bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostate Surface Distension and Tumor Texture Descriptors From Pre-Treatment MRI Are Associated With Biochemical Recurrence Following Radical Prostatectomy: Preliminary Findings
Authors: Shiradkar Rakesh , Ghose Soumya , Mahran Amr , Li Lin , Hubbard Isaac , Fu Pingfu , Tirumani Sree Harsha , Ponsky Lee , Purysko Andrei , Madabhushi Anant 
Published: May 2022

ObjectiveTo derive and evaluate the association of prostate shape distension descriptors from T2-weighted MRI (T2WI) with prostate cancer (PCa) biochemical recurrence (BCR) post-radical prostatectomy (RP) independently and in conjunction with texture radiomics of PCa.MethodsThis retrospective study comprised 133 PCa patients from two institutions who underwent 3T-MRI prior to RP and were followed up with PSA measurements for ≥3 years. A 3D shape atlas-based approach was adopted to derive prostate shape distension descriptors from T2WI, and these descriptors were used to train a random forest classifier (CS) to predict BCR. Texture radiomics was derived within PCa regions of interest from T2WI and ADC maps, and another machine learning classifier (CR) was trained for BCR. An integrated classifier CS+R was then trained using predictions from CS and CR. These models were trained on D1 (N = 71, 27 BCR+) and evaluated on independent hold-out set D2 (N = 62, 12 BCR+). CS+R was compared against pre-RP, post-RP clinical variables, and extant nomograms for BCR-free survival (bFS) at 3 years.ResultsCS+R resulted in a higher AUC (0.75) compared to CR (0.70, p = 0.04) and CS (0.69, p = 0.01) on D2 in predicting BCR. On univariable analysis, CS+R achieved a higher hazard ratio (2.89, 95% CI 0.35–12.81, p &lt; 0.01) compared to other pre-RP clinical variables for bFS. CS+R, pathologic Gleason grade, extraprostatic extension, and positive surgical margins were associated with bFS (p &lt; 0.05). CS+R resulted in a higher C-index (0.76 ± 0.06) compared to CAPRA (0.69 ± 0.09, p &lt; 0.01) and Decipher risk (0.59 ± 0.06, p &lt; 0.01); however, it was comparable to post-RP CAPRA-S (0.75 ± 0.02, p = 0.07).ConclusionsRadiomic shape descriptors quantifying prostate surface distension complement texture radiomics of prostate cancer on MRI and result in an improved association with biochemical recurrence post-radical prostatectomy.
Social Media Listening to Understand the Lived Experience of Individuals in Europe With Metastatic Breast Cancer: A Systematic Search and Content Analysis Study
Authors: Mazza Manuelita , Piperis Maria , Aasaithambi Sathyaraj , Chauhan Jyoti , Sagkriotis Alexandros , Vieira Claudia 
Published: May 2022

BackgroundDespite a wealth of real-world data on metastatic breast cancer (mBC), insights into the lived experience are lacking. This study aimed to explore how the lived experience of mBC is described on social media.MethodsA predefined search string identified posts relevant to the lived experience of mBC from Twitter, patient forums, and blogs across 14 European countries. The final data set was analyzed using content analysis.ResultsA total of 76,456 conversations were identified between November 1, 2018, and November 30, 2020. Twitter was the most commonly used social media platform across all 76,456 conversations from the raw data set (n = 61,165; 80%). Automated and manual relevancy checks followed by a final random sampling filter identified 820 conversations for content analysis. The majority of data from the raw data set was generated from the United Kingdom (n = 31,346; 41%). From this final data set, 61% of posts were authored by patients, 15% by friends and/or family members of patients, and 14% by caregivers. A total of 686 conversations described the patient journey (n = 686/820; 84%); 64% of these (n = 439) concerned breast cancer treatment, with approximately 40% of discussions regarding diagnosis and tests (n = 274/686) and less than 20% of discussions surrounding disease management (n = 123/686; 18%). Key themes relating to a lack of effective treatment, prolonged survival and associated quality of life, debilitating consequences of side effects, and the social impacts of living with mBC were identified.ConclusionsThe findings from this study provided an insight into the lived experience of mBC. While retrospective data collection inherently limits the amount of demographic or clinical information that can be obtained from the population sample, social media listening studies offer training to healthcare professionals in communication, the importance of quality of life, organization of healthcare, and even the design of clinical trials. As new targeted therapies are gradually incorporated into clinical practice, innovative technologies, such as social media listening, have the potential to support regulatory procedures and drug toxicity monitoring, as well as provide the patient voice in the regulation of new and existing medicines.
The Alteration of T-Cell Heterogeneity and PD-L1 Colocalization During dMMR Colorectal Cancer Progression Defined by Multiplex Immunohistochemistry
Authors: Yan Hongkai , Li Yaqi , Wang Xiaoyu , Qian Juanjuan , Xu Midie , Peng Junjie , Huang Dan 
Published: May 2022

BackgroundImmune checkpoint inhibitors (ICIs) are quickly becoming key instruments in the treatment of mismatch repair-deficient (dMMR) colorectal cancers (CRCs). Despite their clinical value, ICIs have several limitations associated with their use. Only approximately 15% of all CRCs have a dMMR status, and the overall response rate of ICIs is approximately 40%. The mechanism of ICI resistance is not clear, and its study is limited by the lack of information available on the characterization of the immune microenvironment during the progression from early- to advanced-stage dMMR CRC.MethodsWe used multiplex immunohistochemistry (mIHC) with two panels, each containing five markers, to simultaneously analyze the proportions of immune microenvironment constituents in 59 patients with advanced-stage dMMR CRC and 24 patients with early-stage dMMR CRC. We detected immune cell–associated signatures in the epithelial and stromal regions and evaluated the predictive value of these immune molecules. Student’s t-tests, Mann–Whitney U tests, Cox proportional hazards regression modeling, univariate Cox modeling, and Kaplan–Meier estimation were used to analyze immune cell proportions and survival data.ResultsWe observed significantly higher proportions of CD8+ cytotoxic T cells (CD8+) (p = 0.001), CD8+ memory T cells (CD8+CD45RO+) (p = 0.032), and CD4+ regulatory T cells (CD4+FOXP3+) (p = 0.011) in the advanced-stage dMMR CRCs than in the early-stage dMMR CRCs. Furthermore, CD3+ T cells with PD-L1 colocalization (CD3+PD-L1+) (p = 0.043) and CD8+ T cells with PD-L1 colocalization (CD8+PD-L1+) (p = 0.005) were consistently more numerous in patients in the advanced stage than those in the early stage. Our analyses revealed that a high proportion of CD3+PD-1+ T cells was an independent prognostic factor of overall survival (OS) [hazard ratios (HR) = 9.6, p &lt; 0.001] and disease-free survival (DFS) (HR = 3.7, p = 0.010) in patients in the advanced stage.ConclusionHigh numbers of CD8+ cytotoxic T cells and CD8+ memory T cells, which usually represent a cytotoxic function of the adaptive immune system and possibly enhanced inhibition factors, such as CD4+ regulatory T cells and PD-L1 colocalized T cells, were associated with the transformation of the immune microenvironment from the early stage to the advanced stage in dMMR CRCs. Furthermore, CD3+PD-1+ T cells are a prognostic factor for patients with dMMR.
Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma
Authors: Yang Szu-Chun , Lin Chien-Chung , Chen Yi-Lin , Su Wu-Chou 
Published: May 2022

BackgroundTo compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma.Materials and MethodsWe developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed.ResultsIn terms of testing costs, tissue-first approach incurred US$2,354($1,963–$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010–$5,480), $6,778 ($5,923–$7,600), and $7,006 ($6,047–$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively.ConclusionThe tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.
Impact of Baseline Muscle Mass and Myosteatosis on the Development of Early Toxicity During First-Line Chemotherapy in Patients With Initially Metastatic Pancreatic Cancer
Authors: Hong Sun , Kim Kyung Won , Park Hyo Jung , Ko Yousun , Yoo Changhoon , Park Seo Young , Khang Seungwoo , Jeong Heeryeol , Lee Jeongjin 
Published: May 2022

ObjectivesAlthough chemotherapy is the only treatment option for metastatic pancreatic cancer (PDAC), patients frequently encounter adverse events during chemotherapy leading deterioration of patients’ quality of life and treatment interruption. We evaluated the role of baseline CT-assessed body composition in predicting early toxicity during first cycle of the first-line chemotherapy in patients with metastatic PDAC.MethodsThis retrospective study included 636 patients with initially metastatic PDAC who underwent first-line chemotherapy from January 2009 to December 2019. Chemotherapy regimen, baseline laboratory data, and body composition parameters acquired from baseline CT were obtained. The skeletal muscle index (SMI) was used to identify patients with a low muscle mass (SMI &lt; 41 cm2/m2 for women, and &lt; 43 cm2/m2 [body mass index &lt; 25 cm/kg2] or &lt; 53 cm2/m2 [body mass index ≥ 25 cm/kg2] for men), and myosteatosis was defined as low-attenuated muscle area divided by skeletal muscle area (LAMA/SMA index) ≥ 20%. Univariate and multivariable binary logistic regression analyses were performed using bootstrapping with 500 interactions to identify predictors of grade 3–4 toxicity and any treatment-modifying toxicity which led to a dose reduction, delayed administration, drug skip or discontinuation.ResultsDuring the first cycle of the first-line chemotherapy, grade 3–4 toxicity and treatment-modifying toxicity occurred in 160 patients (25.2%) and in 247 patients (38.8%), respectively. The presence of both low muscle mass and myosteatosis was significantly associated with the occurrence of both grade 3-4 toxicity (odd ratio [OR], 1.73; 95% confidence interval [CI], 1.14–2.63) and treatment-modifying toxicity (OR, 1.83; 95% CI, 1.26–2.66) whereas low muscle mass alone did not.ConclusionsThe presence of both low muscle mass and myosteatosis assessed on baseline CT may be used to predict early chemotherapy-related toxicity in patients with metastatic PDAC.
Risk Factors of Non-en Bloc Resection and Non-R0 Resection During Endoscopic Resection in the Treatment of Superficial Duodenal Epithelial Lesions
Authors: Fu Shifeng , Gong Jian , Zhou Mei , Wang Yongjun , Liu Deliang , Tan Yuyong 
Published: May 2022

BackgroundSuperficial duodenal epithelial lesions are precancerous lesions of duodenal carcinoma. Upper gastrointestinal endoscopy has been widely used in the screening and treatment of this disease. This article will collect the data of patients who underwent endoscopic resection of superficial duodenal epithelial lesions in our hospital from 2010 to 2021, aiming to describe the efficacy and safety of endoscopic resection, as well as to explore the risk factors of non-en bloc resection and non-R0 resection.MethodsPatients who underwent endoscopic resection for superficial duodenal epithelial lesions in our hospital from January 2010 to September 2021 were selected. The curative effect was expressed by the en bloc resection rate and R0 resection rate. The safety was expressed by intra- or postoperative complications, such as bleeding and perforation. The potential risk factors of curative effect were analyzed by logistic regression.ResultsA total of 137 patients were included. The en bloc resection rate was 95.62% (131/137), R0 resection rate was 91.97% (126/137), the postoperative bleeding rate was 2.19% (3/137), and no postoperative perforation was found. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection (OR: 8.86, 95% CI: 1.38-56.92); the lesion size ≥2 cm was the risk factor of non-R0 resection (OR: 12.55, 95% CI: 2.95-53.38).ConclusionEndoscopic resection is a safe and effective method for the treatment of superficial duodenal epithelial lesions. The histology result of ectopic gastric mucosa was the risk factor of non-en bloc resection and the lesion size ≥2 cm was the risk factor of non-R0 resection.
The Causes of Death and Their Influence in Life Expectancy of Children Aged 5–14 Years in Low- and Middle-Income Countries From 1990 to 2019
Authors: Liang Juanjuan , Du Yuanze , Qu Xiang , Ke Changrong , Yi Guipeng , Liu Mi , Lyu Juncheng , Ren Yanfeng , Xing Jie , Wang Chunping , Liu Shiwei 
Published: May 2022

IntroductionAlthough child and adolescent health is the core of the global health agenda, the cause of death and its expected contribution to life expectancy (LE) among those aged 5–14 are under-researched across countries, especially in low- and middle-income countries (LMICs).MethodsDeath rates per 10 years age group including a 5–14-year-old group were calculated by the formula, which used the population and the number of deaths segmented by the cause of death and gender from the 2019 Global Burden of Disease (GBD) study. LE and cause-eliminated LE in 10-year intervals were calculated by using life tables.ResultsIn 2019, the global mortality rate for children and adolescents aged 5–14 years was 0.522 (0.476–0.575) per 1,000, and its LF was 71.377 years. In different-income regions, considerable heterogeneity remains in the ranking of cause of death aged 5–14 years. The top three causes of death in low-income countries (LICs) are enteric infections [0.141 (0.098–0.201) per 1,000], other infectious diseases [0.103 (0.073–0.148) per 1,000], and neglected tropical diseases and malaria [0.102 (0.054–0.172) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5–14 age group by 0.085, 0.062, and 0.061 years, respectively. The top three causes of death in upper-middle income countries (upper MICs) are unintentional injuries [0.066 (0.061–0.072) per 1,000], neoplasm [0.046 (0.041–0.050) per 1,000], and transport injuries [0.045 (0.041–0.049) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5–14 age group by 0.045, 0.031, and 0.030 years, respectively.ConclusionThe mortality rate for children and adolescents aged 5–14 years among LMICs remains high. Considerable heterogeneity was observed in the main causes of death among regions. According to the main causes of death at 5–14 years old in different regions and countries at different economic levels, governments should put their priority in tailoring their own strategies to decrease preventable mortality.
The Role of CXC Chemokines in Cardiovascular Diseases
Authors: Lu Xiyi , Wang Zhen , Ye Di , Feng Yongqi , Liu Menglin , Xu Yao , Wang Menglong , Zhang Jishou , Liu Jianfang , Zhao Mengmeng , Xu Shuwan , Ye Jing , Wan Jun 
Published: May 2022

Cardiovascular disease (CVD) is a class of diseases with high disability and mortality rates. In the elderly population, the incidence of cardiovascular disease is increasing annually. Between 1990 and 2016, the age-standardised prevalence of CVD in China significantly increased by 14.7%, and the number of cardiovascular disease deaths increased from 2.51 million to 3.97 million. Much research has indicated that cardiovascular disease is closely related to inflammation, immunity, injury and repair. Chemokines, which induce directed chemotaxis of reactive cells, are divided into four subfamilies: CXC, CC, CX3C, and XC. As cytokines, CXC chemokines are similarly involved in inflammation, immunity, injury, and repair and play a role in many cardiovascular diseases, such as atherosclerosis, myocardial infarction, cardiac ischaemia-reperfusion injury, hypertension, aortic aneurysm, cardiac fibrosis, postcardiac rejection, and atrial fibrillation. Here, we explored the relationship between the chemokine CXC subset and cardiovascular disease and its mechanism of action with the goal of further understanding the onset of cardiovascular disease.
Miya Improves Osteoarthritis Characteristics via the Gut-Muscle-Joint Axis According to Multi-Omics Analyses
Authors: Xu Tianyang , Yang Dong , Liu Kaiyuan , Gao Qiuming , Liu Zhongchen , Li Guodong 
Published: May 2022

Background: The gut microbiota is associated with osteoarthritis (OA) progression. Miya (MY) is a product made from Clostridium butyricum, a member of gut microbiota. This study was conducted to investigate the effects of MY on OA and its underlying mechanisms.Methods: An OA rat model was established, and MY was used to treat the rats for 4 weeks. Knee joint samples from the rats were stained with hematoxylin-eosin, and fecal samples from the OA and OA+MY groups were subjected to 16S rDNA sequencing and metabolomic analysis. The contents of succinate dehydrogenase and muscle glycogen in the tibia muscle were determined, and related genes and proteins were detected using quantitative reverse transcription polymerase chain reaction and western blotting.Results: Hematoxylin and eosin staining showed that treatment with MY alleviated the symptoms of OA. According to the sequencing results, MY significantly increased the Chao1, Shannon, and Pielou evenness values compared to those in the untreated group. At the genus level, the abundances of Prevotella, Ruminococcus, Desulfovibrio, Shigella, Helicobacter, and Streptococcus were higher in the OA group, whereas Lactobacillus, Oscillospira, Clostridium, and Coprococcus were enriched after MY treatment. Metabolomic analysis revealed 395 differentially expressed metabolites. Additionally, MY treatment significantly increased the succinate dehydrogenase and muscle glycogen contents in the muscle caused by OA (p &gt; 0.05). Finally, AMPK, Tfam, Myod, Ldh, Chrna1, Chrnd, Rapsyn, and Agrin were significantly downregulated in the muscles of OA mice, whereas Lcad, Mcad, and IL-1β were upregulated; MY significantly reversed these trends induced by OA.Conclusions: MY may promote the repair of joint damage and protect against OA via the gut-muscle-joint axis.
Treatment Effect of Long-Term Antipsychotics on Default-Mode Network Dysfunction in Drug-Naïve Patients With First-Episode Schizophrenia: A Longitudinal Study
Authors: Deng Mengjie , Liu Zhening , Shen Yanyu , Cao Hengyi , Zhang Manqi , Xi Chang , Zhang Wen , Tan Wenjian , Zhang Jinqiang , Chen Eric , Lee Edwin , Pu Weidan 
Published: May 2022

Background: The maintenance of antipsychotic treatment is an efficient way to prevent the relapse of schizophrenia (SCZ). Previous studies have identified beneficial effects of antipsychotics on brain structural and functional abnormalities during mostly the acute phase in SCZ, but seldom is known about the effects of long-term antipsychotics on the brain. The present study focused on the long-term antipsychotic effect on the default mode network (DMN) dysfunction in SCZ.Methods: A longitudinal study of the functional connectivity (FC) of 11 DMN subdivisions was conducted in 86 drug-naive first-episode patients with SCZ at the baseline and after a long-term atypical antipsychotic treatment (more than 6 months) based on the resting-state functional magnetic resonance image. In total, 52 patients completed the follow-up of clinical and neuroimaging investigations.Results: At the baseline, relative to healthy controls, altered connectivities within the DMN and between the DMN and the external attention system (EAS) were observed in patients. After treatment, along with significant relief of symptoms, most FC alterations between the DMN and the EAS at the baseline were improved after treatment, although the rehabilitation of FC within the DMN was only observed at the link between the posterior cingulate cortex and precuneus. Greater reductions in negative and positive symptoms were both related to the changes of DMN-EAS FC in patients.Conclusion: Our findings provide evidence that maintenance antipsychotics on SCZ is beneficial for the improvement of DMN-EAS competitive imbalance, which may partly contribute to the efficient relapse prevention of this severe mental disorder.
Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits
Authors: Totten Katherine M.C. , Cunningham Scott A. , Gades Naomi M. , Etzioni Athema , Patel Robin 
Published: May 2022

The therapeutic value of phage as an alternative to antibiotics for the treatment of bacterial infections is being considered in the wake of mounting antibiotic resistance. In this study, the pharmacokinetic properties ofStaphylococcus aureusphage K following intravenous and intra-articular administration were investigated in a rabbit model. Using a traditional plaque assay and a novel quantitative PCR assay to measure phage levels in specimens over time, it was found that intra-articularly administered phage enters the systemic circulation; that phage may be detected in synovial fluid up to 24 h following the intra-articular, but not intravenous, administration; and that qPCR-based enumeration is generally more sensitive than plaque enumeration, with fair to moderate correlation between the two methods. Findings presented should inform the design of phage therapy experiments and therapeutic drug monitoring in preclinical and human phage studies.