bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant tislelizumab and tegafur/gimeracil/octeracil (S-1) plus oxaliplatin in patients with locally advanced gastric or gastroesophageal junction cancer: Early results of a phase 2, single-arm trial
Authors: Yin Yuping , Lin Yao , Yang Ming , Lv Jianbo , Liu Jiaying , Wu Ke , Liu Ke , Li Anshu , Shuai Xiaoming , Cai Kailin , Wang Zheng , Wang Guobin , Shen Jianfeng , Zhang Peng , Tao Kaixiong 
Published: August 2022

BackgroundRecently, the combination of immunotherapy with chemotherapy has been recommended as first-line treatment of metastatic gastric/gastroesophageal junction (G/GEJ) in the clinical guidelines of many countries; the therapeutic potential of this application needs to be further investigated for neoadjuvant therapy of advanced G/GEJ cancer patients.MethodsWe performed a prospective, single-arm, open-label, phase 2 trial of the PD-1 inhibitor tislelizumab combined with S-1 plus oxaliplatin (SOX) in patients with advanced LAG/GEJ cancer. All patients underwent the three-cycle (21 days/cycle) treatment except for one patient who underwent two cycles. The primary endpoints were tumor major pathology response (MPR) and other events of tumor response assessed by the RECIST 1.1 and Becker criteria. Moreover, we constructed a few-shot learning model to predict the probability of MPR, which could screen those patients who might benefit from the neoadjuvant immunotherapy–chemotherapy scheme. This study was registered at https://clinicaltrials.gov/ct2/show/NCT0-4890392.ResultsThirty-two patients were enrolled; 17 patients (53.1%) achieved MPR (≤10% viable tumor cells) after treatment, and among them, 8 (25.0%) had a pathological complete response (pCR). The 1-year overall survival (OS) rate was 91.4% and the 1-year recurrence-free survival (RFS) rate was 90.0%. Adverse events occurred in 24 patients (65.6%) and grade III–IV adverse events were observed in 4 patients (12.5%) during the neoadjuvant period. Furthermore, we found commonly used preoperative assessment tools such as CT and EUS, which presented limited accuracy of tumor therapeutic response in this study; thus, we developed a therapeutic response predictive model that consisted of TNFα, IFNγ, IL-10, CD4, and age of patient, and the AUC of this FSL model was 0.856 (95% CI: 0.823–0.884).DiscussionOur study showed that the neoadjuvant PD-1 inhibitor tislelizumab combined with SOX had promising application potential and presented no increasing treatment-related adverse events in patients with advanced G/GEJ cancer. Moreover, the predictive model could help therapists to evaluate the therapeutic response of this scheme accurately.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT0-4890392, identifier [NCT04890392].
Auto-segmentation for total marrow irradiation
Authors: Watkins William Tyler , Qing Kun , Han Chunhui , Hui Susanta , Liu An 
Published: August 2022

PurposeTo evaluate the accuracy and efficiency of Artificial-Intelligence (AI) segmentation in Total Marrow Irradiation (TMI) including contours throughout the head and neck (H&amp;N), thorax, abdomen, and pelvis.MethodsAn AI segmentation software was clinically introduced for total body contouring in TMI including 27 organs at risk (OARs) and 4 planning target volumes (PTVs). This work compares the clinically utilized contours to the AI-TMI contours for 21 patients. Structure and image dicom data was used to generate comparisons including volumetric, spatial, and dosimetric variations between the AI- and human-edited contour sets. Conventional volume and surface measures including the Sørensen–Dice coefficient (Dice) and the 95th% Hausdorff Distance (HD95) were used, and novel efficiency metrics were introduced. The clinical efficiency gains were estimated by the percentage of the AI-contour-surface within 1mm of the clinical contour surface. An unedited AI-contour has an efficiency gain=100%, an AI-contour with 70% of its surface&lt;1mm from a clinical contour has an efficiency gain of 70%. The dosimetric deviations were estimated from the clinical dose distribution to compute the dose volume histogram (DVH) for all structures.ResultsA total of 467 contours were compared in the 21 patients. In PTVs, contour surfaces deviated by &gt;1mm in 38.6% ± 23.1% of structures, an average efficiency gain of 61.4%. Deviations &gt;5mm were detected in 12.0% ± 21.3% of the PTV contours. In OARs, deviations &gt;1mm were detected in 24.4% ± 27.1% of the structure surfaces and &gt;5mm in 7.2% ± 18.0%; an average clinical efficiency gain of 75.6%. In H&amp;N OARs, efficiency gains ranged from 42% in optic chiasm to 100% in eyes (unedited in all cases). In thorax, average efficiency gains were &gt;80% in spinal cord, heart, and both lungs. Efficiency gains ranged from 60-70% in spleen, stomach, rectum, and bowel and 75-84% in liver, kidney, and bladder. DVH differences exceeded 0.05 in 109/467 curves at any dose level. The most common 5%-DVH variations were in esophagus (86%), rectum (48%), and PTVs (22%).ConclusionsAI auto-segmentation software offers a powerful solution for enhanced efficiency in TMI treatment planning. Whole body segmentation including PTVs and normal organs was successful based on spatial and dosimetric comparison.
Dissecting a hypoxia-related angiogenic gene signature for predicting prognosis and immune status in hepatocellular carcinoma
Authors: Zhang Guixiong , Xiao Yitai , Zhang Xiaokai , Fan Wenzhe , Zhao Yue , Wu Yanqin , Wang Hongyu , Li Jiaping 
Published: August 2022

BackgroundHypoxia and angiogenesis, as prominent characteristics of malignant tumors, are implicated in the progression of hepatocellular carcinoma (HCC). However, the role of hypoxia in the angiogenesis of liver cancer is unclear. Therefore, we explored the regulatory mechanisms of hypoxia-related angiogenic genes (HRAGs) and the relationship between these genes and the prognosis of HCC.MethodsThe transcriptomic and clinical data of HCC samples were downloaded from public datasets, followed by identification of hypoxia- and angiogenesis-related genes in the database. A gene signature model was constructed based on univariate and multivariate Cox regression analyses, and validated in independent cohorts. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves were generated to evaluate the model’s predictive capability. Gene set enrichment analysis (GSEA) was performed to explore signaling pathways regulated by the gene signature. Furthermore, the relationships among gene signature, immune status, and response to anti-angiogenesis agents and immune checkpoint blockade (ICB) were analyzed.ResultsThe prognostic model was based on three HRAGs (ANGPT2, SERPINE1 and SPP1). The model accurately predicted that low-risk patients would have longer overall survival than high-risk patients, consistent with findings in other cohorts. GSEA indicated that high-risk group membership was significantly associated with hypoxia, angiogenesis, the epithelial-mesenchymal transition, and activity in immune-related pathways. The high-risk group also had more immunosuppressive cells and higher expression of immune checkpoints such as PD-1 and PD-L1. Conversely, the low-risk group had a better response to anti-angiogenesis and ICB therapy.ConclusionsThe gene signature based on HRAGs was predictive of prognosis and provided an immunological perspective that will facilitate the development of personalized therapies.
Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age
Authors: Havdal Lise Beier , Bøås Håkon , Bekkevold Terese , Bakken Kran Anne-Marte , Rojahn Astrid Elisabeth , Størdal Ketil , Debes Sara , Døllner Henrik , Nordbø Svein Arne , Barstad Bjørn , Haarr Elisebet , Fernández Liliana Vázquez , Nakstad Britt , Inchley Christopher , Flem Elmira 
Published: August 2022

ObjectiveTo evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection.Study designWe prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015–2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data.ResultsRisk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71–16.7)], having siblings [aOR: 1.65 (95% CI 1.05–2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35–4.24)]. The length of hospital stay &gt;72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65–7.54)], having siblings [aOR: 1.45 (95% CI 1.01–2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31–3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support.ConclusionIn a large cohort of children &lt;59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.
Multi-lingual “Asthma APP” improves health knowledge of asthma among Australian First Nations carers of children with asthma
Authors: Versteegh Lesley A. , Chang Anne B. , Chirgwin Sharon , Tenorio Fransisca P. , Wilson Catherine A. , McCallum Gabrielle B. 
Published: August 2022

BackgroundAmong Australian First Nations people, asthma is associated with worse morbidity and mortality than non-First Nations people. Improving the delivery of health education that is innovative and culturally relevant to linguistically diverse populations is needed. Digital platforms, such as mobile applications (APP), have the potential to improve evidence-based health education, particularly in settings where access to specialist services is limited and turnover of staff is high, such as in remote Australia. In response to consumer needs, we developed a multi-lingual Asthma APP from our existing asthma flipchart, with a “voice-over” in seven local First Nations languages and English, using a mixture of static and interactive formats. In this study, we evaluated (a) the functionality and usability of the APP with First Nations health professionals with and without asthma and (b) whether the APP improves health knowledge and understanding of asthma among First Nations carers of children with asthma.MethodsIn total, 7 First Nations health professionals participated in semi-structured interviews prior to the evaluation with 80 First Nations carers of children with asthma from the Northern Territory and Queensland, Australia. Carers underwent pre- and post-education questionnaires (maximum score = 25), where the post-questionnaire was administered immediately post the APP education session.ResultsHealth professionals found that APP was easy to navigate and culturally appropriate. Among the 80 carers, most were mothers (86%), aged between 26 and 50 years (75%) and 61% lived in remote settings (&gt;100 km from a tertiary hospital). Most carers chose English audio (76%) with the remainder choosing one of the First Nations languages. Overall, asthma knowledge significantly improved post-education (median scores pre = 21 [interquartile range (IQR), 19–22; post = 24 (IQR 22–24), p = 0.05].ConclusionThe First Nations-specific multi-lingual Asthma APP was easy to use and acceptable for the use by health professionals that also significantly improved short-term asthma knowledge among First Nations carers of children with asthma. The Asthma APP is an innovative and culturally acceptable method of delivering evidence-based, health education to culturally and linguistically diverse populations among Australian First Nations people.
Determinants of potentially harmful traditional cord care practices among mothers in Ethiopia
Authors: Merga Bedasa Taye , Fekadu Gelana , Raru Temam Beshir , Ayana Galana Mamo , Hassen Fila Ahmed , Bekana Miressa , Negash Belay , Eshetu Bajrond , Birhanu Abdi , Mulatu Gutema , Balis Bikila 
Published: August 2022

BackgroundGlobally, newborn deaths have declined from 5 million in 1990 to 2.4 million in 2019; however, the risk of death in the first 28 days is high. Harmful umbilical cord care contributes to neonatal infection, which accounts for millions of neonatal deaths. This study assessed determinants of potentially harmful traditional cord care practices in Ethiopia using data from a nationally representative survey.Materials and methodsSecondary data analyses were employed using data from the 2016 Ethiopian Demographic and Health Survey. Weighted samples of 4,402 mothers who gave birth in the last 3 years prior to the survey were included in the analysis. Binary logistic regression was fitted to identify associations of outcome variables with explanatory variable analysis, and the results were presented with an adjusted odds ratio (AOR) at a 95% confidence interval (CI), declaring statistical significance at a p-value &lt; 0.05 in all analyses.ResultsAbout 13.70% (95% CI: 12.7%, 14.7%) of mothers practice harmful traditional umbilical cord care. Maternal age (25–34 years, AOR = 1.77, 95% CI: 1.36, 2.31, 35–49 years, AOR = 1.53, 95% CI: 1.07, 2.19), maternal education (primary: AOR = 0.54, 95% CI: 0.41, 0.70 and secondary and above: AOR = 0.61, 95% CI: 0.40, 0.94), parity (para two, AOR = 0.71, 95% CI: 0.55, 0.92), and place of delivery (home delivery, AOR = 1.96, 95% CI: 1.51, 2.56) were factors associated with potentially harmful traditional umbilical cord care practices.ConclusionMaternal educational status, parity, maternal age, and place of delivery were associated with harmful traditional cord care practices. Thus, improving mothers’ education, strengthening antenatal and postnatal care (PNC), and utilization of institutional delivery would help to reduce harmful traditional cord care practices.
Parents’ experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (the DETECT study): A qualitative interview study
Authors: Saron Holly , Carter Bernie , Siner Sarah , Preston Jennifer , Peak Matthew , Mehta Fulya , Lane Steven , Lambert Caroline , Jones Dawn , Hughes Hannah , Harris Jane , Evans Leah , Dee Sarah , Eyton-Chong Chin-Kien , Carrol Enitan D. , Sefton Gerri 
Published: August 2022

BackgroundFailure to recognize and respond to clinical deterioration in a timely and effective manner is an urgent safety concern, driving the need for early identification systems to be embedded in the care of children in hospital. Pediatric early warning systems (PEWS) or PEW scores alert health professionals (HPs) to signs of deterioration, trigger a review and escalate care as needed. PEW scoring allows HPs to record a child’s vital signs and other key data including parent concern.AimThis study aimed to explore the experiences and perceptions of parents about the acceptability of a newly implemented electronic surveillance system (the DETECT surveillance system), and factors that influenced acceptability and their awareness around signs of clinical deterioration and raising concern.MethodsDescriptive, qualitative semi-structured telephone interviews were undertaken with parents of children who had experienced a critical deterioration event (CDE) (n = 19) and parents of those who had not experienced a CDE (non-CDE parents) (n = 17). Data were collected between February 2020 and February 2021.ResultsQualitative data were analyzed using generic thematic analysis. Analysis revealed an overarching theme of trust as a key factor that underpinned all aspects of children’s vital signs being recorded and monitored. The main themes reflect three domains of parents’ trust: trust in themselves, trust in the HPs, and trust in the technology.ConclusionParents’ experiences and perceptions of the acceptability of a whole-hospital, pro-active electronic pediatric early warning system (The DETECT system) were positive; they found it acceptable and welcomed the use of new technology to support the care of their child.
Akebia saponin D protects hippocampal neurogenesis from microglia-mediated inflammation and ameliorates depressive-like behaviors and cognitive impairment in mice through the PI3K-Akt pathway
Authors: Liu Qin , Zhang Jinqiang , Xiao Chenghong , Su Dapeng , Li Liangyuan , Yang Changgui , Zhao Zhihuang , Jiang Weike , You Zili , Zhou Tao 
Published: August 2022

Given the ability of akebia saponin D (ASD) to protect various types of stem cells, in the present study, we hypothesized that ASD could promote the proliferation, differentiation, and survival of neural stem/precursor cells (NSPCs), even in a microglia-mediated inflammatory environment, thereby mitigating inflammation-related neuropsychopathology. We established a mouse model of chronic neuroinflammation by exposing animals to low-dose lipopolysaccharide (LPS, 0.25 mg/kg/d) for 14 days. The results showed that chronic exposure to LPS strikingly reduced hippocampal levels of PI3K and pAkt and neurogenesis in mice. In the presen of a microglia-mediated inflammatory niche, the PI3K-Akt signaling in cultured NSPCs was inhibited, promoting their apoptosis and differentiation into astrocytes, while decreasing neurogenesis. Conversely, ASD strongly increased the levels of PI3K and pAkt and stimulated NSPC proliferation, survival and neuronal differentiation in the microglia-mediated inflammatory niche in vitro and in vivo. ASD also restored the synaptic function of hippocampal neurons and ameliorated depressive- and anxiety-like behaviors and cognitive impairment in mice chronically exposed to LPS. The results from network pharmacology analysis showed that the PI3K-AKT pathway is one of the targets of ASD to against major depressive disorder (MDD), anxiety and Alzheimer’s disease (AD). And the results from molecular docking based on computer modeling showed that ASD is bound to the interaction interface of the PI3K and AKT. The PI3K-Akt inhibitor LY294002 blocked the therapeutic effects of ASD in vitro and in vivo. These results suggested that ASD protects NSPCs from the microglia-mediated inflammatory niche, promoting their proliferation, survival and neuronal differentiation, as well as ameliorating depressive- and anxiety-like behaviors and cognitive impairment by activating the PI3K-AKT pathway. Our work suggests the potential of ASD for treating Alzheimer’s disease, depression and other cognitive disorders involving impaired neurogenesis by microglia-mediated inflammation.
Using real-world data for supporting regulatory decision making: Comparison of cardiovascular and safety outcomes of an empagliflozin randomized clinical trial versus real-world data
Authors: Jang Ha Young , Kim In-Wha , Oh Jung Mi 
Published: August 2022

Aims: In countries where a randomized clinical trial (RCT) is difficult to perform, a real-world evidence (RWE) study with a design similar to an RCT may be an option for drug regulatory decision-making. In this study, the objective was to find out to what extent the safety of empagliflozin from the RWE study in Korea is different from the one in RCT by emulating the design of foreign RCT. The outcome covers various safety outcomes including cardiovascular safety.Methods: The EMPA-REG OUTCOME trial (NCT01131676) was selected for comparison. The inclusion/exclusion criteria and follow-up method for the RWE were matched to the comparison RCT. Major adverse cardiovascular events (MACEs) were used as a primary outcome and 15 other outcomes were also included for analysis.Result: We followed 23,126 matched patients with type 2 diabetes mellitus (11,563 empagliflozin users and 11,563 sitagliptin users) for 2.7 years (median). Empagliflozin use was associated with a significantly decreased risk of MACEs [EMPA-REG DUPLICATE RWE: adjusted HR 0.87, 95% confidence interval (CI) 0.79–0.96]. The predefined estimate agreement, regulatory agreement, and standardized difference for RCT duplication were achieved [EMPA-REG OUTCOME RCT: adjusted HR 0.86, 95% (CI) 0.74–0.99]. According to the predefined criteria for 15 outcomes, 10 outcomes were evaluated as good, and three as moderate.Conclusion: Our study results suggest that RWE in one country in comparison with an RCT has the potential for providing evidence for future regulatory decision-making in an environment where RCT could not be performed.
Yang-xin-xue keli exerts therapeutic effects via regulating mitochondrial homeostasis and function in doxorubicin-induced rat heart failure
Authors: Long Kunlan , Zhao Ziyi , Chen Jun , Zhi Lijia , Wang Chunxia , Liao Dan , Wang Meng , Gao Peiyang 
Published: August 2022

Background: Heart failure, especially chronic heart failure, is generally induced by the accumulation of reactive oxygen species (ROS), as well as the subsequent loss of mitochondrial permeability transition pore (mPTP) openings and pathological mitochondrial dysfunction. Herein, we explored the therapeutic effects of the Chinese medicine Yangxin Keli (YXXKL) on chronic heart failure and its underlying working mechanism.Methods: To mimic oxidative stress-induced chronic heart failure, a rat heart failure model was induced by the administration of DOX. Transthoracic echocardiography was performed to confirm the successful establishment of the heart failure model by observing significantly decreased cardiac function in the rats. Mitochondrial membrane potential, function, and ATP synthesis activity were measured after YXXKL was employed.Results The administration of YXXKL not only significantly improved cardiac function but also reversed the myocardium loss and fibrosis induced via DOX. Moreover, the administration of YXXKL also increased ATP synthesis and mitochondrial DNA mass in left ventricular tissues, which indicated that mitochondria may be a key target of YXXKL. Thus, we employed rat cardiomyocyte H9c2 and primary rat cardiac myocytes (RCMs) to induce oxidative stress-induced myocardial injury via DOX treatment. YXXKL-medicated serum promoted cell proliferation, which was inhibited by the addition of IC30 DOX, and the serum also inhibited cell apoptosis, which was promoted by the addition of IC50 DOX. YXKL-medicated serum was able to scavenge ROS and maintain the mitochondrial membrane potential as well as promote mitochondrial function, including the promotion of ATP synthesis, mitochondrial DNA mass, and transcriptional activity. Furthermore, we also observed that YXXKL-medicated serum inhibited DOX-induced autophagy/mitophagy by scavenging ROS.Conclusion: Taken together, we conclude that YXXKLI may exert therapeutic effects on oxidative stress-related heart failure via the regulation of mitochondria.