bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sintilimab Plus Apatinib and Chemotherapy as Second‑/Third-Line treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a prospective, Single-Arm, phase II trial
Authors: Zhang Le , Wang Weixue , Ge Shaohua , Li Hongli , Bai Ming , Duan Jingjing , Yang Yuchong , Ning Tao , Liu Rui , Wang Xia , Ji Zhi , Wang Feixue , Zhang Haiyang , Ba Yi , Deng Ting 
Published: March 2023

Abstract
Background
The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients.

Methods
In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety.

Results
From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred.

Conclusion
Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer.

Trial registration
ClinicalTrials.gov: NCT05025033, 27/08/2021.
Electrocardiographic and biochemical analysis of anthracycline induced cardiotoxicity in breast cancer patients from Southern Sri Lanka
Authors: Sandamali Jayasinghe Arachchige Nirosha , Hewawasam Ruwani Punyakanthi , Fernando Madappuli Arachchige Chaminda Sri S , Jayatilaka Kamani Ayoma Perera Wijewardana 
Published: March 2023

Abstract
Background
The clinical application of anthracycline chemotherapy is hindered due to the cumulative dose-dependent cardiotoxicity followed by the oxidative stress initiated during the mechanism of action of anthracyclines. Due to a lack of prevalence data regarding anthracycline-induced cardiotoxicity in Sri Lanka, this study was conducted to determine the prevalence of cardiotoxicity among breast cancer patients in Southern Sri Lanka in terms of electrocardiographic and cardiac biomarker investigations.

Methods
A cross-sectional study with longitudinal follow-up was conducted among 196 cancer patients at the Teaching Hospital, Karapitiya, Sri Lanka to determine the incidence of acute and early-onset chronic cardiotoxicity. Data on electrocardiography and cardiac biomarkers were collected from each patient, one day before anthracycline (doxorubicin and epirubicin) chemotherapy, one day after the first dose, one day and six months after the last dose of anthracycline chemotherapy.

Results
Prevalence of sub-clinical anthracycline-induced cardiotoxicity six months after the completion of anthracycline chemotherapy was significantly higher (p < 0.05) and there were strong, significant (p < 0.05) associations among echocardiography, electrocardiography measurements and cardiac biomarkers including troponin I and N-terminal pro-brain natriuretic peptides. The cumulative anthracycline dose, > 350 mg/m2 was the most significant risk factor associated with the sub-clinical cardiotoxicity in breast cancer patients under study.

Conclusion
Since these results confirmed the unavoidable cardiotoxic changes following anthracycline chemotherapy, it is recommended to carry out long-term follow-ups in all patients who were treated with anthracycline therapy to increase their quality of life as cancer survivors.
Primary retroperitoneal mucinous cystic tumour of borderline malignancy mimicking kidney duplicate: cases report and literature review
Authors: Zhang Junlong , Zeng Qinsong , Kang Jihui , Chen Junxing , Luo Guiyuan , Liang Yueyou 
Published: March 2023

Abstract
Background
Primary retroperitoneal mucinous cystic tumours with borderline malignancy (PRMC-BM) are rare and difficult to diagnose preoperatively. We are the first to report two cases of PRMC-BM which mimic a duplex kidney and evaluate the outcomes of different surgical procedures.

Case presentation
We describe two cases of retroperitoneal cystic tumours. Both were diagnosed with duplex kidney with hydronephrosis on computed tomography scan. The first patient underwent robot-assisted laparoscopic surgery and was found to have a retroperitoneal cystic tumour. The other patient underwent an ultrasound-guided puncture before surgery and was diagnosed with retroperitoneal lymphangioma. Retroperitoneal cystectomy was performed using an open transperitoneal procedure. The final pathologic diagnosis in both cases implies PRMC-BM. The open surgical approach was associated with a shorter operation time, less intraoperative blood loss, and protected cyst wall integrity by comparing the different surgical approaches. During follow-up, the patient in the first case had tumour recurrence six months post-surgery, and the other patient was healthy without recurrence or metastasis 12 months post-surgery.

Conclusions
Primary retroperitoneal mucinous cystic tumours with borderline malignancy can be enclosed within the kidney and misdiagnosed as other cystic diseases of the urinary system. Thus, an open surgical approach may be more suitable for this type of tumour.
Association of G6PD status and haemolytic anaemia in patients receiving anti-malarial agents: a systematic review and meta-analysis
Authors: Nelwan Erni J. , Shakinah Sharifah , Pasaribu Adeline 
Published: March 2023

Abstract
Background
Some anti-malarial drugs often cause haemolytic anaemia in glucose-6-phosphate-dehydrogenase deficiency (G6PDd) patients. This study aims to analyse the association of G6PDd and anaemia in malaria patients receiving anti-malarial drugs.

Methods
A literature search was performed in major database portals. All studies searched using keywords with Medical Subject Headings (MeSH) were included, without date or language restriction. Pooled mean difference of haemoglobin and risk ratio of anaemia were analysed using RevMan.

Results
Sixteen studies comprising 3474 malaria patients that included 398 (11.5%) with G6PDd were found. Mean difference of haemoglobin in G6PDd/G6PD normal (G6PDn) patients was − 0.16 g/dL (95% CI − 0.48, 0.15; I2 5%, p = 0.39), regardless of the type of malaria and dose of drugs. In particular with primaquine (PQ), mean difference of haemoglobin in G6PDd/G6PDn patients with dose < 0.5 mg/kg/day was − 0.04 (95% CI − 0.35, 0.27; I2 0%, p = 0.69). The risk ratio of developing anaemia in G6PDd patients was 1.02 (95% CI 0.75, 1.38; I2 0%, p = 0.79).

Conclusion
Single or daily standard doses of PQ (0.25 mg/kg/day) and weekly PQ (0.75 mg/kg/week) did not increase the risk of anaemia in G6PDd patients.
A simplified point-of-service model for hepatitis C in people who inject drugs in South Africa
Authors: Saayman Elaine , Hechter Vanessa , Kayuni Ndoliwe , Sonderup Mark W. 
Published: March 2023

Abstract
Background
Globally, 9% of people who inject drugs (PWID), a key hepatitis C-infected population, reside in sub-Saharan Africa. In South Africa, hepatitis C seroprevalence in PWID is high. It is almost 84% in Pretoria and hepatitis C genotypes 1 and 3 predominate. Access to hepatitis C care for PWID is inadequate given low referral rates, socio-structural barriers, homelessness and limited access to harm reduction. Traditional care models do not address the needs of this population. We piloted a simplified complete point-of-service care model, a first of its kind in the country and sub-continental region.

Methods
Community-based recruitment from Pretoria’s PWID population occurred over 11 months. Participants were screened with point-of-care rapid diagnostic tests for HBsAg (Alere Determine™), hepatitis C and HIV antibodies (OraQuick®). Qualitative HCV viremia was confirmed on site with Genedrive® (Sysmex), similarly at week 4, end of treatment and to confirm sustained virological response. Viremic hepatitis C participants were initiated on 12 weeks of daily sofosbuvir and daclatasvir. Harm reduction and adherence support, through directly observed therapy, peer support, a stipend and transport, was provided.

Results
A total of 163 participants were screened for hepatitis C antibody, and 66% were positive with 80 (87%) viremic. An additional 36 confirmed hepatitis C viremic participants were referred. Of those eligible to initiate treatment, 87 (93%) were commenced on sofosbuvir and daclatasvir, with 98% (n = 85) male, 35% (n = 30) HIV co-infected, 1% (n = 1) HBV co-infected and 5% (n = 4) HIV/HBV/HCV triple infected. Some 67% (n = 58) accessed harm reduction packs, 57% (n = 50) opioid substitution therapy and 18% (n = 16) stopped injecting. A per protocol sustained virological response of 90% (n = 51) was achieved with 14% (n = 7) confirmed reinfections following a sustained virological response. HCV RNA qualitative testing performance was acceptable with all sustained virological responses validated against a laboratory assay. Mild adverse effects were reported in 6% (n = 5). Thirty-eight percent (n = 33) of participants were lost to follow-up.

Conclusion
In our setting, a simplified point-of-service hepatitis C care model for PWID yielded an acceptable sustained virological response rate. Retention in care and follow-up remains both challenging and central to success. We have demonstrated the utility of a model of care for our country and region to utilize this more community acceptable and simplified practice.
Role and mechanism of PIM family in the immune microenvironment of diffuse large B cell lymphoma
Authors: Wang Changying , Chen Qitian , Luo Haichao , Chen Ran 
Published: March 2023

Abstract
Background
Diffuse large B cell lymphoma (DLBCL) is a more common non-Hodgkin lymphoma (NHL). This study aims to explore the prognostic value of PIM kinase family in DLBCL and its relationship with the immune microenvironment, to provide a certain reference for the prognosis and treatment of DLBCL.

Methods
The prognostic value of PIM kinase family in DLBCL from the data set GSE10846 was verified through survival analysis and cox regression analysis. Mutations in PIM kinase family and its relationship with immune cell infiltration were explored with online cBioPortal, TIMER database, and single-gene GSEA analysis. Finally, the expression of PIM kinase family in tissues from DLBCL clinical samples was validated through immunohistochemical staining.

Results
The proteins of PIM kinase family were highly expressed in DLBCL patients, which are good prognostic factors for DLBCL patients. Then, PIM1-3 proteins were positively correlated with the immune infiltration of B cells, whose types of mutations also showed different degrees of correlation with B cells. PIM kinase family proteins also showed a high correlation with PDL1. In addition, PIM kinase family was also associated with the commonly mutated genes in DLBCL, such as MYD88, MYC, and BTK.

Conclusion
PIM kinase family may be a potential therapeutic target for DLBCL patients.
T cell effects and mechanisms in immunotherapy of head and neck tumors
Authors: Xiang Yizhen , Gong Mengdan , Deng Yongqin , Wang Hongli , Ye Dong 
Published: March 2023

AbstractHead and neck tumors (HNCs) are a common tumor in otorhinolaryngology head and neck surgery, accounting for 5% of all malignant tumors in the body and are the sixth most common malignant tumor worldwide. In the body, immune cells can recognize, kill, and remove HNCs. T cell-mediated antitumor immune activity is the most important antitumor response in the body. T cells have different effects on tumor cells, among which cytotoxic T cells and helper T cells play a major killing and regulating role. T cells recognize tumor cells, activate themselves, differentiate into effector cells, and activate other mechanisms to induce antitumor effects. In this review, the immune effects and antitumor mechanisms mediated by T cells are systematically described from the perspective of immunology, and the application of new immunotherapy methods related to T cells are discussed, with the objective of providing a theoretical basis for exploring and forming new antitumor treatment strategies.
Integration of longitudinal deep-radiomics and clinical data improves the prediction of durable benefits to anti-PD-1/PD-L1 immunotherapy in advanced NSCLC patients
Authors: Farina Benito , Guerra Ana Delia Ramos , Bermejo-Peláez David , Miras Carmelo Palacios , Peral Andrés Alcazar , Madueño Guillermo Gallardo , Jaime Jesús Corral , Vilalta-Lacarra Anna , Pérez Jaime Rubio , Muñoz-Barrutia Arrate , Peces-Barba German R. , Maceiras Luis Seijo , Gil-Bazo Ignacio , Gómez Manuel Dómine , Ledesma-Carbayo María J. 
Published: March 2023

Abstract
Background
Identifying predictive non-invasive biomarkers of immunotherapy response is crucial to avoid premature treatment interruptions or ineffective prolongation. Our aim was to develop a non-invasive biomarker for predicting immunotherapy clinical durable benefit, based on the integration of radiomics and clinical data monitored through early anti-PD-1/PD-L1 monoclonal antibodies treatment in patients with advanced non-small cell lung cancer (NSCLC).

Methods
In this study, 264 patients with pathologically confirmed stage IV NSCLC treated with immunotherapy were retrospectively collected from two institutions. The cohort was randomly divided into a training (n = 221) and an independent test set (n = 43), ensuring the balanced availability of baseline and follow-up data for each patient. Clinical data corresponding to the start of treatment was retrieved from electronic patient records, and blood test variables after the first and third cycles of immunotherapy were also collected. Additionally, traditional radiomics and deep-radiomics features were extracted from the primary tumors of the computed tomography (CT) scans before treatment and during patient follow-up. Random Forest was used to implementing baseline and longitudinal models using clinical and radiomics data separately, and then an ensemble model was built integrating both sources of information.

Results
The integration of longitudinal clinical and deep-radiomics data significantly improved clinical durable benefit prediction at 6 and 9 months after treatment in the independent test set, achieving an area under the receiver operating characteristic curve of 0.824 (95% CI: [0.658,0.953]) and 0.753 (95% CI: [0.549,0.931]). The Kaplan-Meier survival analysis showed that, for both endpoints, the signatures significantly stratified high- and low-risk patients (p-value< 0.05) and were significantly correlated with progression-free survival (PFS6 model: C-index 0.723, p-value = 0.004; PFS9 model: C-index 0.685, p-value = 0.030) and overall survival (PFS6 models: C-index 0.768, p-value = 0.002; PFS9 model: C-index 0.736, p-value = 0.023).

Conclusions
Integrating multidimensional and longitudinal data improved clinical durable benefit prediction to immunotherapy treatment of advanced non-small cell lung cancer patients. The selection of effective treatment and the appropriate evaluation of clinical benefit are important for better managing cancer patients with prolonged survival and preserving quality of life.
J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies
Authors: He Linfeng , Zheng Wenbin , Li Zeyu , Chen Lu , Kong Wen , Zeng Tianshu 
Published: March 2023

AbstractBackgroundPrevious studies have reported that high fasting plasma glucose (FPG), even that within the normal range, is associated with the risk of type 2 diabetes (T2D). Nevertheless, these findings are limited to specific populations. Thus, studies in the general population are imperative.MethodsThis study included two cohorts comprising 204 640 individuals who underwent physical examinations at the Rich Healthcare Group present at 32 locations in 11 cities of China from 2010 to 2016 and 15 464 individuals who underwent physical tests at the Murakami Memorial Hospital in Japan. Cox regression, restricted cubic spline (RCS), Kaplan–Meier (KM) curves, and subgroup analysis were used to determine the relationship between FPG and T2D. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of FPG for T2D.ResultsThe mean age of the 220 104 participants (204 640 Chinese and 15 464 Japanese participants) was 41.8 years (41.7 years for the Chinese and 43.7 years for the Japanese participants). During follow-up, 2611 individuals developed T2D (2238 Chinese and 373 Japanese participants). The RCS demonstrated a J-shaped relationship between FPG and T2D risk, with inflexion points of 4.5 and 5.2 for the Chinese and Japanese populations, respectively. Multivariate-adjusted hazard ratio (HR) was 7.75 for FPG and T2D risk after the inflexion point (7.3 for Chinese and 21.13 for Japanese participants).ConclusionsIn general Chinese and Japanese populations, the normal baseline FPG range showed a J-shaped relationship with the risk of T2D. Baseline FPG levels help identify individuals at high risk of T2D and may enable early primary prevention to improve their outcomes.
CAR T cell therapy for T cell leukemia and lymphoma: latest updates from 2022 ASH Annual Meeting
Authors: Huang Qiusha , Zhang Xiao-hui , Liu Delong 
Published: March 2023

AbstractDue to the concern of fratricide, clinical development of CAR T cells for the therapy of T cell malignancies lags behind that for B cell malignancies. Attempts are being made to revise T cell biomarkers so that the re-engineered CAR T cells can target T cell malignancies. CD3 and CD7 are the two pan-T cell surface biomarkers that have been either knocked out or knocked down through genome base- editing technology or by protein expression blockers so that the re-engineered T cells can target T cells without fratricide. We summarized several latest reports on the CAR T cells for the therapy of T cell leukemia /lymphoma from the 2022 ASH Annual Meeting, with latest updates on clinical trials of TvT CAR7, RD-13-01, and CD7 CART.
Shock index as predictor of massive transfusion and mortality in patients with trauma: a systematic review and meta-analysis
Authors: Carsetti Andrea , Antolini Riccardo , Casarotta Erika , Damiani Elisa , Gasparri Francesco , Marini Benedetto , Adrario Erica , Donati Abele 
Published: March 2023

Abstract
Background
Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality.

Methods
This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2.

Results
Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR−) were 4.24 [3.18–5.65] and 0.39 [0.29–0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR− were 1.39 [1.36–1.42] and 0.87 [0.85–0.89], respectively.

Conclusions
Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.
S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity
Authors: Muñoz-Bernart Melina , Budnik Nicolás , Castro Araceli , Manzi Malena , Monge María Eugenia , Pioli Julieta , Defranchi Sebastián , Parrilla Gustavo , Santilli Juan Pablo , Davies Kevin , Espinosa Joaquín M. , Kobayashi Ken , Vigliano Carlos , Perez-Castro Carolina 
Published: March 2023

Abstract
Background
Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown.

Results
Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features.

Conclusions
These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.
A green protocol ball milling synthesis of dihydropyrano[2,3-c]pyrazole using nano-silica/aminoethylpiperazine as a metal-free catalyst
Authors: Mallah Dina , Mirjalili Bi Bi Fatemeh 
Published: March 2023

Abstract
Background
Ball mill is an effective, and green method for the synthesis of heterocyclic compounds in very good yields. This method is a simple, economical, and environmentally friendly process. In this work, an efficient approach for the synthesis of pyranopyrazoles (PPzs) using ball milling and metal-free nano-catalyst (Nano-silica/aminoethylpiperazine), under solvent-free conditions was reported.

Results
The new nano-catalyst silica/aminoethylpiperazine was prepared by immobilization of 1-(2-aminoethyl)piperazine on nano-silica chloride. The structure of the prepared nano-catalyst was identified by FT-IR, FESEM, TGA, EDX, EDS-map, XRD, and pH techniques. This novel nano-catalyst was used for the synthesis of dihydropyrano[2,3-c]pyrazole derivatives under ball milling and solvent-free conditions.

Conclusions
Unlike other pyranopyrazoles synthesis reactions, this method has advantages including short reaction time (5–20 min), room temperature, and relatively high efficiency, which makes this protocol very attractive for the synthesis of pyranopyrazoles derivatives.