Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers.

Gene upregulation through genome editing is important for plant research and breeding. Targeted insertion of short transcriptional enhancers (STEs) into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with transgenesis. Here, we introduce an "in locus activation" technique in rice that leverages well-characterized STEs for refined, heritable, and multiplexed gene upregulation.

Frailty is associated with worse cognitive functioning in older adults.

Introduction: Frailty and impaired cognitive functioning often co-occur in older adults and are associated with adverse health outcomes. However, their relationship is unclear. This study sought to examine the association of frailty status with cognitive functioning in older adults.

Automatic Extraction of Medication Mentions from Tweets-Overview of the BioCreative VII Shared Task 3 Competition.

This study presents the outcomes of the shared task competition BioCreative VII (Task 3) focusing on the extraction of medication names from a Twitter user's publicly available tweets (the user's 'timeline'). In general, detecting health-related tweets is notoriously challenging for natural language processing tools. The main challenge, aside from the informality of the language used, is that people tweet about any and all topics, and most of their tweets are not related to health.

Multicenter Validation of Natural Language Processing Algorithms for the Detection of Common Data Elements in Operative Notes for Total Hip Arthroplasty: Algorithm Development and Validation.

Background: Natural language processing (NLP) methods are powerful tools for extracting and analyzing critical information from free-text data. MedTaggerIE, an open-source NLP pipeline for information extraction based on text patterns, has been widely used in the annotation of clinical notes. A rule-based system, MedTagger-total hip arthroplasty (THA), developed based on MedTaggerIE, was previously shown to correctly identify the surgical approach, fixation, and bearing surface from the THA operative notes at Mayo Clinic.

Improvement of base editors and prime editors advances precision genome engineering in plants.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein (Cas)-mediated gene disruption has revolutionized biomedical research as well as plant and animal breeding. However, most disease-causing mutations and agronomically important genetic variations are single base polymorphisms (single-nucleotide polymorphisms) that require precision genome editing tools for correction of the sequences. Although homology-directed repair of double-stranded breaks (DSBs) can introduce precise changes, such repairs are inefficient in differentiated animal and plant cells.

Improving Early Identification of Significant Weight Loss Using Clinical Decision Support System in Lung Cancer Radiation Therapy.

Purpose: Early identification of patients who may be at high risk of significant weight loss (SWL) is important for timely clinical intervention in lung cancer radiotherapy (RT). A clinical decision support system (CDSS) for SWL prediction was implemented within the routine clinical workflow and assessed on a prospective cohort of patients.

Materials And Methods: CDSS incorporated a machine learning prediction model on the basis of radiomics and dosiomics image features and was connected to a web-based dashboard for streamlined patient enrollment, feature extraction, SWL prediction, and physicians' evaluation processes.

Radiation-Induced Skin Dermatitis: Treatment With CamWell® Herb to Soothe® Cream in Patients With Head and Neck Cancer Receiving Radiation Therapy.

Background: Radiation-induced skin dermatitis (RISD) is a common outcome experienced by adult patients with head and neck cancer (HNC) who have undergone radiation therapy. There is no standardized recommended agent for the prevention or management of RISD.

Objectives: The primary objective of this study was to retrospectively evaluate for effectiveness of a botanical topical agent, CamWell® Herb to Soothe® cream, on RISD.

Early Elevation of Fibrosis-4 Liver Fibrosis Score Is Associated With Adverse Outcomes Among Patients With Coronavirus Disease 2019.

Background: Limited prior data suggest that preexisting liver disease is associated with adverse outcomes among patients with coronavirus disease 2019 (COVID-19). Fibrosis-4 (FIB-4) is a noninvasive index of readily available laboratory measurements that represents hepatic fibrosis. We evaluated the association between FIB-4 at the early stage of infection and COVID-19 outcomes.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

Background: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear.

Methods: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020.

A multi-institutional phase 2 trial of stereotactic body radiotherapy in the treatment of bone metastases in pediatric and young adult patients with sarcoma.

Background: Metastasectomy is standard of care for pediatric patients with metastatic sarcoma with limited disease. For patients with unresectable disease, stereotactic body radiotherapy (SBRT) may serve as an alternative. Herein, the authors report the results of a prospective, multi-institutional phase 2 trial of SBRT in children and young adults with metastatic sarcoma.

Patient-Reported Outcome Measures and Dosimetric Correlates for Early Detection of Acute Radiation Therapy-Related Esophagitis.

Background: We investigate the time to and clinical factors associated with patient-reported difficulty swallowing in lung cancer patients treated with radiation therapy (RT).

Methods: Between October 2016 and October 2019, lung cancer patients treated with conventionally fractionated RT at a tertiary cancer center were identified. Weekly, patients reported difficulty swallowing (patient-reported outcome version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE] v.

Isolated progression of metastatic lung cancer: Clinical outcomes associated with definitive radiotherapy.

Background: Progressive, metastatic non-small cell lung cancer (NSCLC) often requires the initiation of new systemic therapy. However, in patients with NSCLC that is oligoprogressive (≤3 lesions), local radiotherapy (RT) may allow for the eradication of resistant microclones and, therefore, the continuation of otherwise effective systemic therapy.

Methods: Patients treated from 2008 to 2019 with definitive doses of RT to all sites of intracranial or extracranial oligoprogression without a change in systemic therapy were identified.

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram.

Background: Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined.

Patients And Methods: Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified.

Propensity score adjusted analysis of patients with isolated locoregional recurrence versus de novo locally advanced NSCLC treated with definitive therapy.

Objectives: Definitive intent treatment of isolated locoregional recurrence (iLR) for non-small cell lung cancer (NSCLC) is becoming more common. This study explores outcomes associated with the definitive local treatment of iLR and compares these outcomes to newly diagnosed locally advanced NSCLC (LA-NSCLC) patients.

Materials And Methods: Patients with NSCLC treated with curative therapy between 2008 and 2019 at a tertiary academic institution were screened for iLR treated with subsequent definitive salvage therapy.

Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact.

Background: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized.

Methods: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified.

Spatial Radiation Dose Influence on Xerostomia Recovery and Its Comparison to Acute Incidence in Patients With Head and Neck Cancer.

Purpose: Radiation-induced xerostomia is one of the most prevalent symptoms during and after head and neck cancer radiation therapy (RT). We aimed to discover the spatial radiation dose-based (voxel dose) importance pattern in the major salivary glands in relation to the recovery of xerostomia 18 months after RT, and to compare the recovery voxel dose importance pattern to the acute incidence (injury) pattern.

Methods And Materials: This study included all patients within our database with xerostomia outcomes after completion of curative intensity modulated RT.

Multi-view radiomics and dosiomics analysis with machine learning for predicting acute-phase weight loss in lung cancer patients treated with radiotherapy.

We propose a multi-view data analysis approach using radiomics and dosiomics (R&D) texture features for predicting acute-phase weight loss (WL) in lung cancer radiotherapy. Baseline weight of 388 patients who underwent intensity modulated radiation therapy (IMRT) was measured between one month prior to and one week after the start of IMRT. Weight change between one week and two months after the commencement of IMRT was analyzed, and dichotomized at 5% WL.

Exploring the Relationship of Radiation Dose Exposed to the Length of Esophagus and Weight Loss in Patients with Lung Cancer.

Purpose: We investigate whether esophageal dose-length parameters (L) can robustly predict significant weight loss-≥5% weight loss during radiation therapy (RT) compared with the weight before RT-in patients with lung cancer treated with definitive intent.

Methods And Materials: Patients with lung cancer treated with conventionally fractionated RT between 2010 and 2018 were retrospectively identified. L and L, the length of full- and partial-circumferential esophagus receiving greater than a threshold dose in Gy, respectively, were created.

Applying Non-Homogeneous Dose Optimization to Improve Conventionally Fractionated Radiation Plan Quality in Patients with Non-Small Cell Lung Cancer.

Purpose: Nonhomogeneous dose optimization (NHDO) is exploited in stereotactic body radiation therapy (SBRT) to increase dose delivery to the tumor and allow rapid dose falloff to surrounding normal tissues. We investigate changes in plan quality when NHDO is applied to inverse-planned conventionally fractionated radiation therapy (CF-RT) plans in patients with non-small cell lung cancer.

Methods And Materials: Patients with near-central non-small cell lung cancer treated with CF-RT in 2018 at a single institution were identified.

DiabetesSistersVoices: Virtual Patient Community to Identify Research Priorities for Women Living With Diabetes.

Background: Women with or at high risk of diabetes have unique health concerns across their life course. Effective methods are needed to engage women living with diabetes to develop and carry out a patient-centered research agenda.

Objective: This study aimed to (1) describe the creation of DiabetesSistersVoices, a virtual patient community for women living with and at risk for diabetes and (2) assess the feasibility and acceptability of DiabetesSistersVoices for engaging women in talking about their experiences, health care, and research priorities.

A TCM acupoints ranking approach towards post-stroke dysphagia based on an improved MCTS decision method.

Traditional Chinese Medicine (TCM) multiple-acupoints stimulation is widely used to improve dysphagia among post-stroke patients. However, prior research in evidence-based acupuncture mostly focused on the treatment effects of single acupoint's on dysphagia, while the evidence of optimal sequence of multiple-acupoints stimulation remains limited. In this paper, we developed an evaluation method of hybrid knowledge (deterministic knowledge and the experiential group decision knowledge) sequences based on segmentation mechanism of sub-sequence fragments, and then, we proposed a Monte Carlo Tree Search (MCTS) sequential decision-making method under the hybrid knowledge.

Machine Learning Methods Uncover Radiomorphologic Dose Patterns in Salivary Glands that Predict Xerostomia in Patients with Head and Neck Cancer.

Purpose: Patients with head-and-neck cancer (HNC) may experience xerostomia after radiation therapy (RT), which leads to compromised quality of life. The purpose of this study is to explore how the spatial pattern of radiation dose (radiomorphology) in the major salivary glands influences xerostomia in patients with HNC.

Methods And Materials: A data-driven approach using spatially explicit dosimetric predictors, voxel dose (ie, actual radiation dose in voxels in parotid glands [PG] and submandibular glands [SMG]) was used to predict whether patients would develop xerostomia 3 months after RT.

Genome Engineering in Rice Using Cas9 Variants that Recognize NG PAM Sequences.

CRISPR/Cas9 genome editing relies on sgRNA-target DNA base pairing and a short downstream PAM sequence to recognize target DNA. The strict protospacer adjacent motif (PAM) requirement hinders applications of the CRISPR/Cas9 system since it restricts the targetable sites in the genomes. xCas9 and SpCas9-NG are two recently engineered SpCas9 variants that can recognize more relaxed NG PAMs, implying a great potential in addressing the issue of PAM constraint.