bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal risk stratification of non-metastatic lung adenocarcinoma using AI on histology and immunohistochemistry slides.
Authors: Adjadj Benjamin , Bannier Pierre-Antoine , Papadakis Andreas , Fournier Nancy , Rayes Roni , Marza Reem , Srivastava Archana , Agulnik Jason S. , Spicer Jonathan , Fiset Pierre-Olivier , Wang Hangjun , Schutte Kathryn , Spatz Alan 
Published: June 2024

e20083 Background: While immunohistochemistry (IHC) slides are commonly used to assess the presence of actionable biomarkers, the recent advances in artificial intelligence (AI) focus exclusively on hematoxylin and eosin (H&E) slides. Nonetheless, many IHC slides, potentially rich in prognostic information, remain underexplored for risk stratification and outcome prediction. Our study aims to assess the complementarity of H&E and IHC slides through the development of a multimodal prognostic AI model for lung adenocarcinoma patients. Methods: We collected 1 H&E slide, 8 IHC slides (PD-L1, FOXP3, HELA2, CD3, CD4, CD8, CD163, KI67), and 2 double-stained slides (PDL1-CD163 and CD3-CD163) from 245 resected patients with lung adenocarcinoma at two different hospitals (median OS = 54.0 months [11.3 - 138.0]). Patients underwent various adjuvant treatments (chemotherapy n=92; immunotherapy n=4; other n=36; no treatment n=152). We cross-validated 11 AI models (one model per staining) to predict overall survival in these patients. We used Harell’s C-index and the 70-month cumulative AUC to evaluate the performance of our models. To assess their stratification power, each model’s predictions were split into high-risk and low-risk populations to compute a Hazard Ratio and a log-rank test p-value. Subsequently, a Cox proportional hazards model aggregated the predictions of the 11 models to compute a final risk score. We performed a grid search to find the combination of markers yielding the highest C-index. We calculated the hazard ratios to determine each biomarker's predictive value. Results: The H&E model was the best unimodal model, with a C-index of 0.69 [0.67 - 0.71]. The best-performing multivariate model was obtained by combining the risk scores from univariate models in a Cox regression using H&E, CD8, PD-L1, HELA2, and FOXP3 slides, reaching a C-index of 0.71 [0.69 - 0.73] (Table). We found that the predictions from H&E (HR = 1.39; P = 0.03) and PD-L1 (HR = 1.17; P = 0.04) were significantly associated with survival. Conclusions: By significantly improving patient stratification with non-metastatic lung adenocarcinoma, our multivariate model proves that some IHC markers contain complementary proteomic information to H&E slides. Consequently, this study paves the way for developing more comprehensive risk assessment tools from H&E and IHC stainings. [Table: see text]
A preliminary study on the timing of radiotherapy for chemoimmunotherapy in oligometastatic non-small-cell lung cancer with negative driver genes.
Authors: Ma YingYing , Liao Ziyi 
Published: June 2024

e20084 Background: Local radiotherapy (LRT) is reported to provide durable local and distant disease control for oligometastatic non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. We conducted a study to preliminarily evaluate the timing of radiotherapy for chemoimmunotherapy in Oligometastatic Non-small-cell lung cancer with negative driver genes. Methods: 50 patients diagnosed with Oligometastatic Non-small-cell lung cancer with negative driver genes who were treated with chemoimmunotherapy and radiotherapy were retrospectively recruited between January 2018 and October 2023. They were divided into two groups: one early to initiate radiotherapy group (≤2 cycles of immunotherapy, EAR group) and one deferred radiotherapy group (>2 cycles of immunotherapy, DEF group). The clinical efficacy and adverse reactions were compared between the two groups. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier curves, the Cox proportional hazard model was used to find out predictors of PFS and OS. Results: The tumor control rates had no significance was observed when comparing these two groups (50.0% and 26.9%, respectively, p = 0.093). The PFS in the RAE group was significantly higher than that in the DEF group (median PFS: 12.2 months vs 5.3 months, P<0.05). The OS in two groups were no significance (median OS: 20.5months vs 23.1months, P>0.05). The results of the Cox multivariate regression analysis revealed that the number of metastatic lesions and organs were independent prognostic factors for PFS. The number of metastatic lesions and organs, maintain therapy were independent predictors associated with OS. All patients well tolerated the treatments. Conclusions: Early initiation of local radiotherapy resulted in better PFS and no significant increase in adverse reactions was observed.
Incidence trends and factors affecting survival in mucinous adenocarcinoma of the lung: Insights from SEER data.
Authors: Aimalla Nikhila , Kesireddy Meghana , Yadukumar Lekha 
Published: June 2024

e20090 Background: Lung cancer is the second most common cancer in terms of incidence and the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of cases. Adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma are the main subtypes of NSCLC. Mucinous adenocarcinoma is the least common subtype of lung adenocarcinoma with poor prognosis. Our study aims to identify demographics, incidence trends, and factors impacting overall survival (OS) in mucinous adenocarcinoma of the lung. Methods: We conducted a retrospective cohort analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to investigate patients diagnosed with mucinous adenocarcinoma of the lung between the years 2000 and 2020. Demographics, treatment data were characterized using descriptive statistics. The Cox proportional regression analysis was used to identify the factors that impact the OS. Results: Between 2000-2020, a total of 7,953 patients were diagnosed with mucinous adenocarcinoma of the lung. The highest incidence of mucinous adenocarcinoma was in older adults, accounting for 67% of all cases. Females had a higher incidence rate at 53.6%. Caucasians comprised the majority of patients at 83.1%, followed by blacks at 8.8%. The majority of patients, 89.3% resided in urban areas, and 43.6% had annual incomes exceeding $75k. Most of the patients were married at 58.2%. The incidence trends revealed a significant increase from 2000 to 2020. The incidence rates were: 15.76% (2000 -2004), 16.37% (2005 -2009), 31.08% (2010 - 2014), and 36.79% (2015-2020). However, the survival rates improved over time (See table). Among the demographic factors: adults, females, Asian/ Natives/ & other races combined, urban residence, higher annual income (> $75k), and married status had better OS outcomes than their counterparts. Among disease stages, localized disease had the best, while regional disease had a better OS than distant disease. In terms of treatment, surgery was associated with better OS; interestingly, receipt of radiation or chemotherapy was not associated with better OS. The HRs of all these factors are shown in Table. Conclusions: Our study, the largest to date on mucinous adenocarcinoma of the lung, demonstrated a rising incidence yet with improved OS rates from 2000-2020. Our findings shed light on the demographics and other factors influencing OS in this rare subtype of NSCLC. [Table: see text]
Tazemetostat in combination with topotecan and pembrolizumab in patients with recurrent small cell lung cancer.
Authors: Desai Parth Anil , Takahashi Nobuyuki , Lissa Delphine , Nichols Samantha , Sciuto Linda , Abel Melissa Lauren , Schroeder Brett , Schultz Christopher , Steinberg Seth M. , Pinkiert Danielle , Vilimas Rasa J , Thomas Anish 
Published: June 2024

TPS8130 Background: Small-cell lung cancer (SCLC) is the most fatal type of lung cancer characterized by exquisite chemo-sensitivity at diagnosis and chemoresistance at relapse. Despite a highly mutated genome, patients with SCLC derive little benefit from immunotherapy. EZH2 (enhancer of zeste homolog 2) is a master epigenetic regulator of SCLC neuroendocrine cell fate and plasticity. EZH2 inhibition 1) promotes upregulation of Schlafen 11 (SLFN11) which irreversibly blocks replication in response to DNA damaging agents and 2) enhances intrinsic immune signaling, leading to constitutive MHC I recovery, sensitizing resistant SCLC models to DNA damaging chemotherapy and immunotherapy. Tazemetostat is a selective oral EZH2 inhibitor. Methods: This is an investigator-initiated, NCI Cancer Therapy Evaluation Program (CTEP) sponsored, phase I dose escalation and dose expansion study which will evaluate safety and tolerability of combination of tazemetostat with topotecan, a selective TOP1 inhibitor, and programmed cell death protein 1 (PD-1) inhibitor antibody pembrolizumab. Adult patients with relapsed/recurrent SCLC after at least platinum doublet (limited stage-SCLC) or chemo-immunotherapy (extensive stage-SCLC) and ECOG performance 0-1 are eligible. The regimen design involves a 7-day “run-in” of oral tazemetostat BID followed by 21-day cycles of tazemetostat (1-21 days), intravenous (IV) topotecan (day 1-5) and IV pembrolizumab (Day 1). The dose escalation cohort aims to determine safety and optimal doses of tazemetostat and topotecan (with standard dose of pembrolizumab) using a 3+3 design by assessing for dose limiting toxicities. The dose expansion cohort aims to assess safety, tolerability and preliminary efficacy of the combination in 15 additional patients with relapsed SCLC. The study involves collection of mandatory biopsies at pre-treatment and post-treatment (cycle 1) to gain insights into mechanism of action and resistance of the combination using single cell and spatial transcriptomic approaches. For more questions regarding enrollment and eligibility please contact Rasa.vilimas@nih.gov or anish.thomas@nih.gov . Clinical trial information: NCT05353439 .
The use of stem cells in the treatment of diabetes mellitus and its complications - review
Authors: Ochyra Łukasz , Łopuszyńska Anna 
Published: June 2024

Introduction and purpose Diabetes is a disease resulting from impaired action or secretion of insulin. The number of patients currently amounts to approximately 422 million, and approximately 1.5 million deaths per year are directly attributed to this disease. Diabetes significantly reduces the quality of life and, if poorly controlled, can lead to serious complications. Mesenchymal stem cells are multipotent cells capable of differentiation. They have the ability to self-renew and have a modulating function. There are reports that they can be used in the treatment of this disease. The aim of the review was to present a new method of therapy and their possible effects. Material and methods The review was based on articles obtained from PubMed scientific database in the years 2015-2023, using the following keywords: diabetes mellitus, stem cells, diabetes complications. Results Implanted stem cells are able to transform into cells that produce and secrete insulin, and also enable better glycemic control. They can alleviate chronic inflammation and reduce fibrosis. Taking into account the complications that occur during long-term diabetes, the use of stem cells may be associated with improving the function of specific organs and tissues such as the kidneys, heart, eyes and nerves. Studies also report a positive effect of these cells on the healing process of wounds and ulcers. Conclusions Stem cells are a promising object of analysis. They can control glycemia and have a positive effect on the functioning of the kidneys, heart, eyes and nerves, and accelerate wound healing, but further, extensive research is needed to assess the effectiveness and safety of this therapy.
Risks to Human Capital
Authors: Ebrahimian Mehran , Wachter Jessica A. 
Published: June 2024

We build a model with inalienable human capital, in which investors finance individuals who can potentially become skilled. Although investment in skill is always optimal, it does not take place in some states of the world, due to moral hazard. In intermediate states of the world, individuals acquire skill; however outside investors and individuals inefficiently share risk. We show that this simple moral hazard problem, combined with risk aversion of individuals and outside investors, amplifies the equity premium, lowers the risk-free rate, and leads to disaster states that fall especially heavily on some agents but not on others. We show that the possibility of disaster states distorts risk prices and affects wealth inequality, even under calibrations in which they never occur in equilibrium. This paper was accepted by Lukas Schmid, finance. Funding: M. Ebrahimian acknowledges funding from the Swedish House of Finance. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2022.03068 .
The prevalence and risk of mortality associated with intradialytic hypertension among patients with end-stage kidney disease on haemodialysis: A systematic review and meta-analysis
Authors: Adejumo Oluseyi Ademola , Edeki Imuetinyan Rahsida , Oyedepo Dapo Sunday , Yisau Olawale Elijah , Ige Olanrewaju Olumide , Ekrikpo Inyeneabasi Udeme , Moussa Ayman Sabri , Palencia Hansel , Noubiap Jean Jacques , Ekrikpo Udeme Ekpenyong 
Published: June 2024

Introduction
Intradialytic hypertension (IDHTN) is a common but less frequently recognised complication of haemodialysis. However, it is associated with increased overall mortality in patients on haemodialysis. This systematic review and meta-analysis aimed to determine the prevalence of IDHTN and associated mortality risk in the global haemodialysis population.

Method
A systematic search of PubMed and EMBASE was undertaken to identify articles with relevant data published between 1990 and 2023. The pooled prevalence of IDHTN in the global haemodialysis population was determined using the DerSimonian-Laird random-effects meta-analysis. The pooled hazards ratio for mortality in patients with IDHTN was also computed from the studies that reported mortality among haemodialysis patients with IDHTN. The study protocol was registered with PROSPERO (CRD42023388278).

Results
Thirty-two articles from 17 countries were included, with a pooled population of 127,080 hemodialysis patients (median age 55.1 years, 38.2% females). Most studies had medium methodological quality (53.1%, n = 17). The overall pooled prevalence of IDHTN was 26.6% [(95% CI 20.2–33.4%), n = 27 studies, I2 = 99.3%, p<0.001 for heterogeneity], with significant differences depending on the definition used. The pooled proportion of haemodialysis sessions with IDHTN was 19.9% [(95% 12.5–28.6%, n = 8 studies, I2 = 99.3%, p<0.001 for heterogeneity)] with significant differences across the different definition criteria. The p-value for the Begg test was 0.85. The median pre-dialysis blood pressure was not significantly associated with IDHTN. The pooled hazard ratio for mortality was 1.37 (95% CI 1.09–1.65), n = 5 studies, I2 = 13.7%, and p-value for heterogeneity = 0.33.

Conclusion
The prevalence of IDHTN is high and varies widely according to the definition used. A consensus definition of IDHTN is needed to promote uniformity in research and management. The increased mortality risk forecasted by IDHTN highlights the need for optimal blood pressure control in patients on hemodialysis.
Comparative evaluation of HPV genotyping: A study on the performance concordance between Anyplex II HPV28 detection and Linear Array genotyping tests in nationwide studies in Brazil
Authors: Bandeira Isabel Cristina , Comerlato Juliana , Bessel Marina , Fernandes Bruna Vieira , Mota Giana , Villa Luisa Lina , de Souza Flávia Moreno Alves , Pereira Gerson Fernando Mendes , Wendland Eliana Marcia 
Published: June 2024

Background
Advances in laboratory techniques for HPV diagnosis necessitate a thorough assessment of the efficiency, replicability, sensitivity, and specificity of those methods. This study aims to validate and compare HPV detection/genotyping using the Anyplex™ II HPV28 Detection assay (Seegene) assay and the Linear Array HPV Genotyping test (Roche Diagnostics) on genital samples for use in epidemiological studies.

Methods
From 6,388 penile and cervical DNA samples collected in the POP-Brazil, 1,745 were randomly selected to be included in this study. The samples were submitted to HPV detection and genotyping following the manufacturers’ protocols. DNA was genotyped using the Anyplex™ II HPV28 Detection kit (Seegene), and the results were compared to those obtained using the Linear Array HPV Genotyping test (Roche Diagnostics). Concordance of HPV genotyping results was assessed by the percentage agreement and Cohen’s kappa score (κ).

Results
The agreement between the two methodologies was deemed good for HPV detection (κ = 0.78). Notably, Anyplex™ II HPV28 demonstrated enhanced capability in detecting a broader spectrum of genotypes compared to Linear Array.

Conclusion
Anyplex™ II HPV28 exhibited comparable results to the Linear Array assay in clinical specimens, showcasing its potential suitability for a diverse array of research applications requiring the detection and genotyping of HPV. The study supports the utility of Anyplex™ II HPV28 as an effective tool for HPV screening in epidemiological studies, emphasizing its robust performance in comparison to established diagnostic tests.
The effect of outcome-based education on clinical performance and perception of pediatric care of the third-year nursing students in Mongolia
Authors: Lkhagvaa Khishigdelger , Tsogbadrakh Basbish , Gochoosuren Gankhuyag , Badamdorj Oyungoo , Stark Azadeh 
Published: June 2024

Background
Mongolian government has set improvement of clinical proficiency of nursing students as one of its priorities. Nursing professionals have the sentinel role in providing healthcare services in rural areas. Outcome-based education (OBE) offers a promising pedagogical approach to actively mentally engage students to strengthen their clinical proficiencies. We implemented a pilot project with the objective of comparing students’ clinical performance under OBE with our traditional didactic techniques.

Methods
The researchers implemented a non-equivalent two-armed quasi-experimental post-test-only’ design approach study. The intervention arm (n = 34) received OBE pediatric training, while the control arm (n = 32) received the traditional pedagogical pediatric nursing training. Each arm of the study completed 16 hours of theory, 32 hours of clinical skills practice and 32 hours of seminars in pediatric nursing care. Data were collected using a five-section instrument, Demographic, Competency Inventory, Nursing Students’ Satisfaction, Course Experience, and Objective Structured Clinical Examination. Performance and knowledge proficiencies were evaluated by applying the two-sided independent T-test. The distributions of categorical variables were assessed by Fisher’s exact test or chi-squared test of significance.

Results
The intervention arm had higher mean score value in the competency inventory (X¯ = 238.70, SD = ± 23.07) compared to the control arm (X¯ = 222.11, SD = ± 39.94) (P = 0.04); similarly, the mean value for nursing students’ satisfaction was higher for the intervention arm (X¯ = 117.87, SD = ± 15.94) compared to the control group (X¯ = 109.76, SD = ± 16.94) (P = 0.049). Additionally, the difference in the mean value for course experience questionnaire between the intervention arm (X¯ = 125.33, SD = ± 19.30) and the control arm (X¯ = 110.41, SD = ± 11.28) was statistically significant (P = 0.0001). Finally, the intervention arm had a higher mean value (X¯ = 85.40, SD = ± 6.11) for objective structural clinical examination compared to the control arm (X¯ = 81.56, SD = ± 7.01) (P = 0.023).

Conclusion
OBE pedagogical approach offers promising benefits to improving nursing students’ clinical competencies; additionally, the OBE approach seems to increase students’ satisfactions with their clinical curriculum.
New species of Corydalis DC. (Fumariaceae) from Western Caucasus
Authors: Mikhailova Marina A. , Shilnikov Dmitry S. , Sochivko Andrey V. 
Published: June 2024

A new species, Corydalis arkhyzica Mikhailova et Shilnikov (sect. Corydalis), is described from Western Caucasus, the Karachayevo-Circassian Republic, the Pkhiya Pass at the junction of Abishir Akhuba and Arkasara ridges. The species differs from C. teberdensis A. P. Khokhr. by lemon-yellow (not white) corolla and shorter style, from C. paczoskii N. Busch by lemon-yellow (not purple-rose) corolla and shape of bracts, from both of them by thick (not thin) leaves.
MEMBANGUN INDEKS KOMPOSIT DALAM MENGEVALUASI EFEKTIVITAS KEBIJAKAN SNI WAJIB: LITERATURE REVIEW
Authors: Pramumardani Ery Vita , Bachtiar Arfan , Arvianto Ary 
Published: June 2024

Masih ditemukannya produk yang tidak sesuai standar yang beredar di pasar menjadi dasar perlunya pengukuran efektivitas dari kebijakan SNI wajib di Indonesia. Indeks komposit merupakan salah satu metode yang banyak digunakan untuk menganalisis kebijakan public dan dapat mempermudah dalam monitoring dan kaji ulang kebijakan secara berkala. Penelitian ini bertujuan untuk memberikan informasi yang diharapkan dapat digunakan sebagai rujukan dalam penelitian pengukuran indeks efektivitas kebijakan SNI wajib, dengan cara melakukan analisis bibliometrik untuk mengetahui tren penelitian saat ini, serta melakukan Systematic Literature Review untuk mengetahui metode dan indikator apa saja yang dapat digunakan. Hasilnya diketahui walaupun terdapat peningkatan tren penelitian 10 tahun terakhir pada jurnal internasional, namun tidak ditemukan penelitian pada bidang standar produk dalam tren tersebut melainkan lebih banyak ditemukan pada kebijakan yang bersifat lingkungan seperti iklim, polusi, sustainability, dan sejenisnya. Sementara itu metode yang paling banyak digunakan adalah Principal Component Analysis (PCA), Benefit of Doubt (BoD), equal weight, entropy weight, dan Analytic Hierarchy Process (AHP). Indikator efektivitas yang paling sering digunakan adalah penurunan impor dan kesesuaian hasil uji pengawasan pasar. Abstract [Building A Composite Index In Evaluating The Effectiveness of Mandatory SNI Policies: Literature Review] The discovery of products that do not comply with standards circulating on the market is the basis for measuring the effectiveness of the mandatory SNI policy in Indonesia. The composite index is a method that is widely used to analyze public policy and can ease to monitor and review policies periodically. This research aims to provide information that is expected to be used as a reference in research measuring the effectiveness index of mandatory SNI policies, by conducting bibliometric analysis to determine current research trends, as well as conducting a Systematic Literature Review to find out what methods and indicators can be used. The results show that although there has been an increase in research trends in the last 10 years in international journals, there was no research found in the field of product standards in this trend, but more was found in environmental policies such as climate, pollution, sustainability, and the like. Meanwhile, the methods most widely used are Principal Component Analysis (PCA), Benefit of Doubt (BoD), equal weight, entropy weight, and Analytic Hierarchy Process (AHP). The most frequently used indicators of effectiveness are the reduction in imports and the suitability of market surveillance test results.Keywords: composite index; policy effectiveness; product standards; effectiveness indicators; weighting method