bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative CT findings and prognosis of pulmonary sarcomatoid carcinoma: comparison with conventional NSCLC of similar tumor size
Authors: Tang Wenjian , Wen Chunju , Pei Yixiu , Wu Zhen , Zhong Junyuan , Peng Jidong , Zhong Jianping
Published: August 2023

Background

Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) but differs in terms of treatment strategies compared with conventional-NSCLC (c-NSCLC). However, preoperative CT differentiation between PSC and c-NSCLC remains a challenge. This study aimed to explore the CT findings and prognosis of PSC compared with c-NSCLC of similar tumor size.

Methods

Clinical data and CT findings of 31 patients with PSC and 87 patients with c-NSCLC were retrospectively analyzed. Clinical data included sex, age, and smoking history. CT findings included tumor size, tumor location, calcification, vacuole/cavity, pleural invasion, mean CT value, and low-attenuation area (LAA) ratio. Kaplan‒Meier curves and log-rank tests were used for survival analysis. A Cox regression model was constructed to evaluate prognostic risk factors associated with overall survival (OS). The Spearman correlation among clinicoradiological outcomes were analyzed.

Results

The mean tumor size of PSC and c-NSCLC were both 5.1 cm. The median survival times of PSC and c-NSCLC were 8 months and 34 months, respectively (P < 0.001). Calcification and vacuoles/cavities were rarely present in PSC. Pleural invasion occurred in both PSC and c-NSCLC (P = 0.285). The mean CT values of PSC and c-NSCLC on plain scan (PS), arterial phase (AP), and venous phase (VP) were 30.48 ± 1.59 vs. 36.25 ± 0.64 Hu (P = 0.002), 43.26 ± 2.96 vs. 58.71 ± 1.65 Hu (P < 0.001) and 50.26 ± 3.28 vs. 64.24 ± 1.86 Hu (P < 0.001), the AUCs were 0.685, 0.757 and 0.710, respectively. Compared to c-NSCLC, PSC had a larger LAA ratio, and the AUC was 0.802, with an optimal cutoff value of 20.6%, and the sensitivity and specificity were 0.645 and 0.862, respectively. Combined with the mean CT value and LAA ratio, AP + VP + LAA yielded the largest AUC of 0.826. The LAA ratio were not independent risk factors for PSC in this study. LAA ratio was negatively correlated with PS (r = -0.29), AP (r = -0.58), and VP (r = -0.66). LAA showed a weak positive correlation with tumor size(r = 0.27).

Conclusions

PSC has a poorer prognosis than c-NSCLC of similar tumor size. The mean CT value and LAA ratio contributes to preoperative CT differentiation of PSC and c-NSCLC.
An investigation of neuromelanin distribution in substantia nigra and locus coeruleus in patients with Parkinson’s disease using neuromelanin-sensitive MRI
Authors: Liu Qiang , Wang Pan , Liu Chenghe , Xue Feng , Wang Qian , Chen Yuqing , Hou Ruihua , Chen Teng
Published: August 2023

Loss of neuromelanin in the midbrain is known in Parkinson’s disease(PD), which can now be directly detected by neuromelanin-sensitive MRI(NM-MRI). This case-control study was to investigate the distribution of neuromelanin in the substantia nigra(SN) and the locus coeruleus(LC) using NM-MRI technique and evaluate its potential as a diagnostic marker for PD. 10 early PD patients(H&Y stage I, II), 11 progressive PD patients(H&Y stage III-V), and 10 healthy controls matched in age and gender were recruited. All participants completed clinical and psychometric assessments as well as NM-MRI scans. Neuromelanin signal intensities in SN and LC were measured by contrast-to-noise ratios(CNRs) derived from NM-MRI scans. There were significant decreases of CNRs in SNpc(including anterior, central, and posterior) and LC in PD patients compared to controls. There were also significant differences of CNR between the left and right sides. CNR in LC had a negative correlation with the Non-Motor Symptoms Scale(NMSS) score in PD patients(|R|=0.49), whereas CNR in SNpc did not correlate with Unified Parkinson Disease Rating Scale(UPDRS) score(|R|<0.3). The receiver operating characteristic(ROC) curves revealed that the CNR in LC had a high diagnostic specificity of 90.1% in progressive patients. This study provides new evidence for the asymmetric distribution of neuromelanin in SN and the LC of patients with PD. The neuromelanin loss is bilateral and more predominately in LC than that in SN. This distinct neuromelanin distribution pattern may offer a potential diagnostic marker and a potential neuropharmacological intervention target for PD patients.
CRISPR-Cas9 identifies growth-related subtypes of glioblastoma with therapeutical significance through cell line knockdown
Authors: Zhao Nannan , Weng Siyuan , Liu Zaoqu , Xu Hui , Ren Yuqin , Guo Chunguang , Liu Long , Zhang Zhenyu , Ji Yuchen , Han Xinwei
Published: August 2023

Background

Glioblastoma (GBM) is a type of highly malignant brain tumor that is known for its significant intratumoral heterogeneity, meaning that there can be a high degree of variability within the tumor tissue. Despite the identification of several subtypes of GBM in recent years, there remains to explore a classification based on genes related to proliferation and growth.

Methods

The growth-related genes of GBM were identified by CRISPR-Cas9 and univariate Cox regression analysis. The expression of these genes in the Cancer Genome Atlas cohort (TCGA) was used to construct growth-related genes subtypes (GGSs) via consensus clustering. Validation of this subtyping was performed using the nearest template prediction (NTP) algorithm in two independent Gene Expression Omnibus (GEO) cohorts and the ZZ cohort. Additionally, copy number variations, biological functions, and potential drugs were analyzed for each of the different subtypes separately.

Results

Our research established multicenter-validated GGSs. GGS1 exhibits the poorest prognosis, with the highest frequency of chr 7 gain & chr 10 loss, and the lowest frequency of chr 19 & 20 co-gain. Additionally, GGS1 displays the highest expression of EGFR. Furthermore, it is significantly enriched in metabolic, stemness, proliferation, and signaling pathways. Besides we showed that Foretinib may be a potential therapeutic agent for GGS1, the worst prognostic subtype, through data screening and in vitro experiments. GGS2 has a moderate prognosis, with a slightly higher proportion of chr 7 gain & chr 10 loss, and the highest proportion of chr 19 & 20 co-gain. The prognosis of GGS3 is the best, with the least chr 7 gain & 10 loss and EGFR expression.

Conclusions

These results enhance our understanding of the heterogeneity of GBM and offer insights for stratified management and precise treatment of GBM patients.
A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)
Authors: O’Hearn Katie , Menon Kusum , Weiler Hope A. , Amrein Karin , Fergusson Dean , Gunz Anna , Bustos Raul , Campos Roberto , Catalan Valentina , Roedl Siegfried , Tsampalieros Anne , Barrowman Nick , Geier Pavel , Henderson Matthew , Khamessan Ali , Lawson Margaret L. , McIntyre Lauralyn , Redpath Stephanie , Jones Glenville , Kaufmann Martin , McNally Dayre ,   the Canadian Critical Care Trials Group
Published: August 2023

Background

Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.

Methods

We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.

Results

Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).

Conclusions

A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.

Trial Registration.

Clinicaltrials.gov NCT02452762 Registered 25/05/2015.
Trusted residents and housing assistance to decrease violence exposure in New Haven (TRUE HAVEN): a strengths-based and community-driven stepped-wedge intervention to reduce gun violence
Authors: Tong Guangyu , Spell Virginia T. , Horton Nadine , Thornhill Thomas , Keene Danya , Montgomery Christine , Spiegelman Donna , Wang Emily A. , Roy Brita
Published: August 2023

Background

We describe the rationale and study design for “TRUsted rEsidents and Housing Assistance to decrease Violence Exposure in New Haven (TRUE HAVEN),” a prospective type 1 hybrid effectiveness/implementation study of a multi-level intervention using a stepped wedge design. TRUE HAVEN aims to lower rates of community gun violence by fostering the stability, wealth, and well-being of individuals and families directly impacted by incarceration through the provision of stable housing and by breaking the cycle of trauma.

Design

TRUE HAVEN is an ongoing, multi-level intervention with three primary components: financial education paired with housing support (individual level), trauma-informed counseling (neighborhood level), and policy changes to address structural racism (city/state level). Six neighborhoods with among the highest rates of gun violence in New Haven, Connecticut, will receive the individual and neighborhood level intervention components sequentially beginning at staggered 6-month steps. Residents of these neighborhoods will be eligible to participate in the housing stability and financial education component if they were recently incarcerated or are family members of currently incarcerated people; participants will receive intense financial education and follow-up for six months and be eligible for special down payment and rental assistance programs. In addition, trusted community members and organization leaders within each target neighborhood will participate in trauma-informed care training sessions to then be able to recognize when their peers are suffering from trauma symptoms, to support these affected peers, and to destigmatize accessing professional mental health services and connect them to these services when needed. Finally, a multi-stakeholder coalition will be convened to address policies that act as barriers to housing stability or accessing mental healthcare. Interventions will be delivered through existing partnerships with community-based organizations and networks. The primary outcome is neighborhood rate of incident gun violence. To inform future implementation and optimize the intervention package as the study progresses, we will use the Learn As You Go approach to optimize and assess the effectiveness of the intervention package on the primary study outcome.

Discussion

Results from this protocol will yield novel evidence for whether and how addressing structural racism citywide leads to a reduction in gun violence.

Trial registration

ClinicalTrials.gov Identifier: NCT05723614. Registration date: February 01, 2023. Please refer to https://clinicaltrials.gov/ct2/show/NCT05723614 for public and scientific inquiries.
Characterization of tea (Camellia sinensis L.) flower extract and insights into its antifungal susceptibilities of Aspergillus flavus
Authors: Chen Fangfang , Chen Yu-Pei , Wu Hongtan , Li Ya , Zhang Shudi , Ke Jincheng , Yao Jeng-Yuan
Published: August 2023

Background

Tea (Camellia sinensis L.) flowers will compete with tea leaves in nutrition and are abandoned as an undesirable by-product. In this study, the biological efficacy of tea flowers was investigated. Further exploration of its antifungal activity was explained.

Methods

Tea flowers harvested from China were characterized in term of component, antioxidant ability, tyrosinase inhibition, and antifungal ability. Chemical compounds of tea flowers were analyzed by LC-MS. Disinfectant compounds were identified in tea flowers, and 2-ketobutyric acid exhibited antifungal activity against Aspergillus flavusCCTCC AF 2023038. The antifungal mechanism of 2-ketobutyric acid was further investigated by RNA-seq.

Results

Water-soluble tea flower extracts (TFEs) exhibited free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) as well as a high ferric-reducing ability. However, no inhibition of tyrosinase activity was observed. In the antifungal test, 6.4 mg/mL TFE reached 71.5% antifungal rate and the electrical conductivity of the culture broth increased with increasing concentration of TFE, implying that it damaged the fungal cell membrane by the TFE. Several disinfectants were identified in TFE by LC-MS, and 2-ketobutyric acid was also confirmed to be capable of fungal inhibition. Propidium iodide (PI) staining indicated that 2-ketobutyric acid caused damage to the cell membrane. RNA-seq analysis revealed that 3,808 differentially expressed genes (DEGs) were found in A. flavus CCTCC AF 2023038 treated by 2-ketobutyric acid, and more than 1,000 DEGs involved in the integral and intrinsic component of membrane were affected. Moreover, 2-ketobutyric acid downregulated aflatoxin biosynthesis genes and decreased the aflatoxin production.

Conclusions

Overall, TFE exhibited excellent antioxidant ability and fungal inhibition against A. flavus CCTCC AF 2023038 due to its abundant disinfectant compounds. As a recognized food additive, 2-ketobutyric acid is safe to use in the food industry and can be utilized as the basis for the research and development of strong fungicides.
Shared decision making and advance care planning: a systematic literature review and novel decision-making model
Authors: Rosca Ana , Karzig-Roduner Isabelle , Kasper Jürgen , Rogger Niek , Drewniak Daniel , Krones Tanja
Published: August 2023

Background and Aims

Shared decision making (SDM) and advance care planning (ACP) are important evidence and ethics based concepts that can be translated in communication tools to aid the treatment decision-making process. Although both have been recommended in the care of patients with risks of complications, they have not yet been described as two components of one single process. In this paper we aim to (1) assess how SDM and ACP is being applied, choosing patients with aortic stenosis with high and moderate treatment complication risks such as bleeding or stroke as an example, and (2) propose a model to best combine the two concepts and integrate them in the care process.

Methods

In order to assess how SDM and ACP is applied in usual care, we have performed a systematic literature review. The included studies have been analysed by means of thematic analysis as well as abductive reasoning to determine which SDM and ACP steps are applied as well as to propose a model of combining the two concepts into one process.

Results

The search in Medline, Cinahl, Embase, Scopus, Web of science, Psychinfo and Cochrane revealed 15 studies. Eleven describe various steps of SDM while four studies discuss the documentation of goals of care. Based on the review results and existing evidence we propose a model that combines SDM and ACP in one process for a complete patient informed choice.

Conclusion

To be able to make informed choices about immediate and future care, patients should be engaged in both SDM and ACP decision-making processes. This allows for an iterative process in which each important decision-maker can share their expertise and concerns regarding the care planning and advance care planning. This would help to better structure and prioritize information while creating a trustful and respectful relationship between the participants.PROSPERO 2019.CRD42019124575
The impact of the three-level collaboration exercise on collaboration and leadership during scenario-based hospital evacuation exercises using flexible surge capacity concept: a mixed method cross-sectional study
Authors: Phattharapornjaroen Phatthranit , Carlström Eric , Atiksawedparit Pongsakorn , Holmqvist Lina Dahlén , Pitidhammabhorn Dhanesh , Sittichanbuncha Yuwares , Khorram-Manesh Amir
Published: August 2023

Background

Hospitals play a crucial role in responding to disasters and public health emergencies. However, they are also vulnerable to threats such as fire or flooding and can fail to respond or evacuate adequately due to unpreparedness and lack of evacuation measures. The United Nations Office for Disaster Risk Reduction has emphasised the importance of partnerships and capacity building in disaster response. One effective way to improve and develop disaster response is through exercises that focus on collaboration and leadership. This study aimed to examine the effectiveness of using the 3-level collaboration (3LC) exercise in developing collaboration and leadership in districts in Thailand, using the concept of flexible surge capacity (FSC) and its collaborative tool during a hospital evacuation simulation.

Methods

A mixed-method cross-sectional study was conducted with 40 participants recruited from disaster-response organisations and communities. The data from several scenario-based simulations were collected according to the collaborative elements (Command and control, Safety, Communication, Assessment, Triage, Treatment, Transport), in the disaster response education, “Major Incident Medical Management and Support” using self-evaluation survey pre- and post-exercises, and direct observation.

Results

The 3LC exercise effectively facilitated participants to gain a mutual understanding of collaboration, leadership, and individual and organisational flexibility. The exercise also identified gaps in communication and the utilisation of available resources. Additionally, the importance of early community engagement was highlighted to build up a flexible surge capacity during hospital evacuation preparedness.

Conclusions

the 3LC exercise is valuable for improving leadership skills and multiagency collaboration by incorporating the collaborative factors of Flexible Surge Capacity concept in hospital evacuation preparedness.
Effect of two insect meals on the gut commensal microbiome of healthy sea trout (Salmo trutta vr. trutta)
Authors: Józefiak Agata , Rawski Mateusz , Kierończyk Bartosz , Józefiak Damian , Mazurkiewicz Jan
Published: August 2023

Background

The balance of the intestinal commensal microbiome of fish and other animals plays an important role in the physiological processes of healthy animals, contributes to the defense against pathogens, stimulates the immune system and facilitates nutrient metabolism. In the last decade, the interest in the application of the insects in fish nutrition increased, although little is known regarding the effects of insect meals on the gastrointenstinal tract microbiome of the sea trout fingerlings. The aim of this study was to evaluate the effect of two diets containing mealworm (MW) and superworm (SW) on the microbiome of the digesta of sea trout fingerlings and the relative abundances of different taxa among communities under controlled conditions.

Results

The insect meals produced a similar weight gain and survival rate to sea trout fed fishmeal. The most abundant bacterial phylum in all the treatment groups was Firmicutes followed by Proteobacteria and Actinobacteria, and significant differences in the amount of Cyanobacteria were observed in the SW group.

Conclusions

The insect meals did not produce differences in the three most abundant phyla in the sea trout digesta. However, the effect of each type of meal on the lower taxonomic levels was evident, particularly in the case of the superworm meal. These microbiome differences indicated that mealworm meal was more related to fishmeal than superworm meal. Our results highlight the potential effects of insect meals, such as mealworm and superworm meals, on the microbiota of sea trout.
The RNA-binding protein KSRP aggravates malignant progression of clear cell renal cell carcinoma through transcriptional inhibition and post-transcriptional destabilization of the NEDD4L ubiquitin ligase
Authors: Yang Yi-Chieh , Lin Yung-Wei , Lee Wei-Jiunn , Lai Feng-Ru , Ho Kuo-Hao , Chu Chih-Ying , Hua Kuo-Tai , Chen Ji-Qing , Tung Min-Che , Hsiao Michael , Wen Yu-Ching , Chien Ming-Hsien
Published: August 2023

Background

KH-type splicing regulatory protein (KHSRP, also called KSRP), a versatile RNA-binding protein, plays a critical role in various physiological and pathological conditions through modulating gene expressions at multiple levels. However, the role of KSRP in clear cell renal cell carcinoma (ccRCC) remains poorly understood.

Methods

KSRP expression was detected by a ccRCC tissue microarray and evaluated by an in silico analysis. Cell loss-of-function and gain-of-function, colony-formation, anoikis, and transwell assays, and an orthotopic bioluminescent xenograft model were conducted to determine the functional role of KRSP in ccRCC progression. Micro (mi)RNA and complementary (c)DNA microarrays were used to identify downstream targets of KSRP. Western blotting, quantitative real-time polymerase chain reaction, and promoter- and 3-untranslated region (3'UTR)-luciferase reporter assays were employed to validate the underlying mechanisms of KSRP which aggravate progression of ccRCC.

Results

Our results showed that dysregulated high levels of KSRP were correlated with advanced clinical stages, larger tumor sizes, recurrence, and poor prognoses of ccRCC. Neural precursor cell-expressed developmentally downregulated 4 like (NEDD4L) was identified as a novel target of KSRP, which can reverse the protumorigenic and prometastatic characteristics as well as epithelial-mesenchymal transition (EMT) promotion by KSRP in vitro and in vivo. Molecular studies revealed that KSRP can decrease NEDD4L messenger (m)RNA stability via inducing mir-629-5p upregulation and directly targeting the AU-rich elements (AREs) of the 3’UTR. Moreover, KSRP was shown to transcriptionally suppress NEDD4L via inducing the transcriptional repressor, Wilm's tumor 1 (WT1). In the clinic, ccRCC samples revealed a positive correlation between KSRP and mesenchymal-related genes, and patients expressing high KSRP and low NEDD4L had the worst prognoses.

Conclusion

The current findings unveil novel mechanisms of KSRP which promote malignant progression of ccRCC through transcriptional inhibition and post-transcriptional destabilization of NEDD4L transcripts. Targeting KSRP and its pathways may be a novel pharmaceutical intervention for ccRCC.
Rhizopus stolonifer biomass catalytic transesterification capability: optimization of cultivation conditions
Authors: Elhussieny Nadeem I. , El-Refai Heba A. , Mohamed Sayeda S. , Shetaia Yousseria M. , Amin Hala A. , Klöck Gerd
Published: August 2023

Background

Using fungal biomass for biocatalysis is a potential solution for the expensive cost of the use o enzymes. Production of fungal biomass with effective activity requires optimizing the cultivation conditions.

Results

Rhizopus stoloniferbiomass was optimized for transesterification and hydrolysis of waste frying oil (WFO). Growth and biomass lipolytic activities ofR. stoloniferimproved under shaking conditions compared to static conditions, and 200 rpm was optimum. As biomass lipase and transesterification activities inducer, olive oil was superior to soybean, rapeseed, and waste frying oils. Biomass produced in culture media containing fishmeal as an N-source feedstock had higher lipolytic capabilities than corn-steep liquor and urea. Plackett Burman screening of 9 factors showed that pH (5–9), fishmeal (0.25–1.7%, w/v), and KH2PO4(0.1–0.9%, w/v) were significant factors with the highest main effect estimates 11.46, 10.42, 14.90, respectively. These factors were selected for response surface methodology (RSM) optimization using central composite design (CCD). CCD models for growth, biomass lipase activity, and transesterification capability were significant. The optimum conditions for growth and lipid modification catalytic activities were pH 7.4, fishmeal (2.62%, w/v), and KH2PO4 (2.99%, w/v).

Conclusion

Optimized culture conditions improved the whole cell transesterification capability ofRhizopus stoloniferbiomass in terms of fatty acid methyl ester (FAME) concentration by 67.65% to a final FAME concentration of 85.5%, w/w.
Elevated levels of neutrophil related chemokine citrullinated histone H3, interleukin-8 and C-reaction protein in patients with immune checkpoint inhibitor therapy: predictive biomarkers for response to treatment
Authors: Wang Xueping , Huang Hao , Zhang Lin , Wu Yaxian , Wen Yingsheng , Weng Xuezi , Chen Qi , Liu Wanli
Published: August 2023

Background

Immune checkpoint inhibitor (ICI) therapy has been used in various tumors. The biomarkers predictive of a response to ICI treatment remain unclear, and additional and combined biomarkers are urgently needed. Secreted factors related to the tumor microenvironment (TME) have been evaluated to identify novel noninvasive predictive biomarkers.

Methods

We analyzed 85 patients undergoing ICI therapy as the primary cohort. The associations between ICI response and all biomarkers were evaluated. A prediction model and a nomogram were developed and validated based on the above factors.

Results

Seventy-seven patients were enrolled in the validation cohort. In the primary cohort, the baseline serum levels of H3Cit, IL-8 and CRP were significantly higher in nonresponder patients. A model based on these three factors was developed, and the “risk score” of an ICI response was calculated with the formula: “risk score” = 3.4591×H3Cit + 2.5808×IL8 + 2.0045 ×CRP– 11.3844. The cutoff point of the “risk score” was 0.528, and patients with a “risk score” lower than 0.528 were more likely to benefit from ICI treatment (AUC: 0.937, 95% CI: 0.886–0.988, with sensitivity 80.60%, specificity 91.40%). The AUC was 0.719 (95% CI: 0.600-0.837, P = 0.001), with a sensitivity of 70.00% and specificity of 65.20% in the validation cohort.

Conclusions

A model incorporating H3Cit, IL-8 and CRP has an excellent prediction ability for ICI response; thus, patients with a lower “risk score” selectively benefit from ICI treatment, which may have significant clinical implications for the early detection of an ICI response.
Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study
Authors: Carneiro Adriana Munhoz , Pereira Danilo Assis , Fernandes Fernando , Baptista Makilim Nunes , Brunoni André Russowsky , Moreno Ricardo Alberto
Published: August 2023

Background

Distorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients’ perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period.

Method

These are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24.

Results

Results showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment.

Conclusion

Cognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions.

Trial registration

NCT02268487.
The impact of government subsidy programs on equity in health financing
Authors: Mohammadzadeh Yousef , Sheikhmali Aysan , Yahyavi Dizaj Jafar , Mosadeghrad Ali Mohammad , Yusefzadeh Hasan , Refah Kahriz Arash
Published: August 2023

Background

Iran government implemented the targeted subsidy plan in December 2010 to reduce energy consumption and inequality. In addition, the Health Transformation Plan was implemented by the Ministry of Health to reduce out-of-pocket payments. This study aimed to examine the impact of these two government subsidy programs on equity in health financing.

Method

In this study, data on 528,046 households were collected using household surveys during 14 years (2007–2020). The Fairness in Financial Contribution index and Catastrophic Health Expenditures index were calculated. Also, a Logistic regression model was performed by the applied software of Stata V.14 to examine the effects of the two mentioned policies and other socioeconomic characteristics of households on their exposure to Catastrophic Health Expenditures.

Results

The FFC index was 0.829 and 0.795 respectively in 2007 and 2020. The trend analysis did not show significant changes in the FFC index between 2007 and 2020. TSP and HTP implementations do not reduce households’ exposure to CHE significantly. Crowded households with more elder people, belonging to low-income deciles, without houses, and living in rural areas and deprived provinces, are more likely to be at risk of CHE. Health insurance coverage did not protect households from CHE. Highly educated and employed households were exposed to less CHE.

Conclusion

The government subsidy programs have not been effective in improving FFC and reducing CHE indices. None of them has been able to realize the goal of the 6th National Development Plan of reducing CHE to 1%. The government should devise support packages for target households (households with more elderly people, lower incomes, without private houses, crowded, rural, and inhabited in deprived provinces), so they can protect households against CHE. Modifying and improving the quality of insurance coverage is strongly recommended due to its inefficiency.
PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus
Authors: Wu Qing , Du Xingxing , Cheng Jianing , Qi Xiuying , Liu Huan , Lv Xiaohong , Gong Xieyang , Shao Changxin , Wang Muhong , Yue Luxiao , Yang Xin , Li Shiyu , Zhang Yafang , Li Xuemei , Yang Huike
Published: August 2023

Background

Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer.

Methods

The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests.

Results

DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT.

Conclusions

PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC.

Graphical Abstract
A case series on recurrent and persisting IgA vasculitis (Henoch Schonlein purpura) in children
Authors: Marro Julien , Williams Chloe , Pain Clare E. , Oni Louise
Published: August 2023

Background

IgA vasculitis (IgAV) is a small vessel vasculitis that is more common in childhood. Very limited evidence exists on patients who experience an atypical disease course. The aim of this study was to describe a cohort of children diagnosed with recurrent or persisting IgAV to identify any themes associated with their disease course and areas of unmet needs.

Methods

A single centre retrospective study of children diagnosed with recurrent or persisting IgAV at Alder Hey Children’s Hospital (Liverpool, UK). Clinical data, including features at presentation and during follow up, potential triggers, abnormal laboratory and histology results, treatment and outcome at last clinical review were retrospectively collected. Key themes were identified.

Results

A total of 13 children met the inclusion criteria (recurrent disease, n = 4; persisting disease, n = 9). Median age at first presentation was 10.2 years [2.6–15.5], female:male ratio 1.2:1. Children in the atypical cohort were significantly older than a larger cohort of children who followed a non-complicated disease course (median age 5.5 years (range [0.6–16.7], p = 0.003)). All children re-presented with a purpuric rash (either recurring or persisting), accompanied by joint involvement in 92% of patients (12/13). Disease-modifying anti-rheumatic drugs (DMARDs) were used in 8/13 (62%) children. The median time from first presentation to diagnosis of atypical disease was 18.4 months [5.3-150.8] and the time from first presentation to treatment was 24.1 months [1.8–95.4]. Use of corticosteroids was significantly higher in children with renal involvement (p = 0.026). During follow up, 8/13 (62%) children were admitted at least once, whilst 10/13 (77%) had re-presented at least once to the emergency department. Five (38%) children were referred to psychology services and 7 (54%) children reported feelings of frustration.

Conclusions

This series describes some characteristics of a small cohort of children with atypical IgAV. It also identifies unmet needs in children with atypical IgAV, which includes delays in diagnosis and lengthy waits for treatment, lack of high-quality evidence regarding treatment choices and a high unrecognised disease burden. Further research is needed to study this subgroup of children as evidence is lacking.
Exacerbating effects of single-dose acute ethanol exposure on neuroinflammation and amelioration by GPR110 (ADGRF1) activation
Authors: Banerjee Sharmistha , Park Taeyeop , Kim Yoo Sun , Kim Hee-Yong
Published: August 2023

Background

Neuroinflammation is a widely studied phenomenon underlying various neurodegenerative diseases. Earlier study demonstrated that pharmacological activation of GPR110 in both central and peripheral immune cells cooperatively ameliorates neuroinflammation caused by systemic lipopolysaccharide (LPS) administration. Ethanol consumption has been associated with exacerbation of neurodegenerative and systemic inflammatory conditions. The goal of this study is to determine the effects of single-dose acute ethanol exposure and GPR110 activation on the neuro-inflammation mechanisms.

Methods

For in vivo studies, GPR110 wild type (WT) and knockout (KO) mice at 10–12 weeks of age were given an oral gavage of ethanol (3 g/kg) or maltose (5.4 g/kg) at 1–4 h prior to the injection of LPS (1 mg/kg, i.p.) followed by the GPR110 ligand, synaptamide (5 mg/kg). After 2–24 h, brains were collected for the analysis of gene expression by RT-PCR or protein expression by western blotting and enzyme-linked immunosorbent assay (ELISA). Microglial activation was assessed by western blotting and immunohistochemistry. For in vitro studies, microglia and peritoneal macrophages were isolated from adult WT mice and treated with 25 mM ethanol for 4 h and then with LPS (100 ng/ml) followed by 10 nM synaptamide for 2 h for gene expression and 12 h for protein analysis.

Results

Single-dose exposure to ethanol by gavage before LPS injection upregulated pro-inflammatory cytokine expression in the brain and plasma. The LPS-induced Iba-1 expression in the brain was significantly higher after ethanol pretreatment in both WT and GPR110KO mice. GPR110 ligand decreased the mRNA and/or protein expression of these cytokines and Iba-1 in the WT but not in GPR110KO mice. In the isolated microglia and peritoneal macrophages, ethanol also exacerbated the LPS-induced expression of pro-inflammatory cytokines which was mitigated at least partially by synaptamide. The expression of an inflammasome marker NLRP3 upregulated by LPS was further elevated with prior exposure to ethanol, especially in the brains of GPR110KO mice. Both ethanol and LPS reduced adenylate cyclase 8 mRNA expression which was reversed by the activation of GPR110. PDE4B expression at both mRNA and protein level in the brain increased after ethanol and LPS treatment while synaptamide suppressed its expression in a GPR110-dependent manner.

Conclusion

Single-dose ethanol exposure exacerbated LPS-induced inflammatory responses. The GPR110 ligand synaptamide ameliorated this effect of ethanol by counteracting on the cAMP system, the common target for synaptamide and ethanol, and by regulating NLRP3 inflammasome.
Deep learning based automatic segmentation of organs-at-risk for 0.35 T MRgRT of lung tumors
Authors: Ribeiro Marvin F. , Marschner Sebastian , Kawula Maria , Rabe Moritz , Corradini Stefanie , Belka Claus , Riboldi Marco , Landry Guillaume , Kurz Christopher
Published: August 2023

Background and purpose

Magnetic resonance imaging guided radiotherapy (MRgRT) offers treatment plan adaptation to the anatomy of the day. In the current MRgRT workflow, this requires the time consuming and repetitive task of manual delineation of organs-at-risk (OARs), which is also prone to inter- and intra-observer variability. Therefore, deep learning autosegmentation (DLAS) is becoming increasingly attractive. No investigation of its application to OARs in thoracic magnetic resonance images (MRIs) from MRgRT has been done so far. This study aimed to fill this gap.

Materials and methods

122 planning MRIs from patients treated at a 0.35 T MR-Linac were retrospectively collected. Using an 80/19/23 (training/validation/test) split, individual 3D U-Nets for segmentation of the left lung, right lung, heart, aorta, spinal canal and esophagus were trained. These were compared to the clinically used contours based on Dice similarity coefficient (DSC) and Hausdorff distance (HD). They were also graded on their clinical usability by a radiation oncologist.

Results

Median DSC was 0.96, 0.96, 0.94, 0.90, 0.88 and 0.78 for left lung, right lung, heart, aorta, spinal canal and esophagus, respectively. Median 95th percentile values of the HD were 3.9, 5.3, 5.8, 3.0, 2.6 and 3.5 mm, respectively. The physician preferred the network generated contours over the clinical contours, deeming 85 out of 129 to not require any correction, 25 immediately usable for treatment planning, 15 requiring minor and 4 requiring major corrections.

Conclusions

We trained 3D U-Nets on clinical MRI planning data which produced accurate delineations in the thoracic region. DLAS contours were preferred over the clinical contours.
Histopathological features of asymmetric lacrimal gland enlargement in patients with thyroid eye disease
Authors: Gounder Pav , Oliphant Huw , Juniat Valerie , Koenig Michael , Selva Dinesh , Rajak Saul N.
Published: August 2023

Purpose

Lacrimal gland enlargement can be a feature of thyroid eye disease (TED). Unilateral or asymmetric lacrimal gland enlargement is poorly described and may impede diagnosis. We present the histological and clinical findings of four patients with asymmetric lacrimal gland enlargement.

Methods

A retrospective case note review was performed for patients over two tertiary orbital clinics (Royal Adelaide Hospital, South Australia and the Sussex Eye Hospital, Brighton, United Kingdom) presenting with an asymmetrical lacrimal gland enlargement with a background of TED that underwent biopsy to exclude alternate diagnoses. Baseline data was collected for each patient and histopathological images and reports were reviewed.

Results

All four patients were hyperthyroid at time of lacrimal gland biopsy. Biopsy demonstrated nonspecific, lymphoid aggregates, typically of B cell type, with no diagnostic findings to support lymphocyte clonality or IgG4-related disease. One biopsy specimen demonstrated evidence of some fibrosis.

Conclusion

Asymmetrical lacrimal gland enlargement can occur as part of the TED spectrum but may require biopsy to exclude alternate pathology. Histology demonstrates a non-specific lymphocytic infiltrate.
Gamified family-based health exercise intervention to improve adherence to 24-h movement behaviors recommendations in children: “3, 2, 1 Move on Study”
Authors: Alonso-Martínez Alicia M. , Legarra-Gorgoñon Gaizka , García-Alonso Yesenia , Ramírez-Vélez Robinson , Alonso-Martínez Loreto , Erice-Echegaray Blanca , Izquierdo Mikel
Published: August 2023

Background

Evidence suggests that movement patterns, including physical activity, sedentary behavior, and sleep duration, throughout a 24-h period, have a significant impact on biological processes and health outcomes for both young and adult populations. However, 80% of adolescents worldwide are not sufficiently active, and many children do not meet international physical activity recommendations for their age. Thus, the aim of this study is to evaluate the impact of a 12-week gamified family-based health and exercise intervention on physical fitness, basic motor competencies, mental and behavioral health, and adherence to 24-h movement guidelines in children aged 4 to 5 years old. The study will evaluate changes in sedentary levels, physical fitness, basic motor competencies, mental and behavioral disorders, adherence to the exercise program, and compliance with physical activity recommendations. In addition, the aim of this protocol is to describe the scientific rationale in detail and to provide information about the study procedures.

Methods/design

A total of 80 children, aged 4 to 5 years old, will be randomly assigned in a 1:1 ratio to one of two groups: the exercise group and the routine care group. The exercise group will undergo a 12-week exercise intervention, followed by a 12-week follow-up period. On the other hand, the routine care group will undergo a 12-week period of routine care, followed by a 12-week follow-up control period. The exercise program will be implemented in a family setting and facilitated through a gamified web platform with online supervision, with the hypothesis that it will have a positive impact on physical fitness, anthropometric measures, basic motor competencies, and adherence to 24-h movement guidelines.

Discussion

The results of this study will provide valuable insights into the impact of a gamified, family-oriented health and exercise program on various aspects of health, including physical fitness, basic motor competencies, mental and behavioral well-being, and adherence to 24-h movement guidelines. The findings will contribute to closing the gap in current knowledge on the effectiveness of these types of interventions for children and their parents. These findings will also contribute to  the development of future guidelines for promoting physical activity in children who do not meet the World Health Organization’s recommended levels. An online “3, 2, 1 Move on Study” is believed to increase accessibility, promoting health equity, and reducing economic barriers for all children and their families across diverse social groups.

Trial registration

Trial registration: NCT05741879. Registered February 14, 2023, Version 1.
Slittable sheath supported right ventricular pacing lead implantation in persistent left superior vena cava with absent right superior vena cava: a case report
Authors: Plášek Jiří , Vrtal Jiří , Šipula David , Grézl Tomáš , Václavík Jan
Published: August 2023

Background

Persistent left superior vena cava (PLSVC) is the most common variant of systemic venous drainage. In the absence of the right superior vena cava (RSVC), implantation of a right ventricular pacing lead may be challenging. Therefore specific implantation techniques and experiences in PLSVC are worth reporting.

Case presentation

We present a case report of a 90-year-old Caucasian female patient with PLSVC during single chamber pacemaker implantation due to the third-degree atrioventricular block. With common implantation techniques, we did not even reach the right ventricle. Therefore slittable CPS Direct ™ Universal sheath was employed to overcome the acute angle from PLSVC to tricuspid valve and ensure more fixation stability for longer 100-cm right ventricular lead placement.

Conclusion

This case demonstrates safe implantation of 100-cm long right ventricular bipolar active fixation pacing lead using common slittable CPS Direct ™ Universal sheath after failed attempts with „C“ and „J“ stylet shaped electrode. This sheath provides different angle towards tricuspid valve and more fixation stability in patient with PLSVC and absent connection to right atrium.
New insights into the important roles of phase seperation in the targeted therapy of lung cancer
Authors: Zou Ying , Zheng Hongmei , Ning Yue , Yang Yang , Wen Qiuyuan , Fan Songqing
Published: August 2023

Lung cancer is a complex and heterogeneous disease characterized by abnormal growth and proliferation of lung cells. It is the leading cause of cancer-related deaths worldwide, accounting for approximately 18% of all cancer deaths. In recent years, targeted therapy has emerged as a promising approach to treat lung cancer, which involves the use of drugs that selectively target specific molecules or signaling pathways that are critical for the growth and survival of cancer cells. Liquid–liquid phase separation (LLPS) is a fundamental biological process that occurs when proteins and other biomolecules separate into distinct liquid phases in cells. LLPS is essential for various cellular functions, including the formation of membraneless organelles, the regulation of gene expression, and the response to stress and other stimuli. Recent studies have shown that LLPS plays a crucial role in targeted therapy of lung cancer, including the sequestration of oncogenic proteins and the development of LLPS-based drug delivery systems. Understanding the mechanisms of LLPS in these processes could provide insights into new therapeutic strategies to overcome drug resistance in lung cancer cells.