bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial
Authors: Tang Lin-Quan , Li Xiao-Yun , Li Zhi-Ming , Liu Zhi-Gang , Lin Miao-Zhen , Zhou Huan , Yu Qi-Wen , Zhou Jian , Zhao Chong , Chen Ze-Bin , Wang Xi-Cheng , Peng Jia-Yu , Chen Qiu-Yan , Fang Wen-Feng , Yang Yun-Peng , Zhang Bei , Xia Liang-Ping , Hu Pi-Li , Hu Wei-Han , Li Yi-Jie , Mai Hai-Qiang , Cai Xiu-Yu 
Published: March 2023

Abstract
Background
Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy.

Methods
In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon’s two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1–14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.

Results
We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1–52.1) and 85.9% (95% CI, 75.0–93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8–21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0–10.0) and the median OS was 15.7 months (95% CI, 11.3–20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3–4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed.

Conclusions
Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity.

Trial registration
Chi-CTR1800017229.
Engaging early career researchers in a global health research capacity-strengthening programme: a qualitative study
Authors: Hawcroft Claire , Rossi Evelina , Tilouche Nerissa , d’Oliveira Ana Flavia , Bacchus Loraine J. 
Published: March 2023

Abstract
Background
Research capacity-strengthening is recognized as an important component of global health partnership working, and as such merits monitoring and evaluation. Early career researchers are often the recipients of research capacity-strengthening programmes, but there is limited literature regarding their experience.

Methods
We conducted a qualitative study as part of an internal evaluation of the capacity-strengthening programme of the international HERA (HEalthcare Responding to violence and Abuse) research group. Semi-structured interviews were conducted with group members, and thematic analysis was undertaken.

Results
Eighteen group members participated; nine of these were early career researchers, and nine were other research team members, including mid-career and senior researchers. Key themes were identified which related to their engagement with and experience of a research capacity-strengthening programme. We explored formal/planned elements of our programme: mentoring and supervision; training and other opportunities; funding and resources. Participants also discussed informal/unplanned elements which acted as important facilitators and/or barriers to engaging with research capacity-strengthening: English language; open relationships and communication; connection and disconnection; and diversity. The sustainability of the programme was also discussed.

Conclusions
Our study gives voice to the early career researcher experience of engaging with a research capacity-strengthening programme in a global health group. We highlight some important elements that have informed adaptations to our programme and may be relevant for consideration by other global health research capacity-strengthening programmes. Our findings contribute to the growing literature and important discussions around research capacity-strengthening and how this relates to the future directions of global health partnership working.
NOMe-HiC: joint profiling of genetic variant, DNA methylation, chromatin accessibility, and 3D genome in the same DNA molecule
Authors: Fu Hailu , Zheng Haizi , Chen Xiaoting , Weirauch Matthew T. , Muglia Louis J. , Wang Li , Liu Yaping 
Published: March 2023

AbstractCis-regulatory elements are coordinated to regulate the expression of their targeted genes. However, the joint measurement of cis-regulatory elements’ activities and their interactions in spatial proximity is limited by the current sequencing approaches. We describe a method, NOMe-HiC, which simultaneously captures single-nucleotide polymorphisms, DNA methylation, chromatin accessibility (GpC methyltransferase footprints), and chromosome conformation changes from the same DNA molecule, together with the transcriptome, in a single assay. NOMe-HiC shows high concordance with state-of-the-art mono-omic assays across different molecular measurements and reveals coordinated chromatin accessibility at distal genomic segments in spatial proximity and novel types of long-range allele-specific chromatin accessibility.
Verification of prognostic expression biomarkers is improved by examining enriched leukemic blasts rather than mononuclear cells from acute myeloid leukemia patients
Authors: Pogosova-Agadjanyan Era L. , Hua Xing , Othus Megan , Appelbaum Frederick R. , Chauncey Thomas R. , Erba Harry P. , Fitzgibbon Matthew P. , Jenkins Isaac C. , Fang Min , Lee Stanley C. , Moseley Anna , Naru Jasmine , Radich Jerald P. , Smith Jenny L. , Willborg Brooke E. , Willman Cheryl L. , Wu Feinan , Meshinchi Soheil , Stirewalt Derek L. 
Published: March 2023

Abstract
Background
Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers.

Methods
To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes.

Results
Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN risk, with only 11 genes remaining significant for overall survival in both cell populations (CEP70, COMMD7, DNMT3B, ECE1, LNX2, NEGR1, PIK3C2B, SEMA4D, SMAD2, TAF8, ZNF444). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN risk and age, expression of 4 genes (CEP70, DNMT3B, ECE1, and PIK3CB) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells.

Conclusions
This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.
RTiSR: a review-driven time interval-aware sequential recommendation method
Authors: Shi Xiaoyu , Liu Quanliang , Bai Yanan , Shang Mingsheng 
Published: March 2023

AbstractThe emerging topic of sequential recommender (SR) has attracted increasing attention in recent years, which focuses on understanding and learning the sequential dependencies of user behaviors hidden in the user-item interactions. Previous methods focus on capturing the point-wise sequential dependencies with considering the time evenly spaced. However, in the real world, the time and semantic irregularities are hidden in the user’s successive actions. Meanwhile, with the tremendous increase of users and items, the hardness of modeling user interests from spare explicit feedback. To this end, we seek to explore the influence of item-aspect reviews sequence with varied time intervals on sequential modeling. We present RTiSR, a review-driven time interval-aware sequential recommendation framework, to predict the user’s next purchase item by jointly modeling the sequence dependencies from aspect-aware reviews. The main idea is twofold: (1) explicitly learning user and item representation from reviews by assigning different weights, and (2) leveraging a hybrid neural network to capture the collective sequence patterns with a flexible order from aspect-aware review sequences. We conduct extensive experiments on industrial datasets to evaluate the effectiveness of RTiSR. Experimental results demonstrate the superior performance of RTiSR in different evaluation metrics, compared to the state-of-the-art competitors.
Plugged-in electric vehicle-assisted demand response strategy for residential energy management
Authors: Alfaverh Khaldoon , Alfaverh Fayiz , Szamel Laszlo 
Published: March 2023

AbstractDemand response (DR) management systems are a potentially growing market due to their ability to maximize energy savings by allowing customers to manage their energy consumption at times of peak demand in response to financial incentives from the electricity supplier. Successful execution of a demand response program requires an effective management system where the home energy management system (HEMS) is a promising solution nowadays. HEMS is developed to manage energy use in households and to conduct the management of energy supply, either from the grid or the alternative energy sources like solar or wind power plants. With the increase of vehicle electrification, in order to achieve a more reliable and efficient smart grid (SG), cooperation between electric vehicles (EVs) and residential systems is required. This cooperation could involve not only vehicle to grid (V2G) operation but a vehicle to home (V2H) too. V2H operation is used to transfer the power and relevant data between EVs and residential systems. This paper provides an efficient HEMS enhanced by smart scheduling and an optimally designed charging and discharging strategy for plugged-in electric vehicles (PEVs). The proposed design uses a fuzzy logic controller (FLC) for smart scheduling and to take the charging (from the grid)/discharging (supply the household appliances) decision without compromising the driving needs. Simulations are presented to demonstrate how the proposed strategies can help to reduce electricity costs by 19.28% and 14.27% with 30% and 80% state of charge (SOC) of the PEV respectively compared to the case where G2V operation only used along with the photovoltaic (PV) production, improve energy utilization by smoothing the energy consumption profile and satisfy the user’s needs by ensuring enough EV battery SOC for each planned trip.
Angelica herbal supplement AGN-CognI.Q acute dose safety and pharmacokinetics (PK) dose-response in patients with prostate cancer (PK Dose Trial).
Authors: Joshi Monika , Raman Jay D. , Liu Xin , Shank Doris , Schell Todd D. , Liao Jiangang Jason , Lu Junxuan 
Published: March 2023

TPS404 Background: There are currently no FDA approved modalities for intercepting biochemically recurrent prostate cancer (PCa) after standard of care surgery and radiation therapies to delay or prevent the need of androgen deprivation therapy (ADT) for localized disease. Preclinical modeling has suggested herbal alcoholic extracts of Angelica gigas Nakai (AGN) root, their signature pyranocoumarins and metabolite decursinol, as potential novel modalities to address this unmet clinical need. We hypothesize that CognI.Q at the higher doses has an acceptable safety profile in prostate cancer patients and pharmacokinetics (PK) exposure metrics will be increased proportional to dose increment. Methods: This is a single institution, phase 1 PK study, N=12. Primary objective- PK, pharmacodynamic (PD) biomarkers with a single ascending dose (SAD)-PK response design. After a subject is enrolled, a 14-day gap must occur before the next subject can be enrolled. If one subject develops a dose limiting toxicity (DLT) at any dose level, that subject will stop participation; If a 2nd subject develops DLT at the same dose level, the trial will be stopped, and the dose level below will be the maximum tolerated dose (MTD). Any subject at a higher dose level at the time of occurrence of 2nd DLT will also stop participation. All subjects will initially start at the 800 mg x 1dose, with further single dose escalation to 1200mg, 1600mg, 2000mg doses of AGN-CognI.Q; each dose will be 1-2 weeks apart. Inclusion criteria: Treated PCa, not on ADT; no active cancer. Subjects will be assessed for safety- clinical, labs (CBC, CMP, baseline and after 24hrs) and EKGs. PK blood will be taken at hourly intervals from 2-7hrs and 24hrs. Plasma pyranocoumarin content will be measured by LC-MS. Immunophenotyping of NK and T cell subtypes will be assessed at baseline and 24 h. Primary Endpoint: MTD. Secondary Endpoint: PK metrics; genotype CYP 2C19 and 3A4 metabolizer status and explore relationship to PK metrics and safety metrics; NK and inflammatory and immune cytokines as PD biomarkers. Trial is now open to accrual (Clinical trial registration NCT05375539). We anticipate that the acute dose safety and PK/PD information will inform the optimal design and execution of the longer-term safety and efficacy (phase I/II) trials. Research Support: MPI 1R01CA260901-01A. Clinical trial information: Clinical trial registration NCT05375539 .
Pathway Alterations in Stage II/III Primary Melanoma
Authors: Kostrzewa Caroline E. , Luo Li , Arora Arshi , Seshan Venkatraman E. , Ernstoff Marc S. , Edmiston Sharon N. , Conway Kathleen , Gorlov Ivan , Busam Klaus , Orlow Irene , Hernando-Monge Eva , Thomas Nancy E. , Berwick Marianne , Begg Colin B. , Shen Ronglai ,   for InterMEL
Published: March 2023

PURPOSE Genomic classification of melanoma has thus far focused on the mutational status of BRAF, NRAS, and NF1. The clinical utility of this classification remains limited, and the landscape of alterations in other oncogenic signaling pathways is underexplored. METHODS Using primary samples from the InterMEL study, a retrospective cohort of cases with specimens collected from an international consortium with participating institutions throughout the United States and Australia, with oversampling of cases who ultimately died of melanoma, we examined mutual exclusivity and co-occurrence of genomic alterations in 495 stage II/III primary melanomas across 11 cancer pathways. Somatic mutation and copy number alterations were analyzed from next-generation sequencing using a clinical sequencing panel. RESULTS Mutations in the RTK-RAS pathway were observed in 81% of cases. Other frequently occurring pathways were TP53 (31%), Cell Cycle (30%), and PI3K (18%). These frequencies are generally lower than was observed in The Cancer Genome Atlas, where the specimens analyzed were predominantly obtained from metastases. Overall, 81% of the cases had at least one targetable mutation. The RTK-RAS pathway was the only pathway that demonstrated strong and statistically significant mutual exclusivity. However, this strong mutual exclusivity signal was evident only for the three common genes in the pathway ( BRAF, NRAS, and NF1). Analysis of co-occurrence of different pathways exhibited no positive significant trends. However, interestingly, a high frequency of cases with none of these pathways represented was observed, 8.4% of cases versus 4.0% expected ( P < .001). A higher frequency of RTK-RAS singletons (with no other pathway alteration) was observed compared with The Cancer Genome Atlas. Clonality analyses suggest strongly that both the cell cycle and RTK-RAS pathways represent early events in melanogenesis. CONCLUSION Our results confirm the dominance of mutations in the RTK-RAS pathway. The presence of many mutations in several well-known, actionable pathways suggests potential avenues for targeted therapy in these early-stage cases.
105 Value of Atlas-Based Data and Intraoperative Testing in Deep Brain Stimulation
Authors: Paulo Danika Lea , Narasimhan Saramati , Gonzalez Hernan F. J. , Allen Jackson , Li Rui , Rodriguez William , Konrad Peter , Neimat Joseph , Shah Hamid M. , Bick Sarah K. B. , Dawant Benoit M. , Englot Dario J. 
Published: March 2023

INTRODUCTION:
Deep brain stimulation (DBS) is commonly performed awake to collect intraoperative microelectrode recordings (MER) and macrostimulation to optimize efficacy and minimize side effects (Bour et al, 2010). With supplementary information from an atlas-based database (CranialVault), efficacy heat maps guide initial targeting, intraoperative final electrode position (FEP) selection and post-operative programming (D’Haese et al, 2012). A better understanding of how this data is integrated to inform all stages of DBS can assist in reducing OR time, optimizing electrode position, expediting programming, and enhancing patient outcomes.

METHODS:
451 individual patients who underwent DBS for Parkinson’s Disease, Essential Tremor or Dystonia, treated with 822 individual leads, at Vanderbilt University Medical Center between 2011-2021 were included. Intraoperative testing data including MER firing rate, macrostimulation efficacy and coordinates of FEP were retrieved from the CranialVault database. Average coordinates of planned target, midpoint and bottom of FEP, active contact and centroid of heat maps per target in patient space were calculated and visualized. Medical charts were reviewed for 1-year post-operative outcomes.

RESULTS:
The distribution of FEPs per target include 55.2% of leads placed in center track. Average coordinates in patient space of planned target, centroid of heatmap, midpoint and bottom of FEP and active contact were recorded. MER data demonstrates how multiunit activity changes at different depths relative to target, per target. Patients who achieve 4th quartile efficacy intraoperatively are more likely to achieve maximal benefit at 1-year post-op (p = 0.003, chi-squared).

CONCLUSIONS:
Atlas-based data and intraoperative testing is valuable, often leads to changes in FEP and can predict post-operative outcomes.
112 RNA Sequencing Analysis of Endothelium in a Patient-Specific Intracranial Aneurysm Model
Authors: Samarage Hasitha Milan , Kaneko Naoki 
Published: March 2023

INTRODUCTION:
Ruptured intracranial aneurysms are responsible for 5-10% of all strokes yet can carry a mortality rate as high as 50%. The growth and rupture of aneurysms is a consequence of complex arterial wall remodeling resulting from complex interactions between cellular biological processes

METHODS:
A total of eight aneurysm casts were created from patients’ 3D rotational angiographic data in our institution's database. Models represented two morphologies (bifurcation and sidewall aneurysms), four locations (middle cerebral artery bifurcation, basilar tip bifurcation, internal cerebral artery-posterior communicating artery sidewall, internal cerebral artery-superior hypophyseal artery sidewall), and two clinical conditions (stable aneurysms and growing aneurysms). The lumen were coated with fibronectin, connected to a pump infusing a cell suspension of HUVEC cells. After culturing to achieve confluence, specimens from the aneurysm and parent artery were separately cut to extract RNA used for sequencing.

RESULTS:
A total of 358 DEGs were identified between aneurysm and parent vessel, 222 DEGs were identified between sidewall and bifurcation aneurysm morphologies and 20437 DEGs were identified between growing and stable aneurysms. Genes such as SYNPO, CHSY3 ALKBH8 were found to be upregulated in endothelial cells within the aneurysms while genes such as FABP4, ANGPT2, SMAD6 and ADAMTS18 were found to be downregulated in comparison with endothelial cells within the parent artery. SERPINB6 was found to be upregulated and FOXN2 was found to be downregulated in growing aneurysms compared to stable aneurysms.

CONCLUSIONS:
We demonstrate the successful development of a patient specific, in-vitro pulsatile intracranial aneurysm cell culture model which can be used to study the complex interactions of endothelial cell biology, specifically the unique transcriptomic profiles of various endothelial cell populations that are subject to varying hemodynamic conditions based on location within the vasculature
125 Survival Analysis by Molecular Subtype for Surgically Treated Breast Cancer Spine Metastases
Authors: Duvall Julia , Massaad Elie , Fourman Mitchell , Siraj Layla , Shankar Ganesh , Shin John H. , Kiapour Ali 
Published: March 2023

INTRODUCTION:
Breast cancer spine metastases are a devastating and pervasive clinical problem. Discoveries in tumor biology and the pathophysiology of metastatic disease have expanded systemic treatment options for metastatic breast cancer. The implications of evolving treatment strategies should inform the surgical treatment of spine metastases and the predicted prognosis to guide personalized approaches.

METHODS:
This is a multi-institutional, retrospective, observational cohort study of patients who underwent spine surgery for symptomatic breast cancer spine metastases from 2008-2020. We studied overall survival, stratified by breast cancer molecular subtype and calculated hazard ratios adjusting for demographics, tumor characteristics, treatments, and laboratory values. We tested the performance of established models (Tokuhashi, Bauer, SORG, NESMS) to predict and compare all-cause mortalities using time-dependent performance metrics.

RESULTS:
A total of 98 patients surgically treated for breast cancer spine metastases were identified. The 1-year probabilities of survival for HR+, HR+/HER2+, HER2+, and TNBC were 63%, 83%, 0%, and 12% (P <0.001). Postoperative chemotherapy and endocrine therapy were associated with prolonged survival. The SORG prognostic model had the highest discrimination. The performance of all prognostic scores improved when preoperative molecular data was considered in addition to postoperative systemic treatment data.

CONCLUSIONS:
Advanced HR+, HR+/HER2+ breast cancer portended significantly longer overall survival compared with HER2+ and TNBC tumors after surgery for symptomatic spine metastases. Hormone receptor status and postoperative systemic therapy should be considered in prediction models for a more accurate assessment of prognosis.