bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a LAMP method with lateral flow DNA chromatography to diagnose toxoplasmosis in immunocompromised patients
Authors: Mikita Kei , Mori Takehiko , Komine Tamayo , Kobayashi Seiki , Iwata Satoshi , Suzuki Koichi , Hasegawa Naoki 
Published: July 2024

Abstract
Background
Rapid and accurate diagnosis of toxoplasmosis is critical, particularly for immunocompromised patients. Several molecular methods could have value for toxoplasmosis diagnosis, but often require sophisticated and expensive equipment, and as such are impractical for use in resource-limited countries. Our study aimed to develop a new rapid diagnostic test for toxoplasmosis that can be used in developed countries as well as low- or middle-income countries.

Methods
Common primers for conventional loop-mediated isothermal amplification (LAMP) and the new LAMP DNA chromatography method were designed based on a 529-bp repeat present in Toxoplasma gondii genomic DNA. A total of 91 clinical samples from 44 patients suspected of having toxoplasmosis who were treated at several hospitals across Japan were tested using the new LAMP DNA chromatography method, conventional LAMP, and nested PCR and the sensitivity and specificity of the methods was compared.

Results
The LAMP DNA chromatography method showed better sensitivity and specificity (68.2% and 100%, respectively) compared with the nested PCR (45.4% and 100%, respectively) and conventional LAMP (63.6% and 100%, respectively) methods for diagnosis of toxoplasmosis in immunocompromised patients. LAMP DNA chromatography also has better sensitivity and specificity (75% and 100%, respectively) than nested PCR (50.0% and 93.5%, respectively) and conventional LAMP (62.5% and 100%, respectively) to diagnose toxoplasma encephalitis using CSF samples.

Conclusion
We developed a LAMP DNA chromatography method to detect T. gondii DNA in clinical samples. This method also successfully detected T. gondii DNA in CSF from patients with toxoplasma encephalitis. This newly developed method can be a valuable rapid diagnostic test for toxoplasmosis in a range of settings, including resource-limited areas like those in low- or middle-income countries.
Breaking from the paradigm of antibody-drug conjugates: Evaluation of clinical pharmacokinetics and safety of bicycle toxin conjugates (BTCs).
Authors: Bader Justin , McKean Meredith , DeMars Leslie Robbins , Lu Yasong , Li Mengyao , Dickson Amy , Bennett Gavin , Arroyo Santiago , Fontana Elisa , Carter Louise , Rodon Ahnert Jordi , Falchook Gerald Steven , Xu Hongmei 
Published: July 2024

3088 Background: Bicycle toxin conjugates (BTCs) are chemically synthesized molecules comprising a small (~4.5 kDa) bicyclic peptide linked to a cytotoxin. BT8009 and BT5528 are BTCs linked to monomethyl auristatin E (MMAE) targeting nectin-4 and EphA2, respectively, and have shown preliminary activity. BTCs are a unique therapeutic class of small size, with corresponding pharmacokinetic (PK) properties distinct from antibody-drug conjugates (ADCs). MMAE-containing ADCs demonstrate anti-tumor efficacy but substantial safety issues attributable to the slow clearance of ADCs, which increases uptake into off-target tissues and exposure to plasma proteases (ie, payload release).To evaluate BTC PK and safety relative to ADCs, we present results of the ongoing Phase I/II trials for BT8009 (NCT04561362) and BT5528 (NCT04180371). Methods: Patients with advanced solid tumors receiving IV BT8009 (n=147) or BT5528 (n=109) monotherapy were evaluated. Doses were given as 2.5–10 mg/m2 weekly (QW), every 2 weeks (Q2W), or 2 weeks on/1 week off for BT8009 and 2.2–10 mg/m2 QW or Q2W for BT5528. Population PK (PPK) models for BT8009 and BT5528 were developed. PK exposures (Cycle 1 area under the concentration curve [AUC]) for BTCs, conjugated MMAE, and unconjugated MMAE were simulated for 5 mg/m2 QW BT8009 and BT5528 and compared with those of an MMAE-containing ADC (approved regimen, using the PPK model in the literature). Treatment-related adverse events (TRAEs) were tabulated for BT8009 and BT5528. Results: BTCparent drugs were rapidly eliminated (half-life [t1/2] <1 hour) while unconjugated MMAE exhibited persistent exposures and gradual elimination (MMAE t1/2, 1.9 days [D] for both BT8009 and BT5528), in contrast with the ADC (parent drug t1/2, 3.6 D; MMAE t1/2, 2.6 D). Conjugated MMAE exposures for the ADC were higher than for BT8009 and BT5528 (75- and 73-fold, respectively). Unconjugated MMAE exposures for BT8009 and BT5528 were comparable to the ADC (25% and 8% higher, respectively). Among the BTC regimens most thoroughly evaluated (BT8009 5 mg/m2 QW and BT5528 6.5 mg/m2 Q2W), TRAEs of interest occurred with low frequency and severity (Table). Conclusions: Preliminary data show substantial differences between BTC and ADC PK, and a promising BTC safety profile, possibly resulting from the distinct PK and selectivity (and specificity) of Bicycle peptides. These data highlight the potential value of BTCs as a platform for developing therapies against advanced malignancies. Clinical trial information: NCT04561362 and NCT04180371 . [Table: see text]
A prospective phase II study of an exercise-nutrition-psychology integrated rehabilitation model based on mobile health and virtual reality for patients with cancer.
Authors: Qi Yuan , Xue Ya , Wang MengJie , Yue Jingyan , Meng Weifen , Zhu Wenyu , Pu Xiaolin , Li Dongqing , Jiang Hua 
Published: July 2024

e13786 Background: The optimal rehabilitation model for patients with cancer is unclear. Nutritional and psychological interventions have proven to be beneficial for this population. Although mobile health (mHealth) and virtual reality (VR) advances have transformed many clinical areas including cardiovascular and psychiatric care, they are relatively nascent in cancer care. Due to the multidimensional rehabilitation needs of patients, here we explored the feasibility of an exercise-nutrition-psychology rehabilitation model in cancer patients, which based on VR and mHealth. Methods: A single-center, single-arm, prospective phase II study was conducted from November 2022 to April 2023. With the help of mHealth participants received standard cancer therapy and integrated interventions featuring in-person group-based exercise classes, at-home physical activity prescription, behavior change education, nutritional instruction, oral nutritional supplements (Ainst, China), music therapy (MT), VR treatment and psychological counselling. The rehabilitation was provided by a team of medical oncologists, dietitians, psychotherapists, and technicians. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (total 8 weeks). The primary endpoint was the feasibility. The paired T test was used to analyze and compare the differences. Results: At the cutoff date of April,10, 2023. 165 patients were screened, 123 were recruited, and the recruitment rate was 75% (123/165). 14 (11.4%) patients were lost to follow-up, and 4 (3.25%) withdrew halfway. Respectively, the completion rate of exercise, nutrition, and VR and mHealth based psychology were 55% (68 / 123), 85% (105 / 123), and 63% (78 / 123). The parameters in nutrition, psychology, and muscle mass after the rehabilitation showed significant improvements than before (P<0.05). There was no significant statistical difference (P> 0.05)in 6-minute walking speed and handgrip strength. All functional domains of life quality were significantly improved, except role optimization function (P> 0.05). Conclusions: The mHealth and VR based exercise-nutrition-psychology integrated rehabilitation model is feasible for cancer patients and shows potential benefits. The mHealth application (app) we used is a rudimentary version and needs to be optimized in the future. This rehabilitation model warrants further investigation in a larger cohort trial. Clinical trial information: ChiCTR2200065748.
Whole exome sequencing analysis of intratumoral heterogeneity, tumor neoantigen burden and human leukocyte antigen loss of heterozygosity in HCC.
Authors: Liao Wenting , Xiao Yue , Guo Wei 
Published: July 2024

e16003 Background: Hepatocellular Carcinoma (HCC) patients has a high postoperative recurrence within 2 years and a low 5-year survival rate. However, molecular mechanisms for early recurrence are poorly understood. Immune checkpoint blockades (ICBs) show clinical benefits in HCC, with the immune microenvironment influencing ICBs therapeutic effects. Exploring the relationship between intratumoral heterogeneity (ITH), tumor neoantigen burden (TNB), and human leukocyte antigen loss of heterozygosity (HLA LOH) can deepen our understanding of the immune evasion mechanisms. Methods: In this study, whole exome sequencing (WES) was employed to analyze tumor specimens and matched peripheral blood controls derived from a cohort of 235 HCC patients. PD-L1 expression levels were assessed in the samples using immunohistochemistry. NetMHCpan was applied to predict neoantigen and quantified the peptide affinity of MHC-I genes measured by IC50. Neoantigen-MHC affinity was categorized as strong (IC50≤50nM), weak (50nM < IC50≤500nM), and negative (IC50 > 500nM). TNB was defined by the number of high affinity neoantigens per megabase in WES. Analysis of LOH was performed on HLA-I class genes and categorized as strong positive, weak positive, and negative groups. We used PyClone to conduct ITH analysis to assess the distribution of multiple subclones within a tumor. The average Cancer Cell Fraction (CCF) for each somatic mutation cluster was calculated, and these clusters were classified into major clones and subclones. Results: In 235 HCC samples, median TMB and TNB were 2.48 Muts/Mb and 0.30 Neos/Mb. Only 6.81% exhibited TMB-H (TMB≥10 Muts/Mb). TMB and TNB are significantly positively correlated (p < 0.0001). HLA LOH occurred in 19.57% HCC patients, with high LOH samples having more high-affinity neoantigens (mean TNB 1.65 Neos/Mb). ITH analysis showed that 83.83% samples harbored subclonal clusters. HCC samples were divided into high (ITH≥0.908) and low (ITH < 0.908) groups according to the median ITH of 0.908. High ITH group had higher TNB (median 0.43 vs 0.20 Neos/Mb) , more HLA LOH (9.24% vs 5.17% strong positive LOH). The high ITH groups exhibited a lower percentage of samples with elevated PD-L1 expression (14.29% vs 25.86%). The Combined Positive Score (CPS) revealed a significant difference between the groups (Fisher's test p = 0.03). Conclusions: In HCC, the high ITH group exhibited a higher proportion of HLA LOH compared to the low ITH group. Moreover, a decreased proportion of PD-L1 positive samples was observed in the high ITH group, suggesting that high ITH may be a key factor influencing treatment failure in immunotherapy. ITH analysis demonstrated a potential multi-subclonal origin of recurrent tumor cells, which is associated with immune escape, tumor malignancy,as well as the development of resistance.
SLC7A11 as a prognostic biomarker for hepatocellular carcinoma.
Authors: Wang Yuxi , Li Xi , Zhou Ya , Meng Xiao , Wang Ying , Liu Xiaomei 
Published: July 2024

e16004 Background: Disulfidptosis has been discovered as a mechanism of cell death mediating by SLC7A11. Nonetheless, little is known about the relationship between SLC7A11 and hepatocellular carcinoma (HCC). Methods: The clinical and follow-up data of 84 consecutive HCC cases who met the inclusion criteria from 2016 to 2019 were retrospectively analyzed. The expression level of SLC7A11 in tissue samples was determined by immunohistochemistry. Kaplan-Meier and Cox regression analyses were performed to assess the correlation between survival and SLC7A11 expression in HCC patients. Results: We observed that SLC7A11 expression in HCC tissue is significantly higher than that in corresponding para-cancer tissue. Positive immunostaining SLC7A11 of was mainly located in the cytoplasm of HCC. Univariate analysis indicated that clinical pathological features such as expression level of SLC7A11, cirrhosis and stages were all risk factors affecting OS (P < 0.001). Multivariate COX analysis showed that expression level of SLC7A11 was independent risk factors for OS and high-level expression of SLC7A11 indicated poor overall survival for pHCC (P < 0.001). Conclusions: Our study showed that SLC7A11 might be a potential poor prognostic biomarker in HCC and represents a novel diagnostic marker and therapeutic target for HCC. Keywords: SLC7A11; disulfidptosis; hepatocellular carcinoma; prognostic biomarker.
The feasibility and tolerability of anlotinib plus PD-1 blockades among patients with previously immunotherapy treated advanced esophageal squamous cell carcinoma (ESCC): Update results of a retrospective exploratory study.
Authors: Huang Jing , Hong Yong-Gui , Liu Jun , Lu Ping , Chang Zhiwei , Zhang Guifang , Ma Xiumei , Liang Wei , Tian Yongjing , Xia Jin , Cao Heng 
Published: July 2024

e16006 Background: Immunotherapy (ICI) demonstrated promising efficacy for patients with advanced ESCC in both second-line and first-line treatment clinically. Therefore, whether the patients might benefit from the PD-1 blockades-related regimens when they failed after the previous ICI remained to be identified and the feasibility of PD-1 blockades rechallenge in ESCC was warranted to be explored. As a novel oral multi-targeted tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferation, anlotinib was an efficacious second-line monotherapy for ESCC in China and the combination of anlotinib plus PD-1 blockades might be a promising strategy for patients with previously ICI treated advanced ESCC. Methods: This multicenter, retrospective study was planned to include 110 patients with previously ICI treated advanced ESCC from 9 hospitals in China who were treated with anlotinib plus PD-1 blockades in clinical practice from July 2018 to November 2022 consecutively. The Outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and safety. Results: At the date of data-cutoff (May 12 2023), 110 eligible patients were available to be analyzed. Characteristics were as follows: median age of 64 years, male/female 74.5%/25.5%, ECOG PS 0/1/2 22.7%/75.5%/1.8%, clinical stage II/III/IV 0.9%/20.9%/78.2%. All the patients had received ICIs and 10.9% patients were treated with TKIs previously. 39.1% patients had received first-line therapy, 41.8% patients had received second-line, 19.1% patients had received third or above line previously. Prognostic outcomes exhibited that the median OS was 11.1 months (95%CI: 8.6-13.7), 12-month OS rate, 24-month OS rate were 47.6% and 30.8%, separately. Additionally, the median PFS was 5.6 months (95%CI: 4.4-6.8). In 110 patients, ORR was 19.1% (95%CI: 12.2%-27.7%), DCR 69.1% (95%CI: 59.6%-77.6%). Safety profile of anlotinib plus PD-1 blockades indicated that the treatment related adverse events (TRAEs) were 89.1%. The most common TRAEs were anaemia (62.7%), hypothyroidism (25.5%), hypoalbuminemia (21.8%), lymphocytopenia (20%), leukopenia (19.1%). Conclusions: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and tolerable adverse reactions among patients with advanced ESCC who had received immunotherapy previously and the feasibility of PD-1 blockades rechallenge in ESCC was promising to be elucidated. Clinical trial information: ChiCTR2300070777.
Predictive value of positive lymph node ratio in patients with locally advanced gastric remnant cancer.
Authors: Zhuo Meng , Han Ting , Lin Xiaolin , Xiao Xiuying 
Published: July 2024

e16119 Background: Traditional lymph node stage (N stage) has limitations in advanced gastric remnant cancer (GRC)patients; therefore, establishing a new predictive stage is necessary.To explore the predictive value of positive lymph node ratio (LNR) according to clinicopathological characteristics and prognosis of locally advanced GRC. Methods: Seventy-four patients who underwent radical gastrectomy and lymphadenectomy for locally advanced GRC were retrospectively reviewed. The relationship between LNR and clinicopathological characteristics was analyzed. The survival analysis was performed using Kaplan–Meier survival curves and Cox regression model. Results: Number of metastatic LNs, tumor diameter, depth of tumor invasion, Borrmann type, serum tumor biomarkers, and tumor–node–metastasis (TNM) stage were correlated with LNR stage and N stage. Univariate analysis revealed that the factors affecting survival included tumor diameter, anemia, serum tumor biomarkers, vascular or neural invasion, combined resection, LNR stage, N stage, and TNM stage (all P < 0.05). The median survival time for those with LNR0, LNR1, LNR2 and LNR3 stage were 61, 31, 23 and 17 mo, respectively, and the differences were significant ( P = 0.000). Anemia, tumor biomarkers and LNR stage were independent prognostic factors for survival in multivariable analysis (all P < 0.05). Conclusions: The new LNR stage is uniquely based on number of metastatic LNs, with significant prognostic value for locally advanced GRC, and could better differentiate overall survival, compared with N stage.
Efficacy and safety of transarterial therapy combined with donafenib plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A multicenter retrospective study.
Authors: Shang Changzhen , Zhong Jinyi , Luo Xuan , Zhang Bo , Chen Huanwei , Wang Fengjie , Jiang Xiaofeng , Cao Liangqi , Shen Shun-Li , Chen Yajin 
Published: July 2024

e16133 Background: Based on the different anti-malignant mechanisms of tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) and transarterial therapy, several studies have demonstrated the potential of combining these three treatments to improve outcomes in patients with unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of transarterial therapy plus donafenib and ICIs for uHCC patients in a real-world setting. Methods: This multicenter retrospective study included patients with uHCC who had received at least one cycle of transarterial therapy (hepatic arterial infusion chemotherapy, HAIC, or transarterial chemoembolization, TACE) and donafenib and ICIs (anti-PD-1 available in China) at five cancer centers. Other key inclusion criteria were: (1) no prior systemic treatment; (2) at least one follow-up image data. The primary endpoint was progression-free survival (PFS) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included overall survival (OS), objective response rate (ORR) and toxicity. Results: Of the 61 eligible patients enrolled, 56 (91.8%) were men, 54 (88.5%) had HBV infection, 26 (42.6%) had AFP level > 400 ng/mL, 38 (62.3%) were at BCLC stage C, 32 (52.5%) had macrovascular invasion, 14 (23.0%) had extrahepatic metastasis, 47 (77.0%) had multiple tumors and the median maximum tumor size was 86.0 mm (IQR, 61.5–122.6). Four kinds of ICIs were employed, including tislelizumab (n = 29), camrelizumab (n = 21), sintilimab (n = 9), toripalimab (n = 2). Up to the date of November 24, 2023, the median follow-up time was 13.0 months. The median PFS was 12.7 months (95%CI, 8.4–NA), with a 1-year PFS rate of 52.7% (95%CI, 37.9%–73.1%). The median OS was not reached, and 1-year OS rate was 88.4% (95%CI, 79.9%–97.8%). The ORR according to mRECIST was 70.5%. Twelve (19.7%) patients had received conversion resection, and the median conversion time was 3.1 months (95%CI, 2.37–NA). Overall, 51 (83.6%) patients experienced at least one treatment-related adverse events (TRAEs), 22 (36.1%) had grade 3 or 4 AEs, and no patients died due to AEs. The most common AEs greater than 15% were hand-foot skin reaction (47.5%), liver dysfunction (27.9%), decreased platelet count (19.7%) and hypoalbuminemia (16.4%). Conclusions: This retrospective real-world study showed that transarterial therapy combined with donafenib plus ICIs in the treatment of uHCC patients was well tolerated and comparable clinical efficacy to other triple therapies. This combination strategy may be an appropriate treatment option for uHCC patients.
Efficacy and safety analysis of donafenib combined with transarterial chemoembolization in the treatment of unresectable hepatocellular carcinoma: A prospective, single-arm, single center, phase II clinical study.
Authors: Li Jinpeng , Chen Hua , Song Jinlong 
Published: July 2024

e16134 Background: To observe and assess the efficacy of donafenib combined with TACE in the treatment of unresectable hepatocellular carcinoma. Methods: It was a prospective, single-arm, single center, and phase II clinical study. A total of 34 initial unresectable HCC patients who had not received any systemic treatment were enrolled. The patients received donafenib ( 100mg po bid), TACE and or not and camrelizumab (200mg iv Q3W). The primary endpoint was short-term efficacy based on mRECIST criteria, with secondary endpoints including PFS, TTR, DCR and adverse events (AEs).The diameter of tumor feeding artery was measured. Results: A total of 36 patients were included in the study, including 26 who received donafenib and TACE and 10 who received donafenib and TACE plus PD-1 inhibitors. A total of 34 subjects were eligible for efficacy evaluation, and among them, there were 4 cases of CR, 17 cases of PR, 10 cases of SD and 3 cases of PD; Four patients (11.8%) successfully underwent conversion therapy and all achieved R0 resection. Two patients achieved a complete pathological response. The ORR was 61.8% and the DCR was 91.2% based on mRECIST criteria. The mPFS was 10.7 months (95%CI: 8.37-NA months), median OS was not reached, median TTR was 1.4 months ( 95% CI: 0.8-6.9 months). The 6 moths and 12 moths progression-free survival rate were 73.4% and 47.9% respectively. Treatment related adverse events (TRAEs) occurred in all 25 subjects, and grade 3 TRAE occurred in 4 subjects (11.3%), and no grade 4 or 5 TRAE occurred. The tumor feeding artery diameter was (4.5±1.4)mm pre-treatment, and reduced to (3.2±1.1)mm post-treatment (P = 0.036). The multivariable analysis indicated that the sum of baseline target lesion diameters、best tumor response and post-treatment tumor artery diameter were independent predictor for PFS. Conclusions: TACE combined with donafenib could reduce the tumor feeding artery diameter, which had a good safety profile and a high objective response rate in patients with unresectable HCC. Clinical trial information: ChiCTR2100054041.