bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel artificial intelligence-enhanced electrochemical method for rapid methylation detection in cfDNA: Advancing multi-cancer early diagnosis.
Authors: Sun Li-Yue , Zeng Xin-Xin , Jiang Yu-Ying , Shen Ju , Xian Ke-Xin , Li Hua-Gen , Wang Rui-Qi , Wang Fang , Jiang Sun-Fang 
Published: August 2024

181 Background: The detection of methylation in circulating free DNA (cfDNA) has become a pivotal approach for the early screening and diagnosis of cancer. Traditional methods, face challenges including high detection limits, inconvenience, and elevated costs. Our prior work developed a rapid, cost-effective, and sensitive electrochemical methylation detection method for multi-cancer early detection (MCED), yet it couldn't identify the tissue of origin (TOO). We aimed to enhance this method by integrating traditional tumor biomarkers with artificial intelligence (AI) algorithms for improved cfDNA methylation detection and rapid TOO determination. Methods: A training cohort of 626 individuals was analyzed, including 173 colorectal cancer (CRC) patients, 49 patients with hematological tumors, 273 patients with other types of tumors, and 131 healthy controls. This analysis utilized electrochemical detection, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9). We evaluated the diagnostic performance of these markers using ten types of AI algorithms. The optimal algorithm was selected to construct diagnostic models for CRC and hematological tumors. These models were then validated in an external cohort comprising 100 cancer patients. Results: In the training cohort, the logistic algorithm outperformed others, achieving AUC of 0.915 for CRC, 0.850 for hematological tumors, and 0.860 for other tumors. Based on these results, we opted to utilize the logistic algorithm for the development of diagnostic models for CRC and hematological tumors. The CRC model surpassed the performance of the electrochemical adsorption rate (AUC = 0.817) in CRC, though it showed limited efficacy for hematological tumors (AUC = 0.544) and other tumor types (AUC = 0.806). Conversely, the hematological tumors model achieved its highest performance in hematological tumors (AUC = 0.833), with commendable results for CRC (AUC = 0.831) and other cancers (AUC = 0.799) as well. In the validation cohort, the CRC model accurately identified 32 out of 35 CRC patients, and 17 of these were also detected by the hematological tumors model. Among the hematological tumors patients, 18 out of 20 positive with the hematological tumors model, and 15 were detected by the CRC model. For the remaining 45 patients with various other cancer, 22 tested positive with the CRC model and 28 with the hematological tumors model. Conclusions: Integrating machine learning with electrochemical cfDNA methylation detection and tumor markers provides a powerful approach for accurate cancer detection and TOO determination, promising to improve early diagnosis and personalized treatment strategies.
Illness uncertainty, coping, and quality of life in patients with advanced cancer and family caregivers: A dyadic study.
Authors: Guan Ting , Chapman Mimi , Zerden Lisa , Zimmer Catherine , Northouse Laurel L. , Song Lixin 
Published: August 2024

185 Background: Illness uncertainty is prevalent among patients with cancer and their family caregivers. While the relationship between illness uncertainty, coping, and quality of life (QOL) has been explored individually for patients or caregivers, it remains largely unexamined within patient-caregiver dyads. Guided by Mishel’s Uncertainty in Illness Theory, this study examined the relationships between illness uncertainty, coping, and QOL among patients with advanced cancer and family caregivers. Methods: This cross-sectional study analyzed the data from a randomized clinical trial that examined the effects of a dyadic-based intervention on psychological outcomes for patients with advanced cancer and family caregivers. Illness uncertainty, coping, and QOL were measured using the shorten version of the Mishel Uncertainty in Illness Scale for Adult, the Brief Cope, and the Functional Assessment of Cancer Therapy, respectively. The actor-partner interdependence mediation model was used to achieve the aim. Results: This study included 484 patient-caregiver dyads, with patients diagnosed with advanced breast (32.4%), lung (29.1%), colorectal (25.4%), and prostate cancer (13.0%). Patients’ avoidant coping mediated the relationship between their own illness uncertainty and QOL ( p < .001). Caregivers’ active coping and avoidant coping mediated the relationship between their own illness uncertainty and QOL ( p < .001). Notably, caregivers’ illness uncertainty was positively associated with patients’ avoidant coping ( b = 0.113; p < .01). Conclusions: This study is one of the first to use a dyadic approach to investigate the relationships between illness uncertainty, coping, and QOL in advanced cancer patients and caregivers. Our findings highlight the importance of viewing patient-caregiver dyads as the unit of care. These findings support targeted interventions offered to both patients and family caregivers to manage their illness uncertainty and improve their QOL. Giving the effect of caregivers’ uncertainty on patients’ coping, healthcare professionals should advocate for additional psychosocial supports for family caregivers. Clinical trial information: NCT00709176 .
Association of peripheral edema with immune checkpoint inhibitors: A systematic review.
Authors: Tsuchiya Kazuya , Elias Evelyn , Koseki Mako , Estaris Jonathan , Chesta Fnu , Takaoka Kensuke , Nishimura Yoshito , Rohs Nicholas Cole , Fujiwara Yu 
Published: August 2024

187 Background: Immune checkpoint inhibitors (ICIs) are widely used to treat patients with cancer but immune-related adverse events occasionally disrupt treatments and affect their quality of life. Peripheral edema from ICI therapy appears rare but can occur due to increased peripheral vascular permeability. Thus, we aimed to report the incidence and outcomes of peripheral edema from ICIs. Methods: Medline, Embase, and Web of Science were searched to identify phase 3 randomized controlled trials (RCTs) reporting the incidence of peripheral edema in patients treated with ICIs. We calculated the incident rate of peripheral edema based on treatment patterns (monotherapy and combination therapy) and ICI subtypes (PD-1, PD-L1, and CTLA-4 inhibitors). We also performed a systematic review to identify articles reporting treatment outcomes of peripheral edema from ICIs. Results: Overall, 60 RCTs comprising 22,590 patients were identified for the incidence analysis. Treatment-related peripheral edema (Grade 1-5) occurred in 2.8% from ICI monotherapy (n = 195/6969; PD-1 inhibitors: 2.2% [n = 104/4694], PD-L1: 3.7% [n = 58/1557], CTLA-4: 4.6% [n = 33/718]), 5.0% (n = 112/2257) from ICI with chemotherapy, and 8.7% (n = 205/2349) from ICI with molecular-targeted therapy. Grade 3-5 treatment-related peripheral edema occurred in 0.3% of patients treated with ICI monotherapy (Table). For treatment outcomes of peripheral edema, a systematic review identified 19 studies (17 case reports/series,1 phase 1/2 clinical trial, 1 pharmacovigilance study) comprising 40 patients with immune-related peripheral edema. In total, 82.5% (n = 33/40) of cases received glucocorticoid treatment, and 55.0% (n = 22/40) required a high dose (≥ 1 mg/kg/day) of prednisone. ICI was discontinued in 77.5% (n = 31/40) due to peripheral edema (permanent discontinuation in 35% [n = 14/40]). Conclusions: Peripheral edema occasionally occurs in patients treated with ICIs but its occurrence often requires glucocorticoid administration, which may impact cancer treatment outcomes. [Table: see text]
Efficacy and safety of low-dose versus standard-dose immune checkpoint inhibitor as monotherapy in patients with solid tumors: A meta-analysis and systematic review.
Authors: Qian Yu , Wu Yuan , Qin Jianing , Jin Xin 
Published: August 2024

188 Background: Immunotherapy is a novel anti-cancer therapy with different mechanisms compared with chemotherapy. Several studies have reported that low dose of immune checkpoint inhibitors (ICIs) is effective. However, it is unknown whether the efficacy of low-dose immunotherapy is inferior to that of standard dose immunotherapy. We aimed to compare the existing randomized clinical trials on the efficacy of immunotherapy at low dose and standard dose as a single agent for patients with solid tumors. Methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized clinical trials with the clinical outcomes of low dose and standard dose of programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor as monotherapy until November 30, 2023. The low dose is defined as lower than the dose approved by FDA. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and disease control rate (DCR) were collected. The Stata 15.0 software was used to analyze the data. Results: Twenty-two studies with 3226 patients with five ICIs for 22 solid tumors were included. There is no difference in OS (HR 1.12, 95% CI = 0.97-1.31; p > 0.05), ORR (Odds ratio (OR) 0.92, 95% CI = 0.76-1.11; p > 0.05) and DCR (OR 0.83, 95% CI = 0.65-1.06; p > 0.05) for patients with low dose and standard dose of PD-1/PD-L1 inhibitors. Conclusions: Our results suggested that PD-1/PD-L1 inhibitor as monotherapy with a low dose may be as effective as standard dose for patients with solid tumors. The regular dose-response relationship may not be appropriate for ICIs. Further work is needed to explore the optimal dose of ICIs based on the comprehensive consideration of efficacy, safety, and economic assessment.
Exploring depression risk among breast cancer survivors: A nationwide cohort study in South Korea.
Authors: Choi Hea Lim , Kim Bongsung , Han Kyungdo , Shin Dong Wook 
Published: August 2024

19 Background: With advances in early diagnosis and treatment, the population of breast cancer survivors globally continues to grow. Depression among these survivors poses a significant concern for their long-term survivorship and overall quality of life. This study aims to investigate the incidence of depression among breast cancer survivors and identify associated risk factors. Methods: We used the National Health Insurance Service database of Korea from 2010 to 2016 and examined 59,340 breast cancer survivors and 1:2 age-matched individuals without breast cancer to investigate the incidence of depression. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The risk of depression was assessed based on age, categorizing individuals as under or over 50 years old. We conducted 1-year, 3-year, and 5-year lag sensitivity analysis to demonstrate changes in risk over time. The study identified risk factors for developing depression through multivariable Cox regression, and Kaplan-Meier analysis was conducted to illustrate the incidence probabilities of depression in breast cancer survivors. Results: Breast cancer survivors exhibited a 39% increased risk of depression compared to individuals without breast cancer, and those under the age of 50 years facing higher risk than their older counterparts (HR 1.64, 95% CI 1.58-1.70 and HR 1.23, 95% CI 1.20-1.27, respectively). Chemotherapy (anthracycline and taxane) and endocrine therapy (tamoxifen and aromatase inhibitor) emerged as potential risk factors for depression among breast cancer survivors. Sensitivity analysis revealed a decreasing trend in depression risk over time, particularly among survivors aged older than 50 years. Conclusions: This study highlights a significant increase in depression risk among breast cancer survivors, particularly those under 50 years old. Specific treatments such as chemotherapy and endocrine therapy were identified as potential risk factors. These findings emphasize the necessity for targeted interventions and support strategies to address the heightened risk of depression in breast cancer survivors, ultimately improving their long-term well-being and quality of life.
Accuracy of gravity based automatic infusion system applied to chemoport for intravenous infusion.
Authors: Choi Jonggwon 
Published: August 2024

191 Background: When a vesicant drug is administered to the peripheral vein, a gravity drip method rather than an peristaltic infusion pump is recommended. In addition, it is reported that the gravity based pump has less particle generation than the peristaltic pump that injects fluid through constant peristaltic movement. However, it is pointed out that the disadvantage of gravity based pump is that the rate of administration can easily change according to the change in the location of the injection site. We evaluate the accuracy of new gravity based pump (pressure-sensitive speed control fluid injection device, Accudrip made by Hanvit MD ) at various injection rates and hanging heights common to hospital settings. Methods: The accuracy and safety of the intravenous (IV) flow controller were evaluated for patients receiving IV chemotherapy in the oncology department. It was verified whether the accurate injection rate could be maintained even in various fluid heights, fluid amounts, and types of anticancer drugs that could affect the injection rate. Various anticancer drugs, including immune checkpoint inhibitor, were mixed with 250 ml/500 ml of normal saline and administered for 30 min/60 min, and glucose 500 ml/1000 ml was administered for 60 min/120 min to measure accuracy, each progressed 25 times. Medical staff were surveyed on the ease and limitations of medical practice for each peristaltic infusion pump and new gravity based pump. In addition, side effects occurring in patients during fluid administration were recorded. Results: The mean degree of error in the estimated end time of gravity based automatic infusion system was 3.09% (2.09 ~ 4.10). The error of the gravity based automatic infusion system was statistically significant depending on the patient age (p=.001) and the infusion time (p=.016), but the degree of error according to the type of fluids (p=.302) and fluid concentration (p=.844) was not statistically significant. Among the subjects of the study, nurses' satisfaction with the application of gravity based pump was 4.10 (±0.62) out of 5, and among the general characteristics of nurses, age ( p<.078), and working department (p<.91) did not show a statistically significant difference, but work experience ( p <.021) showed a statistically significant difference. Conclusions: The accuracy of Gravity based automatic infusion system was determined because the degree of error in the expected end time of infusion was not significant according to the infusion variable. In a survey of nurses who have used gravity based pump directly, it was found that the ease of use and satisfaction were similar to those of the conventional peristaltic pump. These findings will contribute greatly to the precise drug administration (over or under-administration) and minimization of adverse events in real-world hospital settings.
Acupuncture for patients with cancer in a palliative care team in Japan: A prospective case series study.
Authors: Masuyama Shoko , Yamashita Hitoshi , Amino Tamami , Kawamoto Ryouko , Tsuji Ryota , Nakanishi Hiromoto , Yoshida Hiroshi 
Published: August 2024

193 Background: In the joint guideline of the Society for Integrative Oncology and ASCO, acupuncture is recommended for general or musculoskeletal pain from cancer, chemotherapy-induced peripheral neuropathy, and other conditions. However, Japanese acupuncture needles are thinner and less stimulating than those used in other countries. To assess whether adding Japanese-style acupuncture to usual palliative care alleviates subjective symptoms in hospitalized cancer patients, we conducted a prospective case series study at an urban core hospital in Japan. Methods: Acupuncture treatment was administered to participating cancer patients once or twice a week, for a maximum of six sessions over three weeks. Each treatment session lasted approximately 30 minutes. Patients in the study continued to receive standard care. The main outcome measure was the change in the 10 cm visual analog scale (VAS) for the primary subjective symptoms immediately after treatment. We regarded a reduction in VAS of 20% or more as a minimal clinically important difference (MCID). The protocol of the study was approved by the Clinical Research Ethics Committee of Osaka General Medical Center (CRB5180013). Results: During the study period, 83 cancer patients gave written consent to receive acupuncture treatment. The mean age was 66.1 years (SD 10.7), with 66% of patients in stage 4, and 70% using opioids. Significant reductions in VAS scores for subjective symptoms were observed immediately after treatment for pain (1st session: from 5.4 to 3.9 on average, P<0.001; 2nd: 4.9 to 3.4, P<0.001; 3rd: 3.9 to 2.6, P<0.001; 4th: 4.7 to 2.8, P=0.002), edema (2nd: 5.5 to 3.7, P<0.001), paresthesia (2nd: 6.2 to 4.6, P=0.005), nausea (1st: 6.5 to 3.9, P=0.012; 2nd: 3.3 to 2.0, P=0.008), stiffness (1st: 6.8 to 3.1, P=0.011; 2nd: 4.3 to 2.8, P=0.022), and breathing difficulty (1st: 5.9 to 3.2, P=0.012). However, there was no significant improvement in malaise across any sessions. The maximum percentages of patients experiencing symptom relief beyond MCID in pain, edema, paresthesia, nausea, stiffness, and breathing difficulty were 67%, 75%, 60%, 80%, 88%, and 83%, respectively, across the treatment sessions for each symptom. There was no significance in odds ratios for age, sex, previous acupuncture experience, or opioid use associated with clinically meaningful pain reduction. All recorded adverse events were mild and transient. Conclusions: The symptom relief observed in this study is only a short-term effect immediately after treatment and includes non-specific effects such as the placebo effect. Future research should explore the specific effects of acupuncture using an exploratory trial design. However, determining the appropriate control group for acupuncture trials remains controversial. At least from a clinical perspective, acupuncture may be a possible option for palliative care for cancer patients, including in Japan.
Identifying risk factors associated with self-reported lower quality of life (QoL) in individuals with PTEN hamartoma tumor syndrome.
Authors: Schmidt Terralyn , Anthony Kristin , Gorman Nicholas , George Amy , Ales Claudio 
Published: August 2024

194 Background: PTEN Hamartoma Tumor Syndrome (PHTS) is a multisystem disorder that affects various organs and systems in the body, presenting with a range of clinical manifestations. Individuals with PHTS face elevated risks of cancer and neurological symptoms, along with significant physical and psychological challenges, which underscores the need for ongoing research and the development of effective management strategies. The purpose of this study is to identify risk factors that are associated with a lower self-reported quality of life in individuals with PHTS using quantitative data from the PTEN Hamartoma Tumor Syndrome Foundation's patient registry surveys. Methods: Spearman correlation analysis of survey answers from 232 registry members in the foundation revealed negative correlations between quality of life and clinical features such as autism spectrum disorder (-.20**) and cancer diagnoses (-.21**). Results: This suggests that the more severe and penetrant cases of PHTS on the spectrum of variability face challenges that negatively impact quality of life. Additionally, 72.6% of participants reported that reducing cancer risk is a top priority. Conclusions: The findings highlight the need for healthcare providers to anticipate the need for extra care and psychosocial attention for individuals with PHTS who have an autism diagnosis, and to provide education and counseling about cancer prevention strategies to those with a heightened cancer risk. [Table: see text]
Assessing the efficacy and safety of a novel, registration-free, CT-guided percutaneous transthoracic needle biopsy navigation system (RC120): A multicenter, prospective, single-arm clinical trial.
Authors: Zhou Caicun , Wang Lei , Min Xuhong , Song Biao , Zhang Zheng , Bo Bing , Xiong Anwen , Ye Lingyun , Xie Dacheng , Li Juanjuan , Wang Shanghu , Li Yuan , Song Qilong , Wang Zhaohua , Wang Mengjie , Cao Yanan , Liu Jian , Niu Bing , Fang Chunfu , Shen Shuting 
Published: August 2024

197 Background: Current optical and electromagnetic navigation systems for CT-guided percutaneous transthoracic needle biopsies (PTNB) have limitations. They require surface markers on the patient and intraoperative registration. Specific patient positioning during biopsies is required. Our team developed a new navigation system that addresses these issues. It doesn’t rely on patient surface markers or intraoperative registration, and it provides more flexibility in patient positioning during biopsies. Our research evaluates the effectiveness and safety of this system. Methods: A single-arm prospective study was conducted, including participants aged 18-80 years prepared for percutaneous lung core biopsy at two clinical centers in China. The primary endpoint was the success rate of biopsies within 2 needle adjustments. The secondary endpoint was the success rate of biopsies within a single needle adjustment. Safety endpoints were defined by the occurrence of adverse events. The number of CT scans patients underwent during the procedure was used to assess radiation dosage. Follow-up was conducted on subsequent pathological and molecular diagnoses. Results: The study included 98 patients from two sites, with a median age of 64 years. Most participants were males, accounting for 72.45% (71 out of 98). The primary endpoint was achieved with a biopsy success rate of 98.98%, requiring a maximum of two needle adjustments. The secondary endpoint was met, demonstrating a biopsy success rate of 97.96% with a maximum of one needle adjustment. The overall success rate was 98.98%, with a 95% confidence interval (CI) of 94.45% to 99.97%, significantly exceeding the target value of 85% (P < 0.0001). The median number of CT scans was 3, ranging from 3 to 12. The average duration of the procedure was 18.0 minutes. Regarding safety endpoints, the two most common adverse events were hemorrhage in the lesion (14 instances, 29.17%) and pneumothorax (8 instances, 16.67%). Other adverse events included elevated blood pressure (5 instances, 10.42%), hemoptysis (4 instances, 8.33%), and other common adverse events such as cough, constipation, anemia, and bloody sputum, each occurring twice. There were 9 other less common adverse events, each occurring once. These adverse events are common in PTNB and can be attributed to the puncture operation itself, not our navigation system. Conclusions: Our new registration-free navigation system proved to be an effective, efficient, safe, and well-utilized system for assisting percutaneous lung biopsies in clinical practice. Clinical trial information: ChiCTR2300072197 .