bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the VA opioid safety initiative on pain management for cancer patients.
Authors: Marar Mallika , Nalawade Vinit , Panjwani Neil , Riviere Paul , Furnish Timothy , Lin Lewei A. , Thompson Reid F. , Murphy James Don , Vitzthum Lucas K. 
Published: June 2021

102 Background: Limited research exists on how risk reduction policies in response to the opioid epidemic have impacted pain management among cancer patients. This study investigated the impact of the Veteran’s Health Administration (VHA) Opioid Safety Initiative (OSI) on opioid prescribing patterns and opioid-related toxicity among patients undergoing definitive cancer treatment. Methods: This retrospective cohort study included 42,064 opioid-naïve patients receiving definitive local therapy for prostate, lung, breast, and colorectal cancer at the VHA from 2011-2016. Interrupted time series analysis with segmented regression was used to evaluate the impact of the OSI, which launched October 2013. The primary outcome was the incidence of new opioid prescriptions with diagnosis or treatment. Secondary outcomes included rates of high daily dose opioid (≥ 100 morphine milligram equivalent) and concomitant benzodiazepine prescriptions. Additional long-term outcomes included persistent opioid use, opioid abuse diagnoses, pain-related ED visits, and opioid-related admissions. Results: Prior to OSI implementation, the incidence of opioid prescriptions among new cancer patients increased from 26.7% (95% CI 25.0 – 28.4) in the first quarter (Q1) of 2011 to 50.6% (95% CI 48.3 – 53.0) in Q3 2013. There was a monthly increase in opioid prescription rate pre-OSI followed by a monthly decrease post-OSI (Table). High-dose opioid prescriptions were rare, and the monthly rate was stable before and after the OSI. Monthly incidence of concomitant benzodiazepine prescriptions was stable pre-OSI and decreased post-OSI. Persistent opioid use increased pre-OSI and decreased post-OSI. Pain-related ED visits had an incidence of 0.8% (95% CI 0.4 – 1.0) in Q1 2011, 0.3% (95% CI 0.1 – 0.6) in Q3 2013, and 1.8% (95% CI 0.9 – 2.7) in Q4 2016, with an increasing monthly rate after the OSI. At three years, the cumulative incidence of opioid abuse was 1.2% for both the pre- and post-OSI groups but opioid-related admissions were greater in the pre-OSI cohort than the post-OSI cohort (0.9% vs. 0.5%, p < 0.001). Conclusions: The OSI was associated with a decrease in new, persistent, and certain high-risk opioid prescribing as well as an increase in pain-related ED visits. Further research on patient-centered outcomes is required to optimize opioid prescribing policies for patients with cancer.[Table: see text]
Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.
Authors: Lopes Cardozo Josephine , Drukker Caroline , Schmidt Marjanka , van 't Veer Laura , Glas Annuska , Witteveen Anke , Cardoso Fatima , Piccart-Gebhart Martine J. , Poncet Coralie , Rutgers Emiel J. 
Published: June 2021

500 Background: Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy (CT) and are currently included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint) an additional threshold was established within the low risk category to identify patients with an ultralow risk of distant recurrence. In independent cohorts, these patients had excellent breast cancer specific survival at 15 years, suggesting that ultralow risk cancers represent indolent disease (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). Here we evaluate survival of patients with an ultralow risk 70-gene signature who participated in the randomized phase 3 MINDACT trial (Piccart, Lancet Oncol 2021). Methods: Of the 6,693 patients enrolled in the MINDACT trial (EORTC 10041/BIG 3-04) between 2007-2011, profiling revealed an ultralow risk 70-gene signature in 1,000 patients (15%). We assessed 5- and 8-year distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) in patients stratified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk. For these exploratory analyses, we used Kaplan-Meier estimates for time to event endpoints and Cox-regression models to calculate hazard ratio’s (HR). Results: Median follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67% were ≥50 years, 81% had tumors < 2cm, 80% were lymph node negative, 96% had grade 1 or 2 tumors and 99% were ER-positive. Systemic therapy was received by 83% of patients (69% endocrine therapy (ET), 14% ET + CT) and 16% received no adjuvant systemic treatment (AST). Survival estimates for all endpoints are shown in the table; 8-year DMFI was 97.0% (95% CI 95.8-98.1) for ultralow risk. The 8-year DMFI in ultralow risk patients who received no AST or ET only was 97.8% (95% CI 95.3-100) and 97.4% (95% CI 96.1-98.7), respectively. The HR for DMFI was 0.66 (95% CI 0.46-0.95) for ultralow vs low risk, after adjusting for tumor and treatment characteristics (preliminary results). Conclusions: In this prospective study, patients with an ultralow risk 70-gene signature have an excellent prognosis with 8-year BCSS above 99% regardless of clinical risk status, and with an 8-year DMFI of 95-98%.[Table: see text]
Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study.
Authors: Litton Jennifer Keating , Beck Joseph Thaddeus , Jones Jason M. , Andersen Jay , Blum Joanne Lorraine , Mina Lida A. , Brig Raymond , Danso Michael A. , Yuan Yuan , Abbattista Antonello , Noonan Kay , Chakrabarti Jayeta , Czibere Akos , Symmans William Fraser , Telli Melinda L. 
Published: June 2021

505 Background: Talazoparib (TALA) is a poly(ADP-ribose) polymerase inhibitor approved as monotherapy for treating adult patients (pts) with g BRCA1/2-mutated HER2-negative locally advanced or metastatic BC. Methods: This phase 2, non-randomized, single-arm, open-label study (NCT03499353) evaluated the efficacy and safety of TALA in the neoadjuvant setting for pts with early g BRCA1/2-mutated HER2− BC. Primary endpoint was evaluation of pathologic complete response (pCR) as assessed by Independent Central Review (ICR) after completing 24 weeks of neoadjuvant TALA monotherapy 1 mg QD (0.75 mg for moderate renal impairment) followed by surgery. Secondary endpoints included pCR by investigator (INV) and residual cancer burden (RCB) by ICR (RCB: 0 [pCR], I [minimal], II [moderate], III [extensive]). The evaluable population included pts who received at least 80% of the TALA dose prescribed at treatment start and underwent breast surgery and pCR assessment, plus those who progressed before pCR could be assessed. The intent-to-treat (ITT) population included all pts who received at least 1 dose of TALA. Results: Of 61 pts treated with TALA (ITT and safety populations), 48 comprised the evaluable population. All pts had triple-negative BC. 60 pts had adenocarcinoma and 1 had squamous cell histology, with the following staging: I=20, II=27, III=14. Mean age was 44.6 years, mean duration of 4.5 wks since disease onset, mean duration of treatment of 23.3 wks, and mean overall relative dose intensity of 84.5% (ITT population). pCR (assessed by ICR and INV) and RCB (by ICR) for the evaluable and ITT populations are shown in the table below. Ten (16.4%) patients discontinued treatment due to progressive disease. One pt had a disruption of treatment as a result of COVID-19 restrictions, 2 pts for other reasons: to undergo surgery early and consent withdrawal; 9 patients received <80% dose. Treatment-emergent adverse events (AEs) were reported in 98.4% of pts (27.9% grade [G] 1, 23.0% G2, 45.9% G3, 1.6% G4); the most common were fatigue (78.7%; G1 54.1%; G2 21.3%; G3 3.3%), nausea (68.9%; G1 54.1%; G2 13.1%; G3 1.6%), and alopecia (57.4%; G1 54.1%; G2 3.3%). Three (4.9%) pts discontinued treatment due to AEs (G3 anemia [n=2] and G3 vertigo [n=1]) and continued on study. Conclusions: TALA monotherapy in the neoadjuvant setting was active and showed pCR rates comparable to those observed with combination anthracycline and taxane-based chemotherapy regimens and was generally well tolerated. Clinical trial information: NCT03499353. [Table: see text]
Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC).
Authors: Loibl Sibylle , Schneeweiss Andreas , Huober Jens Bodo , Braun Michael , Rey Julia , Blohmer Jens U. , Furlanetto Jenny , Zahm Dirk Michael , Hanusch Claus , Thomalla Jörg , Jackisch Christian , Staib Peter , Link Theresa , Rhiem Kerstin , Solbach Christine , Fasching Peter A. , Burchardi Nicole , Denkert Carsten , Untch Michael 
Published: June 2021

506 Background: The GeparNuevo trial investigated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor (CPI), to standard neoadjuvant chemotherapy (NACT) in patients with early TNBC. Durvalumab increased the pathological complete response (pCR) rate particularly in patients treated with durvalumab alone before start of chemotherapy (Loibl et al. Ann Oncol 2019). Methods: GeparNuevo randomized patients with cT1b-cT4a-d tumors and centrally confirmed TNBC to durvalumab (D) 1.5 g i.v. or placebo every 4 weeks. D/placebo monotherapy (0.75 g i.v.) was given for the first 2 weeks (window phase), followed by D/placebo plus nab-paclitaxel 125 mg/m² weekly for 12 weeks, followed by D/placebo plus epirubicin/cyclophosphamide (EC) q2 weeks for 4 cycles. Randomization was stratified by stromal tumor infiltrating lymphocytes (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). The primary objective was pCR (ypT0 ypN0). Secondary time-to-event endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 174 patients were enrolled between June 2016 and September 2017. The pCR rate with durvalumab was 53.4% versus placebo 44.2% (OR 1.45, 95% CI 0.80–2.63, unadjusted Wald p = 0.224). Durvalumab effect was seen only in the window cohort (pCR 61.0% versus 41.4%, OR 2.22, 95% CI 1.06–4.64, p = 0.035; interaction p = 0.048). After a median follow-up of 42.2 months, 34 events occurred in 174 patients. 3-year iDFS in pCR vs non pCR was 92.0% vs 71.9% (log-rank p = 0.002). 3-year iDFS was 84.9% with durvalumab vs 76.9% with placebo (HR 0.54, 95%CI 0.27-1.09, stratified log-rank p = 0.0559); 3-year DDFS 91.4% vs 79.5% (HR 0.37, 95%CI 0.15-0.87, p = 0.0148); 3-year OS 95.1% vs 83.1% (HR 0.26, 95%CI 0.09-0.79, p = 0.0076). No difference was seen in iDFS, DDFS and OS between the window and no window cohort. Conclusions: Durvalumab added to neoadjuvant chemotherapy in TNBC significantly improved long-term outcome despite a small pCR increase and no continuation after surgery. It needs to be questioned whether adjuvant therapy with CPI is needed at all. Clinical trial information: NCT02685059.
When form meets function: the cells and signals that shape the lymphatic vasculature during development
Authors: Francois Mathias , Oszmiana Anna , Harvey Natasha L. 
Published: June 2021

ABSTRACT
The lymphatic vasculature is an integral component of the cardiovascular system. It is essential to maintain tissue fluid homeostasis, direct immune cell trafficking and absorb dietary lipids from the digestive tract. Major advances in our understanding of the genetic and cellular events important for constructing the lymphatic vasculature during development have recently been made. These include the identification of novel sources of lymphatic endothelial progenitor cells, the recognition of lymphatic endothelial cell specialisation and heterogeneity, and discovery of novel genes and signalling pathways underpinning developmental lymphangiogenesis. Here, we review these advances and discuss how they inform our understanding of lymphatic network formation, function and dysfunction.
Precise regulation of presenilin expression is required for sea urchin early development
Authors: Bronchain Odile , Philippe-Caraty Laetitia , Anquetil Vincent , Ciapa Brigitte 
Published: June 2021

ABSTRACT
Presenilins (PSENs) are widely expressed across eukaryotes. Two PSENs are expressed in humans, where they play a crucial role in Alzheimer's disease (AD). Each PSEN can be part of the γ-secretase complex, which has multiple substrates, including Notch and amyloid-β precursor protein (AβPP) – the source of amyloid-β (Aβ) peptides that compose the senile plaques during AD. PSENs also interact with various proteins independently of their γ-secretase activity. They can then be involved in numerous cellular functions, which makes their role in a given cell and/or organism complex to decipher. We have established the Paracentrotus lividus sea urchin embryo as a new model to study the role of PSEN. In the sea urchin embryo, the PSEN gene is present in unduplicated form and encodes a protein highly similar to human PSENs. Our results suggest that PSEN expression must be precisely tuned to control the course of the first mitotic cycles and the associated intracellular Ca2+ transients, the execution of gastrulation and, probably in association with ciliated cells, the establishment of the pluteus. We suggest that it would be relevant to study the role of PSEN within the gene regulatory network deciphered in the sea urchin.
The Long-Term Clinical Impact of Thoracic Endovascular Aortic Repair (TEVAR) for Advanced Esophageal Cancer Invading Aorta
Authors: Chen Ke-Cheng , Wu I-Hui , Chang Chih-Yang , Huang Pei-Ming , Lin Mong-Wei , Lee Jang-Ming 
Published: June 2021

Abstract
Background
Advanced esophageal cancer invading the aorta is considered unsuitable for surgery with definitive chemotherapy or chemoradiation as the treatments of choice. In the current study, we evaluated the long-term clinical impact of combining thoracic endovascular aortic repair (TEVAR) with multimodality treatment in caring for such patients.

Methods
We evaluated 48 patients who had advanced esophageal cancer with aortic invasion. The oncological outcome, including overall survival (OS) and progression-free survival (PFS), after multimodality treatment with or without TEVAR is evaluated for these patients.

Results
Overall, 25/48 patients (52.1%) received a TEVAR procedure. There was no significant difference in OS (p = 0.223) between patients who did or did not receive TEVAR; however, patients who received TEVAR had significantly less local tumor recurrence (p = 0.020) and longer PFS (p = 0.019). This impact was most evident in patients who received both TEVAR and esophagectomy, with an incremental increase in hazard ratio (HR) for disease progression of 2.89 (95% confidence interval [CI] 0.86–9.96) and 4.37 (95% CI 1.33–14.33) observed under multivariable analysis, respectively, in comparison with patients who underwent only one or neither of these procedures (p = 0.005 for trend test).

Conclusion
TEVAR is a feasible procedure for esophageal cancers invading the aorta and can be used for curative-intent resection to improve local tumor control and PFS.
Parameterized Algorithms for Power-Efficiently Connecting Wireless Sensor Networks: Theory and Experiments
Authors: Bentert Matthias , van Bevern René , Nichterlein André , Niedermeier Rolf , Smirnov Pavel V. 
Published: June 2021

We study a problem of energy-efficiently connecting a symmetric wireless communication network: given an n-vertex graph with edge weights, find a connected spanning subgraph of minimum cost, where the cost is determined by each vertex paying the heaviest edge incident to it in the subgraph. The problem is known to be NP-hard. Strengthening this hardness result, we show that even o(log n)-approximating the difference d between the optimal solution cost and a natural lower bound is NP-hard. Moreover, we show that under the exponential time hypothesis, there are no exact algorithms running in 2o(n) time or in [Formula: see text] time for any computable function f. We also show that the special case of connecting c network components with minimum additional cost generally cannot be polynomial-time reduced to instances of size cO(1) unless the polynomial-time hierarchy collapses. On the positive side, we provide an algorithm that reconnects O(log n)-connected components with minimum additional cost in polynomial time. These algorithms are motivated by application scenarios of monitoring areas or where an existing sensor network may fall apart into several connected components because of sensor faults. In experiments, the algorithm outperforms CPLEX with known integer linear programming (ILP) formulations when n is sufficiently large compared with c. Summary of Contribution: Wireless sensor networks are used to monitor air pollution, water pollution, and machine health; in forest fire and landslide detection; and in natural disaster prevention. Sensors in wireless sensor networks are often battery-powered and disposable, so one may be interested in lowering the energy consumption of the sensors in order to achieve a long lifetime of the network. We study the min-power symmetric connectivity problem, which models the task of assigning transmission powers to sensors so as to achieve a connected communication network with minimum total power consumption. The problem is NP-hard. We provide perhaps the first parameterized complexity study of optimal and approximate solutions for the problem. Our algorithms work in polynomial time in the scenario where one has to reconnect a sensor network with n sensors and O(log n)-connected components by means of a minimum transmission power increase or if one can find transmission power lower bounds that already yield a network with O(log n)-connected components. In experiments, we show that, in this scenario, our algorithms outperform previously known exact algorithms based on ILP formulations.
Do Electronic Health Record Systems Increase Medicare Reimbursements? The Moderating Effect of the Recovery Audit Program
Authors: Ganju Kartik K. , Atasoy Hilal , Pavlou Paul A. 
Published: June 2021

Electronic health record (EHR) systems allow physicians to automate the process of entering patient data relative to manual entry in traditional paper-based records. However, such automated data entry can lead to increased reimbursement requests by hospitals from Medicare by overstating the complexity of patients. The EHR module that has been alleged to increase reimbursements is the Computerized Physician Order Entry (CPOE) system, which populates patient charts with default templates and allows physicians to copy and paste data from previous charts of the patient and other patients’ records. To combat increased reimbursements by hospitals from Medicare, the Centers for Medicare & Medicaid Services implemented the Recovery Audit Program first as a pilot in six states between 2005 and 2009 and then, nationwide in the entire United States in 2010. We examine whether the adoption of CPOE systems by hospitals is associated with an increase in reported patient complexity and if the Recovery Audit Program helped to attenuate this relationship. We find that the adoption of CPOE systems significantly increases patient complexity reported by hospitals, corresponding to an estimate of $1 billion increase in Medicare reimbursements per year. This increase was attenuated when hospitals were regulated by the Recovery Audit Program. Notably, those recovery auditors who developed the ability to identify the use of default templates, copied and pasted data, and cloned records were the most effective in reducing increased reimbursements. These findings have implications on how to combat Medicare reimbursements paid by taxpayer dollars with the Recovery Audit Program and how this information technology (IT) audit can prevent the misuse of information systems to create artificial business value of IT by hospitals. Contributions to information systems and healthcare research, practice, and public policy are discussed. This paper was accepted by Chris Forman, information systems.
Apple Disease Recognition Based on Small-scale Data Sets
Authors: Song Chenyong , Wang Dongwei , Bai Haoran , Sun Weihao 
Published: June 2021

HighlightsThe proposed data enhancement method can be used for small-scale data sets with rich sample image features.The accuracy of the new model reaches 98.5%, which is better than the traditional CNN method.Abstract: GoogLeNet offers far better performance in identifying apple disease compared to traditional methods. However, the complexity of GoogLeNet is relatively high. For small volumes of data, GoogLeNet does not achieve the same performance as it does with large-scale data. We propose a new apple disease identification model using GoogLeNet’s inception module. The model adopts a variety of methods to optimize its generalization ability. First, geometric transformation and image modification of data enhancement methods (including rotation, scaling, noise interference, random elimination, color space enhancement) and random probability and appropriate combination of strategies are used to amplify the data set. Second, we employ a deep convolution generative adversarial network (DCGAN) to enhance the richness of generated images by increasing the diversity of the noise distribution of the generator. Finally, we optimize the GoogLeNet model structure to reduce model complexity and model parameters, making it more suitable for identifying apple tree diseases. The experimental results show that our approach quickly detects and classifies apple diseases including rust, spotted leaf disease, and anthrax. It outperforms the original GoogLeNet in recognition accuracy and model size, with identification accuracy reaching 98.5%, making it a feasible method for apple disease classification. Keywords: Apple disease identification, Data enhancement, DCGAN, GoogLeNet.
Multiport all-logic optical switch based on thermally altered light paths in a multimode waveguide
Authors: Dang Zhangqi , Chen Tao , Ding Zhenming , Liu Zexu , Zhang Xiaodong , Jiang Xinhong , Zhang Ziyang 
Published: June 2021

A generic multiport optical switch capable of generating all-logic outputs is demonstrated by altering the mode profiles and propagation characteristics in a multimode waveguide through a combination of microheaters. The principles and design rules are introduced. As proof of concept, a 3-bit all-logic switch is fabricated on a polymer waveguide platform. The experimental results are in good agreement with the simulations based on a heat solver and the eigenmode expansion method. The device shows polarization insensitive and colorless operation from 1520 to 1600 nm with an extinction ratio between “On” and “Off” states larger than 11.9 dB in all cases. The maximum heat power is 43.9 mW (for (1, 0, 0) state). The simple, compact, and easily scalable device can be used to construct

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switch networks, showing promising applications in on-chip photonic signal processing and computation.