bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bfra-loaded nanoparticles confer protection against paratuberculosis infection
Authors: Liu Yiduo , Chen Yulan , Liang Zhengmin , Luo Lijia , Wang Yuanzhi , Wang Haoran , Ge Xin , Sreevatsan Srinand , Zhou Xiangmei 
Published: August 2023

AbstractParatuberculosis is a chronic wasting disease of granulomatous enteritis in ruminants caused by Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis, MAP) resulting in heavy economic losses to dairy industries worldwide. Currently, commercial vaccines were not effective in preventing pathogen shedding and were reported with serious side effects. To develop a novel and smarter paratuberculosis vaccine, we utilized PLGA nanoparticles encapsulating the Bfra antigen (Bfra-PLGA NPs). We observed that mice vaccinated with Bfra-PLGA NPs exhibited an enhanced secretory IFN-γ, CD4+ T cells response and antibody IgG against MAP infection. In addition, secretions of the inflammatory cytokine TNF-α and IL-10 were increased following treatment with Bfra-PLGA NPs. A significant reduction in bacterial load was observed in the livers and spleens of animals vaccinated with Bfra-PLGA NPs. Furthermore, Bfra-PLGA NPs were effective to alleviate the pathological lesions of livers in mice. Overall, our approach provides a rational basis for employing PLGA nanoparticles to develop improved vaccines that induced protective immunity against paratuberculosis.
Graphical Abstract
Improving mental health care in depression: A call for action
Authors: Eder Julia , Dom Geert , Gorwood Philip , Kärkkäinen Hikka , Decraene Andre , Kumpf Ulrike , Beezhold Julian , Samochowiec Jerzy , Kurimay Tamas , Gaebel Wolfgang , De Picker Livia , Falkai Peter 
Published: August 2023

Abstract
Depressive disorders have one of the highest disability-adjusted life years (DALYs) of all medical conditions, which led the European Psychiatric Association to propose a policy paper, pinpointing their unmet health care and research needs. The first part focuses on what can be currently done to improve the care of patients with depression, and then discuss future trends for research and healthcare. Through the narration of clinical cases, the different points are illustrated. The necessary political framework is formulated, to implement such changes to fundamentally improve psychiatric care. The group of European Psychiatrist Association (EPA) experts insist on the need for (1) increased awareness of mental illness in primary care settings, (2) the development of novel (biological) markers, (3) the rapid implementation of machine learning (supporting diagnostics, prognostics, and therapeutics), (4) the generalized use of electronic devices and apps into everyday treatment, (5) the development of the new generation of treatment options, such as plasticity-promoting agents, and (6) the importance of comprehensive recovery approach. At a political level, the group also proposed four priorities, the need to (1) increase the use of open science, (2) implement reasonable data protection laws, (3) establish ethical electronic health records, and (4) enable better healthcare research and saving resources.
Zanidatamab (zani), a HER2-targeted bispecific antibody, in combination with docetaxel as first-line therapy (1L) for patients (pts) with advanced HER2-positive breast cancer (BC): Updated results from a phase Ib/II study.
Authors: Wang Xiaojia , Lee Keun Seok , Zeng Xiaohua , Sun Tao , Im Young-Hyuck , Li Huiping , Wang Kun , Li Huiyan , Zhou Ping , Bao Yuanyuan , Jiang Zefei 
Published: August 2023

1 Background: Despite HER2-targeted agents improving outcomes in HER2-positive (+) BC, some pts develop resistance, relapse, or do not respond to current 1L therapies. Zani, also known as ZW25, is a novel HER2-targeted bispecific antibody that binds to two distinct extracellular domains of HER2. Preliminary results from this Phase Ib/II trial (NCT04276493) showed that zani plus docetaxel had a manageable safety profile and demonstrated promising antitumor activity in pts with advanced HER2+ BC; here we present the updated data following enrollment completion. Methods: Cohort 1 of this open-label study is evaluating zani in combination with docetaxel as a 1L therapy in adult females with advanced HER2+ BC who may have received prior neoadjuvant/adjuvant therapy. Cohort 1a pts received zani 30 mg/kg intravenously (IV), Cohort 1b pts received zani 1800 mg IV, both with docetaxel 75 mg/m2 IV every 3 weeks. The primary endpoints were safety and investigator (INV)-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints included INV-assessed duration of response (DoR) and disease control rate (DCR). Results: As of Nov 22, 2022, 37 pts(median age 55.0 years [range: 33-80]) were assigned to Cohort 1a (n=10) or 1b (n=27). Median study follow-up was 15.5 months (range: 1.1-29.3); patients received a median of 13 treatment cycles (range 1-37) and 18 (48.6%) pts remained on treatment. Of the 33-efficacy evaluable (EE) pts, confirmed ORR was 90.9% (95% confidence interval [CI]: 75.7, 98.1). Efficacy data are summarized in the table. In total, 36 (97.3%) pts experienced ≥1 treatment-related adverse event (TRAE); 25 (67.6%) pts experienced ≥grade 3 TRAEs. The most common ≥grade 3 TRAEs were decreased neutrophil count, experienced by 18 (48.6%) pts, and decreased white blood cell count, experienced by 7 (18.9%) pts. Serious TRAEs occurred in 6 (16.2%) pts; no TRAEs led to death. Conclusions: Zani combined with docetaxel demonstrated promising antitumor activity as 1L therapy for advanced HER2+ BC, with a manageable safety profile. Clinical trial information: NCT04276493 . [Table: see text]
Disparities in delayed diagnosis and pain management among African American women with breast cancer.
Authors: Leach Virginia 
Published: August 2023

102 Background: Breast Cancer (BC) mortality rates disproportionately affect African American (AA) women over other racial or ethnic group in the United States. Research demonstrates AA women also have disparate rates of an accurate diagnosis and pain management care. Methods: This study addressed barriers to care in diagnosis and pain management care experienced by members of a non-profit organization called the Tigerlily Foundation (TLF), a breast cancer advocacy organization, who design culturally relevant educational materials to support medically underserved populations. This qualitative study interviewed AA women in an IRB-approved study (University of Illinois at Urbana-Champaign). The total duration of each interview lasted a maximum of 1 hour and 45 minutes with participants answering one pre-interview questionnaire for demographic purposes and completing one interview. Results: Among 20 AA women breast cancer survivors, it was discovered participants 90% were delayed, dismissed, and denied screening options to detect their breast cancer diagnosis as early as possible. After several months of displaying anomalies within their breasts (i.e., lump, swelling, pain, nipple discharge), participants had to negotiate with their PCPs to finally get a mammogram, ultrasound, and biopsy. 70% of participants described radiation as excruciating pain. Pain management varied as 10% of participants were offered access to a wound care specialist and received adequate medication to cope with the pain, while 90% of participants received nothing. Those who did not receive assistance tried homeopathic solutions for pain management. Conclusions: Notable differences among AA women breast cancer survivors demonstrated the need for healthcare institutions to review potentially racially bias policies harming this demographic of patients. Future studies among AA populations with disparate breast cancer diagnosis and pain management are needed to improve health outcomes.
Automated classification of disease response in radiology reports using natural language processing.
Authors: Ong Hai Xiang , Cai Yiyu , Yi Zi Meng , Tee Wen Hui , Tan Ying Cong Ryan Shea , Tan Wei Chong , Bakr Azam Abu 
Published: August 2023

108 Background: Classification of disease response is an essential task in cancer research and needs to be done at scale. Automating this process can improve efficiency in the generation of real-world evidence, potentially leading to better patient outcomes. We aim to develop and evaluate Natural Language Processing (NLP) models for this task. Methods: Using 6203 computed tomography (CT) and 1358 magnetic resonance imaging (MRI) reports from 587 patients with lung cancer of all stages seen at the National Cancer Centre Singapore (NCCS), we trained four NLP models (BioBERT, RadBERT-RoBERTA, BioClinicalBERT, GatorTron) to classify the reports into one of four categories: no evidence of disease, stable disease, partial response or disease progression. Model output was compared against human-curated ground truth and performance was evaluated by accuracy. Results: Of the 4 models, GatorTron performed the best (accuracy = 97.1%), followed by RadBERT-RoBERTA (accuracy = 96.2%), BioBERT (accuracy = 94.2%), with BioClinicalBERT being last (accuracy = 90.4%). NLP Model runtimes for the dataset were relatively short, with BioBERT and BioClinicalBERT taking 3 minutes per epoch, RadBERT-RoBERTA taking 6 minutes per epoch, and GatorTron taking 10 minutes per epoch on a single central processing unit (CPU). Conclusions: We have demonstrated the effectiveness of NLP models for classifying disease responses in radiology reports of lung cancer patients. This has the potential to help derive progression-free survival for real-world evidence generation.
Comparisons between HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 ER+ HER2- breast cancer.
Authors: Ahn Sung Gwe , Kook Yoonwon , Bae Soong June , Lee Sae Byul , Jeong Joon 
Published: August 2023

13 Background: HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among ER+HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. Methods: A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 IHC and SISH test. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS)>25. Multivariable binary logistic-regression analysis was performed. Results: Of these, 944 (41.1%) were assigned in the HER2-zero, and 1351 (58.9%) were in the HER2-low. The averages of RS were 17.082 in the HER2-zero breast cancer and 18.503 in the HER2-low, respectively (P-value<0.005). HER2 score identified by qRT-PCR was 8.912 in the HER2 zero group and was 9.337 in the HER2 low group (P<0.005). When we compared a proportion of high RS between two groups, the high RS rate was 12.4% (117 of 944) in the HER2-zero, while it was 17.0% (230 of 1351) in the HER2-low (p=0.002). In multivariable analysis, HER2-low was demonstrated as an independent factor for high RS with an odds ratio 1.517 (1.172-1.964) independent of ER, PR, and Ki67. Within the subgroup with invasive ductal carcinoma, the high RS rates of HER2-low and HER2-zero were 19% and 14%, respectively. In the all patients, recurrence-free survival and overall survival did not differ between HER2-low and HER2-zero groups. Conclusions: Within ER+HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among ER+HER2- breast cancer remains as an area that requires further study.
Phase 3 randomized controlled trial comparing the effectiveness of dexamethasone in reducing cancer-associated fatigue in patients on palliative chemotherapy.
Authors: Radhakrishnan Venkatraman , Vihari Vamsi , Gopalakrishnan Vidhya , Dasapathi Venkata Siva Kiran Kumar , Jayachandran Perumal Kalaiyarasi , Rajaraman Swaminathan , Veeraiah Surendran 
Published: August 2023

134 Background: Short-term steroids (< 2 weeks) have been used to alleviate fatigue in patients with advanced cancer. However, the efficacy and safety of long-term steroids (12 weeks) in patients with advanced cancer receiving palliative chemotherapy have not been studied. Methods: The study was an open-label, placebo-controlled, phase 3 RCT to evaluate the efficacy and safety of low dose dexamethasone (DEX) in reducing chemotherapy and cancer associated fatigue. Patients aged 18-60 years with performance status ≤2, undergoing palliative chemotherapy for advanced solid malignancies were randomized 1:1 to receive either DEX (4mg/day) or a placebo for 12 weeks. Fatigue was measured using the Symbolic Assessment of Fatigue Extent (SAFE) scale and EORTC FA12 scale, and QOL was assessed using the EORTC QLQ c30 at baseline, 6 weeks, and 12 weeks.The primary endpoint was to compare fatigue between the study arms at 6 weeks. Secondary endpoints were to compare fatigue at 12 weeks, QOL and toxicities. With a power of 80%, α of 5%, 126 patients (including 25% drop-outs) were required to show the superiority of DEX in reducing SAFE fatigue extent score by 50% at 6 weeks. Results: A total of 126 patients were randomized (64 in the placebo arm and 62 in the DEX arm) between Oct 2018-Sep 2022. The median age was 46.5 years and 67% were females. Metastatic breast (28%) and lung (16%) cancer were the common diagnosis. Twelve and 23 patients in the placebo arm and 13 and 22 patients in the DEX arm did not undergo week 6 and 12 assessment respectively due to disease progression. The results showed no significant differences in mean SAFE scores, FA12 scores, or QOL between the study arms at 6 and 12 weeks, except for higher FA12 social sequelae in the DEX arm at 12 weeks (P = 0.048) (Table). There were no significant differences in toxicities between the arms. Conclusions: The results of this study suggest that low-dose DEX is not effective in reducing chemotherapy associated fatigue or improving QOL in patients with advanced cancer. Clinical trial information: CTRI/2018/08/015222 .[Table: see text]
Long-term survival outcome of radiation therapy for unresectable, locally advanced non-small cell lung cancer: Single center experience at Hospital 175.
Authors: Vu Nam , Manh Dao Tien , Cuong Nguyen Viet , Son Nguyen Hong , Viet Tran Quoc , Onishi Hiroshi 
Published: August 2023

142 Background: Lung cancer represents a significant global health burden, with non-small cell lung cancer (NSCLC) being the most prevalent form of this disease. While surgery remains the cornerstone of treatment for early-stage NSCLC, patients with locally advanced or inoperable NSCLC require alternative therapeutic strategies. Purpose: to assess the long-term survival data and determine the associated factors impacting survival outcomes for patients with locally advanced unresectable non-small cell lung cancer (NSCLC) treated with radiotherapy. Methods: We retrospectively analyzed patients diagnosed with inoperable stage III of NSCLC who received radiation therapy at Hospital 175 from January 2019 to June 2022. The patients had a performance status score (PS) of 0-2 and only one primary lung tumor. We collected patients' background information, including age, gender, pathology, TNM, combination chemotherapy, PET/CT characteristics, and radiotherapy plan parameters. All patients received radiotherapy, at a dose equivalent to 60Gy or more. During radiation therapy, patients were monitored for radiation toxicity. We used the Kaplan-Meier method to estimate overall survival (OS) rate and the Cox regression model to identify the risk factors affecting the treatment outcomes. Results: A total of 240 cases, male: 75%, PS 0, 1, 2 respectively: 24%, 72%, 4%. Histopathological types: squamous cell (9%), glandular cell (83.5%), others (7.5%). Which, subgroups of stages IIIA, IIIB, and IIIC: are 32%, 48%, and 20%. The rate of patients having chemotherapy before radiation was 80.3%, and having PET/CT scans was 43.5%. Patients with radiation alone: 73.4% and concurrent chemoradiotherapy: 26.6%. Median follow-up time: 16.3 months, median OS: 19.5 months. OS rates after 1, 2, and 3 years are 76.2%, 38.8%, and 27.4%, respectively. The most common toxicity was grade 2 esophagitis. Patients who received concurrent chemoradiotherapy had a better prognosis than those who received radiation therapy alone. Regimen of radiation therapy, age, histopathological type, and lymph node metastasis were significant factors affecting overall survival outcomes. Conclusions: Radiotherapy is an essential part of treatment for inoperable NSCLC. The best survival benefit is achieved with concurrent chemoradiotherapy. Besides, age, lymph node metastasis, and histopathological type are also potential factors that can influence patient outcomes.
Precision medicine-based platform to guide the treatment of EML4-ALK fusion lung cancers and other non-small cell lung cancers.
Authors: Merrill Nathan , Udager Aaron M. , Qin Angel , Lagisetty Kiran , Aikins Marisa , Bao Liwei , Cheng Xu , Goo Laura , Kathawate Varun , Vandenburg Bryce , Ulintz Peter , Qin Zhaoping , Liu Albert , Serhan Habib , Nagrath Sunitha , Hsu Peggy , Soellner Matthew , Merajver Sofia 
Published: August 2023

146 Background: Lung cancer remains the number one cause of cancer-associated mortality worldwide, with a 10-year survival rate of only 5%. While most lung cancers are smoking related, 25% of non-small cell lung cancer (NSCLC) are diagnosed in patients with little or no smoking history. Fusions involving anaplastic lymphoma kinase (ALK) are the oncogenic driver in ~3–7% of NSCLC. While inhibitors targeting the kinase domain of ALK have proven extremely effective in the treatment of ALK-positive NSCLC, inevitably, resistance develops with limited effective treatment options. Methods: We developed a precision medicine-based platform to screen patient-derived material (PDM) directly from the operating room with curated panels of approved and IND drugs. PDM collected during clinically indicated procedures is dissociated into single cells, plated in culture to generate patient-derived organoids (PDOs), and screened with drugs that are curated to each tumor based on treatment history and clinically relevant sequencing. PDOs are screened at therapeutically relevant levels, drawing from pharmacokinetic data for each drug, when available. We have optimized an assay to rapidly screen for EML4-ALK fusions and can perform next-generation DNA and RNA sequencing in real time (~7 days) to integrate with drug screening results. Results: To date, we have screened 51NSCLC cases, including 7 ALK-positive NSCLC. Screening in highly progressed EML4-ALK patients demonstrates sensitivity to earlier generation ALK TKIs, a known phenomenon in the literature. Our screening results recapitulate known clinical resistance/progression in samples previously exposed to therapy, demonstrating a strong negative predictive value. Longitudinal assessment will be required to robustly assess the positive predictive value (PPV). In one EML4-ALK NSCLC (JTI026) we were able to collect PDM from two distinct regions (pleural effusion and thoracentesis) and screen them with the same panel of drugs, with identical results. These data highlight the reproducibility of our assay. Conclusions: Our precision medicine-based platform captures robust and reproducible results that are consistent with known clinical pathogenesis. Moving forward, we are collecting longitudinal data from enrolled patients in parallel with clinical trials to demonstrate PPV of our platform. We additionally strive to demonstrate reproducibility to obtain Clinical Laboratory Improvement Amendments (CLIA) approval and to deliver results to patients and physicians to help guide clinical care. [Table: see text]
A panel of seven protein tumour markers for effective and affordable multi-cancer early detection by artificial intelligence.
Authors: Mao Mao , Luan Yi , Zhong Guolin , Li Shiyong , Wu Wei , Liu Xiaoqiang , Zhu Dandan , Tu Shichun , Feng Yumin , Zhang Yixia , Duan Chaohui 
Published: August 2023

155 Background: Cancer early detection aims at reducing cancer deaths. Unfortunately, many established cancer screening technologies are not suitable for use in low- and middle-income countries (LMICs) due to cost, complexity, and dependency on extensive medical infrastructure. Methods: Nearly 10,000 participants [1959 cancer cases (containing more than nine common cancer types) and 7423 non-cancer cases] were divided into one training and two independent validation cohorts. One tube of peripheral blood samples was collected from each participant and quantified using a panel of seven selected protein tumour markers (PTMs) by a common clinical electrochemiluminescence immunoassay analyser. An algorithm named OncoSeek was established using artificial intelligence (AI) to distinguish cancer from non-cancer cases by calculating the probability of cancer (POC) index based on the quantification results of the seven PTMs and clinical information including sex and age of the subjects, and to predict the possible affected tissue of origin (TOO) for those who have been detected with cancer signal. Results: The conventional clinical method relied only on a single threshold for each PTM which would make a big problem when combining the results of those markers, the false positive rate would accumulate as the number of markers increased. Nevertheless, OncoSeek was empowered by AI technology to significantly reduce the false positive rate, increasing the specificity from 56·9% [95% confidence interval (CI): 55·8% to 58·0%] to 92·9% (95% CI: 92·3% to 93·5%). In all cancer types, the overall sensitivity of the OncoSeek test was 51·7% (95% CI: 49·4% to 53·9%). And the performance was generally consistent in the training and the two validation cohorts. The sensitivities ranged from 37·1% to 77·6% for the detection of the nine common cancer types (breast, colorectum, liver, lung, lymphoma, oesophagus, ovary, pancreas, and stomach), which account for ~59·2% of global cancer deaths annually. Furthermore, it has shown excellent sensitivity in several high-mortality cancer types for which there are lacking routine screening tests in the clinic, such as the sensitivity of pancreatic cancer was 77·6% (95% CI: 69·3% to 84·6%). The overall accuracy of TOO prediction in the true positives was 66·8%, which could assist the clinical diagnostic workup. Conclusions: OncoSeek significantly outperforms the conventional clinical method, representing a novel blood-based test for multi-cancer early detection (MCED) which is a non-invasive, easy, efficient, and robust approach. Moreover, the accuracy of TOO facilitates the follow-up diagnostic workup and this method is affordable (less than $25) and accessible requiring nothing more than a blood draw at the screening sites, which makes it acceptable and sustainable in LMICs.