bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan metabolites and gut microbiota play an important role in pediatric migraine diagnosis
Authors: Liu Junhui , Xi Kaiyan , Zhang Linlin , Han Mugu , Wang Qingran , Liu Xinjie
Published: January 2024

Background

The pathogenesis of pediatric migraine remains unclear and presents challenges in diagnosis. Recently, growing evidence has indicated that the gut microbiota can exert modulatory functions at the gut-brain axis by directly or indirectly regulating tryptophan metabolism. Consequently, we aimed to elucidate the potential association among gut microbiota, tryptophan metabolism, and pediatric migraine while also identifying diagnostic biomarkers for pediatric migraine.

Methods

The gut microbiota composition of 33 migraine children and 42 healthy children, aged less than ten years, from the GMrepo database, was analyzed using the Shannon index, Simpson index, principal coordinates analysis, and Wilcoxon rank-sum test. Microbial diagnostic biomarkers were identified using linear discriminant analysis effect size, ridge regression, and random forest. Plasma concentrations of tryptophan metabolites investigated by enzyme-linked immunosorbent assay were compared between 51 migraine children and 120 healthy children, aged less than eighteen years, using t tests and analysis of variance. The receiver operating characteristic curve was performed to evaluate the diagnostic value of microbial and metabolite biomarkers in pediatric migraine.

Results

Differences in the composition of gut microbiota, notably the genera that regulate tryptophan metabolism, were observed in pediatric migraine children. Further investigations revealed a significant decrease in plasma kynurenic acid levels (p < 0.001) among migraine children, along with a significant increase in serotonin (p < 0.05) and quinolinic acid (p < 0.001). Subsequently, we established the normal reference intervals for plasma concentrations of tryptophan metabolites in children. More importantly, the ratio of kynurenic acid to quinolinic acid (AUC: 0.871, sensitivity: 86.3%, specificity: 83.3%) exhibited excellent diagnostic efficacy for pediatric migraine.

Conclusion

Our study suggests that the gut microbiota may play an important role in the development of pediatric migraine by regulating tryptophan metabolism. We believe that microbial and metabolite biomarkers are sensitive diagnostic tests for pediatric migraine.

Trial registration

The study was registered at ClinicalTrials.gov (NCT05969990).
Prognostic biomarker discovery based on proteome landscape of Chinese lung adenocarcinoma
Authors: Huang Yuqi , Ma Sheng , Xu Jun-Yu , Qian Kun , Wang Yaru , Zhang Yi , Tan Minjia , Xiao Ting
Published: January 2024

Despite recent innovations in imaging and genomic screening promotes advance in diagnosis and treatment of lung adenocarcinoma (LUAD), there remains high mortality of LUAD and insufficient understanding of LUAD biology. Our previous study performed an integrative multi-omic analysis of LUAD, filling the gap between genomic alterations and their biological proteome effects. However, more detailed molecular characterization and biomarker resources at proteome level still need to be uncovered. In this study, a quantitative proteomic experiment of patient-derived benign lung disease samples was carried out. After that, we integrated the proteomic data with previous dataset of 103 paired LUAD samples. We depicted the proteomic differences between non-cancerous and tumor samples and among diverse pathological subtypes. We also found that up-regulated mitophagy was a significant characteristic of early-stage LUAD. Additionally, our integrative analysis filtered out 75 potential prognostic biomarkers and validated two of them in an independent LUAD serum cohort. This study provided insights for improved understanding proteome abnormalities of LUAD and the novel prognostic biomarker discovery offered an opportunity for LUAD precise management.
Acceptability, values, and preferences of older people for chronic low back pain management; a qualitative evidence synthesis
Authors: Ames Heather , Hestevik Christine Hillestad , Briggs Andrew M.
Published: January 2024

Background

Chronic primary low back pain (CPLBP) and other musculoskeletal conditions represent a sizable attribution to the global burden of disability, with rates greatest in older age. There are multiple and varied interventions for CPLBP, delivered by a wide range of health and care workers. However, it is not known if these are acceptable to or align with the values and preferences of care recipients. The objective of this synthesis was to understand the key factors influencing the acceptability of, and values and preferences for, interventions/care for CPLBP from the perspective of people over 60 and their caregivers.

Methods

We searched MEDLINE, CINAHL and OpenAlex, for eligible studies from inception until April 2022. We included studies that used qualitative methods for data collection and analysis; explored the perceptions and experiences of older people and their caregivers about interventions to treat CPLBP; from any setting globally. We conducted a best fit framework synthesis using a framework developed specifically for this review. We assessed our certainty in the findings using GRADE-CERQual.

Results

All 22 included studies represented older people’s experiences and had representation across a range of geographies and economic contexts. No studies were identified on caregivers. Older people living with CPLBP express values and preferences for their care that relate to therapeutic encounters and the importance of therapeutic alliance, irrespective of the type of treatment, choice of intervention, and intervention delivery modalities. Older people with CPLBP value therapeutic encounters that validate, legitimise, and respect their pain experience, consider their context holistically, prioritise their needs and preferences, adopt a person-centred and tailored approach to care, and are supported by interprofessional communication. Older people valued care that provided benefit to them, included interventions beyond analgesic medicines alone and was financially and geographically accessible.

Conclusions

These findings provide critical context to the implementation of clinical guidelines into practice, particularly related to how care providers interact with older people and how components of care are delivered, their location and their cost. Further research is needed focusing on low- and middle-income settings, vulnerable populations, and caregivers.
Dyslipidemia among adult people living with HIV on dolutegravir – based antiretroviral therapy at a private tertiary hospital in Kampala, Uganda: burden and determinants
Authors: Kigongo Vianney John , Nankabirwa Joaniter I. , Kitutu Freddy Eric , Ssenyonga Ronald , Mutebi Ronald Kasoma , Kazibwe Andrew , Kiguba Ronald , Kambugu Andrew D. , Castelnuovo Barbara
Published: January 2024

Background

Understanding the burden of dyslipidemia and its associated factors among adult people living with HIV on dolutegravir (DTG) based anti-retroviral therapy (ART) is critical to provide clinical guidance and risk reduction strategies in our setting.

Methods

We conducted a cross-sectional study on adult people living with HIV on DTG based ART between July and August 2022 at Mengo Hospital, a private not for profit missionary hospital owned by the Church of Uganda. Dyslipidemia was defined as: Total cholesterol (TC) ≥ 5.2 mmol/l, or high-density lipoprotein (HDL) < 1 mmol/l for men and < 1.3 mmol/l for women, or triglycerides (TG) ≥ 1.7 mmol/l, and low-density lipoprotein (LDL) ≥ 3.4 mmol/l. A participant was considered to have dyslipidemia if they had any of the lipid profile parameters in the above ranges. Socio-demographic information, clinical data and behavioral characteristics were collected. Fasting lipid profile and fasting blood glucose levels were also measured. Bivariate and multivariate analyses were done using a generalized linear model regression of the Poisson family with a log link (modified Poisson) using robust standard errors since the prevalence of dyslipidemia was more than 10%. Adjusted prevalence ratios (PR) were reported with their 95% confidence intervals (CI). A p-value of less than 0.05 was considered statistically significant.

Results

A total of 341 participants were included. The prevalence of dyslipidemia was 78.0%, (95%CI:73.3–82.1). The highest prevalence was for low HDL (72.1%, 95%CI 67.1–76.7) followed by high TG (20.2%, 95%CI: 16.3–24.9), high TC (12.0%, 95%CI: 9.0–15.9) and high LDL (6.5%, 95%CI: 4.3–9.6). Female sex (aPR:1.55, 95%CI: 1.32–1.84, p < 0.001) and previous use of protease inhibitor (PI) based ART regimen (aPR:1.26, 95%CI: 1.04–1.53, p = 0.018) were significantly associated with dyslipidemia.

Conclusion

We demonstrate that the prevalence of dyslipidemia is very high as it was present in more than three quarters of the study participants. Female sex and previous use of PI based ART regimen were significantly associated with dyslipidemia. Management of dyslipidemia should be integrated in the HIV treatment package and we recommend further inquiry into the temporal relationship between dyslipidemia and DTG among ART patients, if any.
Differential distribution of linezolid in diseased and nondiseased bones in patients with spinal tuberculosis
Authors: Li Yuan , Lei Guohua , Dong Weijie , Lan Tinglong , Fan Jun , Qin Shibing
Published: January 2024

Background

Linezolid exhibits antibacterial activity against sensitive and drug-resistant strains of Mycobacterium tuberculosis. Knowledge on the distribution of linezolid in different types of bones in patients with spinal tuberculosis (TB) is lacking, which limits the pharmacokinetic and pharmacodynamic studies of linezolid. This study aimed to evaluate the distribution of linezolid in diseased and nondiseased bones in patients with spinal TB.

Methods

Spinal TB patients treated with linezolid-containing regimens and whose diseased and nondiseased bones were collected during surgery were enrolled retrospectively from January 2017 to February 2022. Blood, nondiseased bones, and diseased bones were collected simultaneously during the operation. Linezolid concentrations in the plasma, nondiseased bones, and diseased bones were subjected to high-performance liquid chromatography–tandem mass spectrometry.

Results

Seven eligible spinal TB patients, including one rifampicin-resistant case, were enrolled. Following a 600 mg oral administration of linezolid before surgery, the median concentrations of linezolid in plasma, nondiseased bone, and diseased bone of the seven patients were 8.23, 1.01, and 2.13 mg/L, respectively. The mean ratios of linezolid concentration in nondiseased bones/plasma, diseased bones/plasma and diseased bones/nondiseased bones reached 0.26, 0.49, and 2.27, respectively. The diseased bones/plasma presented a higher mean ratio of linezolid concentration than nondiseased bones/plasma, and the difference was statistically significant (t = 2.55, p = 0.025). Pearson’s correlation analysis showed the positively correlation of linezolid concentrations in diseased and nondiseased bones (r = 0.810, p = 0.027).

Conclusions

Linezolid exhibits a higher concentration distribution in diseased bones than in nondiseased bones.
Assessing the effect of scanning parameter on the size and density of pulmonary nodules: a phantom study
Authors: Meng Donghua , Wang Zhen , Bai Changsen , Ye Zhaoxiang , Gao Zhipeng
Published: January 2024

Background

Lung cancer remains a leading cause of death among cancer patients. Computed tomography (CT) plays a key role in lung cancer screening. Previous studies have not adequately quantified the effect of scanning protocols on the detected tumor size. The aim of this study was to assess the effect of various CT scanning parameters on tumor size and densitometry based on a phantom study and to investigate the optimal energy and mA image quality for screening assessment.

Methods

We proposed a new model using the LUNGMAN N1 phantom multipurpose anthropomorphic chest phantom (diameters: 8, 10, and 12 mm; CT values: − 100, − 630, and − 800 HU) to evaluate the influence of changes in tube voltage and tube current on the size and density of pulmonary nodules. In the LUNGMAN N1 model, three types of simulated lung nodules representing solid tumors of different sizes were used. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were used to evaluate the image quality of each scanning combination. The consistency between the calculated results based on segmentation from two physicists was evaluated using the interclass correlation coefficient (ICC).

Results

In terms of nodule size, the longest diameters of ground-glass nodules (GGNs) were closest to the ground truth on the images measured at 100 kVp tube voltage, and the longest diameters of solid nodules were closest to the ground truth on the images measured at 80 kVp tube voltage. In respect to density, the CT values of GGNs and solid nodules were closest to the ground truth when measured at 80 kVp and 100 kVp tube voltage, respectively. The overall agreement demonstrates that the measurements were consistent between the two physicists.

Conclusions

Our proposed model demonstrated that a combination of 80 kVp and 140 mA scans was preferred for measuring the size of the solid nodules, and a combination of 100 kVp and 100 mA scans was preferred for measuring the size of the GGNs when performing lung cancer screening. The CT values at 80 kVp and 100 kVp were preferred for the measurement of GGNs and solid nodules, respectively, which were closest to the true CT values of the nodules. Therefore, the combination of scanning parameters should be selected for different types of nodules to obtain more accurate nodal data.
Determinants of late antenatal care attendance among high parity women in Uganda: analysis of the 2016 Uganda demographic and health survey
Authors: Tumwizere Godfrey , K. Mbonye Martin , Ndugga Patricia
Published: January 2024

Background

Timely and adequate Antenatal Care (ANC) effectively prevents adverse pregnancy outcomes and is crucial for decreasing maternal and neonatal mortality. High-parity women (5 + children) are at higher risk of maternal mortality. Limited information on the late timing of ANC among this risky group continues to hamper Uganda’s efforts to reduce maternal mortality ratios and improve infant and child survival. This study aimed to determine factors associated with attendance of the first ANC after 12 weeks of gestation among high-parity women in Uganda.

Methods

This study was based on nationally representative data from the 2016 Uganda Demographic and Health Survey. The study sample comprised 5,266 women (aged 15–49) with five or more children. A complementary log-log regression model was used to identify factors associated with late ANC attendance among high-parity women in Uganda.

Results

Our findings showed that 73% of high parity women delayed seeking their first ANC visit. Late ANC attendance among high-parity women was associated with distance to the health facility, living with a partner, partner’s education, delivery in a health facility, and Desire for more children. Women who did not find the distance to the health facility when going for medical help to be a big problem had increased odds of attending ANC late compared to women who found distance a big problem (AOR = 1.113, CI: 1.004–1.234), women not living with partners (AOR = 1.196, 95% CI = 1.045–1.370) having had last delivery in a health facility (AOR = 0.812, 95% CI = 0.709–0.931), and women who desired to have another child (AOR = 0.887, 95% CI = 0.793–0.993) had increased odds compared to their counterparts.

Conclusions

To increase mothers’ timely attendance and improve maternal survival among high-parity women in Uganda, programs could promote and strengthen health facility delivery and integrate family planning with other services such as ANC and postnatal care education to enable women to seek antenatal care within the recommended first trimester. This study calls for increased support for programs for education, sensitization, and advocacy for health facility-based deliveries. This could be done through strengthened support for VHT and community engagement activities.
The degree of risk factor and accumulation effect for large niche in individuals after cesarean section
Authors: Wang Jing , He Ye , Zhang Mengyuan , Huang Fen , Wu Yuanyuan , Hu Mingjun , Yang Yuanyuan , Wei Wenwen , Pang Qiushi , Wei Zhaolian
Published: January 2024

Background

The risk factors associated with niche on the cesarean scar have been reported, however, the degree of these factors associated with large niche and the accumulation effects of these risk factors on the development of large niche are unclear.

Methods

Large niche was evaluated by transvaginal sonography during mid-follicular phase. Logistic regression model was used to assess 32 risk factors by univariate analysis. Then, a scoring model based on the screened risk factors was generated. The performance of this model was evaluated by area under curve (AUC). Finally, the scoring model was applied in 123 women to assess the external validation.

Result(s)

In the training cohort study, 163 women were diagnosed with large niche. The final scoring model involves eight risk factors with the rating scores including age at delivery (30–34 years: 1 point; ≥ 35 years: 4.5 points), retroflexed uterus (8.5 points), meconium-stained amniotic fluid (4.5 points), twice CSs (4.0 points), postpartum endometritis (4.5 points), premature rupture of membranes (2.5 points), intrahepatic cholestasis of pregnancy (mild to moderate: 3 points; severe: 6.5 points), and cervical dilatation (1-3 cm: 2.0 points; 4-10 cm: 4.5 points). The accumulation effect with a cut-off value of 8.0 in the scoring was associated with the large niche after CS.

Conclusion(s)

This is the first scoring model to objectively quantify the risk of a large niche after CS. Optimal risk factors control by avoiding high score factors and multiple factors accumulation may eliminate the risk of large niche development.
Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma
Authors: Sun Ying , Liu Peiru , Wang Zixi , Zhang Haibo , Xu Ying , Hu Shenghui , Yan Ying
Published: January 2024

Purpose

To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma.

Methods

This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on.

Results

The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS.

Conclusion

GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.
Genetic association analysis of dietary intake and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study
Authors: Zhang Chenwei , Xi Yujia , Zhang Yukai , He Peiyun , Su Xuesen , Fan Fangfang , Wu Min , Kong Xiaomei , Shi Yiwei
Published: January 2024

Background

IPF is a complex lung disease whose aetiology is not fully understood, but diet may have an impact on its development and progression. Therefore, we investigated the potential causal connection between dietary intake and IPF through TSMR to offer insights for early disease prevention recommendations.

Methods

The study incorporated 29 dietary exposure factors, oily fish intake, bacon intake, processed meat intake, poultry intake, beef intake, pork intake, lamb/mutton intake, non-oily fish intake, fresh fruit intake, cooked vegetable intake, baked bean intake, fresh tomato intake, tinned tomato intake, salad/raw vegetable intake, Fresh fruit intake, coffee intake, tea intake, water intake, red wine intake, average weekly beer plus cider intake, alcoholic drinks per week, cereal intake, bread intake, whole-wheat intake, whole-wheat cereal intake, cheese intake, yogurt intake, salt added to food and whole egg intake. The study explored the causal link between diet and IPF using TSMR analysis, predominantly the IVW method, and performed sensitivity analyses to validate the results.

Result

The study revealed that consuming oily fish, yogurt, and dried fruits had a protective effect against IPF, whereas the consumption of alcoholic beverages and beef was linked to an increased risk of IPF.

Conclusion

In this MR study, it was discovered that the consumption of oily fish, yogurt, and dried fruits exhibited a protective effect against IPF, whereas the intake of alcoholic beverages and beef was associated with an elevated risk of IPF. These findings underscore the significance of making informed and timely dietary decisions in IPF prevention.
Impact of prone position on dead-space fraction in COVID-19 related acute respiratory distress syndrome
Authors: Théry Guillaume , Scemama Astrée , Roblin Elvire , Caplan Morgan , Mourvillier Bruno , Goury Antoine
Published: January 2024

Introduction

COVID-19 Related Acute Respiratory Syndrome (C-ARDS) is characterized by a mismatch between respiratory mechanics and hypoxemia, suggesting increased dead-space fraction (DSF). Prone position is a cornerstone treatment of ARDS under invasive mechanical ventilation reducing mortality. We sought to investigate the impact of prone position on DSF in C-ARDS in a cohort of patients receiving invasive mechanical ventilation.

Methods

we retrospectively analysed data from 85 invasively mechanically ventilated patients with C-ARDS in supine and in prone positions, hospitalized in Intensive Care Unit (Reims University Hospital), between November, 1st 2020 and November, 1st 2022. DSF was estimated via 3 formulas usable at patients’ bedside, based on partial pressure of carbon dioxide (PaCO2) and end-tidal carbon dioxide (EtCO2).

Results

there was no difference of DSF between supine and prone position, using the 3 formulas. According to Enghoff, Frankenfield and Gattinoni equations, DSF in supine vs. prone position was in median respectively [IQR]: 0.29 [0.13–0.45] vs. 0.31 [0.19–0.51] (p = 0.37), 0.5 [0.48–0.52] vs. 0.51 [0.49–0.53] (p = 0.43), and 0.71 [0.55–0.87] vs. 0.69 [0.57–0.81], (p = 0.32).

Conclusion

prone position did not change DSF in C-ARDS.
Decision analysis framework for predicting no-shows to appointments using machine learning algorithms
Authors: Deina Carolina , Fogliatto Flavio S. , da Silveira Giovani J. C. , Anzanello Michel J.
Published: January 2024

Background

No-show to medical appointments has significant adverse effects on healthcare systems and their clients. Using machine learning to predict no-shows allows managers to implement strategies such as overbooking and reminders targeting patients most likely to miss appointments, optimizing the use of resources.

Methods

In this study, we proposed a detailed analytical framework for predicting no-shows while addressing imbalanced datasets. The framework includes a novel use ofz-fold cross-validation performed twice during the modeling process to improve model robustness and generalization. We also introduce Symbolic Regression (SR) as a classification algorithm and Instance Hardness Threshold (IHT) as a resampling technique and compared their performance with that of other classification algorithms, such as K-Nearest Neighbors (KNN) and Support Vector Machine (SVM), and resampling techniques, such as Random under Sampling (RUS), Synthetic Minority Oversampling Technique (SMOTE) and NearMiss-1. We validated the framework using two attendance datasets from Brazilian hospitals with no-show rates of 6.65% and 19.03%.

Results

From the academic perspective, our study is the first to propose using SR and IHT to predict the no-show of patients. Our findings indicate that SR and IHT presented superior performances compared to other techniques, particularly IHT, which excelled when combined with all classification algorithms and led to low variability in performance metrics results. Our results also outperformed sensitivity outcomes reported in the literature, with values above 0.94 for both datasets.

Conclusion

This is the first study to use SR and IHT methods to predict patient no-shows and the first to propose performingz-fold cross-validation twice. Our study highlights the importance of avoiding relying on few validation runs for imbalanced datasets as it may lead to biased results and inadequate analysis of the generalization and stability of the models obtained during the training stage.
Splenic proteome profiling in response to Marek’s disease virus strain GX0101 infection
Authors: Wang Chuan , Liu Yuanzi , Yang Yuze , Teng Man , Wan Xuerui , Wu Zixiang , Zhang Zhao
Published: January 2024

Marek’s disease virus (MDV) strain GX0101 was the first reported field strain of recombinant gallid herpesvirus type 2 (GaHV-2). However, the splenic proteome of MDV-infected chickens remains unclear. In this study, a total of 28 1-day-old SPF chickens were intraperitoneally injected with chicken embryo fibroblast (CEF) containing 2000 PFU GX0101. Additionally, a control group, consisting of four one-day-old SPF chickens, received intraperitoneal equal doses of CEF. Blood and various tissue samples were collected at different intervals (7, 14, 21, 30, 45, 60, and 90 days post-infection; dpi) for histopathological, real-time PCR, and label-free quantitative analyses. The results showed that the serum expressions of MDV-related genes, meq and gB, peaked at 45 dpi. The heart, liver, and spleen were dissected at 30 and 45 dpi, and their hematoxylin-eosin staining indicated that virus infection compromised the normal organizational structure at 45 dpi. Particularly, the spleen structure was severely damaged, and the lymphocytes in the white medulla were significantly reduced. Furthermore, liquid chromatography-mass spectrometry (LC-MS) and label-free techniques were used to analyze the difference in splenic proteome profiles of the experimental and control groups at 30 and 45 dpi. Proteomic analysis identified 1660 and 1244 differentially expressed proteins (DEPs) at 30 and 40 dpi, respectively, compared with the uninfected spleen tissues. According to GO analysis, these DEPs were involved in processes such as organelle organization, cellular component biogenesis, cellular component assembly, anion binding, small molecule binding, metal ion binding, cation binding, cytosol, nuclear part, etc. Additionally, KEGG analysis indicated that the following pathways were linked to MDV-induced inflammation, apoptosis, and tumor: Wnt, Hippo, AMPK, cAMP, Notch, TGF-β, PI3K-Akt, Rap1, Ras, Calcium, NF-κB, PPAR, cGMP-PKG, Apoptosis, VEGF, mTOR, FoxO, TNF, JAK-STAT, MAPK, Prion disease, T cell receptor, and B cell receptor. We finally screened 674 DEPs that were linked to MDV infection in spleen tissue. This study improves our understanding of the MDV response mechanism in the spleen.
Assembling Au8 clusters on surfaces of bifunctional nanoimmunomodulators for synergistically enhanced low dose radiotherapy of metastatic tumor
Authors: Zhang Rui , Jia Mengchao , Lv Hongying , Li Mengxuan , Ding Guanwen , Cheng Ge , Li Juan
Published: January 2024

Background

Radiotherapy is one of the mainstays of cancer therapy and has been used for treating 65–75% of patients with solid tumors. However, radiotherapy of tumors has two limitations: high-dose X-rays damage adjacent normal tissue and tumor metastases cannot be prevented.

Results

Therefore, to overcome the two limitations of radiotherapy, a multifunctional core–shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer were fabricated by assembling Au8NCs on the surface of a bifunctional nanoimmunomodulator R837/BMS nanocore using nanoprecipitation followed by electrostatic assembly. Formed R837/BMS@Au8 NP composed of R837, BMS-1, and Au8 clusters. Au8NC can enhance X-ray absorption at the tumor site to reduce X-ray dose and releases a large number of tumor-associated antigens under X-ray irradiation. With the help of immune adjuvant R837, dendritic cells can effectively process and present tumor-associated antigens to activate effector T cells, meanwhile, a small-molecule PD-L1 inhibitor BMS-1 can block PD-1/PD-L1 pathway to reactivate cytotoxic T lymphocyte, resulting in a strong systemic antitumor immune response that is beneficial for limiting tumor metastasis. According to in vivo and in vitro experiments, radioimmunotherapy based on R837/BMS@Au8 nanoparticles can increase calreticulin expression on of cancer cells, reactive oxygen species generation, and DNA breakage and decrease colony formation. The results revealed that distant tumors were 78.2% inhibited depending on radioimmunotherapy of primary tumors. Therefore, the use of a novel radiosensitizer R837/BMS@Au8 NPs realizes low-dose radiotherapy combined with immunotherapy against advanced cancer.

Conclusion

In conclusion, the multifunctional core–shell R837/BMS@Au8 nanoparticles as a novel radiosensitizer effectively limiting tumor metastasis and decrease X-ray dose to 1 Gy, providing an efective strategy for the construction of nanosystems with radiosensitizing function.
Spatial features of specific CD103+CD8+ tissue-resident memory T cell subsets define the prognosis in patients with non-small cell lung cancer
Authors: Yang Guanqun , Cai Siqi , Hu Mengyu , Li Chaozhuo , Yang Liying , Zhang Wei , Sun Jujie , Sun Fenghao , Xing Ligang , Sun Xiaorong
Published: January 2024

Background

Tissue-resident memory T (TRM) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of TRM cells but we know little about it.

Methods

Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of TRM cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a TRM-based spatial immune signature (TRM-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α).

Results

The density of TRM cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of TRM cell subsets was defined, including TRM1 (PD-1−Tim-3−TRM), TRM2 (PD-1+Tim-3−TRM), TRM3 (PD-1−Tim-3+TRM) and TRM4 (PD-1+Tim-3+TRM). The cytotoxicity of TRM2 was the strongest while that of TRM4 was the weakest. Compare with TRM1 and TRM2, TRM3 and TRM4 had better infiltration and stronger interaction with cancer cells. The TRM-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63–3.60), P < 0.001] and showed a better performance than the TNM staging system for recurrence prediction. Furthermore, by CD103-related GSEA and mIF validation, we found a negative association between tumor angiogenesis and infiltration of TRM cells.

Conclusions

These findings reveal a significant heterogeneity in the functional status and spatial distribution of TRM cells, and support it as a biomarker for the prognosis of NSCLC patients. Regulating TRM cells by targeting tumor angiogenesis may be a potential strategy to improve current immunotherapy.
Part 5: Allogeneic HSCT in refractory SJIA with lung disease; recent cases from centers in North America & Europe
Authors: Grom Alexei A. , Canna Scott W. , Abu-Arja Rolla F. , Sinha Rashmi , Peixoto Luciana , Cannizzaro Elvira , Chandrakasan Shanmuganathan , Driest Kyla , Marsh Rebecca , Neven Bénédicte , Onel Karen , Prahalad Sampath , Prockop Susan , Quartier Pierre , Roth Johannes , Schulert Grant , Silva Juliana M.F. , Wall Donna , Zeilhofer Ulrike
Published: January 2024

It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions.
Bedside personalized methods based on electrical impedance tomography or respiratory mechanics to set PEEP in ARDS and recruitment-to-inflation ratio: a physiologic study
Authors: Pavlovsky Bertrand , Desprez Christophe , Richard Jean-Christophe , Fage Nicolas , Lesimple Arnaud , Chean Dara , Courtais Antonin , Mauri Tommaso , Mercat Alain , Beloncle François
Published: January 2024

Background

Various Positive End-Expiratory Pressure (PEEP) titration strategies have been proposed to optimize ventilation in patients with acute respiratory distress syndrome (ARDS). We aimed to compare PEEP titration strategies based on electrical impedance tomography (EIT) to methods derived from respiratory system mechanics with or without esophageal pressure measurements, in terms of PEEP levels and association with recruitability.

Methods

Nineteen patients with ARDS were enrolled. Recruitability was assessed by the estimated Recruitment-to-Inflation ratio (R/Iest) between PEEP 15 and 5 cmH2O. Then, a decremental PEEP trial from PEEP 20 to 5 cmH2O was performed. PEEP levels determined by the following strategies were studied: (1) plateau pressure 28–30 cmH2O (Express), (2) minimal positive expiratory transpulmonary pressure (Positive PLe), (3) center of ventilation closest to 0.5 (CoV) and (4) intersection of the EIT-based overdistension and lung collapse curves (Crossing Point). In addition, the PEEP levels determined by the Crossing Point strategy were assessed using different PEEP ranges during the decremental PEEP trial.

Results

Express and CoV strategies led to higher PEEP levels than the Positive PLe and Crossing Point ones (17 [14–17], 20 [17–20], 8 [5–11], 10 [8–11] respectively, p < 0.001). For each strategy, there was no significant association between the optimal PEEP level and R/Iest (Crossing Point: r2 = 0.073, p = 0.263; CoV: r2 < 0.001, p = 0.941; Express: r2 < 0.001, p = 0.920; Positive PLe: r2 = 0.037, p = 0.461). The PEEP level obtained with the Crossing Point strategy was impacted by the PEEP range used during the decremental PEEP trial.

Conclusions

CoV and Express strategies led to higher PEEP levels than the Crossing Point and Positive PLe strategies. Optimal PEEP levels proposed by these four methods were not associated with recruitability. Recruitability should be specifically assessed in ARDS patients to optimize PEEP titration.
The effect of background information and motion speed on the performance of TTC estimation
Authors: Tong Yao , Zhou Tie-min
Published: January 2024

Background

In previous studies, most research on motion perception have been conducted under background-free condition when the stimulus moved in a plane parallel to the observer. In real-life situations, people’s perception of the motion state of objects is usually done under different visual noise. Based on the occlusion paradigm, this study aimed to investigate whether different background information and motion speed affect the trend and accuracy of time-to-collision (TTC) estimation when stimuli move in a plane parallel to the observer.

Methods

Thirty five college students (mean age = 20.94, SD = 2.95, range = 18-28 years) participated in experiment 1, and used a 2 (background orientation: horizontal, vertical) × 3 (motion speed: slow, medium, fast) design to explore the effect of different line segment orientations and motion speed on TTC estimation performance; 36 college students (mean age = 20.81, SD = 2.82, range = 18-28 years) participated in experiment 2, and used a 2 (background dimension: two-dimensional background, three-dimensional background) × 3 (motion speed: slow, medium, fast) design to explore the effect of different background dimensions and motion speed on the performance of TTC estimation. The data were analyzed using SPSS 25.0.

Results

The results revealed that: (1) The TTC was underestimated for the slow speed condition and overestimated for the medium and fast speed conditions. (2) The highest accuracy of TTC estimation was obtained for the fast condition. (3) The TTC were overestimated for the vertical background condition and underestimated for the horizontal background condition. (4) Compared to the two-dimensional background, the TTC was overestimated in the three-dimensional background.

Conclusions

Object motion speed affected the TTC estimation performance, and different background information affected the TTC estimation performance when the object moved in a plane parallel to the observer. Meanwhile, the impact of background orientation and motion speed showed significant interactions.
Private Payers and Cancer Care: Revisiting the Land of Opportunity
Authors: Kolodziej Michael A. , Klein Ira
Published: January 2024

Ten years ago we charted a course for oncology payment reform. We summarize what went wrong and propose ways to fix it.
Seated Elliptical Exercise, But Not Periodic Standing, Alleviates Sitting-Induced Changes to Arterial Wave Reflections
Authors: ATHAIDE CHLOE E. , ROBERTSON ANDREW D. , DEVRIES MICHAELA C. , AU JASON S.
Published: January 2024

Purpose

Sedentary behavior may contribute to increased central wave reflection due to associated peripheral vasoconstriction, yet its impact on central hemodynamics and the mitigating effects of interventional strategies have not been thoroughly investigated. We tested whether standing or seated elliptical breaks alleviate the deleterious effects of prolonged sitting on central wave reflections.

Methods

Eighteen healthy adults (9 9 females, 25 ± 3 yr) completed three 3-h protocols on separate days: uninterrupted sitting, sitting with periodic standing, and sitting with periodic seated elliptical activity. Central wave reflection, central pulse wave velocity, and lower-limb pulse wave velocity were measured before and after each intervention.

Results

Central relative wave reflection magnitude (RM) increased during sitting (0.31 ± 0.05 to 0.35 ± 0.05; P < 0.01) but did not change after standing (0.30 ± 0.05 to 0.32 ± 0.04; P = 0.19) or elliptical protocols (0.30 ± 0.05 to 0.30 ± 0.04; P > 0.99). The change in RM during prolonged sitting (ΔRM) was attenuated with elliptical activity (0.04 ± 0.05 vs 0.00 ± 0.03; P = 0.02) but not with periodic standing (0.04 ± 0.04 vs 0.02 ± 0.05; P = 0.54). In addition, augmentation index and central pulse wave velocity increased after sitting (both P < 0.01) and periodic standing (both P < 0.01) but were unchanged after elliptical activity. Lower limb pulse wave velocity did not change after sitting (P = 0.73) or standing (P = 0.21) but did decrease after elliptical activity (P = 0.03).

Conclusions

Prolonged sitting without interruptions increased central wave reflection, whereas elliptical but not standing interruptions were able to ameliorate multiple sitting-induced vascular consequences. More work is required to examine the long-term effectiveness of interruption strategies, as well as the optimal type, frequency, and duration for reducing vascular risk associated with sedentary behaviors.
Cone-beam computed tomography in implant dentistry - guidelines, current concepts and limitations for practice
Authors: Popińska Zuzanna , Ślusarczyk Daniel , Żmuda Bartłomiej , Jakubowska Wiktoria , Pisera Piotr , Kiełkowicz Aleksandra , Żuberek Michał , Pactwa Filip
Published: January 2024

This article issues scientific background of Cone-beam computed tomography (CBCT) and the importance of taking x-rays before and after implant placement in daily practice as a common care. The review will introduce cone-beam computed tomography guidelines, restrictions and intraoperartive issues for instance nerve damage and bleeding incidents. Modern CBCT technology enables specialists to avoid making a wrong diagnosis, which translates into a higher percentage of people with a positive treatment outcome.

Diagnostic radiology is a crucial element of every dental treatment planning. CBCT market is expanding gradually since two decades, there are more than 85 distinct CBCT tools available. CBCT is a three-dimensional (3D) imaging used nowadays in dentistry with increased frequency and offers volumetric data on jaw bones and teeth with relatively low radiation doses and costs. Currently, the greatest advantage of CBCT examinations over radiographs is the fact that the image obtained is presented in a 3D projection and not, as is the case, in 2D. It has the ability to help a wider range of patients, but the use of CBCT also has negative consequences. Routine or excessive use has resulted in increased radiation doses accumulating in the patient's body, which translates into an increased risk of adverse effects. The risk varies according to the age of the patient under study and is directly proportional to it, that is, it is highest for young people and lower for older people. The potential risk is also slightly higher in the female population. For this reason, creating awareness of the mandatory patient safety management of CT scans is a key process by which X-ray exposures can be optimised.
Skin and mucosal lesions in the course of HIV infection
Authors: Jakubowska Wiktoria , Ślusarczyk Daniel , Pisera Piotr , Kiełkowicz Aleksandra , Pactwa Filip , Popińska Zuzanna , Żmuda Bartłomiej , Żuberek Michał
Published: January 2024

Introduction:

Dermatological conditions are prevalent expressions of HIV and AIDS, often aiding in initial diagnoses due to their visibility on the skin and mucous membranes. Given HIV's primary transmission through sexual contact, dermatologists play a crucial role in identifying and managing these infections. Understanding the range of skin and mucosal lesions occurring throughout the course of the disease is vital, particularly as these symptoms can manifest in atypical ways or even precede other signs of immune deficiency. While most associated skin disorders can be treated in outpatient settings, some severe conditions significantly impact health outcomes.

Aim of the study:

The study aims to consolidate knowledge on the typical manifestations of HIV on the skin and mucous membranes, providing a comprehensive overview of these disease entities. The most common skin and mucosal symptoms associated with HIV infection are summarized and described.

Materials and methods:

The literature available in the PubMed database was reviewed using the following keywords: “HIV”, “AIDS”, “Skin lesions”, “Mucosal lesions”.

Conclusions:

Skin conditions are widespread in HIV-infected individuals, often displaying heightened severity compared to the general population. While many of these dermatological issues aren't unique to this group, their manifestations can be more pronounced. HIV-related skin problems vary widely, including specific eruptions linked to AIDS, opportunistic infections, and AIDS-related cancers. Although some HIV-associated skin diseases have decreased due to antiretroviral therapy, there's been a noticeable increase in drug reactions and other non-infectious skin conditions.
The both–and approach in healthcare organisations: reframing paradoxes to improve practice
Authors: Cunha Miguel Pina e , Berti Marco , Canhão Helena , Barros Pedro Pita , Fonseca Filipa Breia
Published: January 2024

In this article, Miguel Pina e Cunha and colleagues discuss the both–and approach to paradox and how this may be applied to healthcare organisations in order to reduce errors, while allowing practitioners to learn from mistakes so that they can continuously improve.
Is technology optimised in surgical hubs and community diagnostic centres?
Authors: Harpham Barbara
Published: January 2024

An investigation by the Medical Technology Group found variations in the use of technology and evaluation of procedures in surgical hubs and community diagnostic centres across England. This article highlights the key findings, with recommendations for reducing variation and truly optimising these centres.
Settling into primary care
Authors: Green Jennifer
Published: January 2024

As more paramedics transition across various roles, Band 6 paramedic, Jennifer Green shares her journey in a new monthly column in 2024, as she makes her way from the ambulance setting into general practice
A Comparative Study and Characterization of Green Solvent and Hexane Extracted Bioactive lipids from Heterospathe elata Fruit
Authors: Shukla Abha , Dubey Supriya , Kumar Shukla Rishi , Kumar Ajay , Vats Swati , Pokhriyal Priyanka
Published: January 2024

Our study aims to investigate the extraction of fixed oil from the fruit of Heterospathe elata, using traditional petroleum-based solvent hexane and green solvent dimethyl carbonate (DMC), evaluation of physicochemical parameters, chemical composition, and biological activities of extracted oil. The resulting oil components were subjected to GC-FID analysis. The evaluation of different biological activities like antioxidant, anti-inflammatory, and photoprotective activities has been done by the spectrophotometric method. The results obtained from GC-FID analysis proved the presence of fatty acids, of which myristic acid was the most prevalent component in the DMC and hexane fractions, respectively. Additionally, DMC-extracted oil possess stronger antioxidant, anti-inflammatory, and photoprotective activities than hexane-extracted oil. The findings showed that DMC is effective in replacing potentially hazardous solvents to extract oil from the Heterospathe elata fruit, rich in components relevant to the human diet, including vital polyunsaturated fatty acids and phenolic compounds, with better biological activity.