controls of similar age and BMI were included. ISR AUC30min positively correlated with AIRarg (r=0.55), AIRpot (r=0.62), and AIRmax (r=0.46) and with ACRarg (r=0.59), ACRpot (r=0.60), and ACRmax (r=0.51) (all P<0.001). ISR AUC30min strongly predicted AIRarg (concordance=0.86), AIRpot (concordance=0.89), and AIRmax (concordance=0.76) at lower mean GPA values, but underestimated AIRarg, AIRpot, and AIRmax at higher GPA-defined β-cell secretory capacity. Between test agreement was unaltered by adjustment for study group, OGTT glucose category, and BMI.

Conclusion

Early-phase insulin secretion during MMTT can accurately predict GPA-derived measures of β-cell function and secretory capacity when functional β-cell mass is reduced. These data can inform future multicenter studies requiring reliable, standardized, and technically feasible testing mechanisms to quantify β-cell function and secretory capacity.
Two-stage low-carbon optimal dispatch of the power system considering demand response to defend large uncertainties and risks
Authors: Cai Linjun , Xie Dongliang , Xue Feng , Zhang Huilin
Published: February 2024

Introduction: In order to promote the consumption of renewable energy, reduce carbon emissions, and take into account the uncertainty of renewable energy output and load fluctuations in the new power system that can affect the normal operation of market mechanism, a two-stage low-carbon optimization scheduling method for power system that considers demand response under multiple uncertainties is proposed in this paper.

Methods: Uncertain scene sets are generated through Latin hypercube sampling and heuristic synchronous backpropagation method is used to reduce scenes to obtain typical scenes and their probabilities. Then, a one-stage optimization model is established with the goal of maximizing energy efficiency and corresponding demand response strategies are obtained. Green certificate carbon trading joint mechanism model consisting of tiered green certificate trading and time-sharing tiered carbon trading are established, and the output of two-stage units are optimized with the goal of minimizing comprehensive operating costs.

Result: The simulation results show that the carbon emissions are decreased by 251.57 tons, the consumption rate of renewable energy is increased by 8.64%, and the total costs are decreased by 124.0612 million yuan.

Discussion: From this, it can be seen that the dual layer low-carbon optimization scheduling strategy for power system considering demand response under multiple uncertainties can effectively reduce the operating costs and carbon emissions of the system, while balancing the economic and environmental aspects of power system operation.
Tick cysteine protease inhibitors suppress immune responses in mannan-induced psoriasis-like inflammation
Authors: Wu Huimei , Jmel Mohamed Amine , Chai Jinwei , Tian Maolin , Xu Xueqing , Hui Yuan , Nandakumar Kutty Selva , Kotsyfakis Michail
Published: February 2024

Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients.
Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy
Authors: Wang Man , Yu Fei , Zhang Yuan , Li Peifeng
Published: February 2024

Notch signaling pathway is a highly conserved system of cell-to-cell communication that participates in various biological processes, such as stem cell maintenance, cell fate decision, cell proliferation and death during homeostasis and development. Dysregulation of Notch signaling has been associated with many aspects of cancer biology, such as maintenance of cancer stem-like cells (CSCs), cancer cell metabolism, angiogenesis and tumor immunity. Particularly, Notch signaling can regulate antitumor or pro-tumor immune cells within the tumor microenvironment (TME). Currently, Notch signaling has drawn significant attention in the therapeutic development of cancer treatment. In this review, we focus on the role of Notch signaling pathway in remodeling tumor immune microenvironment. We describe the impact of Notch signaling on the efficacy of cancer immunotherapies. Furthermore, we summarize the results of relevant preclinical and clinical trials of Notch-targeted therapeutics and discuss the challenges in their clinical application in cancer therapy. An improved understanding of the involvement of Notch signaling in tumor immunity will open the door to new options in cancer immunotherapy treatment.
The secretome of macrophages has a differential impact on spinal cord injury recovery according to the polarization protocol
Authors: Lentilhas-Graça José , Santos Diogo J. , Afonso João , Monteiro Andreia , Pinho Andreia G. , Mendes Vera M. , Dias Marta S. , Gomes Eduardo D. , Lima Rui , Fernandes Luís S. , Fernandes-Amorim Fernando , Pereira Inês M. , de Sousa Nídia , Cibrão Jorge R. , Fernandes Aline M. , Serra Sofia C. , Rocha Luís A. , Campos Jonas , Pinho Tiffany S. , Monteiro Susana , Manadas Bruno , Salgado António J. , Almeida Ramiro D. , Silva Nuno A.
Published: February 2024

Introduction

The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed.

Methods

In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues.

Results

We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation.

Discussion

Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications.
Evaluation of the ecological carrying capacity of Wailingding marine ranching in Zhuhai, China by high-resolution remote sensing
Authors: Wang Ziwen , Yao Lijun , Yu Jing , Chen Pimao , Li Zhen , Yang Weiwei
Published: February 2024

Evaluation of the ecological carrying capacity of marine ranching is a prerequisite and guarantee for ensuring the sustainable development of aquaculture activities, protecting and maintaining the stability and security of marine ecosystems. Based on high-resolution satellite remote sensing data and survey data of Wailingding marine ranching in Zhuhai from 2006 to 2021, this study constructed a marine ecological carrying capacity (MECC) index system with three levels: resources, environment, and ecology. A combination of the analytic hierarchy process (AHP) method and entropy method was applied to assign values to indexes, and then, the MECC of marine ranching was evaluated based on the state-space model and the weighted Bonferroni mean (WBM) model. Results showed that the MECC of Wailingding marine ranching increased from 0.49 (2006) before the marine ranching construction to 0.79 (2021) after the marine ranching construction. Marine ranching had elevated MECC from a loadable state to a fully loaded state. The intertidal subsystem, with a weight of 52.51%, dominates the MECC of marine ranching, in which resource and environmental factors are the major influencing factors. The increased rate of the state-space model (61.73%) was higher than that of the WBM model (44.34%), indicating that the state-space model is more feasible for the MECC assessment of Wailingding marine ranching.
Pulmonary inflammation decreases with ultra-protective ventilation in experimental ARDS under VV-ECMO: a positron emission tomography study
Authors: Deniel Guillaume , Dhelft François , Lancelot Sophie , Orkisz Maciej , Roux Emmanuel , Mouton William , Benzerdjeb Nazim , Richard Jean-Christophe , Bitker Laurent
Published: February 2024

Background

Experimentally, ultra-protective ventilation (UPV, tidal volumes [VT] < 4 mL.kg−1) strategies in conjunction with veno-venous extracorporeal membrane oxygenation (VV-ECMO) are associated with lesser ventilator-induced lung injuries (VILI) during acute respiratory distress syndrome (ARDS). However, whether these strategies reduce lung inflammation more effectively than protective ventilation (PV) remains unclear. We aimed to demonstrate that a UPV strategy decreases acute lung inflammation in comparison with PV in an experimental swine model of ARDS.

Methods

ARDS was induced by tracheal instillation of chlorhydric acid in sedated and paralyzed animals under mechanical ventilation. Animals were randomized to receive either UPV (VT 1 mL.kg−1, positive end-expiration pressure [PEEP] set to obtain plateau pressure between 20 and 25 cmH2O and respiratory rate [RR] at 5 min−1 under VV-ECMO) or PV (VT 6 mL.kg−1, PEEP set to obtain plateau pressure between 28 and 30 cmH2O and RR at 25 min−1) during 4 h. After 4 h, a positron emission tomography with [11C](R)-PK11195 (ligand to TSPO-bearing macrophages) injection was realized, coupled with quantitative computerized tomography (CT). Pharmacokinetic multicompartment models were used to quantify regional [11C](R)-PK11195 lung uptake. [11C](R)-PK11195 lung uptake and CT-derived respiratory variables were studied regionally across eight lung regions distributed along the antero-posterior axis.

Results

Five pigs were randomized to each study group. Arterial O2 partial pressure to inspired O2 fraction were not significantly different between study groups after experimental ARDS induction (75 [68–80] mmHg in a PV group vs. 87 [69–133] mmHg in a UPV group, p = 0.20). Compared to PV animals, UPV animals exhibited a significant decrease in the regional non-aerated compartment in the posterior lung levels, in mechanical power, and in regional dynamic strain and no statistical difference in tidal hyperinflation after 4 h. UPV animals had a significantly lower [11C](R)-PK11195 uptake, compared to PV animals (non-displaceable binding potential 0.35 [IQR, 0.20–0.59] in UPV animals and 1.01 [IQR, 0.75–1.59] in PV animals, p = 0.01). Regional [11C](R)-PK11195 uptake was independently associated with the interaction of regional tidal hyperinflation and regional lung compliance.

Conclusion

In an experimental model of ARDS, 4 h of UPV strategy significantly decreased lung inflammation, in relation to the control of VT-derived determinants of VILI.
Exploring the secrets of virus entry: the first respiratory syncytial virus carrying beta lactamase
Authors: De Ávila-Arias Marcio , Villarreal-Camacho Jose Luis , Cadena-Cruz Christian , Hurtado-Gómez Leidy , Costello Heather M. , Rodriguez Alexander , Burgos-Florez Francisco , Bettin Alfonso , Kararoudi Meisam Naeimi , Muñoz Amner , Peeples Mark E. , San-Juan-Vergara Homero
Published: February 2024

Background

Respiratory Syncytial Virus (RSV) presents a significant health threat, especially to young children. In-depth understanding of RSV entry mechanisms is essential for effective antiviral development. This study introduces an innovative RSV variant, featuring the fusion of the beta-lactamase (BlaM) enzyme with the RSV-P phosphoprotein, providing a versatile tool for dissecting viral entry dynamics.

Methods

Using the AlphaFold2 algorithm, we modeled the tertiary structure of the P-BlaM chimera, revealing structural similarities with both RSV-P and BlaM. Functional assessments, utilizing flow cytometry, quantified beta-lactamase activity and GFP expression in infected bronchial epithelial cells. Western blot analysis confirmed the integrity of P-BlaM within virions.

Results

The modeled P-BlaM chimera exhibited structural parallels with RSV-P and BlaM. Functional assays demonstrated robust beta-lactamase activity in recombinant virions, confirming successful P-BlaM incorporation as a structural protein. Quercetin, known for its antiviral properties, impeded viral entry by affecting virion fusion. Additionally, Ulixertinib, an ERK-1/2 inhibitor, significantly curtailed viral entry, implicating ERK-1/2 pathway signaling.

Conclusions

Our engineered RSV-P-BlaM chimera emerges as a valuable tool, illuminating RSV entry mechanisms. Structural and functional analyses unveil potential therapeutic targets. Quercetin and Ulixertinib, identified as distinct stage inhibitors, show promise for targeted antiviral strategies. Time-of-addition assays pinpoint quercetin’s specific interference stage, advancing our comprehension of RSV entry and guiding future antiviral developments.
Alpine glacier algal bloom during a record melt year
Authors: Millar Jasmin L. , Broadwell Emily L. M. , Lewis Madeleine , Bowles Alexander M. C. , Tedstone Andrew J. , Williamson Christopher J.
Published: February 2024

Glacier algal blooms dominate the surfaces of glaciers and ice sheets during summer melt seasons, with larger blooms anticipated in years that experience the greatest melt. Here, we characterize the glacier algal bloom proliferating on Morteratsch glacier, Switzerland, during the record 2022 melt season, when the Swiss Alps lost three times more ice than the decadal average. Glacier algal cellular abundance (cells ml−1), biovolume (μm3 cell−1), photophysiology (Fv/Fm, rETRmax), and stoichiometry (C:N ratios) were constrained across three elevations on Morteratsch glacier during late August 2022 and compared with measurements of aqueous geochemistry and outputs of nutrient spiking experiments. While a substantial glacier algal bloom was apparent during summer 2022, abundances ranged from 1.78 × 104 to 8.95 × 105 cells ml−1 of meltwater and did not scale linearly with the magnitude of the 2022 melt season. Instead, spatiotemporal heterogeneity in algal distribution across Morteratsch glacier leads us to propose melt-water-redistribution of (larger) glacier algal cells down-glacier and presumptive export of cells from the system as an important mechanism to set overall bloom carrying capacity on steep valley glaciers during high melt years. Despite the paradox of abundant glacier algae within seemingly oligotrophic surface ice, we found no evidence for inorganic nutrient limitation as an important bottom-up control within our study site, supporting our hypothesis above. Fundamental physical constraints may thus cap bloom carrying-capacities on valley glaciers as 21st century melting continues.
Understanding bacterial pathogenicity: a closer look at the journey of harmful microbes
Authors: Soni Jyoti , Sinha Sristi , Pandey Rajesh
Published: February 2024

Bacteria are the most prevalent form of microorganisms and are classified into two categories based on their mode of existence: intracellular and extracellular. While most bacteria are beneficial to human health, others are pathogenic and can cause mild to severe infections. These bacteria use various mechanisms to evade host immunity and cause diseases in humans. The susceptibility of a host to bacterial infection depends on the effectiveness of the immune system, overall health, and genetic factors. Malnutrition, chronic illnesses, and age-related vulnerabilities are the additional confounders to disease severity phenotypes. The impact of bacterial pathogens on public health includes the transmission of these pathogens from healthcare facilities, which contributes to increased morbidity and mortality. To identify the most significant threats to public health, it is crucial to understand the global burden of common bacterial pathogens and their pathogenicity. This knowledge is required to improve immunization rates, improve the effectiveness of vaccines, and consider the impact of antimicrobial resistance when assessing the situation. Many bacteria have developed antimicrobial resistance, which has significant implications for infectious diseases and favors the survival of resilient microorganisms. This review emphasizes the significance of understanding the bacterial pathogens that cause this health threat on a global scale.
Metabolomics analysis reveals novel serum metabolite alterations in cancer cachexia
Authors: More Tushar H. , Hiller Karsten , Seifert Martin , Illig Thomas , Schmidt Rudi , Gronauer Raphael , von Hahn Thomas , Weilert Hauke , Stang Axel
Published: February 2024

Background

Cachexia is a body wasting syndrome that significantly affects well-being and prognosis of cancer patients, without effective treatment. Serum metabolites take part in pathophysiological processes of cancer cachexia, but apart from altered levels of select serum metabolites, little is known on the global changes of the overall serum metabolome, which represents a functional readout of the whole-body metabolic state. Here, we aimed to comprehensively characterize serum metabolite alterations and analyze associated pathways in cachectic cancer patients to gain new insights that could help instruct strategies for novel interventions of greater clinical benefit.

Methods

Serum was sampled from 120 metastatic cancer patients (stage UICC IV). Patients were grouped as cachectic or non-cachectic according to the criteria for cancer cachexia agreed upon international consensus (main criterium: weight loss adjusted to body mass index). Samples were pooled by cachexia phenotype and assayed using non-targeted gas chromatography-mass spectrometry (GC-MS). Normalized metabolite levels were compared using t-test (p < 0.05, adjusted for false discovery rate) and partial least squares discriminant analysis (PLS-DA). Machine-learning models were applied to identify metabolite signatures for separating cachexia states. Significant metabolites underwent MetaboAnalyst 5.0 pathway analysis.

Results

Comparative analyses included 78 cachectic and 42 non-cachectic patients. Cachectic patients exhibited 19 annotable, significantly elevated (including glucose and fructose) or decreased (mostly amino acids) metabolites associating with aminoacyl-tRNA, glutathione and amino acid metabolism pathways. PLS-DA showed distinct clusters (accuracy: 85.6%), and machine-learning models identified metabolic signatures for separating cachectic states (accuracy: 83.2%; area under ROC: 88.0%). We newly identified altered blood levels of erythronic acid and glucuronic acid in human cancer cachexia, potentially linked to pentose-phosphate and detoxification pathways.

Conclusion

We found both known and yet unknown serum metabolite and metabolic pathway alterations in cachectic cancer patients that collectively support a whole-body metabolic state with impaired detoxification capability, altered glucose and fructose metabolism, and substrate supply for increased and/or distinct metabolic needs of cachexia-associated tumors. These findings together imply vulnerabilities, dependencies and targets for novel interventions that have potential to make a significant impact on future research in an important field of cancer patient care.
Prognostic analysis of lung squamous cell carcinoma patients with second primary malignancies: a SEER database study
Authors: Han Weiqing , Wang Silin , Su Lang , Xu Jianjun , Wei Yiping
Published: February 2024

Background

As lung squamous cell carcinoma (LUSC) patients are at increased risk of developing a second primary cancer, this complicates the patient’s condition and thus makes prognostic assessment more difficult, posing a significant prognostic challenge for clinicians. Our goal was to assess the prognosis of LUSC patients with a second primary tumor, and provide insights into appropriate therapy and monitoring strategies.

Methods

Data was obtained for LUSC patients from the Surveillance, Epidemiology, and End Results (SEER) database. The LUSC patients were divided into three groups (LS-SPM, OT-LUSC and LUSC-only). Univariate and stratified analyses were performed for the baseline and clinical characteristics of the participants. Multiple regression and Kaplan-Meier survival analyses were also performed, followed by a final life table analysis.

Results

In our sample of 101,626 patients, the HR for OS in the LS-SPM group was 0.40 in univariate analysis. Kaplan-Meier survival curves showed that LS-SPM patients had considerably longer lifespans compared to the other groups. The LS-SPM patients had median and mean survival times of 64 months and 89.11 months. Unadjusted and adjusted multiple regression analyses showed that LS-SPM patients had a superior survival compared to LUSC-only and OT-LUSC groups.

Conclusion

LS-SPM patients have a good prognosis with aggressive therapy and immune monitoring. The present study offers novel insights into the pathophysiological causes and treatments for LS-SPM.
Not only a therapeutic target; mTOR in Hodgkin lymphoma and acute lymphoblastic leukemia
Authors: Cuéllar Mendoza Miguel Enrique , Chávez Sánchez Francisco Raúl , Dorantes Acosta Elisa María , Niembro Zúñiga Ana María , Pelayo Rosana , Zapata Tarrés Marta
Published: February 2024

Introduction

The mechanistic/mammalian target of rapamycin (mTOR) is a serine/threonine kinase, which is downregulated or upregulated and is implicated in different types of cancer including hematologic neoplasms, skin prostate, and head and neck cancer.

Aim

The aim of this study was to explore the current knowledge of mTOR signaling in acute lymphoblastic leukemia and Hodgkin lymphoma.

Methods

A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Discovery Service for National Autonomous University of Mexico, Registro Nacional de Instituciones y Empresas Científicas y Tecnológicas (RENIECYT), and Scientific Electronic Library Online (SciELO) from 1994 to 2023. A total of 269 papers were identified for acute lymphoblastic leukemia, but based on specific criteria, 15 were included; for Hodgkin lymphoma, 110 papers were identified, but 5 were included after manual searching.

Results

A total of 20 papers were evaluated, where mTOR activity is increased in patients with Hodgkin lymphoma and acute lymphoblastic leukemia by different molecular mechanisms.

Conclusions

mTOR activity is increased in patients with both hematologic neoplasms and NOTCH; interleukin 4, 7, and 9, and nuclear proteins have been studied for their role in the activation of mTOR signaling.
Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study
Authors: Lu Linbin , Fang Wenzheng , Yu Jun , Gao Xianchun , Wang Xinlin , Pan Yan , Han Weili , Yan Junya , Xie Huahong , Yao Liping , Yang Jianjun , Zheng Jianyong , Hong Liu , Li Jipeng , Li Mengbin , Shang Lei , Wu Kaichun , Ji Gang , Nie Yongzhan
Published: February 2024

Background

Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests.

Materials and methods

This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters.

Results

The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63).

Conclusion

The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.
Review of dietary patterns and gastric cancer risk: epidemiology and biological evidence
Authors: Pu Ke , Feng Yang , Tang Qian , Yang Guodong , Xu Chuan
Published: February 2024

Due to rapid research expansion on dietary factors and development of cancer prevention guidelines, the field of dietary pattern and its relationship to cancer risk has gained more focus. Numerous epidemiology studies have reported associations between Gastric Cancer (GC) and both data-driven posteriori dietary pattern and priori dietary pattern defined by predetermined dietary indexes. As dietary patterns have evolved, a series of patterns based on biological markers has advanced, offering deeper insights into the relationship between diet and the risk of cancer. Although researches on dietary patterns and cancer risk are booming, there is limited body of literature focusing specifically on GC. In this study, we compare the similarities and differences among the specific components of dietary patterns and indices, summarize current state of knowledge regarding dietary patterns related to GC and illustrate their potential mechanisms for GC prevention. In conclusion, we offer suggestions for future research based on the emerging themes within this rapidly evolving field.
Bibliometric analysis of breast cancer-related lymphedema research trends over the last 2 decades
Authors: Huang Jinghui , Li Jiamin , Li Ying , Huang Lele , Li Bai , Huang Feng , Lv Can , Fang Fanfu
Published: February 2024

Objective

As breast cancer cases rise globally, post-mastectomy lymphedema garners increasing scholarly attention. This study aims to conduct a comprehensive bibliometric analysis of Breast Cancer-Related Lymphedema (BCRL) research from 2003 to 2022, identifying trends and providing global research insights for future studies.

Method

The literature for this analysis was extracted from the Web of Science (WoS) Core Collection, encompassing 1199 publications, including 702 articles and 101 reviews, totaling 803. Using advanced bibliometric tools such as VOSviewer and CiteSpace, quantitative and visual analyses were performed to map collaboration networks, research clusters, and emerging trends. The search strategy included specific terms related to lymphedema, breast cancer, and BCRL, ensuring a comprehensive representation of the research landscape.

Results

The bibliometric analysis revealed a steady increase in BCRL publications over the studied period, reaching a peak in 2018. The United States emerged as the leading contributor to BCRL literature, with China also demonstrating a significant presence. Collaboration networks were visualized, showcasing the interconnectedness of institutions and researchers globally. Key research hotspots identified include preventive strategies, complex decongestive therapy, and reconstructive interventions.

Conclusion

In conclusion, this pioneering bibliometric analysis provides a comprehensive overview of BCRL research trends and collaborations globally. The findings contribute valuable insights into the evolution of the field, highlighting areas of focus and emerging research themes. This study serves as a foundational resource for researchers, clinicians, and policymakers, fostering evidence-based practices and interventions for BCRL in the future.
Color Doppler ultrasound in high-low risk pregnancies and its relationship to fetal outcomes: a cross-sectional study
Authors: Dixit Snehil , Dixit Nitin Arun , Rawat Anil , Bajpai Akanksha , Alelyani Magbool , Sabah Zia Ul , Raghuwanshi Shailendra
Published: February 2024

Objective

To calculate the multivessel color Doppler indices in high-risk and low-risk pregnancies and relate these to fetal outcomes.

Methods

The investigation involved 60 patients who were pregnant. The patients were separated into groups according to assessment of low and high risk. The patients underwent color Doppler ultrasonography to detect the maternal and fetal blood vessels, and the measured Doppler indices were then analyzed for any association with fetal outcomes.

Results

The gestational stages (in weeks) of the participants at the respective times of investigation and delivery were 32.06 ± 2.98 and 36.2 ± 1.78 in the low-risk group and 29.21 ± 1.95 and 29.83 ± 1.86 in the high-risk group. The pulsatility index (PI), resistive index (RI), and systolic/diastolic ratio (SD) decreased with gestation length in the low-risk group, whereas in the high-risk group, these values increased in the uterine and umbilical arteries. With increased gestational stage, MCA-PSV (peak systolic velocity) in the middle cerebral artery (MCA) increased, while PI decreased. Pulsatile and reversal flow of the uterine vein, the vein of Galen, and the umbilical vein were noted in high-risk pregnancies, and these negatively affected the fetal outcome. The fetal venous parameters were more specific and sensitive for predicting an unfavorable fetal outcome than the arterial factors, with a greater negative predictive value.

Conclusion

The results of our study indicate that abnormal Doppler indices of the blood vessels in high-risk pregnant patients will result in adverse clinical outcomes. Therefore, the patients can be monitored and managed accordingly using Doppler ultrasonography.
Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram
Authors: Sucasas-Alonso Andrea , Pértega-Díaz Sonia , Balboa-Barreiro Vanesa , García-Muñoz Rodrigo Fermín , Avila-Alvarez Alejandro
Published: February 2024

Objective

To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis.

Methods

Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated.

Results

A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792–0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792–0.989).

Conclusions

Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.
A comprehensive review of the anticancer effects of decursin
Authors: Chu Yueming , Yuan Qiang , Jiang Hangyu , Wu Liang , Xie Yutao , Zhang Xiaofen , Li Lin
Published: February 2024

Cancer is a globally complex disease with a plethora of genetic, physiological, metabolic, and environmental variations. With the increasing resistance to current anticancer drugs, efforts have been made to develop effective cancer treatments. Currently, natural products are considered promising cancer therapeutic agents due to their potent anticancer activity and low intrinsic toxicity. Decursin, a coumarin analog mainly derived from the roots of the medicinal plant Angelica sinensis, has a wide range of biological activities, including anti-inflammatory, antioxidant, neuroprotective, and especially anticancer activities. Existing studies indicate that decursin affects cell proliferation, apoptosis, autophagy, angiogenesis, and metastasis. It also indirectly affects the immune microenvironment and can act as a potential anticancer agent. Decursin can exert synergistic antitumor effects when used in combination with a number of common clinical anticancer drugs, enhancing chemotherapy sensitivity and reversing drug resistance in cancer cells, suggesting that decursin is a good drug combination. Second, decursin is also a promising lead compound, and compounds modifying its structure and formulation form also have good anticancer effects. In addition, decursin is not only a key ingredient in several natural herbs and dietary supplements but is also available through a biosynthetic pathway, with anticancer properties and a high degree of safety in cells, animals, and humans. Thus, it is evident that decursin is a promising natural compound, and its great potential for cancer prevention and treatment needs to be studied and explored in greater depth to support its move from the laboratory to the clinic.
A journey into the regulatory secrets of the de novo purine nucleotide biosynthesis
Authors: Ayoub Nour , Gedeon Antoine , Munier-Lehmann Hélène
Published: February 2024

De novo purine nucleotide biosynthesis (DNPNB) consists of sequential reactions that are majorly conserved in living organisms. Several regulation events take place to maintain physiological concentrations of adenylate and guanylate nucleotides in cells and to fine-tune the production of purine nucleotides in response to changing cellular demands. Recent years have seen a renewed interest in the DNPNB enzymes, with some being highlighted as promising targets for therapeutic molecules. Herein, a review of two newly revealed modes of regulation of the DNPNB pathway has been carried out: i) the unprecedent allosteric regulation of one of the limiting enzymes of the pathway named inosine 5′-monophosphate dehydrogenase (IMPDH), and ii) the supramolecular assembly of DNPNB enzymes. Moreover, recent advances that revealed the therapeutic potential of DNPNB enzymes in bacteria could open the road for the pharmacological development of novel antibiotics.
Probiotics as modulators of gut-brain axis for cognitive development
Authors: Kumar Akash , Sivamaruthi Bhagavathi Sundaram , Dey Swarnima , Kumar Yogesh , Malviya Rishabha , Prajapati Bhupendra G. , Chaiyasut Chaiyavat
Published: February 2024

Various microbial communities reside in the gastrointestinal tract of humans and play an important role in immunity, digestion, drug metabolism, intestinal integrity, and protection from pathogens. Recent studies have revealed that the gut microbiota (GM) is involved in communication with the brain, through a bidirectional communication network known as the gut-brain axis. This communication involves humoral, immunological, endocrine, and neural pathways. Gut dysbiosis negatively impacts these communication pathways, leading to neurological complications and cognitive deficits. Both pre-clinical and clinical studies have demonstrated that probiotics can restore healthy GM, reduce intestinal pH, and reduce inflammation and pathogenic microbes in the gut. Additionally, probiotics improve cell-to-cell signaling and increase blood-brain-derived neurotrophic factors. Probiotics emerge as a potential approach for preventing and managing neurological complications and cognitive deficits. Despite these promising findings, the safety concerns and possible risks of probiotic usage must be closely monitored and addressed. This review article provides a brief overview of the role and significance of probiotics in cognitive health.
Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews
Authors: Lino Valéria T. S. , Marinho Daniel S. , Rodrigues Nadia C. P. , Andrade Carlos A. F.
Published: February 2024

The objective of this study is to evaluate the effectiveness and safety of ozone therapy (OT) in the treatment of knee osteoarthritis (KOA), which is the most common form of the disease. We analysed systematic reviews (SRs) of randomised controlled trials (RCTs) using the “A MeaSurement Tool to Assess systematic Reviews” (AMSTAR2) instrument to evaluate their quality. We developed a narrative synthesis report with eight SRs (15 RCTs/3,685 patients) to summarise the findings. The AMSTAR2 analysis indicated that all reviews had critically low confidence ratings. Statistically significant effects in pain reduction using OT compared to placebo groups were reported in three SRs. OT was shown to be comparable to other therapies in one SR and not superior in the other five. Six SRs highlighted the need for additional RCTs with improved methodological quality to confirm the efficacy of OT for KOA. SRs found fewer consistent effects for improving joint function. Regarding safety, seven SRs reported a low prevalence of minor adverse events linked with OT. Finally, this umbrella review highlights the beneficial effects and safety of OT in the treatment of KOA, particularly in pain control. The low methodological quality of RCTs and SRs limits the possibility of drawing conclusions on the effectiveness of the procedure in comparison to other therapies. Ensure adequate compliance with guidelines such as Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and AMSTAR2 has the ability to improve the quality of SRs in this area.
Neuroendocrine effects of the duper mutation in Syrian hamsters: a role for Cryptochrome 1
Authors: Manoogian Emily N. C. , Bahiru Michael Seifu , Wang Emily Jue , Holder Mary , Bittman Eric L.
Published: February 2024

Molecular and physiological determinants of the timing of reproductive events, including the pre-ovulatory LH surge and seasonal fluctuations in fertility, are incompletely understood. We used the Cryptochrome 1-deficient duper mutant to examine the role of this core circadian clock gene in Syrian hamsters. We find that the phase of the LH surge and its stability upon shifts of the light: dark cycle are altered in duper mutants. The intensity of immunoreactive PER1 in GnRH cells of the preoptic area peaks earlier in the day in duper than wild type hamsters. We note that GnRH fibers coursing through the suprachiasmatic nucleus (SCN) contact vasopressin- and VIP-immunoreactive cells, suggesting a possible locus of circadian control of the LH surge. Unlike wild types, duper hamsters do not regress their gonads within 8 weeks of constant darkness, despite evidence of melatonin secretion during the subjective night. In light of the finding that the duper allele is a stop codon in Cryptochrome 1, our results suggest important neuroendocrine functions of this core circadian clock gene.