bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: a large cohort retrospective study
Authors: Sun Teng , Wang Tong , Li Xiangjun , Wang Haibo , Mao Yan 
Published: June 2023

PurposeIt has been reported that breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2) might be a distinct subtype of BC. However, the prognostic effect of low HER2 expression on BC patients remains controversial. We aim to conduct this single-institution retrospective analysis to assess HER2-low-positive BC outcomes in Chinese women and the prognostic role of TILs in HER2-low-positive early-stage BC.MethodWe retrospectively enrolled 1,763 BC patients treated in a single institution from 2017 to 2018. TILs are regarded as continuous variables and are divided into low TILs (≤10%) and high TILs (&gt;10%) for statistical analysis. Univariate and multivariable Cox proportional hazards regression models were used to test the associations between TILs and disease-free survival (DFS) with adjustment for clinicopathologic characteristics.ResultHigh TIL levels (&gt;10%) were associated with tumor size (&gt;2 cm, p = 0.042), age at diagnosis (p = 0.005), Ki-67 index (&gt;25%; p &lt;0.001), HR (hormone receptor) status (positive, p &lt;0.001), advanced pathological stage (p = 0.043), subtype (p &lt;0.001), and HER2 status (p &lt;0.001). The Kaplan−Meier analysis indicated that no significant difference in DFS (p = 0.83) could be found between HER2-positive, HER2-low-positive, and HER2-0 BC. The DFS of HER2-low-positive BC and HER2-nonamplified BC with high levels of TILs was statistically better than that of patients with low levels of TILs (p = 0.015; p = 0.047). In HER2-low-positive BC patients with high TIL levels (&gt;10%), DFS was significantly improved in both the univariate (HR = 0.44, 95% CI 0.22–0.87, P = 0.018) and multivariate (HR = 0.47, 95% CI 0.23–0.95, P = 0.035) Cox models. For further subgroup analysis, HR (+)/HER2-low-positive BC with high TIL (&gt;10%) levels was associated with improved DFS in both the univariate (HR = 0.41, 95% CI 0.19–0.90, P = 0.025) and multivariate (HR = 0.42, 95% CI 0.19–0.93, P = 0.032) Cox models. The HR (−)/HER2-0 BC with high TIL (&gt;10%) level was not statistically significant in the univariate Cox model, but it was statistically significant in the multivariate (HR = 0.16, 95% CI 0.28–0.96, P = 0.045) Cox model.ConclusionAmong early-stage BC, no significant survival difference could be found between the HER2-positive, HER2-low-positive, and HER2-0 cohorts. High levels of TILs were significantly associated with improved DFS in HER2-low-positive patients, especially in the HR (+)/HER2-low-positive subtype.
Emerging trends and research foci in autophagy of pancreatic cancer: a bibliometric and visualized study
Authors: Fan Linlin , Wei Zhiyong , Liu Lili , Qi Xiaojie , Yu Hong 
Published: June 2023

ObjectiveThe purpose of this study was to analyze the trends by year, country, institution, journal, reference and keyword in publications on the autophagy of pancreatic cancer (PC) and to predict future research hotspots.MethodsThe Web of Science Core Collection was used to search for publications. The contributions of various countries/regions, institutes, authors, identified research hotspots, and promising future trends were analyzed using the VOSviewer1.6.16 and CiteSpace6.6.R2 programs. We also summarized autophagy relevant clinical trials of PC.ResultsA total of 1293 papers on the autophagy of PC published between 2013 and 2023 were included in the study. The average number of citations per article was 33.76. The China had the most publications, followed by USA, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed clusters of keywords: metabolic reprogramming and ER stress, mTOR-mediated apoptosis, extracellular trap as the most concerned clusters. The co-occurrence cluster analysis showed pancreatic stellate cell, autophagy-dependent ferroptosis, autophagy-related pathway, metabolic rewiring, on-coding RNA as the highly concerned research topics in recently.ConclusionThe number of publications and research interest have generally increased over the past few years. The China and USA have made prominent contributions to the study of the autophagy of PC. The current research hotspots mainly focus not only on the related modulation, metabolic reprogramming, ferroptosis of tumor cells themselves, but also on tumor microenvironments such as autophagy associated pancreatic stellate cells and new treatments targeting autophagy.
Development of a smartphone virtual reality game to support the radiation therapy of children and adolescents in proton centers
Authors: Schenck Leonardo , Bäumer Christian , Ross Björn , Schäfer Gabriele , Stember Nicole , Thomas Heike , Stieglitz Stefan , Timmermann Beate 
Published: June 2023

IntroductionFor most patients, cancer therapy with radiation is a new experience coming with many unknown challenges. This can be stressful, particularly for children and adolescents. With the aim of reducing this stress and anxiety, a virtual-reality (VR) game, which can be used by patients prior to treatment, was developed and evaluated in a proton therapy center.MethodsThe specifications were derived from literature and from interviews with medical staff and patients. The gantry including the sound of its moving components and the sound of the interlock and safety system were identified as the main features relevant for preparation of a radiation course. Potential implementation difficulties were identified in a literature study and regarded in the design. Within the VR game, patients could interact with modeled equipment of the treatment room and hear the reportedly stress-inducing sounds in a stress-free environment prior to the treatment. The VR game was evaluated in a second series of interviews with patients.Results and DiscussionThis exploratory study demonstrated the specification, implementation and safe application of a VR game dedicated to young proton therapy patients. Initial anecdotal evidence suggested that the VR gaming experience was well received and found to be helpful when preparing young patients for radiation therapy.
How does external reference pricing work in developing countries: evidence from Iran
Authors: Babaie Fatemeh , Motevalli Mohammad Hossein , Mehralian Gholamhossein , Peiravian Farzad , Yousefi Nazila 
Published: June 2023

Introduction: Governments apply different pricing policies to ensure public accessibility, availability, and affordability of medicines. In this way, external reference pricing (ERP) because of its easy implementation is used widely across countries. However, ERP is completely path dependent, and it would both bring pros and cons, related to its implementing strategy which makes understanding of its impact in different countries challenging. In this study, we examine the performance of the ERP approach in Iran as a pricing tool.Method: We conducted a cross-sectional descriptive study. Although Iran officially uses a reference country basket for ERP, in this study, we use different reference countries based on socioeconomic comparability, access to their price data, medicine pricing approaches, and pharmaceutical expenditure to examine the effect of reference countries as well as the method performance. Then, an empirical study was applied to a list of selected samples of medicines in the Iranian market to compare their price with our new reference countries. Then, we discuss the performance of ERP process based on the real prices in the Iranian pharmaceutical market.Result: The prices of 57 medicines, which contain about 69.2% of the imported Iran pharma market in value, were compared with their prices in selected reference countries. It was found that 49.1% of prices were more expensive in at least one of the reference countries, and in 21% of products, the average price in Iran was higher than the average price in reference countries.Conclusion: Achieving efficient and fair pricing of pharmaceuticals between and within countries is still a complex conceptual and policy problem that ERP in short term can handle. ERP cannot be considered a perfect tool for pricing alone, although its effectiveness is acceptable. It is expected that using other pricing methods alongside the ERP will improve patients’ access to medicines. In Iran, we use value base pricing as the main pricing method for every new molecule. Then, we use other methods such as ERP as a complementary method.
Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials
Authors: Guo Yimeng , Jia Junting , Hao Zhiying , Yang Jing 
Published: June 2023

Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy.Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method.Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45–0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47–0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32–1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44–2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03–1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03–1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82–1.31), ORR (RR: 0.79, 95% CI 0.59–1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87–1.12), and AEs leading to death (RR 0.70, 95% CI 0.23–2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy.Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.
Configuration of the active region for the Ge-on-Si photodetector based on carrier mobility
Authors: Chang Chang , Xie Xiaoping , Li Tiantian , Cui Jishi 
Published: June 2023

The design of vertical and lateral PIN Ge-on-Si photodetectors was motivated by the disparity in electron and hole mobilities. In the case of vertical PIN junction detectors, configuring the slab region as n-type doping leads to a notable increase in the bandwidth of approximately 20 GHz compared to utilizing p-type doping for the slab. For lateral PIN junction detectors, we determined that setting the length of the n-type slab region to be 2.8 times that of the p-type slab region, based on the carrier saturation drift rate ratio, does not compromise the bandwidth. This configuration enhances the bandwidth while minimizing light absorption loss from the electrode. The proposed design in this study enhances the performance of Ge-on-Si photodetectors without adding complexity to the fabrication process. The principles applied in this study serve as instructive references for the conceptualization of other photonic or electronic devices, reinforcing the widespread applicability of these design strategies.
Sustainable production of Saussurea costus under different levels of nitrogen, phosphorus and potassium fertilizers in cold desert region of Western Himalaya
Authors: Vishvamitera Sakshi , Dhiman Diksha , Baghla Sidharth , Singh Satbeer , Kumar Manish , Kumar Ashok , Kumar Dinesh , Singh Sanatsujat , Chauhan Ramesh 
Published: June 2023

IntroductionSaussurea costus, an important critically endangered medicinal herb native to the Himalayan region, is commonly used in various ailments,viz. asthma, ulcer, inflammation, and stomach problems. In the international market, the dry roots and essential oil ofS. costushas become an important drug. The lack of appropriate fertilizer dose recommendations is one of the limiting factors for itsex-situconservation and large-scale cultivation, as plant nutrition is vital in determining crop growth and productivity. The study aimed to understand the comparative impact of different levels of fertilizer nutrients on growth, dry root and essential oil yield, and essential oil profile ofS. costus.MethodsA field experiment was conducted in Himachal Pradesh, India's cold desert region (Lahaul valley), during 2020-21. The experiment comprised three levels of nitrogen (60, 90, and 120 kg ha-1), three levels of phosphorus (20, 40, 60 kg ha-1), and two levels of potassium (20 and 40 kg ha-1) in a factorial randomized block design.ResultsThe fertilizer application had an immense effect on growth attributes, root yield attributes, dry root yield, and essential oil yield over control. The treatment combination N120, P60, and K40had the largest effect on the plant height, number of leaves per plant, leaf length and width, root length and diameter, dry matter per plant, dry root yield, and essential oil yield. However, the results were at par with the treatment comprising N90, P40, and K20. Dry root yield increased by 108.9%, and essential oil yield increased by 210.3% with fertilizer applications over unfertilized plots. The regression curve shows an increasing trend in dry root yield till N90, P40, and K20; after that, it nearly stabilized. The heat map showed that applying fertilizer significantly affected the chemical constituents ofS. costusessential oil. Similarly, the plots fertilized with the highest level of NPK recorded the utmost value of available N, P, and K, as compared to unfertilized plots.DiscussionThe results emphasize that for sustainable cultivation ofS. costus, the application of N90, P40, and K20combinations is the most suitable one.
Integrated physicochemical, hormonal, and transcriptomic analysis reveals the underlying mechanism of callus formation in Pinellia ternata hydroponic cuttings
Authors: Duan Xiaoqing , Chen Lin , Liu Youping , Chen Hongping , Wang Fu , Hu Yuan 
Published: June 2023

IntroductionP. ternata is a perennial herb of the family Araceae that grows in China and has various medicinal properties and applications. At present, the artificial cultivation of P. ternata is constrained by seedling propagation. To address the problems of low seedling breeding propagation efficiency and high cost, our group has developed a highly efficient cultivation technology for "hydroponic cuttings of P. ternata "for the first time. P. ternata is used as the source material and is grown in a hydroponic system, increasing the seedling production rate 10-fold compared with the traditional cultivation mode. However, the callus formation mechanism in cuttings from hydroponic cultivation is still remains unclear.MethodsIn order to better understand the biological process of callus formation in cuttings from hydroponic P. ternata, anatomical characterization, endogenous hormone content determination and transcriptome sequencing were performed on five callus stages from early growth to early senescence.ResultsRegarding the four major hormones during the callus developmental stages of P. ternata hydroponic cuttings, cytokinins showed an increasing trend during callus formation. IAA(indole-3-acetic acid) and abscisic acid contents increased at 8d and then decreased, while jasmonic acid content gradually decreased. A total of 254137 unigenes were identified by transcriptome sequencing in five callus formation stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes (DEGs) that differentially expressed unigenes were involved in various plant hormone signaling and hormone synthesis-related pathways. The expression patterns of 7 genes were validated using quantitative real-time PCR.DiscussionThis study presented integrated transcriptomic and metabolic analysis approach to obtain insights into the underlying biosynthetic mechanisms and function of key hormones involved in the callus formation process from hydroponic P. ternata cuttings.
Uncovering placemaking needs with(in) a kindergarten community: a cross-disciplinary approach to participatory design
Authors: Economidou Eléni , Gerner Nathalie , Pichler Christina , Hartl Arnulf , Frauenberger Christopher 
Published: June 2023

IntroductionThe design of early childhood education and care facilities faces the double challenge of creating a stimulating environment for young children and a supportive workplace for staff. The existing body of research suggests that placemaking strategies serve both requirements. A promising approach to meet placemaking needs is the participation of future occupants in the building design.MethodsWe pursued a participatory design study with the community of an Austrian kindergarten aiming to inform the future building renovation. We combined novel cultural fiction probes methods with conventional inquiry methods to gather information from children and teachers about their experience of the built environment. Using thematic and content analyzes we explored placemaking needs from different epistemic perspectives and converged findings through iterative exchange.ResultsReturns of children and teachers were interconnected and complementary. From a design-oriented perspective, children’s experience of place was relatable to spatial, temporo-spatial, and acoustic qualities as well as control needs. From a human-centered perspective, teachers’ experience of place was relatable to the needs of feeling embedded, protected, enacted, and socially connected. The converged findings revealed dynamic placemaking processes involving the elements of space, time, and control at different levels.DiscussionCross-disciplinary collaboration and research consolidation brought forth valuable insights on supportive structures for both children and teachers, facilitated timely knowledge transfer, and converted into design solutions that foster enacted placemaking. Albeit general transferability is limited, findings are interpretable within a solid framework of existing theories, concepts and evidence.
Parental burnout, depression and emotional development of the preschoolers
Authors: Yakupova Vera , Suarez Anna 
Published: June 2023

IntroductionParental burnout is becoming more and more prevalent in the world, mainly incultures with high demands towards parents. Parental burnout is distinctive from depression and might have its unique influence on child development, which isunder current international research. This work contributes to the understanding of parental burnout, maternal depression and child emotional development(specifically emotion comprehension) interrelations. Additionally, we explored whether there are differences in the effects of parental burnout and depressionon boys and girls.MethodsTo analyse the emotional development of the preschoolers, the Russian version of the Test of Emotional Comprehension (TEC) was used. We used the Russian version of the Parental Burnout Inventory (PBI) to analyse the level of PB and the Russian version of Beck depression Inventory (BDI) to assess participants’ depression level.ResultsParental burnout positively correlates with child emotional comprehension skills, specifically understanding of external causes (B = 0.20, CI: 0.03; 0.37) and mental causes of emotions (B = 0.22, CI: 0.05; 0.40). This effect is gender dependent and is significantlyhigher for girls (B = 0.54, CI: 0.09; 0.98). The effect of maternal depression on emotion comprehension skills is also gender dependent: total scores on emotioncomprehension tasks are significantly higher for daughters of mothers with depression (B = 0.59, CI: 0.001; 1.18).DiscussionMaternal depression and parental burnout might provoke development of extra sensitivity and self-regulation strategies in girls.
Dynamics of hospital admissions and all-cause mortality of HIV infected patients in Kazakhstan: data from unified nationwide electronic healthcare system 2014–2019
Authors: Mussina Kamilla , Abbay Anara , Sakko Yesbolat , Syssoyev Dmitriy , Gusmanov Arnur , Abdrakhmanova Ainur , Ashimkhanova Aiymkul , Gaipov Abduzhappar 
Published: June 2023

Background and objectivesAlthough global HIV pandemic has stabilized, it continues to rise in Eastern Europe and Central Asia due to exponential growth of newly acquired cases. Based on UNAIDS, there are currently 35,000 people living with HIV (PLWH) in Kazakhstan. This alarming HIV epidemiologic situation mandates urgent investigation of causes, routes of transmission and other characteristics in order to halt the epidemic. We aimed to analyze the data of all hospitalized patients for the period of 2014–2019 who tested positive for HIV from the Unified National Electronic Health System (UNEHS) of Kazakhstan.MethodsThis cohort study extracted data for all HIV positive patients during 2014–2019 from UNEHS of Kazakhstan to apply descriptive, Kaplan–Meier estimation, and Cox proportional hazards regression model. Crosscheck of the target population data was conducted with tuberculosis, viral hepatitis, alcohol abuse and intravenous drug user (IDU) cohorts in order to create a comprehensive database. All survival functions and factors associated with mortality were tested for significance.ResultsThe cohort population (n = 2,213) mean age was 33.3 ± 13.3 years with 1,375 males (62.1%) and 838 females (37.9%). Incidence rate decreased from 2.05 in 2014 to 1.88 in 2019, however, prevalence and mortality continues to escalate every year, the mortality raised significantly from 0.39 in 2014 to 0.97 in 2019. People aged &gt;50 years, males, retired people, patients from tuberculosis hospital profile had much lower survival probabilities than the corresponding groups. Adjusted Cox regression model death hazard showed strong association of HIV patients with tuberculosis coinfection (HR 1.4, 95% CI 1.1; 1.7, p &lt; 0.001).ConclusionThe results of this study demonstrate high rates of HIV mortality, strong association of HIV with TB coinfection, regional, age specific, gender, hospital profile and social status differences that significantly affect HIV prevalence. Since the prevalence of HIV is continuing to increase, more information is necessary for evaluation and implementation of prevention procedures.